IL SONNO VISTO DAL NEUROLOGO Luigi Ferini Strambi Università Vita-Salute San Raffaele, Milano.
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Transcript of IL SONNO VISTO DAL NEUROLOGO Luigi Ferini Strambi Università Vita-Salute San Raffaele, Milano.
IL SONNO VISTO DAL NEUROLOGO
Luigi Ferini Strambi
Universitagrave Vita-Salute San Raffaele Milano
PARAMETRI FISIOLOGICI PER LA DEFINIZIONE PARAMETRI FISIOLOGICI PER LA DEFINIZIONE DEL SONNODEL SONNO
CM S D
R
IPNOGRAMMAIPNOGRAMMA
Pre - sleep - WPre - sleep - W SWSSWS REM - sleepREM - sleep
Post - sleep - WPost - sleep - W
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
BRAUN et al Brain (1997)
Dijk and Edgar 1999 Lung Biology in Health and Disease vol133
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
PARAMETRI FISIOLOGICI PER LA DEFINIZIONE PARAMETRI FISIOLOGICI PER LA DEFINIZIONE DEL SONNODEL SONNO
CM S D
R
IPNOGRAMMAIPNOGRAMMA
Pre - sleep - WPre - sleep - W SWSSWS REM - sleepREM - sleep
Post - sleep - WPost - sleep - W
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
BRAUN et al Brain (1997)
Dijk and Edgar 1999 Lung Biology in Health and Disease vol133
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
IPNOGRAMMAIPNOGRAMMA
Pre - sleep - WPre - sleep - W SWSSWS REM - sleepREM - sleep
Post - sleep - WPost - sleep - W
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
BRAUN et al Brain (1997)
Dijk and Edgar 1999 Lung Biology in Health and Disease vol133
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Pre - sleep - WPre - sleep - W SWSSWS REM - sleepREM - sleep
Post - sleep - WPost - sleep - W
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
ACTIVATION
High DEACTIVATION
Low DEACTIVATION
BRAUN et al Brain (1997)
Dijk and Edgar 1999 Lung Biology in Health and Disease vol133
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Dijk and Edgar 1999 Lung Biology in Health and Disease vol133
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Arousal
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
SleepSleep No sleepNo sleep
acuteacutesleepsleep
deprivationdeprivation
Cortisol Cortisol (microgdl)(microgdl)
Thyrotropin Thyrotropin (microUml)(microUml)
ProlactinProlactin(ngml)(ngml)
Growth Growth HormoneHormone
(microgL)(microgL)
Clock TimeClock Time
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
10 14 18 22 02 06 10 10 14 18 22 02 06 10
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
0
5
10
15
20
25
0
5
10
15
20
0
5
10
15
20
01
02
03
04
05
10 14 18 22 02 06 10 10 14 18 22 02 06 10
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
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- Slide 13
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- Slide 17
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- Slide 37
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- Slide 39
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- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
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- Slide 49
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- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Cortisol rhythm
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
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- Slide 21
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- Slide 26
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- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Lange et al (2003) Psychosomatic Medicine 65 831-835
Sleep loss impairs the human antibody response to hepatisis A vaccination
total loss of sleep in the night following vaccination impairs immune response 28 days later
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
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- Slide 16
- Slide 17
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- Slide 21
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- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
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- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
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- Slide 49
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- Slide 51
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- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Response to influenza vaccination is impaired in individuals with chronic partial sleep restriction
Spiegel et al (2002) JAMA 288 1471-1472
Sleep restriction to 4 hoursnight for 4 days before and 2 days after vaccination impairs immune response to vaccination
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
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- Slide 19
- Slide 20
- Slide 21
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- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
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- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
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- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Structural MRI of the brains of humans with extensive navigation experience licenced London taxi drivers were analysed and compared to those of control subjects who did not drive taxiThe posterior hippocampi of taxi drivers were significantly larger relative to those of controlsA more anterior hippocampal region was larger in controls than in taxi drivershellip
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Mechanism of brain damage
Neurogenic or vasogenic
Potential contributors of cognitive impairment
Hypoxemia or sleep fragmentation
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
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- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
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- Slide 30
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Sleep-Disordered Breathing Hypoxia and Risk of Mild Cognitive Impairment and Dementia in Older Women Yaffe K et al JAMA 306 613-19 2011
Compared with the 193 women without sleep-disordered breathing the 105 women (352) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (adjusted odds ratioAOR = 185) Elevated oxygen desaturation index (ge15 eventshour) and high percentage of sleep time (gt7) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR= 171 and 204 respectively) Measures of sleep fragmentation (arousal index and wake after sleep onset) were not associated with risk of cognitive impairment
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
The hippocampus is one of the main and most consistently reported brain regions among the neural correlates of mild cognitive impairmenthelliphelliphelliphellip
No medications are known to prevent the progression of mild cognitive impairment to Alzheimerrsquos disease so treating at-risk patients with CPAP for sleep-disordered breathing is a prevention strategy that may be worth testing
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Neurocognitive Function
bull Odds of optimal users exhibiting normalization of memory function were 79 times (p 001) the odds of poor users
bull Normalization of memory abilities in
21 of poor users
44 of moderate users
68 of optimal users
Zimmerman et al CHEST 2006
58 memory impaired OSA
patients
Neuropsychological Testing
Neuropsychological Testing + Compliance
3 months CPAP
Poor Userslt2 hnight
Moderate Users2-6 hnight
Optimal Usersgt6 hnight
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
International Classification of Sleep Disorders 2005
bull INSOMNIAbull SLEEP-RELATED BREATHING DISORDERSbull HYPERSOMNIA OF CENTRAL ORIGINbull CIRCADIAN RHYTHM SLEEP DISORDERSbull PARASOMNIASbull SLEEP RELATED MOVEMENT DISORDERS
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Luyster F et al
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Chen R et al
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
PERIODIC LEGS MOVEMENTS (PLMs)
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Restless Legs Syndrome
Essential criteria
1) An urge to move the legs2) that is present at rest
3) relieved by movement and4) demonstrates a circadian
pattern (peak symptomsoccurring at night or in the
evening)
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Diagnostic criteria for RLS- Non essential but common features
bull Family history
bull Response to dopaminergic therapy
bull Experience of PLM during sleep or during wakefulness
bull Sleep disturbance
bull An increase in severity with advancing age
Allen et al Sleep Med 2003
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
PD patient 69 y male
AHI= 21 PLMI= 28
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Eur Res J in press
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
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- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
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- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
In RLS PLMs induce a repetitive rise in blood pressure and heart rate
RLS and periodic limb movementsRLS and periodic limb movements
Pennestri MH et al Neurology 2007681213ndash1218Siddiqui F et al Clin Neurophysiol 20071181923ndash1930
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
RLS patients show significant sleep microstructure abnormalities (increased cortical arousals)
Acute pramipexole administration seems to exert no action on these abnormalities and the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of pre-sleep RLS symptoms and PLMS
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
PLMS
CORTICAL AROUSALS
AUTONOMIC AROUSAL
INSOMNIA CV RISK
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Narcolepsy Repeated refreshing naps of short duration (lt1hr)
Recurrent hypersomnia Recurrent episodes of 18-20 hrs lasting 3-20 days 1-3 years
Idiopatic hypersomnia Prolonged (1-2 hrs) sleep episodes of NREM sleep and major sleep episode gt8 hrs
Post-traumatic hypersomnia
As above However the sleepiness is most evident in the immediate post-traumatic period and resolves over weeks to months
OSA Sleepiness in a relaxing situation unrefreshing naps (variable duration)
Insufficient sleep syndrome Sleepiness is not present during weekends or vacation time
SLEEPINESS CHARACTERISTICSSLEEPINESS CHARACTERISTICS
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
NarcolepsyNarcolepsy
A disease characterized by loss of clear A disease characterized by loss of clear boundaries between sleep amp wakeboundaries between sleep amp wake
Narcolepsy is characterized by severe Narcolepsy is characterized by severe sleepiness frequent unwanted transitions sleepiness frequent unwanted transitions into sleep during wakefulness as well as into sleep during wakefulness as well as frequent periods of awakenings during frequent periods of awakenings during sleepsleep
Patients with narcolepsy can quickly enter Patients with narcolepsy can quickly enter REM sleep at anytime of the dayREM sleep at anytime of the day
Patients also experience REM sleep-like Patients also experience REM sleep-like episodes intruding into wakefulness such episodes intruding into wakefulness such as loss of muscle tone while awake a as loss of muscle tone while awake a condition known as cataplexycondition known as cataplexy
Dauvilliers et al Neurology 2001572029-2033 Okun et al Sleep 20022527-35
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
NarcolepsyCataplexy PrevalenceNarcolepsyCataplexy Prevalence Estimates Differ Between Ethnic GroupsEstimates Differ Between Ethnic Groups
0
010
020
030
040
050
060
Hublin et al Ann Neurol 199435709 Silber et al Sleep 200225197 Honda Sleep Res 19798191 Tashiro et al J Sleep Res 19921228 Wilner et al Hum Immunol 19882115 Ohayon et al Neurology 2002 581926 Zeman et al BMJ 2004 329724
Western EuropeNorth America
Japan Israel
o
f p
op
ula
tio
n
0026
016
00020035
059Low estimate
High estimate
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
NarcolepsyNarcolepsy Constellation of SymptomsConstellation of Symptoms
Excessive daytime sleepinessExcessive daytime sleepiness
Cataplexy and other REM phenomena Cataplexy and other REM phenomena
Hypnagogichypnopompic hallucinationsHypnagogichypnopompic hallucinations
Sleep paralysisSleep paralysis
Fragmented sleepFragmented sleep
Automatic behaviors Automatic behaviors
Guilleminault Narcolepsy syndrome In Principles and Practice of Sleep Medicine 1994
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
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- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Hypocretin Deficiency Hypocretin Deficiency in Human Narcolepsyin Human Narcolepsy
0
100
200
300
400
500
600
700
Control(n=47)
Narcolepsywith
cataplexy(n=101)
Narcolepsywithout
cataplexy(n=20)
CS
F h
yp
ocr
etin
(p
gm
L)
Mignot et al Arch Neurol 2002591553
47 10
3
88
18
0
3
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Pre-motor features of Parkinsons disease the Honolulu-Asia Aging Study experience
Ross GW et al Mov Disord 2012
The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men born 1900-1919 Beginning in 1965 environmental life-style and physical characteristics including many features associated with pre-motor Parkinsons disease (PD) were ascertained at examinations over 40 years
Impaired olfaction constipation slow reaction time excessive daytime sleepiness and impaired executive function were all associated with future development of PD andor with increased likelihood of either incidental Lewy bodies
Compared with persons without any those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
CPAP improves sleep and daytime sleepiness in patients with PD and sleep
apnea
- Randomized placebo-controlled cross over study
-38 PD patients treated for 6 weeks
- CPAP treated patients showed significantly decrease in AHI and Arousal index and increase in N3 stage
- CPAP also reduced daytime sleepiness measured by MSLT
Neikrug AB et al Sleep 37 177-85 2014
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
CLASSIFICAZIONE INTERNAZIONALE PARASONNIE
DISTURBI DELLrsquoAROUSAL
bull SONNAMBULISMO
bull PAVOR NOCTURNUS (INCUBI)
DISTURBI DEL PASSAGGIO SONNO-VEGLIA
bull MOVIMENTI RITMICI DEL SONNO (STEREOTYPED PARASOMNIAS)
bull MIOCLONIE IPNICHE
bull SONNILOQUIO
PARASONNIE ASSOCIATE AL SONNO REM
bull SOGNI TERRIFICI
bull REM SLEEP BEHAVIOR DISORDER
ALTRE PARASONNIE
bull BRUXISMO
bull ENURESI NOTTURNA
bull DISFAGIA NOTTURNA SALIVARE
bull DISTONIA PAROSSISTICA NOTTURNA
bull MORTE IMPROVVISA IN SONNO (DA CAUSA SCONOSCIUTA)
bullSINDROME DELLA MORTE IMPROVVISA DEL LATTANTE
bull SINDROME DA IPOVENTILAZIONE CENTRALE CONGENITA
bull MIOCLONO BENIGNO NEONATALE IN SONNO
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
- Slide 48
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Sleep TerrorsSleep TerrorsDifferential diagnosis
SLEEPTERRORS
NIGHTMARES
Part of the night First third Last thirdMajor motoractivity
++ +-
Anxiety +++ ++Vocalization ++ +Autonomicdischarge
+++ +
Intellectual function -(Confusion) +(Good)
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
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- Slide 55
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- Slide 57
- Slide 58
- Slide 59
-
Rem Sleep Behavior Disorder (RBD)
bull 1986 ndash 5 patients ndash Mahowald et al
bull RBD is characterized by the intermittent loss of Rem sleep electromyographic (EMG) atonia and by the appearance of elaborate motor activity associated with dream mentation
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
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- Slide 17
- Slide 18
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- Slide 22
- Slide 23
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- Slide 29
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- Slide 31
- Slide 32
- Slide 33
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- Slide 35
- Slide 36
- Slide 37
- Slide 38
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- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
- Slide 47
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- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
REM SLEEP BEHAVIOR DISORDERREM SLEEP BEHAVIOR DISORDER
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
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- Slide 43
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- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Some clinical aspects of RBDSome clinical aspects of RBD
Estimated prevalence 004-05
Male prevalence (MF 91)
Age of onset 526 16 yrs
Altered dream content or enacting behaviors 92
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
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- Slide 15
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- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
Clinical RBD course
RBD
acute
chronic
alcohol (withdrawal)
tryciclic antidepressants (intoxication or
withdrawal)
anti-MAO caffeine (intoxication)
25 Idiopathic form
75 symptomatic form(neurological diseases)
Initial manifestation
Consequent symptom
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
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-
bull Impairment of cortical activitybull Neuropsychological deficitsbull Autonomic dysfunctionsbull Olfactory deficits
Does the idiopathic form of RBD really exist
NEUROLOGY 2005 64780-786
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
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-
INCREASED AGGRESSIVE DREAM CONTENT WITHOUT INCREASED DAYTIME AGGRESSIVENESS
IN REM SLEEP BEHAVIOR DISORDER
ML Fantini A Corona S Clerici and L Ferini-Strambi
Neurology 2005
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
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- Slide 59
-
RESULTS ndash RESULTS ndash Daytime aggressivenessDaytime aggressiveness
bull Two patients with RBD and 4 controls had an AQ score gt96 which is considered suggestive of daytime aggressiveness
RBD
patients Controls p
AQ total score 699 plusmn 161 738 plusmn 203 037
Physical Aggression 165 plusmn 64 204 plusmn 83 0034
Verbal Aggression 150 plusmn 42 144 plusmn 40 059
Anger 179 plusmn 65 173 plusmn 60 067
Hostility 204 plusmn 54 216 plusmn 62 038
bull No between-group difference in overall daytime aggressiveness
bull Patients with RBD showed lower score on ldquoPhysical Aggressionrdquo than controls
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
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- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
RESULTS ndash RESULTS ndash Dream contentDream content
bull Compared to control subjects RBD showed
Dreams with at least one aggression (66 vs 15 plt000001)
ratio AggressionFriendliness interactions (89 vs 44 plt00001)
frequency of Animal characters (19 vs 4 p=00001)
No Dreams with at least one element of sexuality (0 vs 9 plt00001)
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
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- Slide 19
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- Slide 21
- Slide 22
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- Slide 25
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- Slide 36
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- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
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- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Slide 54
- Slide 55
- Slide 56
- Slide 57
- Slide 58
- Slide 59
-
RBD DIFFERENTIAL DIAGNOSES
Sleepwalking and sleep terrors (possibility of overlap)
Nocturnal seizures Obstructive sleep apnea (OSA) with
agitated REM-related arousals Psychogenic dissociative disorders
- Slide 1
- Slide 2
- Slide 3
- Slide 4
- Slide 5
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 11
- Slide 13
- Slide 14
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- Slide 30
- Slide 31
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- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 43
- Slide 44
- Slide 45
- Slide 46
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- Slide 49
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-