1/6/2015

1

Insomnia

Elisabeth Brandauer, MD Department of Neurology, Innsbruck Medical University, Austria

Movement Disorders in SleepBarcelona, Jan 30-31

Characteristics of Insomnia

• Persistent difficulty with sleep initiation, duration,

consolidation or quality that occurs despite adequate

opportunity and circumstances for sleep , and results on some

form of daytime impairment;

• Daytime symptoms typically include fatigue, decreased mood

or irritability, general malaise and cognitive impairment, but

not falling asleep during daytime;

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

International Classification of Sleep

Disorders – ICSD 2

• Insomnia– Adjustment Insomnia

– Psychophysiological Insomnia

– Paradoxical Insomnia

– Idiopathic Insomnia

– Insomnia Due to a Mental Disorder

– Inadequate Sleep Hygiene

– Insomnia Due to Drug or Substance

– Insomnia Due to a Medical Condition

– Insomnia Not Due to Substance or Known PhysiologicCondition, Unspecified

– Physiologic (Organic) Insomnia, Unspecified

1/6/2015

2

ICSD 3

1. Chronic Insomnia Definition ICSD-3 Alternate Names: Chronic insomnia, primary insomnia, secondary insomnia, comorbid insomnia, disorder of initiating and

maintaining sleep, behavioral insomnia of childhood, sleep-onset association disorder, limit-setting sleep disorder.

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

Diagnostic Criteria

Criteria A-F must be met

A. The patient reports, or the patient's parent or caregiver observes, one or more of

the following:

1. Difficulty initiating sleep.

2. Difficulty maintaining sleep.

3. Waking up earlier than desired.

4. Resistance to going to bed on appropriate schedule.

5. Difficulty sleeping without parent or caregiver intervention.

B. The patient reports, or the patient's parent or caregiver observes, one or more of

the following related to the nighttime sleep difficulty:

1. Fatigue/malaise.

2. Attention, concentration, or memory impairment.

3. Impaired social, family, occupational, or academic performance.

4. Mood disturbance/irritability.

5. Daytime sleepiness.

6. Behavioral problems (e.g., hyperactivity, impulsivity, aggression).

7. Reduced motivation/energy/initiative.

8. Proneness for errors/accidents.

9. Concerns about or dissatisfaction with sleep.

C. The reported sleep/wake complaints cannot be explained purely by inadequate

opportunity (i.e., enough time is allotted for sleep) or inadequate circumstances (i.e.,

the environment is safe, dark, quiet, and comfortable) for sleep.

D. The sleep disturbance and associated daytime symptoms occur at least three times

per week.

E. The sleep disturbance and associated daytime symptoms have been present for at

least three months

F. The sleep/wake difficulty is not better explained by another sleep disorder.

2. Short-Term Insomnia Definition ICSD-3 Alternate Names: Acute insomnia, adjustment insomnia.

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

Diagnostic Criteria

Criteria A-E must be met

A. The patient reports, or the patient's parent or caregiver observes, one or more of the

following:

1. Difficulty initiating sleep.

2. Difficulty maintaining sleep.

3. Waking up earlier than desired.

4. Resistance to going to bed on appropriate schedule.

5. Difficulty sleeping without parent or caregiver intervention.

B. The patient reports, or the patient's parent or caregiver observes, one or more of the

following related to the nighttime sleep difficulty:

1. Fatigue/malaise.

2. Attention, concentration, or memory impairment.

3. Impaired social, family, vocational, or academic performance.

4. Mood disturbance/irritability.

5. Daytime sleepiness.

6. Behavioral problems (e.g., hyperactivity, impulsivity, aggression).

7. Reduced motivation/energy/initiative.

8. Proneness for errors/accidents.

9. Concerns about or dissatisfaction with sleep.

C. The reported sleep/wake complaints cannot be explained purely by inadequate

opportunity (i.e., enough time is allotted for sleep) or inadequate circumstances (i.e.,

the environment is safe, dark, quiet, and comfortable) for sleep.

D. The sleep disturbance and associated daytime symptoms have been present for less

than three months.

E. The sleep/wake difficulty is not better explained by another sleep disorder.

1/6/2015

3

3. Other Insomnia Definition ICSD-3 Alternate Names: none.

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

Diagnostic Criteria

This diagnosis is reserved for individuals who complain of

difficulty initiating and maintaining sleep and yet do not

meet the full criteria for either chronic insomnia disorder

or short-term insomnia disorder. In some cases, this

diagnosis may be assigned on a provisional basis when

more information is needed to establish a diagnosis of

chronic insomnia disorder or short-term insomnia

disorder. It is expected that this diagnosis will be used

sparingly, given its nonspecific nature.

Demographics

Chronic Insomnia

• Full clinical syndrome in 10%

of population

• Transient Insomnia symptoms

in 30-35%

• Female > male

• At any age, but more

commonly in older age (age

related deterioration in sleep

continuity, medical

comorbidities, medication that

increase insomnia risk)

Short –Term Insomnia

• Can occur at any age, more

prevalent in older age groups

• Exact prevalence unknown

• One year prevalence in adults

in range of 15-20%

• Females > males

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

Pathophysiology

Chronic Insomnia

• increased physiological arousal, characterized by increased heart rate, altered heart rate variability, increased whole body metabolic rate, elevated cortisol, adrenocorticotropichormone and CRF levels, increasedbody temperature and increasedhigh-frequenzy EEG activity duringNREM sleep;

• Heightened activity of thesympathetic nervous system andhypothalamic-pituitary-adrenal axis

• No discrete structural brainpathology

Short –Term Insomnia

• Research on the pathology andpathophysiology of short-term variants of insomnia disorder isgenerally lacking because themajority of studies addressing thisissue have focused on samples withchronic insomnia disorders.

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

1/6/2015

4

Differential Diagnosis

• Circadian Rhythm Sleep Disorders

• Sleep difficulties arising from sleep-disruptive environmental circumstances

• Insufficient sleep syndrome

• Insomnia as comorbidity with other sleep disorders:

• Sleep apnea

• Restless Legs Syndrome

• Parasomnias

International Classification of Sleep Disorders 3rd

American Academy of Sleep Medicine, 2014

Diagnostic steps in Insomnia

Clinical history

• Sleep habits, structured interview on sleep disorders

• Clinical findings

Actigraphy and sleep log

• Verification of subjective sleep

• Detection of circadian rhythm sleep disorders

Diagnostic steps in Insomnia

Polysomnography:

Especially useful to rule out other sleep disorders

• Findings in insomnia:

• Increased sleep latency

• Increased wake after sleep onset

• Reduced sleep efficiency

• Increased stage 1 sleep

• Decreased slow wave sleep

• Elevated high frequency power in EEG

MSLT (Multiple Sleep Latency Test)

• Normal daytime alertness

1/6/2015

5

Insomnia in Parkinson´s Disease

• Insomnia one of the most common non-motor symptoms in PD

• 40-50% of PD patients affected (Lee 2007, Martinez-Martin 2007),

37% (Barone 2009)

• Increase with disease duration

• Main complaints: sleep fragmentation and early awakening;

• Most common sleep complaint in PD is fatigue: 58% (Barone 2009)

Poewe W, Högl B: Curr Opin Neurol 2000,13:423-26

Sleep Disorders in PDContributing Factors

Sleep-Regulating nuclei possibly underlying primary slee pdisturbances in Parkinson‘s disease

Nucleus /Area Main Transmitter FunctionConsequence ofDysfunction in PD

Nucleus pedunculopontinus Ach

Regulation of REM sleepRBD

Locus coeruleus NARegulation of REM sleep Reduction / absence of

REM sleep

Area peri-locuscoeruleus ?

Inhibition of spinal motoneurons via nucleus magnocellularis

Loss of muscle atoniaduring REM → RBD

Raphe nuclei in midbrain and pons

5HT Regulation of slow-wave sleep Reduction of SWS

From Diederich NJ, Comella CL in Chokroverty, 2013

Midbrain tegmentalarea

DA Thalamocortical arousal Reduction of SWSExcessive daytimesleepiness

Hypothalamus Orexin/Hypocretin

Maintenance of daytimevigilance

Abrupt napping andmicrosleeps duringdaytime

1/6/2015

6

Mov Disord. 2011 Mar; 25(4): 644-52

Trenkwalder et al. 2011

Polysomnography

• Reduction of total sleep time during night

• Frequent awakenings

• Reduction of sleep spindles and K-complexes

in stage 2

• Less slow wave sleep

From Diederich NJ, Comella CL in Chokroverty, 2013

1/6/2015

7

Insomnia in Other Movement

Disorders

• Multiple System Atrophy

– Sleep onset and maintenance insomnia

– Sleep fragmentation more common than in PD;

caused by rigidity and bradykinesia

– Reduced sleep efficiency

– Disrupted circadian pattern

Iranzo, 2007

Abbott et al. 2014

• Corticobasal Degeneration

– Reduced total sleep time and sleep efficiency (Roche 2007)

• Progressive Supranuclear Palsy

– Frequency of sleep disturbance: 50% in a questionnaire study (Santacruz 1998)

– Insomnia worse than in PD patients

– Decreased total sleep time and REM sleep, increase in number and duration of noctural awakenings; decreased spindles, increased alpha-activity (Abbott 2014,

review)

– Status dissociatus with advanced disease (Gross 1978)

• Huntington´s Disease

– Hansotia 1985: reduced sleep efficiency, SWA and

REM sleep, prolonged REM latencies

– Arnulf 2008: early sleep onset; increased N1;

delayed and shortenend REM sleep

– Morton 2005: circadian disturbances in HD,

resulting from pathology in the suprachiasmatic

nucleus; reversal of normal nighttime/daytime

activity patterns

1/6/2015

8

Treatment of Insomnia

Non Drug Treatment: Relaxation

• Relaxation Training

• Biofeedback

• Yoga, Meditation

Non Drug Treatment: sleep hygiene rules

• Getting up same time every day, including

weekends

• Avoid napping during the day

• Avoid falling asleep while watching TV

• No TV, tablet etc. in the bedroom, the

bedroom is just for sleeping

• Avoid caffeine too late in daytime

• Avoid large meals before bed

• Daytime activity, but avoid exercise 2-4 h

before bedtime

• Bedroom should be cool, dark and quiet

Non Drug Treatment: cognitive

behavioral therapy

1/6/2015

9

Drug Treatment of Insomnia

• Benzodiazepins

• Nonbenzodiazepin receptor agonists

• Sedative antidepressants

• Neuroleptics

• Antihistamines

• Herbal Medications

• Melatonin and melatonergic substances

Choice of Drug Treatment

• Disease duration? (chronic insomnia, short term

insomnia)

• Comorbidity? (Depression, Anxiety disorder, medical

disorders, history of substance abuse?)

• Sleep initiation or maintenance disturbance?

• Compliance?

• Age?

Drug Treatment of Insomnia in Parkinsons Disease

• Optimize motor symptoms (slow release levodopa,

dopaminagonist)

• L-Dopa: low dosage can improve sleep continuity

• L-Dopa: higher dosages have an awakening effect

• Drug treatment: cave neuroleptics

1/6/2015

10

Drug Treatment of Insomnia in Parkinsons Disease

Efficacy Safety Practice implications

Controlled-release

formulation of

levodopa/carbidopa

Insufficient evidence Acceptable risk without

specialized monitoring

Investigational

Pergolide Insufficient evidence Acceptable risk with

specialized monitoring

Not useful

Eszopiclone Insufficient evidence Acceptable risk without

specialized monitoring

Investigational

Melatonin 3-5mg Insufficient evidence Acceptable risk without

specialized monitoring

Investigational

Melatonin 50mg Insufficient evidence Insufficient evidence Investigational

Seppi 2011, The Movement Disorder Society Evidence Based Medicine Review

Update: Treatments for the Non-Motor Symptoms of Parkinsons Disease