Post on 12-Jan-2016
Brain InjuryBrain Injury
John M. Lavelle, MS4 OMM FellowJohn M. Lavelle, MS4 OMM FellowMidwestern UniversityMidwestern University
Chicago College of Osteopathic MedicineChicago College of Osteopathic Medicine
The BrainThe Brain
HomunculiHomunculi
Sensory Motor
Lat Med Med Lat
Left HemisphereLeft Hemisphere
Understanding and use of language (listening, Understanding and use of language (listening, reading, speaking and writing) reading, speaking and writing)
Memory for spoken and written messages Memory for spoken and written messages Detailed analysis of information Detailed analysis of information Controls the right side of the bodyControls the right side of the body
Right HemisphereRight Hemisphere
Judging the position of things in space Judging the position of things in space Knowing body position Knowing body position Understanding and remembering things we do and Understanding and remembering things we do and
see see Putting bits of information together to make an entire Putting bits of information together to make an entire
picture picture Controls the left side of the bodyControls the left side of the body
Corpus CallosumCorpus Callosum
FunctionsFunctions Connects right and left Connects right and left
hemisphere to allow for hemisphere to allow for communication between the communication between the hemispheres.hemispheres.
Forms roof of the lateral and Forms roof of the lateral and
third ventricles.third ventricles.
DysfunctionsDysfunctions
Damage to the Corpus Damage to the Corpus Callosum may result in Callosum may result in "Split Brain" syndrome."Split Brain" syndrome.
Frontal LobeFrontal Lobe PREFRONTAL CORTEX SYSTEM – executive controlPREFRONTAL CORTEX SYSTEM – executive control
FunctionsFunctions attention span attention span perseverance perseverance planning planning judgment judgment impulse control impulse control organization organization self-monitoring and supervision self-monitoring and supervision problem solving problem solving critical thinking critical thinking forward thinking forward thinking learning from experience and learning from experience and
mistakes mistakes ability to feel and express ability to feel and express
emotionsemotions
DysfunctionsDysfunctions Loss of spontaneity in interacting Loss of spontaneity in interacting
with others. with others. Loss of flexibility in thinking. Loss of flexibility in thinking. Persistence of a single thought Persistence of a single thought
((PerseverationPerseveration). ). Inability to focus on task Inability to focus on task
((AttendingAttending). ). Mood changes (Mood changes (Emotionally Emotionally
LabileLabile). ). Changes in social behavior. Changes in social behavior. Changes in personality. Changes in personality. Difficulty with problem solving. Difficulty with problem solving. Inablility to express language Inablility to express language
((Broca's AphasiaBroca's Aphasia). ).
Frontal LobeFrontal Lobe
FunctionsFunctions MotorMotor – responsible for – responsible for
making movementsmaking movements PremotorPremotor – selects – selects
movements, selection and movements, selection and direction of motor direction of motor sequencessequences
DysfunctionsDysfunctions Loss of simple movement of Loss of simple movement of
various body parts various body parts ((ParalysisParalysis). ).
Inability to plan a sequence Inability to plan a sequence of complex movements of complex movements needed to complete multi-needed to complete multi-stepped tasks, such as stepped tasks, such as making coffee making coffee
((SequencingSequencing).).
Parietal LobeParietal Lobe FunctionsFunctions
Processes sensory information Processes sensory information Localize touch, pressure, pain, and temperature on the opposite side of the body Localize touch, pressure, pain, and temperature on the opposite side of the body
side side Spatial processing Spatial processing Visual guidance of hands, fingers, eyes, and limbs, head Visual guidance of hands, fingers, eyes, and limbs, head Responsive to eye movements Responsive to eye movements Visual motor guidance for reaching and grabbing objects Visual motor guidance for reaching and grabbing objects Tactile recognition Tactile recognition Information on limb position Information on limb position Localize objects around us Localize objects around us Directing movement in space Directing movement in space Detecting stimuli in space Detecting stimuli in space Distinguishing left from rightDistinguishing left from right
Parietal LobeParietal Lobe
DDominant Parietal ominant Parietal LobeLobe Dysfunctions Dysfunctions
finger agnosia (can’t tell position finger agnosia (can’t tell position of finger with eyes closed) of finger with eyes closed)
agraphia (trouble writing) agraphia (trouble writing) R-L confusion R-L confusion acalculia acalculia dyslexia dyslexia errors in grammar errors in grammar apraxia apraxia inability to copy movements or inability to copy movements or
make gestures make gestures
Non-dominant Parietal Non-dominant Parietal Lobe DysfunctionsLobe Dysfunctions
neglect of left side (such as in neglect of left side (such as in drawing a clock, left side of drawing a clock, left side of drawing a person, left side of drawing a person, left side of words, shaving) words, shaving)
unaware anything is wrong or a unaware anything is wrong or a problem is present problem is present
constructional apraxia (impaired constructional apraxia (impaired at combining blocks to build a at combining blocks to build a design or doing puzzles) design or doing puzzles)
impaired copying, paper cutting, impaired copying, paper cutting, spatial relations, drawing maps, spatial relations, drawing maps, dressing) dressing)
Occipital LobeOccipital Lobe
FunctionsFunctions Vision Vision
DysfunctionsDysfunctions Defects in vision (Defects in vision (Visual Field CutsVisual Field Cuts). ). Difficulty with locating objects in Difficulty with locating objects in
environment. environment. Difficulty with identifying colors Difficulty with identifying colors
((Color AgnosiaColor Agnosia). ). Production of hallucinations Production of hallucinations Visual illusions - inaccurately seeing Visual illusions - inaccurately seeing
objects. objects. Word blindness - inability to Word blindness - inability to
recognize words. recognize words. Difficulty in recognizing drawn Difficulty in recognizing drawn
objects. objects. Inability to recognize the movement Inability to recognize the movement
of an object (of an object (Movement AgnosiaMovement Agnosia). ). Difficulties with reading and writing.Difficulties with reading and writing.
Dominant Temporal LobeDominant Temporal Lobe
Functions Functions Perception of words Perception of words Process language related sounds Process language related sounds Sequential analysis Sequential analysis Increased blood flow during Increased blood flow during
speech perception speech perception Process details, individual units Process details, individual units Intermediate term memory Intermediate term memory Long term memory Long term memory Auditory learningAuditory learning
DysfunctionsDysfunctions Decreased verbal memory (words, Decreased verbal memory (words,
lists, stories) lists, stories) Difficulty placing words or pictures Difficulty placing words or pictures
into discreet categories into discreet categories ((CatagorizationCatagorization). ).
Trouble understanding the context of Trouble understanding the context of words (words (Wernicke's Aphasia)Wernicke's Aphasia)
Aggression, internally or externally Aggression, internally or externally driven driven
Dark or violent thoughts Dark or violent thoughts Sensitivity to slights, mild paranoia Sensitivity to slights, mild paranoia Word finding problems Word finding problems Auditory processing problems Auditory processing problems Reading difficulties Reading difficulties Emotional instabilityEmotional instability
Non-dominant Temporal Non-dominant Temporal LobeLobe
FunctionsFunctions Perception of melodies Perception of melodies Pitch/prosody Pitch/prosody Social cues Social cues Reading facial expression Reading facial expression Increased blood flow during tonal Increased blood flow during tonal
memory memory Decoding vocal intonation Decoding vocal intonation Rhythm Rhythm Visual learningVisual learning
DysfunctionsDysfunctions Difficulty recognizing facial Difficulty recognizing facial
expression (expression (ProsopagnosiaProsopagnosia). ). Difficulty decoding vocal Difficulty decoding vocal
intonation intonation Social skill struggles Social skill struggles Trouble processing music Trouble processing music Poor visual imagery Poor visual imagery Decreased selective attention to Decreased selective attention to
visual input visual input Decreased recall of nonverbal Decreased recall of nonverbal
items – shapes, faces, tunesitems – shapes, faces, tunes
CerebellumCerebellum
FunctionsFunctions Coordination of voluntary Coordination of voluntary
movement movement Balance and equilibrium Balance and equilibrium Some memory for reflex motor Some memory for reflex motor
acts. acts.
DysfunctionsDysfunctions Loss of ability to coordinate fine Loss of ability to coordinate fine
movements (movements (dysmetriadysmetria).). Loss of ability to walk (Loss of ability to walk (ataxiaataxia). ). Inability to reach out and grab Inability to reach out and grab
objects.objects. Intention Tremor. Intention Tremor. Dizziness (Dizziness (VertigoVertigo). ). Slurred Speech (Slurred Speech (Scanning Scanning
SpeechSpeech). ). Inability to make rapid Inability to make rapid
movements (movements (dysdiadocokinesiadysdiadocokinesia). ).
BrainstemBrainstem
FunctionsFunctions Breathing Breathing Heart Rate Heart Rate Swallowing Swallowing Reflexes to seeing and hearing Reflexes to seeing and hearing
((Startle ResponseStartle Response). ). Controls sweating, blood Controls sweating, blood
pressure, digestion, temperature pressure, digestion, temperature ((Autonomic Nervous SystemAutonomic Nervous System). ).
Affects level of alertness. Affects level of alertness. Ability to sleep. Ability to sleep. Sense of balance (Sense of balance (Vestibular Vestibular
FunctionFunction). ).
DysfunctionsDysfunctions Decreased vital capacity in Decreased vital capacity in
breathing, important for speech. breathing, important for speech. Swallowing food and water Swallowing food and water
((DysphagiaDysphagia). ). Difficulty with Difficulty with
organization/perception of the organization/perception of the environment. environment.
Problems with balance and Problems with balance and movement. movement.
Dizziness and nausea (Dizziness and nausea (VertigoVertigo). ). Sleeping difficulties (Insomnia, Sleeping difficulties (Insomnia,
sleep apnea).sleep apnea).
Limbic SystemLimbic System
Functions stores emotional memories modulates motivation controls appetite and sleep cycles promotes bonding directly processes the sense of
smell modulates libido
PartsParts Amygdala: involved in emotion, Amygdala: involved in emotion,
learning and memory. It is part of learning and memory. It is part of a system that processes a system that processes "reflexive" emotions like fear and "reflexive" emotions like fear and anxiety.anxiety.
Cingulate gyrus: processing Cingulate gyrus: processing conscious emotional experience.conscious emotional experience.
Fornix: connects the hippocampus Fornix: connects the hippocampus to other parts of the limbic to other parts of the limbic system.system.
Hippocampus: plays a significant Hippocampus: plays a significant role in the formation of long-term role in the formation of long-term memories.memories.
Limbic SystemLimbic System
DysfunctionsDysfunctions moodiness, irritability, clinical depressionmoodiness, irritability, clinical depression decreased or increased sexual responsivenessdecreased or increased sexual responsiveness increased negative thinking increased negative thinking perceive events in a negative way perceive events in a negative way decreased motivation decreased motivation flood of negative emotions flood of negative emotions appetite and sleep problems appetite and sleep problems social isolationsocial isolation
Basal GangliaBasal Ganglia SStriatum & Globus Pallidus (caudate and putamen)triatum & Globus Pallidus (caudate and putamen)
FunctionsFunctions Initiation and direction of Initiation and direction of
voluntary movement. voluntary movement. Postural BalancePostural Balance Emotional motor expressionEmotional motor expression
(smiling, frowning, laughing, crying(smiling, frowning, laughing, crying))
DysfunctionsDysfunctions
Tremor-at-rest Tremor-at-rest Dyskinesia with hypertoniaDyskinesia with hypertonia
Parkinson’s disease Parkinson’s disease (Loss of (Loss of dopamine)dopamine)
Dyskinesia with hypotoniaDyskinesia with hypotonia
Chorea Chorea
Athetosis Athetosis
Hemiballism Hemiballism (Subthalamic (Subthalamic nucleus)nucleus)
ThalamusThalamus
ThalamusThalamus Sensory FunctionSensory Function Visual input in the lateral geniculate nucleus (LGN) - lesions result in hemianopia.Visual input in the lateral geniculate nucleus (LGN) - lesions result in hemianopia. Auditory input in the medial geniculate nucleus (MGN) - Unilateral lesions have Auditory input in the medial geniculate nucleus (MGN) - Unilateral lesions have
little effect on hearing; auditory information ascends bilaterally. little effect on hearing; auditory information ascends bilaterally. Somatosensory input for position, vibration, pain and temperature in the VPL and Somatosensory input for position, vibration, pain and temperature in the VPL and
VPM nuclei - Lesions cause loss of all sensation on one side of the body. Some VPM nuclei - Lesions cause loss of all sensation on one side of the body. Some patients experience abnormally painful sensations on the anesthetic side - Thalamic patients experience abnormally painful sensations on the anesthetic side - Thalamic Pain syndromePain syndrome
Motor functionMotor function Interruption of the cerebellar input to VA and VL cause ataxiaInterruption of the cerebellar input to VA and VL cause ataxia Interruption of basal ganglia input VA and VL cause akinesia. Interruption of basal ganglia input VA and VL cause akinesia.
Cognitive functionCognitive function Arousal: bilateral lesions affecting the intralaminar thalamic nuclei cause Arousal: bilateral lesions affecting the intralaminar thalamic nuclei cause
unresponsiveness, but the eyes remain open - called coma vigil or akinetic mutism. unresponsiveness, but the eyes remain open - called coma vigil or akinetic mutism. Memory: Lesions affecting medial thalamic structures cause amnesia. Memory: Lesions affecting medial thalamic structures cause amnesia. Aphasia, neglect and visuospatial dysfunctionAphasia, neglect and visuospatial dysfunction
HypothalamusHypothalamus
FunctionsFunctions Homeostasis: body temperature, Homeostasis: body temperature,
BP, circadian rhythmBP, circadian rhythm Endocrine function of pituitary: Endocrine function of pituitary:
FSH, LH, ACTH, TSH, Pr, GH, FSH, LH, ACTH, TSH, Pr, GH, oxytocin, ADHoxytocin, ADH
Anterior Hypothalamus: Anterior Hypothalamus: parasympathetic activityparasympathetic activity
Posterior Hypothalamus: Posterior Hypothalamus: sympathetic activity ("Fight" or sympathetic activity ("Fight" or Flight", stress response. Flight", stress response.
Behavioral patterns: Physical Behavioral patterns: Physical expression of behavior. expression of behavior.
Feeding center. Feeding center. Pleasure center. Pleasure center.
DysfunctionsDysfunctions Hormone imbalancesHormone imbalances Inability to control temperatureInability to control temperature Uncontrolled BP Uncontrolled BP Diabetes Insipidus (DI)Diabetes Insipidus (DI) SIADH SIADH Emotional abnormalitiesEmotional abnormalities Decreased libidoDecreased libido Excessive thirstExcessive thirst Horner’s syndromeHorner’s syndrome
Internal Capsule Internal Capsule
FunctionsFunctions Motor tracts.Motor tracts.
DysfunctionsDysfunctions Contralateral plegia Contralateral plegia
(Paralysis of the opposite (Paralysis of the opposite side of the body)side of the body)
Brain InjuryBrain InjuryCausesCauses
Diffuse Axonal Injury (DAI)Diffuse Axonal Injury (DAI):: caused by strong rotational forces of the caused by strong rotational forces of the head, such as with a car accident. The unmoving brain lags behind the head, such as with a car accident. The unmoving brain lags behind the movement of the skull, causing brain structures to tear. There is extensive movement of the skull, causing brain structures to tear. There is extensive tearing of axons throughout the brain which can disrupt the brains regular tearing of axons throughout the brain which can disrupt the brains regular communication and chemical processes. communication and chemical processes.
Anoxic brain injuryAnoxic brain injury:: when the brain does not receive any oxygen. when the brain does not receive any oxygen.
Hypoxic brain injuryHypoxic brain injury:: when the brain receives some, but not enough when the brain receives some, but not enough oxygen.oxygen.
HematomasHematomas:: swelling or mass of blood in the brain caused by a break in a swelling or mass of blood in the brain caused by a break in a blood vessel. i.e: epidural/subdural/subarachnoid or intracerebral blood vessel. i.e: epidural/subdural/subarachnoid or intracerebral hemmorrhagehemmorrhage
Brain Brain InjuryInjuryCausesCauses
LacerationLaceration:: or tearing of the brain, usually from a or tearing of the brain, usually from a skull fracture or gunshot wound, results in rupture of skull fracture or gunshot wound, results in rupture of large blood vessels with bleeding into the brain and large blood vessels with bleeding into the brain and subarachnoid space. This can result in hematomas, subarachnoid space. This can result in hematomas, edema and increased intracranial pressure. edema and increased intracranial pressure.
ContusionContusion:: a visible bruise (bleeding) on the brain. a visible bruise (bleeding) on the brain.
Coup-contrecoup injuryCoup-contrecoup injury: contusions that are both at : contusions that are both at the site of the impact and on the complete opposite the site of the impact and on the complete opposite side of the brain. side of the brain.
REFLEX ACTIVITYLEFT RIGHT
DORSAL HORN
OF SPINAL CORD
VPL VPM VPM VPL
SPINAL V
CHIEFV
DRGs
UE
LE
FG
FC
ML
IAF
RETICULARFORMATION
INTRALAMINARTHALAMIC
NUCLEI
WIDESPREADCORTEX
DC
TOUCH, 2-PT DISCRIM.,VIBRATION,
CONSCIOUS PROPRIOCEPTION
SUP. COLL. PAG
MES V
NG NCNC NG
SENSORYASSOCIATION
CORTEX
PRIMARY SENSORY CORTEX
SENSORYASSOCIATION
CORTEX
PRIMARY SENSORY CORTEX
DC-ML System
LEFT RIGHT
DORSAL HORN
OF SPINAL CORD
VPL VPM VPM VPL
SPINAL V
CHIEFV
RETICULARFORMATION
INTRALAMINARTHALAMIC
NUCLEI
WIDESPREADCORTEX
SUP. COLL. PAG
MES V
NG NCNC NGFAST PAIN &
TEMP.
SLOW PAIN &TEMP.
LE
UE
DRGs
LE
UE
DRGs
REFLEX ACTIVITY
TST
STT
SpTT
SRTT
ALS
2nd order axonsdecussate 1-2 spinalsegments above their
entry level
Reflex pathway to ventral horn of cervical spinal cord
SENSORYASSOCIATION
CORTEX
PRIMARY SENSORY CORTEX
SENSORYASSOCIATION
CORTEX
PRIMARY SENSORY CORTEX
STT System
Int. CapsulePost. Limb
-
LEFT RIGHTPMC
6SMA
M-I4
CrusCerebri
WithinBasilarPons
Pyramid
VENTRAL HORN OF
SPINAL CORD
awc
DORSAL HORNOF SPINAL CORD
PyramidalDecussation
+
SensoryInformation
All muscles, butprimarily distal
muscles of extremities
Primarily axial muscles
+
S-I PMA3,1,2 5,7
CST
ACST
LCST
CST System
LMNs
XII
XI
X
IX
VII
VI
V
IV
III
CNLMNs
DC-ML
STT
VIII
contralateral projection
DIENCEPHALON
MIDBRAIN
PONS
MEDULLA
CEREBRAL CORTEX
SPINAL CORD
PPRF
UMNs
CST
MOTORCORTEX
SENSORYCORTEX
THALAMUS
STT
ML
BASALGANGLIA
contrasigns
CEREBELLUMipsi signs
hearing, equilibrium
Upper Motor NeuronsUpper Motor Neurons
Paresis (generalized) Paresis (generalized) Increased DTRs Increased DTRs Increased muscle tone Increased muscle tone Spasticity Spasticity Babinski sign present Babinski sign present Clonus may be present Clonus may be present Disuse atrophyDisuse atrophy
Guidelines for Guidelines for Medication Medication
Usage After TBIUsage After TBI Define the problem as objectively and Define the problem as objectively and specifically as possible.specifically as possible.
Use medicines that have some proven Use medicines that have some proven efficacy; don’t just use “something” (e.g. efficacy; don’t just use “something” (e.g. Neurontin).Neurontin).
Develop clear cut goals and metrics to assist Develop clear cut goals and metrics to assist in determining when to stop treatment.in determining when to stop treatment.
Begin low but get to a therapeutic dosing Begin low but get to a therapeutic dosing before abandoning usage. before abandoning usage.
Be alert to side effects and undesired effects.Be alert to side effects and undesired effects.
Alterations in Cognition Alterations in Cognition and Behavior After TBIand Behavior After TBI
HypoarousalHypoarousal HypoattentionHypoattention Memory DeficitsMemory Deficits DepressionDepression DeliriumDelirium AgitationAgitation
Factors Affecting Cognitive Factors Affecting Cognitive and Behavioral Function and Behavioral Function
After TBIAfter TBI Effects of the TBIEffects of the TBI Medical InstabilityMedical Instability
InfectionInfection Metabolic DisturbancesMetabolic Disturbances Hormonal/NeuroEndocrine DisturbancesHormonal/NeuroEndocrine Disturbances HypoxiaHypoxia Sleep-Wake DisturbancesSleep-Wake Disturbances PainPain SeizuresSeizures
Factors Affecting Cognitive Factors Affecting Cognitive and Behavioral Function and Behavioral Function
After TBIAfter TBI Medications Medications
Cognitive-Impairing MedicationsCognitive-Impairing Medications Central Acting Antihypertensives Central Acting Antihypertensives
(Clonidine)(Clonidine) Central Acting Antispasmodics (Tizanidine)Central Acting Antispasmodics (Tizanidine) GI Agents (H2 Blockers, Reglan)GI Agents (H2 Blockers, Reglan) Pain Medications (Narcotics, ? NSAID’s)Pain Medications (Narcotics, ? NSAID’s) Sedatives (Benzodiazepines, Sleep Aids)Sedatives (Benzodiazepines, Sleep Aids) Anticonvulsants (Phenytoin, Anticonvulsants (Phenytoin,
Carbamazepine, Phenobarbital)Carbamazepine, Phenobarbital)
Factors Affecting Cognitive Factors Affecting Cognitive and Behavioral Function and Behavioral Function
After TBIAfter TBI Cognitive-Improving MedicationsCognitive-Improving Medications
Stimulants [Methylphenidate, Stimulants [Methylphenidate, Dextramphetamine]Dextramphetamine]
Amantadine [Symmetrel]Amantadine [Symmetrel] Bromocriptine [Parlodel]Bromocriptine [Parlodel] Selective Serotoninergic Re-Uptake Selective Serotoninergic Re-Uptake
Inhibitors [Prozac, Zoloft, Paxil,Celexa]Inhibitors [Prozac, Zoloft, Paxil,Celexa] Combination Antidepressants [Wellbutrin]Combination Antidepressants [Wellbutrin] ? Levodopa-Carbidopa [Sinemet]? Levodopa-Carbidopa [Sinemet] ? Anti-Alzheimer's Agents [Aricept, Exelon]? Anti-Alzheimer's Agents [Aricept, Exelon]
Coma Intervention Coma Intervention
Directed Multisensory Stimulation Directed Multisensory Stimulation (DMS) demonstrated superior (DMS) demonstrated superior (increased responsiveness, improved (increased responsiveness, improved RLAS, improved GCS) versus Non-RLAS, improved GCS) versus Non-Directed Stimulation (NDS) in RLAS Directed Stimulation (NDS) in RLAS II patientsII patients
Hall:Hall:Brain InjuryBrain Injury 1992:6:435- 1992:6:435-4545
Coma InterventionComa Intervention
Comatose receiving greater therapy Comatose receiving greater therapy intensity (by 60%) demonstrated a intensity (by 60%) demonstrated a 31% decrease in length of stay.31% decrease in length of stay.
Blackerby:Blackerby:Brain InjuryBrain Injury 1989;4:167-73 1989;4:167-73
Cognitive Interventions: Cognitive Interventions: HypoarousalHypoarousal
No reliable data to support the efficacy No reliable data to support the efficacy of pharmacologic intervention in the of pharmacologic intervention in the comatose (RLAS I) or vegetative (RLAS comatose (RLAS I) or vegetative (RLAS II) patient. All you get is a very “alert”-II) patient. All you get is a very “alert”-looking comatose or vegetative patient.looking comatose or vegetative patient.
Small trials do support use of Small trials do support use of neurostimulants (Amantadine 150 mg neurostimulants (Amantadine 150 mg bid) in “emerging” patients (RLAS III).bid) in “emerging” patients (RLAS III).
Kaelin: Arch Phys Med Rehabil 1996;77:6-9Kaelin: Arch Phys Med Rehabil 1996;77:6-9
Cognitive Interventions: Cognitive Interventions: HypoattentionHypoattention
Neurostimulants have been Neurostimulants have been demonstrated to improve attention (and demonstrated to improve attention (and +/- function) in responsive patients +/- function) in responsive patients (RLAS IV-VIII) .(RLAS IV-VIII) .
Methylphenidate has the most clinically Methylphenidate has the most clinically demonstrated efficacy for individuals demonstrated efficacy for individuals who have progressed out of coma.who have progressed out of coma.
Dosing 5-30 mg q 7am and 12 pm.Dosing 5-30 mg q 7am and 12 pm.Kaelin: Arch Phys Med Rehabil 1996;77:6-9Kaelin: Arch Phys Med Rehabil 1996;77:6-9
Methylphenidate Methylphenidate (Ritalin)(Ritalin)
Modes of ActionModes of Action
Release of Dopamine from reserpine sensitive Release of Dopamine from reserpine sensitive presynaptic poolpresynaptic pool
Braestrup: J Pharm. Pharmacol. 1977, 29: 463 - 470.Braestrup: J Pharm. Pharmacol. 1977, 29: 463 - 470.
Inhibition of Dopamine uptakeInhibition of Dopamine uptake Ferris,Tang: J of Pharmacol. Exp. Ther. 1979, 210: 422 - Ferris,Tang: J of Pharmacol. Exp. Ther. 1979, 210: 422 - 428.428.
Inhibition of Monoamine OxidaseInhibition of Monoamine Oxidase Szporny, Gorog: Biochem. Pharmacol. 1961, 8: 263 - 268.Szporny, Gorog: Biochem. Pharmacol. 1961, 8: 263 - 268.
Methylphenidate Methylphenidate (Ritalin)(Ritalin)
PharmacokineticsPharmacokinetics Peak serum levels are reached within 2 Peak serum levels are reached within 2
hours (Half life = 2-4 hrs)hours (Half life = 2-4 hrs) Both a wide inter-individual and intra-Both a wide inter-individual and intra-
individual variability in serum individual variability in serum concentrations existconcentrations exist
MPH levels are not different in MPH levels are not different in responders and non-respondersresponders and non-responders
Gualtieri, CT, et al. J of Amer Acad of Child Psych 1982, 21(1): Gualtieri, CT, et al. J of Amer Acad of Child Psych 1982, 21(1): 19-26.19-26.
Selective Serotonin Re-Selective Serotonin Re-Uptake Inhibitors (SSRI’s)Uptake Inhibitors (SSRI’s)
Prozac, Zoloft, Paxil, CelexaProzac, Zoloft, Paxil, Celexa Inhibit CNS reuptake of SerotoninInhibit CNS reuptake of Serotonin Activating antidepressants, however Activating antidepressants, however
somnolence present w/ Paxil at doses somnolence present w/ Paxil at doses >20 mg/day>20 mg/day
Increase dosage q 4-6 weeksIncrease dosage q 4-6 weeks If treating depression, need to commit If treating depression, need to commit
to 12 month course (or increase to 12 month course (or increase recurrence)recurrence)
Bromocriptine (Parlodel)Bromocriptine (Parlodel) Dopamine receptor agonistDopamine receptor agonist Adjunctive treatment for Parkinson’s Adjunctive treatment for Parkinson’s
diseasedisease Suggested for low level patients, however Suggested for low level patients, however
limited proven efficacylimited proven efficacy Dosage: 2.5-15 mg/day in 2 dosesDosage: 2.5-15 mg/day in 2 doses Increase dosage weeklyIncrease dosage weekly High incidence of N/V and Headaches High incidence of N/V and Headaches
with increasing dosages.with increasing dosages.
Amantadine (Symmetrel)Amantadine (Symmetrel) Potentiates Dopamine (mechanism Potentiates Dopamine (mechanism
unclear)unclear) Adjunctive treatment for Parkinson’s Adjunctive treatment for Parkinson’s
disease (tremor)disease (tremor) Dosage: 100-400mg/day in bid dosing Dosage: 100-400mg/day in bid dosing
(elevated seizure risk above 300 mg/day)(elevated seizure risk above 300 mg/day) Increase dosage weeklyIncrease dosage weekly Hallucinations dose limiting side effect.Hallucinations dose limiting side effect. Probable efficacy in RLAS III patients.Probable efficacy in RLAS III patients.
Other Antidepressants Other Antidepressants [Effexor, Wellbutrin][Effexor, Wellbutrin]
Effexor and Wellbutrin inhibit Serotonin, Effexor and Wellbutrin inhibit Serotonin, NE, and Dopamine reuptake = Activating NE, and Dopamine reuptake = Activating agentsagents
Effexor Dosage: 75-225 mg/day in 2-3 Effexor Dosage: 75-225 mg/day in 2-3 doses (Occasional HTN side effects)doses (Occasional HTN side effects)
Wellbutrin Dosage: 200-450 mg/day in 3 Wellbutrin Dosage: 200-450 mg/day in 3 doses (May have worsening effects on doses (May have worsening effects on agitation)agitation)
Levodopa-Carbidopa Levodopa-Carbidopa [Sinemet][Sinemet]
Increases cerebral dopamineIncreases cerebral dopamine Suggested for low level patients, Suggested for low level patients,
however limited proven efficacyhowever limited proven efficacy Side effects can include dyskinesias Side effects can include dyskinesias
and cognitive changesand cognitive changes Dosage: 400-1600 mg Levodopa/day Dosage: 400-1600 mg Levodopa/day
in 2-3 doses (tablets contain either in 2-3 doses (tablets contain either 100 or 200 mg Levodopa)100 or 200 mg Levodopa)
Anti-Alzheimer's AgentsAnti-Alzheimer's Agents [Aricept, Exelon] [Aricept, Exelon]
Reversible cholinesterase inhibitors Reversible cholinesterase inhibitors = increases cerebral acetylcholine= increases cerebral acetylcholine
Effective in improving memory in Effective in improving memory in individuals with Alzheimer’s diseaseindividuals with Alzheimer’s disease
Limited research suggests efficacy in Limited research suggests efficacy in TBI patientsTBI patients
Extremely expensive, occasional GI Extremely expensive, occasional GI side effectsside effects
Treatment Algorithm: Treatment Algorithm: Hypoarousal/HypoattentiHypoarousal/Hypoattenti
onon Day 1Day 1
Define pathology -> CT/MRI, Mechanism of Injury, Define pathology -> CT/MRI, Mechanism of Injury, Secondary BISecondary BI
Assess function: DRS, FIM, RLAS (limited efficacy in RLAS I-Assess function: DRS, FIM, RLAS (limited efficacy in RLAS I-III)III)
Assess medical status -> Infections, Oxygenation, Assess medical status -> Infections, Oxygenation, Metabolics, Fluid Status, SeizuresMetabolics, Fluid Status, Seizures
Remove medications -> H2 blockers, narcotics, central Remove medications -> H2 blockers, narcotics, central acting anti-HTN/GI, Benzodiazepines, Sleepersacting anti-HTN/GI, Benzodiazepines, Sleepers
Day 1-4Day 1-4 Stabilize/Improve medical statusStabilize/Improve medical status Assess/Improve sleep-wake cycle: Trazadone, AmbienAssess/Improve sleep-wake cycle: Trazadone, Ambien Assess behavior: ABS, Therapy attendance/participation, Assess behavior: ABS, Therapy attendance/participation,
Attention to TaskAttention to Task
Treatment Algorithm: Treatment Algorithm: Hypoarousal/HypoattentiHypoarousal/Hypoattenti
onon Day 5-10Day 5-10
Initiate Methylphenidate 5 mg q 7 am and 12 pm, Initiate Methylphenidate 5 mg q 7 am and 12 pm, increase 5-10 mg/day to 60 mg maximumincrease 5-10 mg/day to 60 mg maximum
Monitor behavior and sleep-wake cycleMonitor behavior and sleep-wake cycle Day 10-20Day 10-20
If Methylphenidate effective, continue at lowest If Methylphenidate effective, continue at lowest effective dose for 2-3 weeks, then wean off in 2-4 dayseffective dose for 2-3 weeks, then wean off in 2-4 days
If Methylphenidate ineffective by 30 mg/day, then If Methylphenidate ineffective by 30 mg/day, then initiate wean and begin new agent.initiate wean and begin new agent.
Recommend: SSRI’s may be appropriate if mild but Recommend: SSRI’s may be appropriate if mild but limited response to Ritalin ( if depression is suspected, limited response to Ritalin ( if depression is suspected, then Ritalin only effective 4-6 weeks and will need then Ritalin only effective 4-6 weeks and will need SSRA for 3 months minimum).SSRA for 3 months minimum).
Cognitive Interventions: Cognitive Interventions: AgitationAgitation
Agitation occurs in >50% of all TBI patients Agitation occurs in >50% of all TBI patients (RLAS IV), however delirium, seizures, pain, (RLAS IV), however delirium, seizures, pain, hypoxia can also manifest with agitation.hypoxia can also manifest with agitation.
True TBI agitation should be treated with True TBI agitation should be treated with environmental and behavioral interventions.environmental and behavioral interventions.
Pharmacologic treatment should only be Pharmacologic treatment should only be implemented in specific behaviors are implemented in specific behaviors are identified and goals established.identified and goals established.
Agitation is defined as an Agitated Behavior Agitation is defined as an Agitated Behavior Scale score Scale score >> 21 21
Cognitive Interventions: Cognitive Interventions: AgitationAgitation
EtiologiesEtiologies EnvironmentalEnvironmental PainPain Seizure activitySeizure activity Delirium (meds, hypoxia, metabolic)Delirium (meds, hypoxia, metabolic) Inadequate sleep/wake hygieneInadequate sleep/wake hygiene
… … or TBI-related confusionor TBI-related confusion
Cognitive Interventions: Cognitive Interventions: AgitationAgitation
TreatmentTreatment Assess for Assess for
correctable etiologycorrectable etiology Sleep/Wake ChartingSleep/Wake Charting Medical Medical
ManagementManagement BehavioralBehavioral
establish desired establish desired behaviorbehavior
positive positive reinforcementreinforcement
shapingshaping structured therapystructured therapy
Agitated Behavior Agitated Behavior ScaleScale
Assess pattern of Assess pattern of agitationagitation
DocumentationDocumentation Evaluate Evaluate
effectiveness of effectiveness of interventionintervention
Physical RestraintPhysical Restraint PharmacologicPharmacologic
ABS ABS >> 28 28
Agitation: MedicationsAgitation: Medications
Day 1-3 Use prn for ABS Day 1-3 Use prn for ABS >>2828 AtivanAtivan RisperidoneRisperidone
Day 4+Day 4+ Schedule agents if persistent ABS Schedule agents if persistent ABS >> 28 28
Aggression - Beta-Blockers (Propranolol)Aggression - Beta-Blockers (Propranolol) Restlessness - AED’s (Tegretol, VPA)Restlessness - AED’s (Tegretol, VPA) Emotional lability - TCA’s (Nortriptyline)Emotional lability - TCA’s (Nortriptyline)
Wean agent when ABS <21 for 3 days.Wean agent when ABS <21 for 3 days.Cifu: J NeuroRehabil 1995;5:245-254Cifu: J NeuroRehabil 1995;5:245-254
Post-Traumatic Seizures: Post-Traumatic Seizures: BackgroundBackground
TBI-related seizures account for 20% of TBI-related seizures account for 20% of symptomatic epilepsy.symptomatic epilepsy. Hauser: Epilepsia 1991:32;429-45Hauser: Epilepsia 1991:32;429-45
PTS accounts for 5% of all cases of epilepsy. PTS accounts for 5% of all cases of epilepsy.
Hauser: Epilepsia 1991:32;429-45Hauser: Epilepsia 1991:32;429-45 Late PTS is present in 4-7% all TBI, nearly Late PTS is present in 4-7% all TBI, nearly
20% rehab TBI, and 35-50% penetrating TBI 20% rehab TBI, and 35-50% penetrating TBI patients. patients.
Yablon: Arch PM&R 1993:74;983-1001Yablon: Arch PM&R 1993:74;983-1001
EEG has no predictive value for PTS.EEG has no predictive value for PTS. Yablon: Arch PM&R 1993:74;983-1001Yablon: Arch PM&R 1993:74;983-1001
Prophylaxis for PTSProphylaxis for PTS
73% reduction in early PTS and 50% 73% reduction in early PTS and 50% reduction in 1 year PTS in individuals reduction in 1 year PTS in individuals given phenytoin for 1 week post-TBI.given phenytoin for 1 week post-TBI.
No proven benefits to giving prophylaxis No proven benefits to giving prophylaxis >7 days post-TBI. >7 days post-TBI. Temkin:N Engl J Med Temkin:N Engl J Med
1990:323;497-5021990:323;497-502
No benefit to use of up to 1 month VPA.No benefit to use of up to 1 month VPA.Temkin: J NeuroSurg 1999:91;593-600Temkin: J NeuroSurg 1999:91;593-600
AANS and AAPM&R recommend 7 days of AANS and AAPM&R recommend 7 days of either PTH or CBZ post-TBI.either PTH or CBZ post-TBI.
Prophylaxis for PTSProphylaxis for PTS
Do not treat seizure in first 24 hours post-TBI Do not treat seizure in first 24 hours post-TBI longer than initial 7 days, unless status longer than initial 7 days, unless status epilepticus.epilepticus.
Seizures in the first week should be treated (1 Seizures in the first week should be treated (1 year) unless there is a non-TBI cause evident year) unless there is a non-TBI cause evident (infection, hypoxia, metabolic, hydrocephalus).(infection, hypoxia, metabolic, hydrocephalus).
Seizures after 1 week must be treated for at Seizures after 1 week must be treated for at least 1 year.least 1 year.
GI Ulcer ProphylaxisGI Ulcer Prophylaxis
Use of H2-Blockers has been Use of H2-Blockers has been demonstrated to decrease ICU-demonstrated to decrease ICU-related stress ulceration of the GI related stress ulceration of the GI tract in specific patient populations tract in specific patient populations (e.g., burns).(e.g., burns).
No specific information in patients No specific information in patients with TBI, with or w/o PEG/J tubes.with TBI, with or w/o PEG/J tubes.
GI Ulcer ProphylaxisGI Ulcer Prophylaxis
Newer H2-Blockers, while Newer H2-Blockers, while expensive, have limited CNS effects.expensive, have limited CNS effects.
High risk patients (h/o PUD, h/o High risk patients (h/o PUD, h/o GERD, comatose, > 65 years old) are GERD, comatose, > 65 years old) are appropriate for prophylaxis while in appropriate for prophylaxis while in ICU.ICU.
No clear indication for all TBI No clear indication for all TBI patients in ICU.patients in ICU.
Spasticity ManagementSpasticity Management
Treatment should be initiated if the Treatment should be initiated if the spasticity is limiting function, ROM, spasticity is limiting function, ROM, or is causing pain.or is causing pain.
Potential side effects of treatment Potential side effects of treatment must be weighed against potential must be weighed against potential benefits.benefits.
Spasticity Management:Spasticity Management:Third LineThird Line
Systemic medications are effective, Systemic medications are effective, but often have systemic side effects:but often have systemic side effects: Hepatotoxicity (Baclofen, Dantrium)Hepatotoxicity (Baclofen, Dantrium) Generalized weakness (Dantrium)Generalized weakness (Dantrium) Lethargy (Zanaflex, Baclofen, Valium)Lethargy (Zanaflex, Baclofen, Valium) Hypotension (Zanaflex)Hypotension (Zanaflex) Addiction (Valium)Addiction (Valium)
Spasticity Management:Spasticity Management:Third LineThird Line
Dantrolene Sodium (Dantrium)Dantrolene Sodium (Dantrium) Acts peripheral by blocking release of Ca++ Acts peripheral by blocking release of Ca++
from the t-tubules of the sarcoplasmic from the t-tubules of the sarcoplasmic reticulum.reticulum.
Hepatotoxicity is not uncommon.Hepatotoxicity is not uncommon. May cause generalized weakness.May cause generalized weakness. No central effects.No central effects. Most often used in Brain Injury and CVA.Most often used in Brain Injury and CVA. Start 25 mg qid -> Max 100 mg qid.Start 25 mg qid -> Max 100 mg qid.
Spasticity Management:Spasticity Management:Third LineThird Line
Tizanidine (Zanaflex)Tizanidine (Zanaflex) Central acting alpha-blocker.Central acting alpha-blocker. Often causes hypotension.Often causes hypotension. May cause lethargy.May cause lethargy. very gradual dose increase.very gradual dose increase. Most often used in SCI.Most often used in SCI. Start 1 mg tid -> Max 8 mg tid.Start 1 mg tid -> Max 8 mg tid.
Spasticity Management:Spasticity Management:Fourth LineFourth Line
Phenol (1-10% Aqueous Solution)Phenol (1-10% Aqueous Solution) Direct neurocidal agent, effect lasts for Direct neurocidal agent, effect lasts for
3-6 months (until nerve regenerates). 3-6 months (until nerve regenerates). Works immediately.Works immediately.
Eliminates spasticity in specific nerve Eliminates spasticity in specific nerve distribution or muscle.distribution or muscle.
Nerve/muscle motor point (where nerve Nerve/muscle motor point (where nerve innervates) must be isolated innervates) must be isolated electrically.electrically.
Inexpensive.Inexpensive.
Spasticity Management:Spasticity Management:Fourth LineFourth Line
Botulinum Toxin (Botox, NeuroTox)Botulinum Toxin (Botox, NeuroTox) Neurotoxin that prevents the release of Neurotoxin that prevents the release of
acetylcholine (Ach) from presynaptic acetylcholine (Ach) from presynaptic vacuoles at the neuromuscular junction.vacuoles at the neuromuscular junction.
Produces paralysis of the muscle for 2-4 Produces paralysis of the muscle for 2-4 months.months.
Maximal effects take 2 weeks.Maximal effects take 2 weeks. Expensive.Expensive.
Spasticity Management:Spasticity Management:Fourth LineFourth Line
Focal blockade needs to be combined Focal blockade needs to be combined with a structured stretching/bracing with a structured stretching/bracing program.program.
Focal blockade often reveals underlying Focal blockade often reveals underlying connective tissue contractures.connective tissue contractures. If they are “soft”, they can be improved If they are “soft”, they can be improved
with stretching.with stretching. If they are hard, surgical intervention is If they are hard, surgical intervention is
indicated.indicated.
Guidelines for Guidelines for Medication Medication
Usage After TBIUsage After TBI Define the problem as objectively and Define the problem as objectively and specifically as possible.specifically as possible.
Use medicines that have some proven Use medicines that have some proven efficacy; don’t just use “something” (e.g. efficacy; don’t just use “something” (e.g. Neurontin).Neurontin).
Develop clear cut goals and metrics to assist Develop clear cut goals and metrics to assist in determining when to stop treatment.in determining when to stop treatment.
Begin low but get to a therapeutic dosing Begin low but get to a therapeutic dosing before abandoning usage. before abandoning usage.
Be alert to side effects and undesired effects.Be alert to side effects and undesired effects.
Thank You!Thank You!
ReferencesReferences Moore, K.L; Agur, A.M. Moore, K.L; Agur, A.M. Essential Clinical AnatomyEssential Clinical Anatomy. .
Lippincott Williams&Wilkins, 2002 Baltimore, MD.Lippincott Williams&Wilkins, 2002 Baltimore, MD. Nolte, J; Nolte, J; The Human Brain: An Introduction to Its The Human Brain: An Introduction to Its
Functional AnatomyFunctional Anatomy, Mosby, 2002 New York, New York., Mosby, 2002 New York, New York. Zasler, ND, Katz, DI, Zafonte, RD; Zasler, ND, Katz, DI, Zafonte, RD; Brain Injury MedicineBrain Injury Medicine, ,
Demos Medical Publishing, 2007, New York, New York.Demos Medical Publishing, 2007, New York, New York. www.brainanatomy.netwww.brainanatomy.net www.neuroskills.comwww.neuroskills.com www.uptodate.comwww.uptodate.com