Brain Injury John M. Lavelle, MS4 OMM Fellow Midwestern University Chicago College of Osteopathic Medicine.

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