1 Medical Management Medical Management of Vestibular of Vestibular Disorders Disorders Dr. W. WATAD Dr. W. WATAD
Dec 22, 2015
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Medical Management of Medical Management of Vestibular DisordersVestibular Disorders
Dr. W. WATADDr. W. WATAD
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IntroductionIntroductionBasic inputs – Basic inputs –
Vision - ocular stabilityVision - ocular stability Proprioception - gait controlProprioception - gait control Vestibular system - balanceVestibular system - balance
Disorders of vestibular system are major Disorders of vestibular system are major disruptors causing spatial disorientationdisruptors causing spatial disorientation
Vestibular DD has remained stable over Vestibular DD has remained stable over the past several decades, but the the past several decades, but the management strategies continue to management strategies continue to improve improve
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The Goal The Goal
To review and discuss the medical To review and discuss the medical management of vestibular disordersmanagement of vestibular disorders
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PathophysiologyPathophysiology
Vestibular labyrinth - detects linear and Vestibular labyrinth - detects linear and angular head movementsangular head movements
Semicircular canals - angularSemicircular canals - angularHair cells - cupulaHair cells - cupula
Otolithic organs (utricle, sacule) - linearOtolithic organs (utricle, sacule) - linearHair cells - maculaHair cells - macula
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Vestibular nerve - superior, inferiorVestibular nerve - superior, inferiorAfferent nerve fibers are bipolar Afferent nerve fibers are bipolar
cell bodies lie within Scarpa’s ganglioncell bodies lie within Scarpa’s ganglion
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pathophysiologypathophysiology
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PathophysiologyPathophysiology
Balance requires –Balance requires –Normal functioning vestibular systemNormal functioning vestibular systemInput from visual system (vestibulo-ocular)Input from visual system (vestibulo-ocular)Input from proprioceptive system (vestibulo-Input from proprioceptive system (vestibulo-
spinal)spinal)Disruption of balance between inputs Disruption of balance between inputs
results in :results in :vertigo (acute) vertigo (acute) disequilibrium (chronic)disequilibrium (chronic)
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PathophysiologyPathophysiology
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Central causes of vestibular dysfunction Central causes of vestibular dysfunction compromise central circuits that mediate compromise central circuits that mediate vestibular influences on posture, gaze control, vestibular influences on posture, gaze control, and autonomic function :and autonomic function : nausea, vomitingnausea, vomiting PallorPallor Respiratory/circulatory changesRespiratory/circulatory changes
Goal of treatment: restore balance between Goal of treatment: restore balance between different inputsdifferent inputs
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Medical TreatmentMedical Treatment
Symptomatic :Symptomatic :Relieve acute symptoms , autonomic Relieve acute symptoms , autonomic
complaints complaints Specific therapy :Specific therapy :
Targeting the underlying cause of vertigoTargeting the underlying cause of vertigo
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Symptomatic PharmacotherapySymptomatic Pharmacotherapy
Predominant targeted vestibular Predominant targeted vestibular neurotransmitters:neurotransmitters: CholinergicCholinergic HistaminergicHistaminergic GABA neurotransmitters - negative inhibitionGABA neurotransmitters - negative inhibition
Vomiting center transmitters:Vomiting center transmitters: Dopaminergic (D2)Dopaminergic (D2) Histaminergic (H1)Histaminergic (H1) Serotonergic (5-HT3)Serotonergic (5-HT3)
Multiple classes of drugs effectiveMultiple classes of drugs effective
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Symptomatic PharmacotherapySymptomatic Pharmacotherapy
Main classes :Main classes :Antihistaminergic - dimenhydrinateAntihistaminergic - dimenhydrinateAnticholinergics - scopolamine, meclizineAnticholinergics - scopolamine, meclizineAnti-dopaminergic - droperidolAnti-dopaminergic - droperidol(gamma)-aminobutyric acid enhancing (gamma)-aminobutyric acid enhancing
(GABA-ergic) agents - lorazepam, valium(GABA-ergic) agents - lorazepam, valiumReduce the severity of vestibular Reduce the severity of vestibular
symptomssymptoms
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Symptomatic PharmacotherapySymptomatic Pharmacotherapy
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Suppressant agents :Suppressant agents :AnticholinergicsAnticholinergicsAntihistaminesAntihistaminesBenzodiazepinesBenzodiazepines
Anti-emetic drugsAnti-emetic drugs
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anticholinergicsanticholinergics
Inhibit stimulation ( exessive impulses ) Inhibit stimulation ( exessive impulses ) from peripheral organs – vestibular n.from peripheral organs – vestibular n.
Inhibit transmission in LVN ( lat. Vestibular Inhibit transmission in LVN ( lat. Vestibular Nucleus )Nucleus )
Non-specific muscarine receptor Non-specific muscarine receptor antagonistantagonist
Reversible overcompensationReversible overcompensation
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Agents not cross BBB are ineffectiveAgents not cross BBB are ineffective Ineffective after symptoms have appearedIneffective after symptoms have appearedScopalamine / atropine Scopalamine / atropine SE : SE :
Dry mouth dilated pupilsDry mouth dilated pupilsUrinary retention sedationUrinary retention sedationConstipation confusionConstipation confusion
C/I : BPH , closed angle glaucomaC/I : BPH , closed angle glaucoma
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antihistaminesantihistamines
Uncertain mechanismUncertain mechanism Central effect ( block H1-R)Central effect ( block H1-R) Inhibiton synaptic transmission on MVN ( medial Inhibiton synaptic transmission on MVN ( medial
vestibular nucleus )vestibular nucleus ) Anticholinergic and sedative effectsAnticholinergic and sedative effects Effective also after symptomes have appearedEffective also after symptomes have appeared Cinnarazine Cinnarazine promethazine / diphenhydramine - sedative promethazine / diphenhydramine - sedative prochlorperazine / miclizine - antiemeticprochlorperazine / miclizine - antiemetic
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benzodiazepinesbenzodiazepines
GABA modulatorsGABA modulatorsCentral suppression of vestibular responseCentral suppression of vestibular responseSedative , hypnotic, muscle relaxant , Sedative , hypnotic, muscle relaxant ,
reduce anxietyreduce anxietyClonazepam / lorazepam / alprazolamClonazepam / lorazepam / alprazolamSE : SE :
Impaired vestibular compensationImpaired vestibular compensationImpaired memoryImpaired memoryaddictionaddiction
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Anti emeticsAnti emetics
Dopamine block activityDopamine block activityNot ideal for emesis from vestibular Not ideal for emesis from vestibular
imbalanceimbalanceAntihistamine effect – promethazine ( H1-Antihistamine effect – promethazine ( H1-
R block)R block)Metoclopramide – potent central Metoclopramide – potent central
antiemetic, speed gastric emptying is not antiemetic, speed gastric emptying is not effective antivertigo drugeffective antivertigo drug
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Sulpiride :Sulpiride :Selective dopamine (D2) antagonistSelective dopamine (D2) antagonistLow incidence of extrapyramidal Low incidence of extrapyramidal Antiemetic action Antiemetic action Improve blood flow, mucosal secretion in GIImprove blood flow, mucosal secretion in GIAntivertigo , anti-migraine headacheAntivertigo , anti-migraine headacheAntidepressant activity ( low doses )Antidepressant activity ( low doses )Antipsychotic activity ( high doses ) Antipsychotic activity ( high doses )
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New antiemetic – 5-HT3 antagonist New antiemetic – 5-HT3 antagonist
serotonin ( 5 hydroxytryptamine subtype 3 serotonin ( 5 hydroxytryptamine subtype 3 receptor ) antagonistreceptor ) antagonist
Ondensetron / granisetronOndensetron / granisetronNausea and vomiting associated with Nausea and vomiting associated with
chemotherapy , post. Operationchemotherapy , post. OperationLess effective for vestibular emesis Less effective for vestibular emesis High costHigh cost
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Other optionsOther options
Ca channel blockers :Ca channel blockers :Vestibular suppression on Ca channel in hair Vestibular suppression on Ca channel in hair
cellscellsFlurnarazine / cinnarazineFlurnarazine / cinnarazineAntihistamines and anticholinergic activityAntihistamines and anticholinergic activityEffective in menier’s and migraneEffective in menier’s and migraneSE : sedation , weight gain , parkinsonismSE : sedation , weight gain , parkinsonism
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Na channel blocker :Na channel blocker :Affect GABA NT , glutamate antagonistAffect GABA NT , glutamate antagonistPhenytoin / nerontin / tegretolPhenytoin / nerontin / tegretolCentral nystagmusCentral nystagmusAnticonvulsants are promising agents for Anticonvulsants are promising agents for
treatment vertigo ( uncertain mechanism )treatment vertigo ( uncertain mechanism )
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Histamine agonist :Histamine agonist :Betahistine – H1/H3 – R agonistBetahistine – H1/H3 – R agonistIncrease circulation to inner earIncrease circulation to inner earSuppress veastibular function Suppress veastibular function Facilitation of compensationFacilitation of compensationSE : nausea , headacheSE : nausea , headacheCaution ; peptic dis , pheochromocytomaCaution ; peptic dis , pheochromocytoma
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Steroids Steroids Reduce duration of vertigo episodesReduce duration of vertigo episodesEffective in meniere’s , vestibular neuritisEffective in meniere’s , vestibular neuritis
SypmpathomimeticsSypmpathomimeticsCounterbalance sedative effect of vestibular Counterbalance sedative effect of vestibular
suppressant - increase compensationsuppressant - increase compensationEphedrine / amphetamine – limitted use Ephedrine / amphetamine – limitted use
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Acetyl- leucineAcetyl- leucineVestibular suppresantVestibular suppresantRapid antivertigo effect ( IV)Rapid antivertigo effect ( IV)
Ginkgo-BilobaGinkgo-BilobaVestibular suppresantVestibular suppresantEffective in tinnitus , improve memoryEffective in tinnitus , improve memory
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Selective Ach antagonistSelective Ach antagonistM2-R antagonist M2-R antagonist Vestibular suppressant without SEVestibular suppressant without SELittle reaserchLittle reaserch
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Alternative medicine agents Alternative medicine agents Ambra grisea D6Ambra grisea D6Anamirta cocculus D4Anamirta cocculus D4Conium maculatum D3Conium maculatum D3Petroleum rectificatum D8Petroleum rectificatum D8
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Specific PharmacotherapySpecific Pharmacotherapy
Vestibular Neuritis *Vestibular Neuritis *Meniere’s Disease *Meniere’s Disease *Benign Paroxysmal Positional Vertigo *Benign Paroxysmal Positional Vertigo *OtosyphilisOtosyphilisVertebrobasilar InsufficiencyVertebrobasilar InsufficiencyMigraine (with vertigo)Migraine (with vertigo)
* * more common more common
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Vestibular NeuritisVestibular Neuritis
Sudden onset of peripheral vertigoSudden onset of peripheral vertigo Inflammation of vestibular nerve - Inflammation of vestibular nerve -
presumably of viral originpresumably of viral originSpontaneous, complete symptomatic Spontaneous, complete symptomatic
recovery with supportive treatmentrecovery with supportive treatmentTreatment aimed at stopping inflammationTreatment aimed at stopping inflammation
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Vestibular NeuritisVestibular Neuritis
Ariyasu et al. (1990)Ariyasu et al. (1990)20 patients: double-blinded, crossover20 patients: double-blinded, crossoverMethylprednisolone vs. placeboMethylprednisolone vs. placebo90% decrease in vertigo within 24 hours vs. 90% decrease in vertigo within 24 hours vs.
30% of placebo group30% of placebo groupPlacebo switched to steroid after 24 hours Placebo switched to steroid after 24 hours
with decrease in vertigo over next 24 hourswith decrease in vertigo over next 24 hours16 patients receiving steroid with resolution 16 patients receiving steroid with resolution
had normal ENG within one monthhad normal ENG within one month
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Meniere’s DiseaseMeniere’s Disease
Hallpike and Cairns - 1938 found Hallpike and Cairns - 1938 found endolymphatic hydrops by histologyendolymphatic hydrops by histology
Precise etiology is unknownPrecise etiology is unknown
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Meniere’s DiseaseMeniere’s Disease
Widely accepted medical treatmentWidely accepted medical treatmentDietary salt restrictionDietary salt restrictionDiureticsDiuretics
Thiazide diureticsThiazide diureticsDecrease Na absorption is distal tubuleDecrease Na absorption is distal tubuleSide effects - hypokalemia, hypotension, Side effects - hypokalemia, hypotension,
hyperuricemia, hyperlipoproteinemiahyperuricemia, hyperlipoproteinemiaCombination potassium sparing agents Combination potassium sparing agents
spironolactone , thiazide + amiloridespironolactone , thiazide + amiloride
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Meniere’s DiseaseMeniere’s Disease
At least 3 months of diuretic therapy At least 3 months of diuretic therapy recommended before discontinuingrecommended before discontinuing
Sulfa allergies - can try loop diuretics or Sulfa allergies - can try loop diuretics or alternate therapiesalternate therapies
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Meniere’s DiseaseMeniere’s Disease
Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors (acetazolamide)(acetazolamide)““inner ear glaucoma”inner ear glaucoma”Decreased Na-H exchange in tubuleDecreased Na-H exchange in tubuleDecreased CSF productionDecreased CSF productionDiuretic effect not as long-lastingDiuretic effect not as long-lastingSide effects - nephrocalcinosis, mild metabolic Side effects - nephrocalcinosis, mild metabolic
acidosis, GI disturbancesacidosis, GI disturbances
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Meniere’s DiseaseMeniere’s Disease
VasodilatorsVasodilatorsBased on hypothesis - pathogenesis results Based on hypothesis - pathogenesis results
from ischemia of stria vascularisfrom ischemia of stria vascularisRationale - improve metabolic functionRationale - improve metabolic functionIV histamine, ISDN, cinnarizine (CA IV histamine, ISDN, cinnarizine (CA
antagonist), betahistine (oral histamine antagonist), betahistine (oral histamine analogue)analogue)
Anecdotal successAnecdotal successNo demonstrated beneficial effects in studiesNo demonstrated beneficial effects in studies
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Meniere’s DiseaseMeniere’s Disease
Newer theoriesNewer theoriesMultifactorial inheritanceMultifactorial inheritanceImmune-mediated phenomenaImmune-mediated phenomenaAssociation of allergiesAssociation of allergies
Study by Gottschlich et al.Study by Gottschlich et al.50% meeting criteria have antibodies to 70-kD 50% meeting criteria have antibodies to 70-kD
heat-shock proteinheat-shock protein70-kD HSP implicated in AI-SNHL70-kD HSP implicated in AI-SNHL
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Meniere’s DiseaseMeniere’s Disease
Immunosuppressive agents gaining favorImmunosuppressive agents gaining favorSystemic and intra-tympanic glucocorticoidsSystemic and intra-tympanic glucocorticoidsCyclophosphamideCyclophosphamideMethotrexateMethotrexate
Shea study - intractable Meniere’sShea study - intractable Meniere’s48 patients IT dexamethasone 48 patients IT dexamethasone 66.7% elimination of vertigo66.7% elimination of vertigo35.4% improvement in hearing (>10dB and/or 35.4% improvement in hearing (>10dB and/or
15% change in word recognition score) 15% change in word recognition score)
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Meniere’s DiseaseMeniere’s Disease
Chemical labyrinthectomyChemical labyrinthectomyDisabling vertigoDisabling vertigoAfter trial of adequate medical therapyAfter trial of adequate medical therapy
Intratympanic aminoglycoside (ITAG)Intratympanic aminoglycoside (ITAG)Allows treatment of unilateral diseaseAllows treatment of unilateral diseaseGentamicinGentamicin
Primarily vestibulotoxicPrimarily vestibulotoxic may impair vestibular dark cells (endolymph)may impair vestibular dark cells (endolymph)
Inherent hearing loss risk - 30%Inherent hearing loss risk - 30%
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ITAGITAG
Stock solution - 40mg/mL gentamicinStock solution - 40mg/mL gentamicin10 to 20 mg injected over round window10 to 20 mg injected over round windowPatient supine, ear up for 30 minutesPatient supine, ear up for 30 minutes Instructed not to swallowInstructed not to swallowBolus injections - weekly or bi-weeklyBolus injections - weekly or bi-weeklyEnd point variable - vestibular hypofunctionEnd point variable - vestibular hypofunctionAudiometry monitoring between injectionsAudiometry monitoring between injectionsTotal vestibular ablation not necessaryTotal vestibular ablation not necessary
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ITAGITAG
MinorMinor91% control of vertigo91% control of vertigo3% rate of profound SNHL (usually sudden)3% rate of profound SNHL (usually sudden)22% recurrence rate22% recurrence rate
Continuous deliveryContinuous deliveryMicrowickMicrowickRound Window MicrocatheterRound Window Microcatheter
Direct injection (labyrinthotomy)Direct injection (labyrinthotomy)Significant hearing lossSignificant hearing lossOut of favorOut of favor
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BPPVBPPV
Most common causeMost common cause Dysfunction of posterior SCCDysfunction of posterior SCC Cupulolithiasis vs. CanalithiasisCupulolithiasis vs. Canalithiasis
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BPPVBPPV
Treatment approachesTreatment approaches Liberatory maneuversLiberatory maneuvers Particle repositioningParticle repositioning Habituation exercisesHabituation exercises
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BPPVBPPV
EpleyEpley CanalithiasisCanalithiasis Canalith repositioningCanalith repositioning Move into vestibuleMove into vestibule Cure ratesCure rates
80% - one treatment80% - one treatment 100% - multiple100% - multiple
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OtosyphilisOtosyphilis
Penicillin established treatmentPenicillin established treatment IM and IV routes acceptableIM and IV routes acceptable IM - 2.4 million units benzathine PCN IM - 2.4 million units benzathine PCN
weekly x 3 consecutive weeks is minimal weekly x 3 consecutive weeks is minimal treatment (some advocate up to 1 year)treatment (some advocate up to 1 year)
IV - 10 million units PCN G qD in divided IV - 10 million units PCN G qD in divided doses x 10 days, followed by 2.4 million doses x 10 days, followed by 2.4 million units benzathine PCN x 2 weeksunits benzathine PCN x 2 weeks
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Vertebrobasilar insufficiencyVertebrobasilar insufficiency
Vertigo, diplopia, dysarthria, gait ataxia Vertigo, diplopia, dysarthria, gait ataxia and bilateral sensory & motor disturbanceand bilateral sensory & motor disturbance
Transient ischemia - low stroke riskTransient ischemia - low stroke riskAntiplatelet therapy - aspirin 325mg qDAntiplatelet therapy - aspirin 325mg qDTiclid Ticlid
Platelet aggregate inhibitorPlatelet aggregate inhibitorRisk of life-threatening neutropeniaRisk of life-threatening neutropeniaOnly in patients unable to tolerate aspirinOnly in patients unable to tolerate aspirin
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MigraineMigraine
Concomitant vertigo and disequilibriumConcomitant vertigo and disequilibriumHeadache control improves vertigoHeadache control improves vertigoDiagnostic criteriaDiagnostic criteria
Personal/family historyPersonal/family historyMotion intoleranceMotion intoleranceVestibular symptoms - do not fit other causesVestibular symptoms - do not fit other causes
Theories - vascular origin, abnormal Theories - vascular origin, abnormal neural activity (brainstem), abnormal neural activity (brainstem), abnormal voltage-gated calcium channel genesvoltage-gated calcium channel genes
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MigraineMigraine
TreatmentTreatmentModifying risk factorsModifying risk factors
Exercise and dietExercise and dietAvoid nicotine, caffeine, red wine and chocolateAvoid nicotine, caffeine, red wine and chocolate
Abortive medical therapyAbortive medical therapyErgotsErgotsSumatriptinSumatriptinMidrinMidrin
Prophylactic medical therapyProphylactic medical therapyB blockers, Ca channel blockers, NSAIDs, B blockers, Ca channel blockers, NSAIDs,
amitryptiline, and lithiumamitryptiline, and lithium
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Vestibular RehabilitationVestibular Rehabilitation
Promoting vestibular compensationPromoting vestibular compensationHabituationHabituationEnhancing adaptation of VOR & VSREnhancing adaptation of VOR & VSRMay have initial exacerbationMay have initial exacerbation
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Vestibular RehabilitationVestibular Rehabilitation
Cawthorne - CookseyCawthorne - CookseyDeveloped in 1940sDeveloped in 1940sHead movementsHead movementsBalance tasksBalance tasksCoordination of eyes with headCoordination of eyes with headTotal body movementsTotal body movementsEyes open & closedEyes open & closedNoisy environmentsNoisy environments
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Vestibular RehabilitationVestibular Rehabilitation
Habituation of pathologic responsesHabituation of pathologic responsesPostural control exercisesPostural control exercisesVisual-vestibular interactionVisual-vestibular interactionConditioning activitiesConditioning activitiesB.I.D., most improve after 4-6 weeksB.I.D., most improve after 4-6 weeks
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VRT - ElderlyVRT - Elderly
Multifactorial causes of balance difficultyMultifactorial causes of balance difficultyNeed 2 of 3 systems functionalNeed 2 of 3 systems functional
vestibular, visual, proprioceptivevestibular, visual, proprioceptive
Good outcome measures with longer timeGood outcome measures with longer time Impact on complications of fallsImpact on complications of falls
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ConclusionsConclusions
Vestibular complaints common to ENTVestibular complaints common to ENTThorough evaluation and understandingThorough evaluation and understandingDx and treat acute symptomsDx and treat acute symptomsWean vestibular suppressantsWean vestibular suppressantsSpecific pharmacotherapy institutedSpecific pharmacotherapy institutedChronic, uncompensated disease benefits Chronic, uncompensated disease benefits
from early VRTfrom early VRT