BRS Movement Disorders 2015_no videos

D A N I S H B H A T T I M DM O V E M E N T D I S O R D E R S D I V I S I O N

MOVEMENTDISORDERS!D B V S . P S Y C H – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”

D E C E M E B E R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .

OUR INTENTIONS:THIS TALK

IS MEANT TOD B V S . P S Y C H – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”

D E C E M E B E R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .

D A N I S H B H AT T I M DM O V E M E N T D I S O R D E R S C o .

T H I N G S W E ’ R E D I S C U S S I N G F O R N E X T 5 6 M I N U T E S :

FU N CT I O N A L A N ATO MYPA RK I N SO N I SM

E SSE N T I A L TRE MO RDYS TO N I A S

C HO RE A S A N D HDT I CS A N D TO U RE TTE

C HE MO DE N E RVAT I O NDE E P B RA I N S T I MU L AT I O N

RE V I E W V I DE O S

D B V S . P S Y C H – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”

N O V E M B E R 1 8 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .


TREMORD A N I S H B H AT T I M D

M O V E M E N T D I S O R D E R S C o .


D E C E M E B R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .

Oscillatorymovementcausedbythealternatingactivationofagonist/antagonistmusclegroups.Canbemostlyatrest(parkinsonian),withaction(EssentialTremor)

andmanyothersubtypes.

CHOREAD A N I S H B H AT T I M D


(fromGreekwordfordance)fast,jerky,involuntarymovementsthatflowrandomlyfromonebodyparttothenextone.



DYSTONIAD A N I S H B H AT T I M D


excessivemusclecontractionthatcausesabnormalmovementsorpostures.



MYOCLONUSD A N I S H B H AT T I M D


veryfast,jerky,shock-likeinvoluntarymovements



TICSD A N I S H B H AT T I M D


abrupt,oftenrepetitive,suddenmovementsorvocalizationsthatareprecededbyanuncomfortablefeelingthatisrelievedbytheact.Whilesuppressingthetics,

thereisabuildingupoftheinternalpressuretoletgo.



AKATHISIAD A N I S H B H AT T I M D


Aninabilitytostaystill.Thereisaninternalneedtomoveconstantly,butthesearevoluntarymovementsthataresuppressible.



STEREOTYPYD A N I S H B H AT T I M D


voluntarystereotypicalmovementsthatareperformedusuallysemiconsciously,morecommonduringalertself-wanderingorunderstress.Usuallynot

pathological,althoughacommonfeatureindevelopmentaldelayandautism.



PREVALANCE OF MOVEMENT DISORDERS

MORE THAN THOUSAND CONDITIONS10% LIFE TIME RISK OF ESSENTIAL TREMOR

10% POPULATION WITH RLS4% RISK OF PARKINSON DISEASE

4% POPULATION WITH TOURETTE SYNDROME1-4% RISK OF ATAXIAS

IMPORTANCE OF MOVEMENT DISORDERS

SOME ARE CURABLE BUT ALL ARE TREATABLEMANY GOOD TREATMENT OPTIONS:

CHEMODENERVATION, DEEP BRAIN STIMULATIONTREATMENT IMPROVES QUALITY OF LIFE

FREQUENTLY MISDIAGNOSED OR UNDIAGNOSED


CLASSIFICATION OF MOVEMENT DISORDERS

HYPOKINETICHYPERKINETIC


D C E M E B E R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .

FUNCTIONAL ANATOMYD A N I S H B H AT T I M D




DIRECT AND INDIRECT PATHWAYSD A N I S H B H AT T I M D







PARKINSONISMPresenceoftwoofthecardinalfeaturesmakesthediagnosis,butat

leastonehastobeamajorfeature.Majorfeaturesincludebradykinesia,restingtremor,rigidityandpostural

instability.Otherfeatures:Rigidity,flexedposture,lossofposturalreflexes,

freezing.



leastonehastobeamajorfeature.Majorfeaturesincludebradykinesia,restingtremor,rigidityandpostural


freezing.D B V S . P S Y C H – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”




leastonehastobeamajorfeature.Major featuresincludebradykinesia,restingtremor,rigidityandpostural


freezing.D B V S . P S Y C H – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”


PARKINSONISM: CLASSIFICATIONPRIMARY

IDIOPATHICPARKINSON-PLUS

SYNDROMESMSAPSP

CBGDDLB

SECONDARYMEDICATION INDUCED

TUMORTRAUMATICINFECTIOUS

PARKINSONISM

PARKINSONISMD A N I S H B H AT T I M D



D E C E M B E R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .


GENETICS OF PARKINSONS

CAUSAL GENESASSOCIATED GENES





D E C M E B E R 2 , 2 0 1 5 – U N M C – O M A H A , N E , U . S . A .

MonoGenicParkinson’sDisease:PARK1-9

PARK1/PARK4:Abnormala-synculein gene,AD,earlyonsetoftypicalPDbeforeage50

PARK8:LRRK2 genemutation,ADorsporadic,mostfrequentcauseoflateonsetPD,typicalPD,manydozensofmutations,ethnicallyspecificmutationsinarabs,jewish andeuropeans.

PARK2:Parkin genemutation,AR,MostcommoncauseofJuvenilePD(<21yearsage),usuallypresentsmidtolateonsettypicalPD.

PARK6:Pink1genemutation,AR,undistinguishablefromotherPD

PARK7:DJ1genemutation

PARK9:ATP13a2genemutation




NEURO-LEPTICNEURO-TOXICITY

NEUROLEPTICMALIGNANTSYNDROME:

lifethreateningMostcommonlyseenwithinitiationanddosechangesHyperthermia, rigidity,mentalstatuschanges,highCPK.Stopdrug, Rxwith levodopa.

AKATHISIAAcuteorTardive

Restlessness

PARKINSONISMfromDA2receptorblockade.

MostresolveafterW/D

TARDIVEDYSKINESIAfromchronicDAreceptorblockadeFacialand lingual stereotypic, repetitive, rhythmicinvoluntarymovements,+/- otherchorea,dystonia, tics,andmyoclonus

Rx:Discontinuedrug (acuteworsening),GABA, DA-depleters, Chemodenervation.

Prognosis: About20%resolve,most respond toRx.

ACUTEDYSTONICREACTION




MONOGENIC PARKINSONS




ASSOCIATED GENES




ASSOCIATED GENES

a-Synuclein gene Most significant risk factor is the variation in the actual a-synculein gene itself.

Some variations cause monogenic parkinsonswhile others increase risk of PD.

LRRK 2 gene Some mutations can cause monogenic PDVariations in LRRK 2 gene increased risk of PDMost common known genetic risk factor for PDAs common as 40% of the patients with PD

B - Gluco-cerebrosidase

Homozygous mutation causes Gauchers disease

Heterozygous mutation increases risks for PD (5 times more likely than general population).People with GBA mutation develop PD at younger age.

TREATMENTD A N I S H B H AT T I M D




Avoidantiemetics andantipsychotics.Onlysafeantiemetics areOndansetronandDomperidone.

Onlysafeanti-psychoticsareSeroquelandClozapine.Youngpatientwithminorsymptoms:Rasagiline (MAOi),Pramipexole andRopinirole

(dopa-agonists)>50yo and/orwithmorethanmildseverity=Levodopa

Sideeffectsfortheexam:Psychosis,orthostasisAgonists:Sleepattacks,OCD,gambling,cognitive.

Levodopa:dyskinesias,nausea.


MSAPA R K IN SO N ISM

AU TO N O MIC DYSFU N C TIO NATA X IA

PY R A MIDA L SIG N SG LIA L C Y TO PLA SMIC IN C LU SIO N S




PSPA X I A L PA R K I N S O N I S M

S U P R A N U C L E A R PA L S YD E M E N T I A

P S E U D O BU L BA R S Y M P TO M SB R A I N S T E M N E U RO F I B R I L A RY TA N G L E S




CBGDA X I A L PA R K I N S O N I S MC O R T I C A L F E AT U R E S

AG N O S I A , A P R A X I A , A L I E N L I M BDYS TO N I A

P O O R L E VO D O PA R E S P O N S EBA LO O N E D H Y P O C H RO M AT I C N E U RO N S



DEEPBRAINSTIMULATIONSURGERY


DEEP BRAIN STIMULATION SURGERY

DBShasproventobebeneficialtoanumberofconditions,includingPD,Essentialtremor,andDystonia

Morethan100,000patientshavereceivedaDBSdeviceProventoimprovequalityoflifePracticalcureforEssentialTremor



STEREOTAXICFRAME

ESSENTIAL TREMORAtremorthatgetsbetterwithAlcohol.

ESSENTIAL TREMORD A N I S H B H AT T I M D


Benign,FamilialEssentialTremorNotthatbenign:associatedwithcoordinationproblems,hearingloss,

andgaitinstability;canprogresstobecomedisablingHighlytreatable,butincrediblyunder-diagnosed

Oralmedications:Primidone,Propranolol,Topiramate.DeepBrainStimulationisapracticalcureinmorethan90%ofpatients

resistanttomedications



DYSTONIASustainedMusclecontractionwithposturing

GESTE ANTAGONISTE

Torticollis to right, laterocollis to the right, right shoulder elevation

Light touch of the hand on the chin allows the head to return to the foreword position.

CLASSIFICATION OF DYSTONIAETIOLOGY

PRIMARY:Genetic(DYT-#)oridiopathicSECONDARY:otherknowndiseases(PD,HD,SCA3,NBIA,Wilson’s,etc),medications,

AGEEARLYONSET:Youngerthan27yo.

LATEONSET:Olderthan27.ANATOMICAL

Focal,segmental,multifocal,hemidystonia,generalized.TIME

Constant,intermittentorsituational.

DYSTONIAOnefootdragging

Tip-toeorin-toeingambulationMusclespasms

Severestiffness(neck,arm,leg)Excessiveeyeclosure(called

blepharospasm)Uncontrollablemovements

(hand,face)

Inabilitytousethehand,withoutweakness(writer’scramp)

Voiceabnormality(spasmodicdysphonia)Tremor

Abnormalpostures(torticollis)



ORALDRUGSAnticholinergics,Gabaergics (bothAandB)anddopaminergicagents,usually

acombinationofmultipledrugsatmoderatedose.Everydystonicpatientshouldbeconsideredforlevodopareplacement

(Dopa-responsivedystonias)CHEMODENERVATION:Botulinumtoxininjections.

SURGERYDeepBrainStimulationorlesional surgery:Globuspallidus parsinterna.





Chemodenervationduetolackofreleaseofacetylcholineatnervemusclejunction.

Thistoxindisruptproteincomplexcriticalfusionofacetylcholinecontainingvesiclewithcellmembrane

Thetoxinsbindstothesurfacereceptorsandthereinternalizethroughendosomesandreleasedtocytoplasmand

Toxinbindstoandcleaveproteininvolvedinendosomefusionwithmembrane.

7botulinumtoxinserotypesfromAtoG.

TypeAandEcleaveSNAP-25 (synaptosomal associatedprotein25).

TypesB,D,FandGcleaveVAMP (vesiclesassociatedmembraneprotein).

TypeCtoxincleavesbothSYNTAXIN andSNAP-25.



NEUROLEPTIC NEUROTOXICITYD A N I S H B H AT T I M D


NEUROLEPTICMALIGNANTSYNDROMElifethreatening

MostcommonlyseenwithinitiationanddosechangesHyperthermia,rigidity,mentalstatuschanges,highCPK.

Stopdrug,Rxwithlevodopa.ACUTEORTARDIVEAKATHISIA

PARKINSONISMfromDA2receptorblockade.MostresolveafterW/D.

TARDIVEDYSKINESIAfromchronicDAreceptorblockade

Facialandlingualstereotypic,repetitive,rhythmicinvoluntarymovements,+/- otherchorea,dystonia,tics,andmyoclonus

Rx:Discontinuedrug(acuteworsening),GABA,DA-depleters,Chemodenervation.Prognosis:About20%resolve,mostrespondtoRx.



ACUTE DYSTONIC REACTIOND A N I S H B H AT T I M D


AssociatedwitharatheracutestateofDAdeficiency.(administrationofDAblockersorwithdrawalfromDAagonists).

Oculo-gyric crisisareusuallyaccompaniedwithopisthotonus,rigidity,rageorfear,catalepsyorblock.UsualtreatmentisBenadrylorBenztropine (anti-ACh),

withresponsewithinanhour.



SEROTONIN SYNDROMESS NMS

Offending drug 5HT and DA excess DA deficiencyOnset to peak time Hours DaysResolution < 24 hrs Days to weeksHyperthermia 45% > 90%Altered LOC 50% > 90 %Autonomic DysFx 50-90% > 90 %Rigidity 50% > 90 %Leukocytosis 11% > 90 %Increased CPK 15% > 75%Hyperreflexia Very common RareMyoclonus Very common RareDA-agonists Exacerbate Improve

TOURETTE SYNDROMEIrresistibleurge

TIC DISORDERSD A N I S H B H AT T I M D


Transientticdisorder(<1yearduration)-24%ofchildren.

Chronicticdisorder(>1yearduration)- motororvocalbutnotboth.

Tourettesyndrome(1- 3.5%ofchildren)

MultiplemotorandatleastonevocalticWaxingandwaningcourseoveratleast1year

Onsetbefore21(usually6-7yearsold)Absenceofprecipitatingdisease



TOURETTE SYNDROMEObsessive-compulsive disorder

30-70%

Attention deficit disorder 50-75%

Anxiety disorders 20-80%

Mood disorders 20-80%

Episodic control disorders 25%

Academic difficulties 50%


TOURETTE SYNDROMECommon:atleasttwopeopleinthisroomhasit.

Sociallyisolating,althoughhighlytreatable.Runsinfamilies,withoutcleargeneticpattern.

COPROLALIA:Utteranceoffoullanguageisuncommon (10%)



CHOREAHuntingtondiseaseSydenhamchorea(rheumaticchorea)

Drug-induced(dopaminergicagents,opiates)

LupuserythematosusThyroiddisease

ChoreagravidarumSecondarytoother

neurodegenerativediseases(Wilson’s,NBIA,SCA-3).

Hemiballismus:Sudden,wide-amplitudechorea,

usuallyduetostrokeofthestriatum>>Sub-thalamicnucleus.

HUNTINGTON DISEASED A N I S H B H AT T I M D


Autosomaldominantdisorder.(4p16.3)Characterizedbyprogressivecognitiveandpsychiatricchanges,choreaandgait

problems(ataxia,falls)40,000peopleintheU.S.haveHD

About250,000peopleareat-riskforHDEqualratiobetweenmenandwomen

Insidiousprogressivecoursewithdeath15-20yearsafteronset.ChoreacanbetreatedwithRespridal,Tetrabenazine (DAdepleter)althoughis

associatedwithsuicidality.Treatdepression,irritabilityasusual.



Main Features of HDMotor function Falls and balance problems

Involuntary movements (chorea)Gait impairmentProblems swallowingOcular movement abnormalities

Cognitive Forgetfulness – Dementia – lack of focus and concentrationPoor judgment.Difficulty learning new informationInability to reason and planning (prioritizing, organizing)

Psychiatric Fast emotional shifts, impassivity. Depression (30-50% risk)Personality change (irritability, anger, apathy, etc.)Psychosis (10% lifetime risk)Increased risk for suicide (As many as 25 % attempt suicide)

HD PATHOLOGY

CAGtrinucleotide repeatsmorethannormalonthehuntingtin proteingene.Chromosome4

RESTLESS LEG SYNDROMED A N I S H B H AT T I M D


Acreepy/crawlysensationusuallyintheLEthatgoesawaybymoving,walking.Rarelygeneralized.

OnofthemostcommonMovementDisorders.Mostcommonatnight.

Primaryorsecondary(parkinsonism,neuropathy,renaldysfunction)Canbeassociatedwithanemia(irondeficiency).

Highlytreatable:responsivetodopamineagonistsandlevodopa.Goodprognosis.



ATAXIAD A N I S H B H AT T I M D


Themostcommoncauseofataxiaistoxic(medications,ETOH)ACUTE

stroke,drugs,hydrocephalus,migraine(inchildren),infectious(VZV)SUBACUTE

tumors,post-infectious,vasculitis,drugsCHRONIC

alcoholism,drugs,paraneoplastic,Multiplesclerosis.



HEREDITARY ATAXIASD A N I S H B H AT T I M D




Difficulttodistinguish,soIalwaysobtaintheataxiacompletepanel(Friedrich,DRPLA,commonSCA’s).Alwaysruleoutsecondaryandtreatablecausesfirst:mass,infection,Wilson,metabolic.

SCA’s=dominant.FA,Edef,A-betalipoprot,AT=recessiveVisualloss?à SCA7.Seizures?à SCA10.Chorea?à DRPLA

Parkinsonism?à SCA2,3,21Olderadult?à SCA6

Childhoodonset?à SCA7,13,DRPLA

MYOCLONUSD A N I S H B H AT T I M D


Physiologic- hiccups,sleepEpileptic- cortical,isatypeofseizure

Essential- subcortical,familial,childhoodonset,benigncourse.Symptomatic(secondary)- metabolic(hepaticfailure,uremia,hypoxia),

degenerative(Alzheimer’s),infectious(priondiseases)Spinal- segmentalorfocal.

Asterixis- Negativemyoclonus



RAPIDFIRE

ROUNDD B V S . P S Y C H . – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”


O f f i c i a l p r e s e n t a t i o n DA N I S H B H AT T I / M O V E M E N T D I S O R D E R S C O .

OUR ATTEMPT ATHIGH NOTE

CLOSER(STUFF THAT REALLY

MATTERS) D B V S . P S Y C H . – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”



never, everin your l i fetime

or anybody's l i fetimegive a dopamine antagonist

to a parkinson patient

Myoclonus think SSHigh CK think NMS, MH

Hyper ref lexia think SS, PAIDLeukocytosis think NMS

Peak 12 hours think NMS

t ics are often non-disruptive and don’t need treatment

most of morbidity is usual ly f rom associated behavior

and cognitive problems

CAG repeats in HD<26 normal

27-34 unstable35-38 border l ine

>39 HD>60 JHD

WORKHARD

AND LOVE YOUR WORK

SAY YESMAY BE A LITTLE MORE

THAN YOU SAY NO

DO GOODWORK

FOR GOODPEOPLE

THIS DOES EXIST. REALLY.

SHORTCASES

D B V S . T R E M O R – “ A L L T H A T S H A K E S I S N O T E T ” – M O V E M E N T D I S O R D E R S L E C T U R E S E R I E S



JUSTBECAUSE:

D B V S . P S Y C H . – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”



THANK YOU!


D B V S . P S Y C H . – B O A R D R E V I E W L E C T U R E S E R I E S - “ M O V E M E N T D I S O R D E R S ”


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BRS Movement Disorders 2015_no videos

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