ABNORMAL MOVEMENTAmbulatory Conference10thAugust,2015Presented by : Nichanan OsataphanConsultant : Aj.Surat TanprawateCase Thai male 55 years old Government employerCase Chief complaint : Tremor of both hands 1 year PTACase 1 year PTA , He has tremor which occur at rest and during working. He developed difficult on movement . No falling 4 months PTA , The symptom progressed, The tremor affected his daily activity. He cant work.CasePast History No underlying disease No history of head trauma No current medicationCase GA:An middle aged man with normal consciousness HEENT: No pale, No jaundice ,No neck vein engorgement, No lymph node enlargement, No thyroid gland enlargement, Lung: Symmetrical contour , normal chest movement ,Clear and equal breath sound Heart : No heaving, No thrill, PMI at 5thICS MCL, Regular rhythm, Normal S1S2, No murmur Abdomen: Normal contour, Splenectomy scar at left-sided abdomen ,active BS, soft ,not tender, No hepatosplenomegaly Extremities : CRT< 2 secs, No pitting edema, Peripheral pulses 2+ allCase Neuro exam E4V5M6 Pupil 3 mm RTLBE Motor power grade V all Sensory intact all Cranial nerve : intact allProblem listsDiscussionAbnormal movementHyperkinetic Movements Tremor Chorea/Athetosis Dystonia Ballism Myoclonus Tics Ataxia Myokymia Myorrhythmia Restless Legs Hyperkplexia AkathesiaHypokinetic Movements Parkinsonism Apraxia Hesitant gaits Hypothyroid slowness RigidityTremor Most common movement disorders Cause by either alternating or synchronous contractions of antagonistic muscles Rhythmic oscillation of a body part with a relatively constant frequency and variable amplitudeTremor classification Resting tremor Action tremor Postural tremor Intention tremor Kinetic tremor Task specific tremor Isometric tremorDeuschol,G.,Bain,P.&Brin,M. Consensus statement of the movement disorder society on Tremor. Mov. Disord.13(Suppl.3),2-23(1998)Consensus Statement of the Movement Disorder Society12345Cardinal signs of ParkinsonismBradykinesiaWith at least 1/3 for diagnosis Resting tremor Rigidity Postural instabilityClassification of Parkinsonism Primary or Idiopathic Parkinsonism (Parkinsons disease) Secondary Parkinsonism Parkinsonism plus syndromes Heredodegenerative ParkinsonismParkinsonismPrimary or Idiopathic (Parkinsons disease) Secondary ParkinsonismParkinsonism plus syndromeHeredodegenerativeParkinsonism- Progressive supranuclear palsy (PSP)- Corticobasal degeneration (CBD)- Multiple system atrophy (MSA)- Wilsons disease- Huntingtons diseaseSecondary ParkinsonismDrug-inducedVascular ParkinsonismToxic/metabolicHydrocephalusInfectionAntipsychotic : Haloperidol, Chlorpromazine, RisperidoneAntiemetics : MetoclopramideAntiepileptic : Sodium valproate, DilantinAntivertigo : Flunarizine, CinnarizineMiscellaneuos : Amiodarone, Lithium, FluoxetineToxin : MPTP, CO, CyanideMetabolic : Hypo/Hyperthyroid, Hypo/Hyperparathyroid, Japanese encephalitisParkinsons diseaseEpidemiology The worldwide prevalence of PD is approximately 300 per 100000 (In population age > 40 years) Incidence 18 per 100000 per year 7.5 million people worldwide with PD Age related disease Gradually increase after age 50 years and disease before age 30 years is rare Equal sex incidencePathophysiology Progressive loss of pigmented neurons in the substantia nigra, decrease in dopamine Symptoms of PD appear after 60-80% of these cells become impaired or die The presence of Lewy bodies is the hallmark of PDUK Parkinsons disease society brain bank clinical diagnostic criteria3 Steps to The Diagnosis of Parkinsons diseaseStep 1 : Diagnosis of ParkinsonismStep 2 : Exclude other causes of ParkinsonismStep 3 : Features that support a diagnosis ofParkinsons disease (three or more required fordiagnosis of definite Parkinsons disease)Hughes AJ, Daniel SE, Kilford L, Lees AJ. JNNP 1992 Mar;55(3):181-4Step 1 : Diagnosis of Parkinsonism Bradykinesia At least one of the following Muscular rigidity 4-6 Hz rest tremor Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunctionHughes AJ, Daniel SE, Kilford L, Lees AJ. JNNP 1992 Mar;55(3):181-4Step 2 : Exclusion criteria for Parkinsons disease History of repeated strokes with stepwise progression of parkinsonian features History of repeated head injury History of definite encephalitis Occulogyric crises Neuroleptic treatment at onset of symptons More than one affected relative Sustained remission Strictly unilateral features after 3 years Supranuclear gaze palsy Cerebellar signs Early severe autonomic involvement Early severe dementia with disturbances of memory, language and praxis Babinski sign Presence of cerebral tumor or communication hydrocephalus on imaging study Negative response to large doses of levodopa in absence of malabsorptionHughes AJ, Daniel SE, Kilford L, Lees AJ. JNNP 1992 Mar;55(3):181-4Step 3 : Features that support a diagnosis of Parkinsons disease3 or more required Unilateral onset Rest tremor present Persistent asymmetry affecting side of onset most Excellent response (70-100%) to levodopa Severe levodopa-induced chorea Levodopa response for 5 years or more Clinical course of ten years or moreHughes AJ, Daniel SE, Kilford L, Lees AJ. JNNP 1992 Mar;55(3):181-4Non-motor symptoms Sleep disturbance Depression Dementia(late stage) Psychosis and confusion Orthostatic hypotension Sexual dysfunctionManagement Medical treatment Levodopa Dopamine agonist MAO-inhibitor COMT-inhibitor Anticholinergic agents Surgical treatment Lesioning-pallidotomy or thalamotomy Deep brain stimulationSites of action of PD drugs1.LevodopaDecarboxylase Inhibitor2.Dopamine agonist3.MAO-B Inhibitor4.COMT InhibitorLevodopa Most effective drug Given with decarboxylase inhibitor (Carbidopa or Benserazide) to block peripheral conversion to dopamine Improves disability and prolongs capacity to maintain ADLs Effective in treating bradykinesia and rigidity Less effective in reducing tremor SE : Nausea, Vomiting, Orthostatic hypotension, Dyskinesias, Visual hallucinations and psychosisDopamine agonist Stimulate dopamine receptors Ergot : Pergolide Non-Ergot : Pramipexole , Ropinirole Monotherapy or adjunct therapy SE : same as levodopa plus drowsiness and peripheral edemaMAO inhibitor Selegiline, Rasagaline Irreversible MAO-B inhibitor , Inhibiting DA metabolism in brain Use : Monotherapy in early PD: Prolong L-dopa effects in moderate to advanced PD SE : nausea, insomnia, Cognitive impairment, weight loss, headache, arthralgiasCathechol-O-methyltrasferaseinhibitor (COMT inhibitors) Newest class : Tolcapone, entacapone Prevent peripheral degradation of levodopa by inhibiting COMT Triple therapy : Levodopa + Decarboxylase inhibitor + COMT inhibitor Helpful for both early and fluctuating PD SE : nausea,diarrhea, urine discoloration Anticholinergics Trihexyphenidyl, Benztropine Dopaminergic depletion Cholinergic overactivity Effective mainly for tremor (rigidity) SE : Dry mouth, Sedation , Delirium, ConstipationTake Home Message Four cardinal signs with gradual progression Autonomic dysfunction and cognitive deficits may occur with progressive disease Exclude other causes of parkinsonism Levodopa-carbidopa is the most effective medication Surgical intervention may be considered for patients with disabling symptoms refractory to medicationsTHANK YOU