1. Session 5: Movement Disorders

2. Vignette 55 yo accountant: –Frozen right shoulder/stiffness –Slowly progressive –Impaired fine motor function –Right hand tremor –Reduced right arm swing –Slow overall –? Sexual function –? Bladder function –? Cognitive function –? Falls –? Hallucinations –? Medications or drug exposure –? Family history

3. Examination No orthostatic hypotension Hypomimia Hypophonia Normal eye movements RUE and neck rigidity Right hand and jaw tremor Reduced right arm swing Slight impairment in postural stability

4. Some Causes of Parkinsonism MSA PD PSP DLBD VP PPFG CBD FTD Meds NPH AD

5. Parkinsonism DDX Parkinson’s disease (PD) Multiple System Atrophy (MSA) Progressive Supranuclear Palsy (PSP) Medication-induced parkinsonism –Antipsychotics –Metoclopramide –Others Parkinsonism with Alzheimer’s Disease (AD) Diffuse Lewy Body Disease (DLBD) Vascular parkinsonism (VP) Corticobasal Degeneration (CBD) Normal Pressure Hydrocephalus (NPH) Gait disorder of the elderly Toxins: CO, CN, Manganese, MPTP, rotenone?, CS 2,

6. Red Flags if Seen Early Falls Cognitive changes Prominent sexual or bladder dysfunction Lack of response to adequate Rx trial Symmetric onset Early bulbar dysfunction

7. Red Flags at Any Time Cortical Sensory Signs Alien Limb/unilateral apraxia No response to L-dopa Impaired vertical eye movements

8. Dementia Parkinsonism Dementia Parkinsonism Initial Symptoms AD DLBD PDD Years Later

9. Diffuse Lewy Body Disease Video Click here to view movie

10. Progressive Supranuclear Palsy Dudley Moore Supranuclear palsy Falls early in course Dysarthria Cognitive impairment Emotional incontinence Abducted arms when ambulating: “gun- slinger’s gait”

11. PSP: Abnormal Voluntary Eye Movements Baylor U

12. Parkinsonism T remor = rhythmical; typically a rest tremor R igidity = resistance to movement A kinesia = slowness/absence of movement P ostural changes = stooped posture

13. Resting Tremor Click here to view movie

14. Rigidity Click here to view movie

15. Akinesia/Bradykinesia Click here to view movie

16. Postural Changes Stooped Posture www.artandmedicine.com Impaired Postural Reflexes Click here to view movie

17. PD: Preferential loss of putamenal dopamine projections Dauer and Przedborski Neuron 2003 Lewy bodies contain synuclein, ubiquitin and other proteins NormalPD

18. Increased Tone Rigidity –Increased tone –Usually bidirectional Paratonia (Gegenhalten) –Inability to relax one’s limb manifesting as resistance to movement Spasticity –Velocity dependent increase in tone –Usually unidirectional –Other upper motor neuron signs are often present: hyper-reflexia, Babinski sign and pyramidal distribution of weakness

19. Definitions Chorea: derived from the Greek word “to dance” to describe the arrhythmic, involuntary flitting movements Athethosis: involuntary writhing movements Hemiballism: large amplitude involuntary movement restricted to one side of the body; usually involves proximal upper limb. Myoclonus: sudden brief jerk or shock-like movements Dystonia: abnormal sustained posture resulting from simultaneous co-contraction of agonist and antagonist muscles. Tremor: rhythmic oscillation of a body part due to alternating or synchronous contractions of opposing muscles Tics: sudden, brief, purposeless, stereotyped simple or complex movements or vocalizations Akathisia: inner restlessness; often associated with external signs of restless behavior

20. ET Treatments Medications Propranolol (Inderal®) Mysoline (Primidone®) Clonazepam (Klonopin®) SurgeriesThalamotomy Thalamic Deep Brain Stimulation (DBS)

21. Tremor Cerebellar disorders –Tremor with action with accompanying dysmetria. Note cerebellar features on exam: asynergia, ataxia, dysarthria, dysdiadochokinesia, dysmetria, gait disturbance, hypotonia, nystagmus, rebound, etc. Essential tremor –Postural and action tremor without parkinsonism; typically life-long and tremor responds to alcohol; may have family history Parkinsonism –Typically has a rest tremor, but may also be present with posture and action or solely the latter

22. Acute Neuroleptic-induced A/Es Acute dystonic reaction –Cervical dystonia (torticollis) –Opisthotonus –Oculogyric crisis –Other Neuroleptic malignant syndrome Akathisia (restlessness)

23. Acute Dystonic Reaction Usually occurs within 48 hours; but sometimes may be up to 5 days after Rx More common with parenteral than oral medications More common in males than females; particularly young males Features: neck, jaw, tongue, oculogyric, opisthotonus, etc. Rx: anticholinergics, antihistaminics

24. Acute Dystonic Reaction http://www.haveinc.com/eps/

25. Opisthotonus www.pharmacology2000.com/ Central/sedhyp/opis1.jpg

26. Akathisia: Restlessness http://www.haveinc.com/eps /

27. Chronic Neuroleptic Exposure Tardive dystonia –Axial more common –Appendicular (limb) Tardive dyskinesia Medication induced parkinsonism Tardive tics/akathisia/tremor, etc.

28. 73 yo woman with action tremor DDx –Essential tremor (ET) Life-long, progressive tremor Alcohol responsiveness Absence of bradykinesia, rigidity, etc. –Parkinson syndrome with action tremor –Medication induced tremor –Could be both ET and PD

29. 56 yo man with progressive chorea, dementia and positive family history

30. Huntington’s Disease Features:Chorea Cognitive decline Cause: Autosomal dominant Amplification of CAG (cytosine adenosine guanine) repeats in the IT-15 gene on chromosome 4

31. SOME TRINUCLEOTIDE REPEAT DISORDERS HD occurs with > 36-38 CAG repeats in the IT15 gene

32. ANTICIPATION: EARLIER ONSET WITH MORE CAG REPEATS AUTOSOMAL DOMINANT TRANSMISSION

33. 32 yo man with recurrent grunting, OCD and unusual involuntary limb movements

34. Tourette’s Syndrome (TS) Tics: Involuntary stereotypic movements or vocalizations TS Features: Presence of both vocal and motor tics Onset before age 18/21 years Tics may be temporarily suppressible With suppression of tics there is often inner tension which is relieved upon performing tics Coprolalia (foul language): only ~17% of cases Co-morbidities: OCD, ADHD, learning disability

35. 54 year-old man who reacts to metaclopramide Age Gender Other factors