Parkinson Disease & other Movement Disorders

1. Parkinson Disease & other Movement Disorders Cherian Abraham Karunapuzha, M.D. Assistant Professor Movement Disorders Division Department of Neurology The University of Oklahoma Health Sciences Center

2. DISCLOSURES • FINANCIAL DISCLOSURE • The speaker is on the speaker bureau for Teva neuroscience and UCB. • UNLABELED/UNAPPROVED USES DISCLOSURE • The speaker has nothing to disclose

3. LEARNING OBJECTIVES • Learn to recognize the phenomenology of various abnormal movements • Learn about common movement disorders associated with such abnormal movements

4. What is a “movement disorder” ? Light Blue – ventricles Red – Caudate nucleus Green – Putamen Dark Blue – Globus Pallidus Black – SubstantiaNigra Brown - Thalamus • Most diseases of BG are not “fixable” but can be alleviated, eg. Parkinson’s, essential tremors, Huntington’s, torticollis, Tourette’s • Conditions arising from a dysfunction of the extrapyramidal system (basal ganglia) – extrapyramidal diseases • Not “weakness” - more like a switchbox with different On and Off switches or programs. • Depending on locus of BG damage, the signs can be bradykinesia, rigidity, tremor, chorea, dystonia, tic, myoclonus…

5. Basal Ganglia Circuit Cortex Thalamus GPi D1 Striatum Direct Pathway Striatum Indirect Pathway D2 GPe STN GPe – Globus Pallidus externa /lateral GPi – Globus Pallidus interna /medial STN – Subthalamic Nucleus D1, D2 – types of dopamine receptors SubstantiaNigra

6. Common phenomenonology and associated symptoms • Parkinsonism • Parkinson disease • Multiple System atrophy • PSP • Drug induced parkinsonism • NPH • Essential Tremor • Drug induced tremor • Huntington disease • Sydenham chorea • Levodopa dyskinesias • Tardive dyskinesias • Torticollis, blepharospasm • Tourette syndrome • Metabolic, CJD • Bradykinesia • Freezing • Rigidity • Tremor – resting • Tremor – action/postural • Chorea, ballism • Stereotypy • Dystonia • Tic • Myoclonus

7. Tremor • Oscillatory, rhythmic and regular movement that affects one or more body parts, such as the limbs, neck, tongue, chin, or vocal cords. • Distribution : • Arms, head, legs, larynx… • Unilateral or asymmetric or symmetric • Context : • Resting – 3-6 Hz • Postural – 5-10 Hz • Action (kinetic) – 5-10 Hz • Terminal (intention) – 2-4 Hz

8. Postural/Action Tremor

9. Essential Tremor • Action or postural tremor of arms, sometimes head and voice, occasionally legs • Family history common • Improves with alcohol. Worsens with Caffeine. • Mild tremor may first appear in teens or young adulthood • Gradually worsen over decades

10. Essential Tremor (Contd.) • Check for hyperthyroidism • Check for drug induced – albuterol, SSRI, Depakote, antipsychotics • MRI brain for mimics - white matter lesions brainstem & cerebellum • Rx: Propranolol 10 mg tid -> 60mg tid or Primidone 25 mg qhs -> 250 mg tid • Surgery: deep brain stimulation (DBS) in thalamus for refractory tremors

11. Cerebellar Tremor – associated findings of dysmetria, dysdiadokinesia , ataxia etc.

12. Psychogenic tremor ?? – improves with distraction - Counseling/clinical psychology

13. Resting Tremor • present in the distal parts of the extremities and the lips while the involved body part is “at rest” & ceases on active movement of the limb • “Pill-rolling” tremor of the fingers • flexion-extension or pronation-supination tremor of the hands

14. Brady/hypokinesia – slowness or decreased amplitude of movement • a loss of automatic movements • slowness in initiating movement on command • reduction in amplitude of the voluntary movement • masked facies, decreased frequency of blinking, soft speech, drooling, small handwriting, shuffling gait, decreased armswing

15. Rigidity - Increased resistance to passive motion .. • ..present equally in all directions of the passive movement, equally in flexors and extensors & throughout the range of motion – extrapyramidal lesions • Stiffness, heaviness, or aching muscle • Cogwheel and Leadpipe rigidity • Spasticity – Another hypertonic state – Damage to the primary motor cortex or the corticospinal tract - velocity dependent, clasp knife phenomenon

16. Parkinson Disease • A clinical syndrome resulting from degeneration of nigro-striatal dopaminergic neurons • Asymmetric onset • TRAP : Tremor (resting), Rigidity, Akinesia (bradykinesia), Postural instability • Diagnosis – clinical exam & response to levodopa (L-dopa) supplementation

17. Parkinson disease (contd.) • MRI brain to look for mimics - enlarged ventricles, subdural hemorrhage, tumor, multiple subcortical strokes

18. Parkinson disease (contd.) • Incidence: 4.5-21 cases/100,000 per year • Cause: combination of genetic and environmental factors • Pathology: Lewy body – abnormal aggregates of protein (alpha synuclein)

19. Parkinson disease (contd.) • slow progression - 10-25 years • independence usually not reduced in first 5-10 years • later: postural instability, freezing, levodopa induced dyskinesia, fluctuating response to meds, dysphagia, incontinence, postural hypotension, dementia

20. Freezing = arrest in initiation or continuation of movement

21. Parkinson disease (contd.) • MAO B inhibitors – Rasagiline, Selegiline – mild symptomatic effect, increase ON time,?disease modifying • Dopamine agonists – Ropinirole, Pramipexole, Rotigotine – moderate symptomatic effect • Dopamine – Carbidopa/Levodopa (Sinemet) 25/100 one tablet TID to 1200mg/day – Robust symptomatic effect • COMT inhibitors – Entacapone – increase ON time • NMDA antagonist – Amantadine - dyskinesias • DBS (deep brain stimulation) or Surgical ablation • PT/OT , speech therapy – Lee silverman voice therapy

22. Choreioform Movements • Chorea - involuntary, irregular, purposeless, nonrhythmic, abrupt, rapid, unsustained movements that seem to move unpredictably from one body part to another • Ballism – larger amplitude and rapid-proximal parts of limb • Athetosis - more sinuous slow, writhing

23. Sydenham Chorea

24. Sydenham Chorea • Post-strep reaction • Demographics: teens, female > male • Chorea; sometimes behavioral (OCD-like) • Testing of limited use: ASOT false pos and neg, infection usually resolved • Tends to subside even without Rx in weeks or months • Valproate can reduce the chorea

25. Huntington’s Disease

26. Huntington’s Disease • Neurodegeneration, initially of striatal ‘medium spiny’ neurons to GPe • Caused by expanded CAG repeat in Huntingtin Gene (autosomal dominant), normal < 35 repeats • Onset young adult, though can be any age • Presents with gradually worsening chorea, cognitive, mood & behavioral changes • Management: antipsychotics, antidepressant, tetrabenazine, behavioral

27. Hemiballismus – Subthalamic Nucleus lesion

28. L-Dopa induced Dyskinesias – usually peak dose about 40 minutes after ingestion of L-Dopa

29. Stereotypy • ‘Coordinated’ movements that repeat continually and identically • When they occur at irregular intervals, stereotypies may not always be easily distinguished from motor tics, compulsions, gestures & mannerisms • Tics - occur paroxysmally out of a background of normal motor behavior and usually associated with an urge

30. Tardive Dyskinesia • Dopamine Antagonists (D2): • Typical > atypical antipsychotics • metoclopramide (Reglan), promethazine (Phenergan) • ? D2 receptor hypersensitivity • Appears after years of use (sometimes even months) • Risk factors: dose, older age, female sex • Classic - Oro-Bucco-Lingual stereotypy (lipsmacking). • Anticholinergics - Artane, Cogentin or even Benadryl worsen it. • Rx - Tetrabenazine 12.5 mg tid • Remove offending drug, or switch to a more atypical antipsychotic

31. Tics • Brief, Stereotyped abnormal movements or sounds • In response to urge (psychic/physical) • Can be complex (sequence, muscles) • The diversity of motor tics is one feature that sets their phenomenology apart from stereotypies

32. Tourette Syndome • Onset < 18 . For > 1 year • Multiple motor tics and vocal tics – coprolalia. Tics evolves over time. • Comorbidities: ADHD, OCD, impulse control disorder • M > F (female relatives may have OCD)

33. Tourette Syndome (contd.) • Adrenergic - Guanfacine, Clonidine (0.1 - 0.3mg tid) • Antipsychotics - Pimozide, Haloperidol, Risperidone(1-16 mg/day div qd-bid) • Dopamine Depletor –Tetrabenazine • Stimulants – Adderall, Ritalin SR (20 – 60 mg/day div qd-bid) • Antidepressants • Behavioral therapy • ? DBS

34. Dystonia • Twisting movements that tend to be sustained at the peak of the movement • Frequently repetitive in the same group of muscles (patterned – unlike Chorea) • Often progresses to prolonged abnormal postures • Can be focal, segmental or generalized • Often induced by action, sometimes task-specific such as writing etc.

35. Adult onset focal dystonia (more common) • Cervical dystonia (torticollis) • Blepharospasm (forced eyelid closure) • Usually idiopathic but sometimes a triggering insult (eg. injury)

36. Primary Torsion Dystonia • Generalized - gradual onset, usually starts in the foot • Juvenile Onset • CAG deletion in DYT1 gene resulting in Torsin A mutation

37. Dystonia (contd.) • Anticholinergic: Cogentin, Artane(2 -16mg per day div. TID titrated gradually over 2-3 months). • Muscle relaxants – Benzos, Baclofen • Botulinum toxin injection – focal dystonias – last 3-4 months • DBS - “Humanitarian Device Exemption”

38. Myoclonus • Sudden lightning-like movement • Can be repetitive but Not rhythmic (if it was, it would be a tremor!) • Can be focal or regional or multifocoal or generalized; epileptic and non epileptic. • Like tremor, myoclonus can arise from disease of many parts of CNS, not just basal ganglia

39. Myoclonus (contd.) • Physiologic (Hypneic, Hiccups) • Serotonin Syndrome • Dementias – Creutzfeld Jakob Disease (CJD) • Multiple Sclerosis • JME (epilepsy) • Rx: clonazepam (0.25-0.5 mg PO bid-tid) or valproic acid or levetiracitam

40. Thank YouQuestions and Comments Contact or Refer - OU Movement disorders clinic or the Medicaid movement disorders clinic www.wemove.org