1. OU Neurology 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. OU Neurology 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. OU Neurology LEARNING OBJECTIVES Learn to recognize the phenomenology of various abnormal movements Learn about common movement disorders associated with such abnormal movements

4. OU Neurology What is a “movement disorder” ? Most diseases of BG are not “fixable” but can be alleviated, eg. Parkinson’s, essential tremors, Huntington’s, torticollis, Tourette’s Light Blue – ventricles Red – Caudate nucleus Green – Putamen Dark Blue – Globus Pallidus Black – Substantia Nigra Brown - Thalamus 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… Conditions arising from a dysfunction of the extrapyramidal system (basal ganglia) – extrapyramidal diseases

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

6. OU Neurology Common phenomenonology and associated symptoms Bradykinesia Bradykinesia Freezing Freezing Rigidity Rigidity Tremor – resting Tremor – resting Tremor – action/postural Tremor – action/postural Chorea, ballism Chorea, ballism Stereotypy Stereotypy Dystonia Dystonia Tic Tic Myoclonus Myoclonus 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

7. OU Neurology 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. OU Neurology Postural/Action Tremor

9. OU Neurology 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. OU Neurology 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. OU Neurology Cerebellar Tremor – associated findings of dysmetria, dysdiadokinesia, ataxia etc.

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

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

18. OU Neurology 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. OU Neurology 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. OU Neurology Freezing = arrest in initiation or continuation of movement

21. OU Neurology 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. OU Neurology 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. OU Neurology Sydenham Chorea

24. OU Neurology 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. OU Neurology Huntington’s Disease

26. OU Neurology 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. OU Neurology Hemiballismus – Subthalamic Nucleus lesion

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

29. OU Neurology 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. OU Neurology 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. OU Neurology 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. OU Neurology Tourette Syndome Onset 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. OU Neurology 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. OU Neurology 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. OU Neurology Adult onset focal dystonia (more common) Cervical dystonia (torticollis) Blepharospasm (forced eyelid closure) Usually idiopathic but sometimes a triggering insult (eg. injury)

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

37. OU Neurology 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. OU Neurology 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. OU Neurology 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. OU Neurology Thank You Questions and Comments Contact or Refer - OU Movement disorders clinic or the Medicaid movement disorders clinic www.wemove.org