Movement Disorders

1. Movement Disorders Tory Davis PA-C UNE PA Program

2. Tremor Classification • Rest vs Action • Body part(s) affected • Frequency- how fast, measured in hertz (cycles/second) • Amplitude- fine or coarse

3. Resting Tremor • Body part affected is supported against gravity, no muscle contraction (hands in lap) • Amplitude •  with mental stress •  with general mvmt (walking) •  with target directed mvmt (finger to nose)

4. Action Tremor • Produced by voluntary muscle contraction • 1. Postural- body part maintaining position against gravity • 2. Isometric- muscle contraction against stationary object (finger squeeze) • 3. Kinetic-with voluntary mvmt

5. Kinetic subtypes • Simple kinetic tremor- assoc with mvmt of extremities (pronate/supinate) • Intention tremor- present during visually-guided, target-directed motion.  amplitude fluctuation on approaching target (finger to nose)

6. Physiologic tremor • Every “normal” person has a • High frequency, low amplitude postural tremor • Enhanced by hyper-adrenergic states: hypoglycemia, thyrotoxicosis, drugs (caffeine), withdrawal, public speaking

7. Benign Essential Tremor • aka benign familial tremor • Most common movement disorder worldwide • Prevalence reported up to 5% of people over 60- BUT, half of people with mild essential tremor aren’t aware • FHx reports vary (20-60%)

8. Essential tremor • Insidious development, slow progression • 95% start w/ postural distal arm tremor • Wrist flex/ext , 4-12 Hz frequency • Bimodal onset: teens and 50s • Unilateral progresses to bilateral • UE, head (yes or no), palate (rare) • Legs usually spared

9. Essential tremor • Amplitude •  with stress, fatigue, CNS stimulants, voluntary activity •  with EtOH, ß-blockade, rest

10. Pt Ed • Avoid stimulants • Avoid fatigue • Avoid stress • …and don’t self-medicate with alcohol

11. Tx: Primidone • Primidone 50-750 mg/day. Anticonvulsant. Start at 25mg qhs and slowly titrate up to avoid sedation. • Contraindicated in asthma • SEs: sedation, dizziness, nausea, mood changes

12. Tx: Beta blocker • ß- Blockade: Propranolol 40-320 mg/day. Better tolerated, no more effective than primidone • Contraindicated in asthma, bradycardia, cardiac conduction defects • SEs: sexual side effects, fatigue, depression

13. Parkinson’s Disease

14. What it is • Neurodegenerative disorder resulting from  dopaminergic transmission in basal ganglia

15. Parkinson’s Disease-4 Cardinal Signs • Tremor • Rigidity • Bradykinesia (slowness of movement) • Postural impairment (comes later in ds)

16. PD Tremor • Present in 85% • 4-6 Hz resting tremor • Distal, unilateral “pill-rolling” •  by voluntary activity,  by stress • One limb or one side of body for months to years • Spares head

17. PD Rigidity • Increased resistance to passive movements • “Cogwheel rigidity” • No weakness • No change in DTRs

18. Bradykinesia • Slowness of movements • Noticed in speech as well as voluntary movements • Start hesitation

19. Postural impairment • Difficulty with balance and gait • Occurs later in disease course. • If you see this early, question dx and refer to neuro

20. Gait • Classic “festinating gait” • Flexed trunk. Legs and hips stiff and flexed. • Arms still (not swinging) • Short fast steps- trying to keep up with the forward center of gravity • Turn “en bloc” • Later in disease, freezing w/ direction change or when entering small space (doorway)

21. “Mask-like” face Widened palpebral fissures Decreased blinking Seborrhea scalp or face Dementia 6x nl population- AD in 40%  rapid alt mvmts “Freezing”/akinesia Sialorrhea Depression Micrographia Hypophonia Dystonia Other features

22. Epidemiology • >1 million in US, 50k new cases yearly • Estimates of 400% increase in coming decades • Peak onset 60 (35-85) • Course 10-25 years • Male > female • Some genetic predisposition

23. Risk factors • + FHx (5-10%) • Male gender • Pesticide exposure • Head trauma • Rural living • Well water

24. Reduced Risk • Coffee drinking • Smoking • NSAID use • Estrogen replacement in post-menopausal women

25. Parkinson’s Dz Pathophysiology • Loss of melanin-containing, dopaminergic neurons in substantia nigra • Lewy bodies- protein lint balls. Pathological hallmark of PD when in basal ganglia, but also seen in other disease states

26. Diagnosis • Difficult! Clinical! • No lab test • No biomarker • And by the time symptoms appear, dopamine depleted by 70%

27. Clinical Dx • Progressive, slow unfolding of characteristic PD s/s during the first few years after onset of sx • Can confirm dx postmortem • Not helpful • Suspect and refer

28. Make the case • Presenting sx: C/o difficulty with dressing, cutting food, writing, getting in/out of car, feeling stiff. Spouse notes slowness, blank face • 1st visit- usually after 1-2 years of minor changes • Check the hx: gradual worsening, fhx of neuro disorder, drug use, hx encephalitis, toxic exposure

29. Office exam I • Tremor- resting, not action. Test it. • How? • Rigidity- Check passive ROM. Feel for mechanical, ratchet-like sensation • Bradykinesia- watch her get out of chair, write*. • *(BET- large, shaky scrawl; PD- micrographia)

30. Office Exam II • Impaired postural reflexes- gait testing- walk away, pivot and return. PD will take extra turning steps. • Pull test. Stand behind and (with warning) pull back on pt. Nl- stops potential fall in 1-2 steps. Be braced to help.

31. NOT PD? • No response to levodopa • Symmetrical, bilateral at onset • Rapid progression, including early falls • Dysautonomia: incontinence, orthostatic hypotension, urinary retention • Early cognitive defects • Abnormal eye movements

32. Drug induced parkinsonism Progressive supranuclear palsy Alzheimer’s disease Normal pressure hydrocephaly Wilson’s Depression Multiple system atrophy Dementia with diffuse Lewy body disease Multi-infarct parkinsonism Huntington’s Essential tremor Differential Dx

33. PD Treatment • No proven clinically neuroprotective drug. But that’s the goal… • Start tx when functional disability starts. Varies based on multiple factors. • Goals: maintain function and QOL, avoid drug-induced complications • (Do no harm.)

34. PD Tx- Dopamine • Levodopa- Gold Standard. Converted to dopamine in brain. (Dopamine itself can’t cross blood/brain barrier.) • Improves all features of PD, but wears off over time • Think “Awakenings”

35. Dopamine • First line for years, but now primarily second line due to • Side effects (see next slide) • Wearing off • Hypothetical (?) concern that free radicals generated by the oxidative metabolism of dopamine contribute further to the degeneration of dopaminergic neurons

36. Dopamine Side Effects • Nausea • Wearing off-when effects of single dose don’t last as long • Dyskinesias- sudden, uncontrollable, jerky movements of arms, legs, head, trunk • On/off response- due to fluctuating levels of dopa • On-  uncontrolled movements • Off-  motion, freezing

37. Add-on meds • Dopamine plus…. • Carbidopa- (decarboxylase inhibitor) • Entacapone (COMT inhibitor, inhibits break down of catecholamines) • Purpose: decreased levodopa breakdown/conversion in bloodstream, maximizes delivery to brain, minimizes nausea

38. Dopamine agonists • Maybe some neuroprotection • Behave like dopamine by stimulating dopamine receptor directly • Can be used as initial monotherapy (first line) to preserve use of dopamine for later in disease course • Add-on to dopamine when levodopa alone no longer effective (or SEs intolerable) • Side effect of sudden-onset sleepiness

39. Dopamine agonists • Bromocriptine (Parlodel) • Pergolide (Permax) • Pramipexole (Mirapex) • Ropinirole (Requip) • Apomorphine- (Apokyn) injectable, rapid-acting, “rescue” med for acute freezing episodes. SE: severe n/v

40. Anticholinergics • Primarily to alleviate tremor. (Balances acetylcholine and dopamine.) • Trihexylphenidyl (Artane), benztropine (Cogentin) • SE- dry mouth, nausea, constipation, palpitations, arrhythmias, urine retention • Contraindications- BPH, narrow angle glaucoma, obstructive GI disease • Poorly tolerated by elderly

41. Amantidine • Antiviral flu drug, also anti-dyskinetic for mild symptoms • ? MOA • SEs: restlessness, confusion, rash, edema, nausea, cardiac arrhythmias

42. MAO-B inhibitor • Monoamine Oxidase type B Inhibitor Selegiline, rasagiline (also used in Alzheimer’s) •  dopa breakdown, may  dopamine reuptake • Modest effect for mild sx, reduces “off” time • May be neuroprotective • SE- confusion, nausea, headache, insomnia

43. Antioxidants • Depleted in PD patients. May be neuroprotective. • Glutathione • Coenzyme Q • Ongoing studies for these relatively new treatments

44. DBS • Deep Brain Stimulation • Surgically implanted neurostimulator in subthalamic nucleus • Blocks abnormal signals that cause PD sx • Only for pts whose sx are uncontrolled by medications

45. Future/Research • Research into causation • Toxic • Environmental • Genetic • Research into treatment • Neuroprotection • Meds to delay, prevent, or reverse effects of disease

46. Huntington’s Disease

47. Definition • Autosomal dominant neurodegenerative disorder. • Triad of motor, cognitive and psychiatric symptoms • Insidious onset, no cure • Age of onset of sx 30-50, usually after people have reproduced • Fatal in 15-20 years

48. Movement disorder • Presence of involuntary movements • Impairment of voluntary movements • Catch 22: Tx of involuntary can worsen impairment of voluntary, and impairment of voluntary movements is correlated with functional disability

49. Involuntary movements • Chorea- “the dance” Primary invol mvmt in HD • Athetosis- proximal limb writhing • Hemiballismus- violent, proximal limb flinging

50. Chorea • Involuntary, irregular, rapid, uncontrolled, excessive movement • Stark contrast to paucity of movement in Parkinson’s • Seem to move randomly from one body part to another • Appears to be almost playful, fidgety • Often not noticed by (nor disturbing to) the pt