Tremor, Rigidity, Tics and Dystonia: The 4 Most Common Movement Disorders

Transcription

1 Tremor, Rigidity, Tics and Dystonia: The 4 Most Common Movement Disorders

2 VIGNETTE 1: HAND SHAKING 62 YOF tremor of both hands for 6 years FHx: Shaking in mother & maternal cousin PMH: Depression, HTN, obesity, asthma Meds: Verapamil, MVI, Paxil, theophylline Exam: Tremors of R>L hand with arms outstretched, with writing, not at rest; mild cogwheeling on PROM Patient is worried she has Parkinson s disease

3 VIGNETTE #1 Is this Parkinson s disease? What is it? What work-up would you do? Would you treat? What would you use? What about the cogwheeling?

4 What Are Tremors? Description: rhythmic, stereotyped, distal>proximal, positional dependent movements. Arm>leg>head Resting tremor - prominent at rest, often slow, pill roll & pronation/supination common Postural tremor - prominent with limbs extended Kinetic tremor - prominent with goal directed movement (writing)

5 TREMOR EXAM Arms completely at rest Outstretched paper on back of hands Finger-nose-finger Write name Archimedes spiral ROM for UE tone

6 TYPE FREQ OCCURS ASSOCIATION Postural 5-9 HZ Rest 3-6 HZ Arms outstretch Rest, Walk Physiologic, ET, ETOH w/d, toxic-metabolic, Parkinson's Dis, rare meds Action 3-10 HZ Movement ET, cerebellar lesions, MS, ETOH

7 ESSENTIAL TREMOR 3-20X as common as PD 50-70% positive family history Postural & kinetic tremor Rapid and distal>proximal Increases with anxiety Clinical examination otherwise normal Less often involvement of head, voice or legs

8 DRUG INDUCED TREMOR Beta adrenergic agonist Theophylline Lithium Steroids Lamotrigine Tricyclic antidepressants SSRIs Depakote Dopa blockers (antipsychotics, anti-emetics, anti-vertigo) Thyroid hormone Cardiac anti-arrhythmics (amiodarone, procainamide) Calcium channel blockers Mercury, lead, arsenic toxic Pseudoephedrine & Caffeine Amphetamines/Ritalin

9 WORK-UP OF POSTURAL TREMOR Family history TSH Medication levels Electrolytes Rarely: MRI and serum Ceruloplasm (for Wilson s disease)

10 Avoid meds causing tremor, caffeine; Relaxation/biofeedback, Wrist weights,?etoh Primidone Beta Blocker Topamax, Benzodiazepines, Neurontin Botulinum Toxin Thalamic ablation/dbs

11 MEDICATION DOSAGES Propranolol (Inderal) max dose 240 mg If contraindication or failure: Primidone (Mysoline) start 25 mg, max 100 mg Consider supplementing with: Gabapentin (Neurontin) 100 mg tid up to 800 mg tid Topiramate (Topamax) mg/d Klonopin & Alprazolam risk of tachyphylaxis & abuse

12 VOICE & HEAD TREMOR Start with beta blocker &/or primidone Try botulinum toxin if not effective

13 VIGNETTE 2: A STIFF OFFICER 59 YOM police officer with stiffness in walking, rolling over in bed, teased for staring, some muscle aching Exam: reduced blinking, doesn t shift or gesture, voice quiet, stiffness noted on PROM of arms, no tremor Walks with short steps, decrease arm swing L>R

14 QUESTIONS What other questions would you ask? What could this be? What do you think of the absent tremor? What work-up if any?

15 BRADYKINETIC-RIGID SYNDROME History Exposure to neuroleptics or anti-nausea med? New medications? Repeated head trauma? Family history of PD? Falls? Cognitive decline? Autonomic sx: postural dizziness, bowel/bladder dysfunction, impotence Sleep disturbances

16 BRADYKINETIC RIGID SYNDROME EXAMINATION Postural BP check Observe spontaneous movements, blinks Check EOMs Tremor: arms out, at rest, F-N-F, walking PROM of arms & head Froment s sign Handwriting: small Gait: initiation, step length, turns, arm swing, Pull test Consider MMSE

17 PD: DIAGNOSIS A Clinical Diagnosis R/O neuroleptic exposure When to test: 1. Rapid or early onset 2. Atypical features 3. Poor response to Tx Test: MRI, slit lamp & serum ceruloplasm (r/o Wilson s disease)

18 RED FLAGS Early onset (<50) Poor response to L-Dopa No tremor Early orthostatic hypotension Early dementia/confusion Early gait impairment Rapid progression Symmetrical from onset Abnormal EOMs

19 PD LOOK- A -LIKES 20% patients misdiagnosed Neuroleptic induced PD Progressive supranuclear palsy (PSP): Decrease up/down gaze, neck very stiff & extended, no rest tremor, early postural instability Diffuse Lewy Body Disease: Dementia then bradykinesia, visual hallucinations, fluctuate Multisystem Atrophy: No tremor, poor response to Tx, cerebellar dysfunction, autonomic problems

20 CARDINAL FEATURES OF PD Resting Tremor Bradykinesia Rigidity Postural Instability

21 PD REST TREMOR Unilateral tremor in hand Worse with rest or walking, better with use of the hand Slow & often pill-rolling or pronation supination in type

22 SYMPTOMATIC THERAPY Anticholinergics Trihexyphenidyl Amantadine MAO inhibitors Selegiline Rasagiline Carbidopa/L-dopa Sinemet Dopamine agonists Pramipexole Ropinirole COMT inhibitors Entacapone

23 LEVODOPA THERAPY: STILL THE MOST EFFECTIVE Sinemet is carbidopa and levodopa. Carbidopa prevents peripheral conversion to dopamine Sinemet 10/100, 25/100, 25/250 Start 25/100 bid or tid Avg patient needs ~ mg L-dopa/day Take on empty stomach Sinemet CR 25/100, 50/200 Reduces dose frequency by 1/3 Take with food Supplementary carbidopa (Lodosyn) 25 mg or Domperidone mg prior to Sinemet if N/V occurs

24 DOPAMINERGIC MEDICATIONS DON T IMPROVE: Motor freezing Autonomic dysfunction Dementia Postural instability modest benefit

25 OTHER EARLY SYMPTOMS Poor dexterity Micrographia Reduced voice volume Difficulty getting out of car, chair Drooling Fatigue

26 DOPAMINE AGONISTS Direct Dopaminergic effect Clinical uses: 1. Early use to delay problem SE of Levodopa 2. Later use to smooth out motor response Side effects: BP, N/V, headache, hallucinations, confusion, dyskinesias

27 THE AGONISTS Mirapex (Pramipexole): mg tid to 1.5 mg tid Requip (Ropinirole): 0.25 mg tid to 8 mg tid Rotigotine patch (Neurpo): apply once a day

28 WHICH DOPA AGONIST SHOULD I USE? Bromocriptine not as effective & more expensive The other 3 are similar in reducing off time and improving the motor score Rotigotine offers potential advantages but no good comparisons with po med

29 MAO INHIBITORS Rasagiline: Mono or adjunctive tx Selegiline: Adjunctive tx only May improve motor fluctuations May be neuroprotective Caution with SSRIs & TCAs

30 COMT INHIBITORS Adjunctive Tx Only Tolcapone (Tasmar): mg tid & Entacapone (Comtan): 200 mg with Sinemet Effects: Increase on time, decrease off Reduce levodopa dosage Slightly more effective than dopa agonists Tasmar requires monitoring

31 ADVERSE EFFECTS Dyskinesias Nausea Diarrhea Tolcapone - 3/60,000 fatal hepatotoxicity, requires LFT monitoring

32 WHEN SHOULD TREATMENT BE STARTED? When the patient is clinically impaired vs early use of rasagiline Younger patients should be treated less aggressively early on in their disease For younger patients direct treatment to their particular symptom

33 IMPORTANT TREATMENT CONSIDERATIONS Dopa agonists: Higher risk of cognitive problems Dopa agonists: Longer to titrate dosage Anticholinergics: Help mild rest tremor, may worsen confusion Dopa agonists: may delay dyskinesias & wearing off symptoms (c/w levodopa)

34 SO WHAT SHOULD YOU DO? Start with low dose Sinemet (1/2 tab 25/100 tid) in older patients Increase q week till symptomatic response or until 2 1/2 tab tid Most patients: satisfactory, sustained response Failures: Most are not true PD, other meds won t help In some younger patients start with anticholinergic (tremor) or dopa agonist

35 AGE OLD CONSIDERATIONS Younger <60-65 More benign course Better cognition Will be treated for many more years Therefore: Start more conservatively, use anticholinergics for tremor or dopa agonist Older>60-65 More rapid course Dementia/confusion more likely Shorter lifespan Therefore: Start earlier with levodopa, watch for confusion

36 PD in the Elderly Carbidopa/levodopa is the most effective medication for PD; optimize dose before adding other drugs in the elderly. Anticholinergics and amantadine have little role in treating elderly PD patients. COMT inhibitors are very expensive for modest gain. Dopamine agonist more likely to cause delusions/hallucinations.

37 PD: COURSE OF THE ILLNESS Initially, many years of well-controlled symptoms After 3-5 years of Sinemet: Wearing off & dyskinesias

38 DYSKINESAS Usually dyskinesia refers to chorea that occurs at the time when Sinemet is at a maximum Treatment: Reduce individual dose (same daily dose more frequently) then reduce daily dose & add amantadine or dopa agonist

39 EVOLVING DOPANINERGIC RESPONSE Response Threshold Dyskinesia Threshold Early PD Moderate PD Late PD When the DA activity is between the blues lines the patient has normal ambulation ( on ) when the activity is above blue lines the patient has dyskinesias & below blue line impaired gait ( off )

40 WEARING OFF Response to Sinemet fades and disappears prior to the next scheduled Sinemet dose Patient can tell you when it will occur Treatment: Increase frequency of dosing, use extended release (Sinemet CR), add rasagiline, selegiline, dopa agonist, amantadine, anticholinergic

41 TREATING OTHER MOTOR FLUCTUATIONS Unpredictable wearing off: Add dopa agonist, rasagiline or entacapone (or combinations)

42 MOTOR FREEZING May be off period or on period Occurs when initiating, turning, crossing doorways Treat: reduce off periods, step to a target (cane, laser pointer), rocking movements, clap hands, trained dog

43 PSYCHOSIS & HALLUCINATIONS Infection, meds may trigger Visual hallucination & paranoia common First try medication reduction - 1 st : Anti-cholinergics - 2 nd : Amantidine - 3 rd : COMT antagonist - 4 th : Dopa agonists Consider neuroleptic next

44 USE OF NEUROLEPTICS IN PD Traditional neuroleptic worsen symtoms Clozapine: reduces hallucinations, no increase PD symptoms, rare agranulocytosis *Quetiapine: slightly less effective, safer 25 mg bid Other atypical neuroleptics not as effective

45 DEMENTIA & DEPRESSION 18-70% develop dementia - often drug related - Reduce meds as in psychosis - Consider cholinesterase inhibitor 40-60% develop depression: Treat with usual antidepressants, avoid anticholinergics - +/- avoid SSRIs with MAO-I - Avoid TCA in elderly or demented patient

46 DEEP BRAIN STIMULATION Subthalamic nucleus> globus pallidus Benefits - Reduction in off-time - Reduces dyskinesia Complications - Neuropsychiatric disturbances - Bleeding

47 TICS Definition: stereotyped, repetitive, nonrhythmic jerks Can be simple of complex Are suppressible --- but then increase May be vocal Rare complex vocal tics: repeat words or obscenities

48 GILLES DE LA TOURETTE S SYNDROME Onset <21 yrs Motor & verbal tics, >1 year Tics change over time Coprolalia (cursing) rare No other medical illness explains the tics +/- Attention deficit disorder +/- Obsessive compulsive disorder

49 TICS IN NON-TOURETTE S PATIENTS Sporadic tics Secondary - Post viral encephalitis - PANDAS - HIV - Lyme - Amphetamines - Ritalin - Sinemet - Cocaine -AEDs - CO - MR - Chromosomal disorders - Stroke - AD - antidepressants Other inherited disorders - Huntington s - Primary dystonia - Tuberous sclerosis - Wilsons

50 TREATMENT OF TICS Neuroleptics: typical and atypical (e.g. resperidone, Haldol, pimozide) Clonidine (Catapres) Tetrabenazine Clonazepam Botulinum toxin Low dose dopamine agonist Guanfacine (Tenex)

51 FOCAL DYSTONIAS

52 FOCAL DYSTONIAS Dystonia: Muscle spasms & limb twisting Focal dystonias - Most common dystonias: 1/ Usually middle age onset - Relatively benign

53 IDIOPATHIC CERVICAL DYSTONIA Most common dystonia - about 30/100,000 63% Women, mean age 41 Mean Age of onset: 41 Head deviation, decrease ROM, neck pain, neck tremor all common

54 Anterocollis Retrocollis Torticollis Lateralcollis

55 BLEPHAROSPASM Onset usually 6-7th decade, F>M Sore & photophobia increased blink spasms Worsens: Lights, wind, read, anxiety DDx: Dry eyes, blepharitis, tics (younger pt)

56 SPASMODIC DYSPHONIA Adductor type: most common, thyroarytenoid muscle involved, voice is strained/strangled, often tremulous Abductor type: Posterior crycoarytenoid muscle, voice is breathy Refer pt to ENT specialist for laryngoscopy & injection with botulinum toxin

57 BOTULINUM TOXIN TREATMENT OF FOCAL DYSTONIA 70-90% improvement Duration 2 ½ - 4 mos Side effects are infrequent, transient, mild & site specific: - Neck: Weak neck, mild dysphagia - Eye: Ptosis, eye closure weakness - Vocal cords: Breathy voice

58 BOTULINUM TOXIN FOR CERVICAL DYSTONIA Botulinum toxin A (Botox) & B (Myobloc) FDA approved Botox!! Oil Can!

59 SUMMARY Essential tremor is tremor alone, best treated with beta blocker or Mysoline PD treatment in elderly is Sinemet, in young is usually a dopa agonist Tics usually improve as child matures, may be treated in severe cases Focal dystonia is best treated with botulinum toxin

60 SNAP QUIZ What type of FOCAL DYSTONIA is demonstrated by the heroines?

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