Classification of Tremors. Tremor& Ac,on& Tremor& Isometric& Tremor& Rest&tremor& Parkinson s* disease* Kine,c& tremor& Task5specific& tremor&

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1 Common Movement Disorders in the Elderly David F. Tang-Wai MDCM FRCPC Assistant Professor (Neurology and Geriatric Medicine), University of Toronto 2013 UHN-MSH Geriatrics Update -- Friday November 1, 2013 Movement Disorders in the Elderly 1 The top 5 movement disorders in the elderly (Tse W et al. Arch Gerontol Geriatr 2008; 46: ) 1. Essential 2. Parkinson s disease* 3. Drug-induced tremor 4. Dystonia 5. Myoclonus * Discussed below TREMOR Definition: a rhythmic, involuntary, oscillating movements of reciprocally innervated agonist and antagonist muscles Classification of Tremors Tremor& Rest&tremor& Ac,on& Tremor& Isometric& Tremor& Parkinson s* disease* Postural& Kine,c& tremor& Task5specific& tremor& Physiologic* Cerebellar* Essen7al* Simple*kine7c* Midbrain* (Holmes)* Cerebellar* Essen7al* Wri7ng* see following page for definitions

2 Movement Disorders in the Elderly 2 Specific Tremor Syndromes Tremor Type Description Frequency Sample Disorders Action tremor Tremor present with movement (voluntary contraction of skeletal muscle) Cerebellar tremor Terminal/intention tremor Essential tremor Holmes Tremor/ Midbrain tremor/ Rubral tremor Kinetic tremor Isometric tremor Postural tremor Physiologic tremor Rest tremor Tremor prominent with voluntary movements in conjunction with cerebellar signs Usually affects proximal muscles, tremor is accentuated as the moving limb nears the target Increased amplitude during pursuit of a target Due to lack of feedback of the cerebellum to motor cortex and involvement of the dentatorubrothalamic pathway Postural or action-involved tremor that is, by definition, not present at rest Commonly affects the upper extremities (90%), head (50%) & voice (30%), legs & chin (15%) Suppression of tremor with EtOH Combination of rest, postural and kinetic tremor of the extremities Caused by interruptions in the midbrain tegmentum (lesions involving the thalamus, brain stem or cerebellum) tremor that appears during movement of a body part. Simple kinetic tremor can be brought out by the clinician by asking the subject to carry out simple rotary movements of the forearm, or moving the wrists up and down. Tremor evoked by voluntary muscle contractions without movement Tremor seen when a limb in maintained against gravity. Low amplitude tremor that is most prominent in outstretched hands Present in all individuals under certain circumstances Exacerbated by excited mental states, metabolic derangements, drugs, alcohol withdrawal, caffeine Tremor occurs when the limb is in a position of repose (body part is completely supported against gravity) Classically pronation-supination of forearm or pill-rolling movement of thumb and fingers 3-5 Hz Mass lesion Demyelinating disease Toxic Ischemic Infectious 4-12 Hz 2-4 Hz stroke trauma multiple sclerosis 8-12 Hz Mental state (e.g. anxiety, stress, fatigue) Metabolic (e.g. thyrotoxicosis, hypoglycemia, fever, pheochromocytoma) Drug-induced (e.g. β-adrenergic agonists, TCA, AEDs, lithium, thyroxine, steroids, neuroleptics) Toxins (e.g. heavy metals, alcohol withdrawal Diet (e.g. caffeine) 3-7 Hz Idiopathic Parkinson s disease Parkinsonism Drug-induced Wilson s disease Other Severe essential tremor

3 Examining tremor: Movement Disorders in the Elderly 3 Instructions Figure 1. Observe the patient at rest for a resting tremor. Can observe a resting tremor in the mouth, chin, forearm, fingers. Can enhance a resting tremor by cognitive distraction (e.g. saying the months of the year backwards; while walking, observe a pill-rolling tremor). 2. With the arms elevated and outstretched in front of the patient, can observe a postural tremor. Legs must be outstretched to reveal postural leg tremor. 3. With the head erect, can observe a head tremor: either a yes-yes tremor (back-and-forth oscillation) or no-no (side-to-side oscillation). 4. Asking the patient to hold a prolonged vowel sound (e.g. ahhh ) reveals a voice tremor. 5. Asking the patient to write or drinking a cup of water with one hand may elicit a tremor (essential and/or task-specific tremor). 6. Cerebellar tremors are elicited by target-directed actions finger-tonose or heel-to-shin. Oscillations increase as the finger approaches the target.

4 Rest & Essential Essential Tremor: Differentiating Essential Tremor from Parkinsonian Tremor Essential Tremor Movement Disorders in the Elderly 4 Rest Tremor (Parkinson s disease) Affects: Frequency Family History: Postural Component: Kinetic Component: Age Effects of alcohol Tremor Onset Muscle Tone Facial expression Gait Upper extremities (95%) Head (34%) - no-no > yes-yes Legs (20%) Voice (12%) Face (5%) There can be gradual somatotopic spread of tremor (ie: starts in arm and spread to head - converse is rare) Head: 2-8 Hz Arms: 4-12 Hz Elderly: Frequently can be slower & can be confused with tremor in PD Positive Essential tremor has both a postural & kinetic component. Patient asked to hold a body part motionless against the force of gravity Examples: Extending the upper limbs horizontally Protruding the tongue Patient asked to to perform a voluntary movement Examples (drinking from a cup, finger-to-nose, writing) Can worsen over years All age groups Reduces tremor Bilateral Normal Normal Normal pill-rolling action of the hands chin lips legs trunk Movement starts in one limb or on one side of the body and usually progresses to include the other side. Can be markedly increased by stress or emotions 4 Hz Usually negative Usually absent More than 25 percent of patients with Parkinson s disease have an associated action tremor. Usually over 60 years old Usually not beneficial Unilateral Rigidity ± cogwheeling Hypomimia/masked facies/decreased eye-blink Decreased arm swing, stooped, decreased stride length

5 Movement Disorders in the Elderly 5 Treatment Options for Essential Tremor (Chen JJ & Lee KC. Consultant Pharmacologist 2006; 21: 58-71; Louis ED. Clin Geriatr Med. 2006; 22: ; Thanvi B, Lo N, & Robinson T. Age & Ageing 2006; 35: ; Zesiewicz T et al; Neurology 2011; Treatment Mechanism of Action Usual Starting Dose Usual Therapeutic Dose Side Effects AAN Practice Guidelines Propanolol Beta-blocker 10 mg/day mg/day as BID dosing Fatigue, bradycardia, hypotension, depression, exercise intolerance Level A evidence Primidone Metabolized to phenobarbital 62.5 mg/day mg/day as QHS to BID dosing Sedation, nausea, vomiting, unsteadiness/ataxia Level A evidence Gabapentin Similar to GABA inhibitory neurotransmitter 300 mg/day mg/day as TID dosing Drowsiness, nausea, dizziness, unsteadiness Level B evidence Topiramate Anticonvulsant with mixed mechanisms of action 25 mg/day mg/day as QHS to BID dosing Paresthesias, weight loss, taste peversion, fatigue, nausea, sedation Level B evidence Alprazolam Benzodiazepine 0.75 mg/day mg/day as BID dosing Sedation, fatigue Level B evidence - recommended with caution due to its abuse potential Botulinum toxin Neuromuscular junction blockade Focal weakness Level C evidence - in medically refractory cases for limb, head and voice tremor Deep brain stimulation Chronic stimulation of VIM nucleus in the thalamus Surgery, finite battery life, foreign body Level B evidence 3,4-DAP; azetazolamide; levetiracetam; methazolamide; mirtazapine; nifedipine; verapamil - are not recommended for the treatment of essential tremor

6 PARKINSON S DISEASE AND OTHER NEURODEGENERATIVE PARKINSONIAN DISORDERS Movement Disorders in the Elderly 6 Parkinson s Disease (PD) Dementia with Lewy Bodies (DLB) Multiple System Atrophy (MSA-C & MSA-P) Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD) Pathology Parkinsonian Features Synucleinopathies Tauopathies Tremor + +/ Rigidity + (limb) + (limb) + (limb) + (axial>>limb) + (limb, very asymmetric) Akinesia Postural Instability Bradyphrenia Response to Levodopa /- +/ / / Hallmark Features REM sleep behaviour disorder (RBD) Autonomic disturbance (late) Dysphagia (late) Dementia with spontaneous visual hallucinations and fluctuations RBD Autonomic disturbance (late) Dysphagia (late) RBD Early autonomic dysfunction (orthostatic hypotension, postprandial hypotension, anhidrosis with thermoregulatory disturbances, constipation, impotence, poor lacrimation and salivation) Urinary incontinence (early) Cerebellar findings (ataxia, kinetic tremor) - MSA-C Nocturnal stridor NO DEMENTIA Marked postural instability cause early falls Vertical ocular gaze paresis Slow saccades Applause sign (clapping after the patient has been instructed to clap 3 times) Ideomotor apraxia Alien limb Marked asymmetry of signs Cortical sensory loss Progressive aphasia (non-fluent primary progressive aphasia presentation)

7 Pharmacologic treatment of Parkinson s Disease in the Elderly (see additional comments) Early Disease Stage Pharmacologic strategies of symptoms as disease progresses Movement Disorders in the Elderly 7 Dopamine Replacement Motor fluctuations (wearing off) - extend dopamine in brain Dyskinesias - smooth out fluctuation in dopamine levels Autonomic Dysfunction Sleep disorder Cognition & Psychosis Levodopa & Carbidopa 25/100 format - 1/2 tablet PO TID 1hour before meals increase weekly by 1/2 tab TID until reach 2 tabs TID or if symptoms are relieved Dopamine agonists ropinirole* Week mg TID Week 2-0.5mg TID Week mg TID Week 4-1.0mg TID pramipexole* Week mg TID Week mg TID Week 3-0.5mg TID Week mg TID Week 5-1.0mg TID Week mg TID Week 7-1.5mg TID *titrate to symptom relief Levodopa & Carbidopa Increase levodopa dose per time OR increase frequency of levodopa until off-time eliminated Monoamine Oxidase Inhibitor - type B selegiline 5mg qam; max 10mg qd rasagiline COMT-Inhibitor entacapone 200mg PO with each levodopa dose (max 1600 mg/day or 8 times a day) Deep brain stimulation Levodopa & Carbidopa Switch to immediate release levodopa/ carbidopa (not CR) to allow for finer titration, better predictability of medication response, and increase frequency of administration COMT-Inhibitor entacapone 200mg PO with each levodopa dose (max 1600 mg/day or 8 times a day) Amantadine mg qd in divided doses Deep brain stimulation Orthostatic hypotension midodrine 5mg TID (before arising in AM, before lunch, and midafternoon) to start; may need to increase to 10mg TID; do NOT administer after midafternoon to prevent nocturnal supine hypertension; skip dose if BP>180/100 mg Hg in either sitting or supine position fludrocortisone mg/day, can increase to mg/day - contraindicated in CHF and chronic renal failure Erectile dysfunction sildenafil 50mg Constipation polyethylene glycol REM sleep Behaviour Disorder (RBD) melatonin 1 capsule (3 or 5mg) qhs and increase by 1 capsule q2weeks if no change in RBD until maximum of 4 capsules clonazepam 0.5mg to 1mg qhs Excessive daytime somnolence modafanil mg daily Dementia - Acetylcholinesterase inhibitors donepezil 5mg qam with food x 1 month then 10mg qam rivastigmine 1.5mg BID with food then increase by 1.5mg BID every month until reach 6.0mg BID Psychosis Clinical judgmentassess if need to treat psychosis (pleasant nonthreatening hallucinations need NOT be treated) Atypical antipsychotics quetiapine 25mg qhs and increase to 50mg qhs if necessary clozapine

8 Comments Dopamine Replacement Motor fluctuations (wearing off) - extend dopamine in brain Dyskinesias Movement Disorders in the Elderly 8 Psychosis Levodopa & Carbidopa development of motor fluctuations (wearing off phenomenon) & dyskinesias in the long term better to use in the elderly and those with cognitive impairment side-effects include nausea (alleviate by adding extra carbidopa or starting domperidone), dizziness, headache, confusion, delusions, agitation, hallucinations, psychosis Monoamine Oxidase Inhibitor - type B can be use an monotherapy early in the disease process (rasagiline) can be used in conjunction with levodopa (selegiline) side-effects include nausea, headaches, dizziness Amantadine renal excretion (beware of renal failure/elevated creatinine) side-effects include hallucinations and confusions, thus do not use in patients with cognitive impairment acute withdrawal of amantadine can cause an acute delirium and neuroleptic malignant syndrome Atypical antipsychotics clozapine - agranulocytosis Dopamine agonists better to use in younger patients (<65 years) to prevent long-term complications of motor fluctuations and dyskinesias in elderly, more prone to the side effects of hallucinations side-effects hypersomnolence/sleep attacks, hallucinations, nausea, orthostatic hypotension, edema, impulse control disorders (pathologic gambling, shopping and sex)