Essential Tremor

1. Essential Tremor David Hilmers MLK Lecture Series April 28, 2008

2. Case 65 year old woman states that she has had trouble holding food on her fork ever since she was a teen ager because she has the “shakes.” She has no other neurologic problems. What is the differential diagnosis? Video clip of ET: http://www.youtube.com/watch?v=nsifBzm_Jw8

3. Background • ET is so-called “benign” disorder but most report significant disability • Incidence increases steadily with age • Most affected become symptomatic in mid-late adulthood • Probably autosomal dominant but no specific genes found • Nearly 5x more likely to have ET if first degree relative with ET • However, 50% of cases without affected family member • Existence of local clusters seem to indicate environmental factors (?toxins like lead?) but no correlations made • Patients often have other movement disorders

4. Pathophysiology • Kinetic arm tremor is hallmark of ET (associated with movement) • Pathways are not well established but seem to involve: • Thalamus • Sensorimotor cortex • Olivary nuclei • Cerebellum • Ablations of lesions in these areas can reduce ET • Some autopsy studies have shown increased Lewy bodies and cerebellar injury in ET

6. Clinical assessment • Check for possible drug causes • Most commonly, beta-2 agonists, valproate, lithium, steroids, thyroxine, TCA’s, neuroloeptics • Cocaine, amphetamines • Underlying conditions (hyperthyroidism, hyperparathyroidism, hypoglycemia) • Withdrawal from substance abuse (ETOH, cocaine) • Overuse of caffeine, energy drinks and supplements

7. Neuro examination • Should have normal tone, strength, coordination • See if tremor is present at rest with distraction (counting backwards), consider other diagnosis if present • Does it occur with walking? (if so, possible PD) • Look for tremor with posture • Hands outstretched then bring hands towards face with fingers almost touching • In ET tremor should be almost immediate while in PD is a delay up to 9 seconds

8. Neuro exam (2) • Look for intention tremor • Finger to nose, pouring water from cup to cup, etc • May be present during these activities but should NOT be worse or only present during test; should not be present at rest • If only intention tremor, think cerebellar dysfunction or Wilson’s disease • Specific tasks • Handwriting size is normal or slightly large in ET • If small, may be PD (micrographia) • Can have patient draw spiral to see amplitude of tremor

9. Effect of alcohol on ability to draw spiral in patient with Essential Tremor

10. Neurophysiologic studies • When differentiating types of tremors is difficult, may use physiological studies • Only done in specialized laboratories • Record EMG in tremor-producing muscles at rest, with posture and during kinetic tasks • Characteristics frequencies and amplitudes may help with diagnosis

12. Differential diagnosis of ET • Enhanced physiological tremor • Usually low amplitude and high frequency • Usually postural and exaggeration of normal amount of tremor present in normal individuals • Often caused by emotion or drugs • Parkinson’s disease • “Pill rolling” tremor • Usually begins on one side (ET is bilateral) • Associated with other signs of PD (bradykinesia, rigidity, and postural instability) • However, some people who have ET go on to develop PD

13. Differential dx (2) • Cerebellar tremor • Lower frequency than ET • Does not occur at rest • Can affect one or both sides • Associated findings of dysmetria, dysynergia upon rapid alternating movements • Commonly see titubation of head or trunk

14. Differential Dx (3) • Dystonic tremor • Often focal, such as head bobbing, without hand involvement • Variable frequency and amplitude is irregular • Remember that ET may also have tremor of jaw or of voice • Psychogenic tremor • Onset is usually sudden • Can appear with rest, with posture, or intention • Often disappears when patient distracted • Unlike ET, can be great source of fatigue for patient

15. Differential Dx (4) • Orthostatic tremor • High frequency (13-18 Hz) • Lower extremities when standing • Improves when patient walks • Will see “rippling” of gastroc or quads • May radiate into upper limbs • Task specific tremor • Only occur during a motor task like writing • Also seen in musicians and athletes

16. Treatment • Reassurance • Tremor may increase in severity but there is treatment available • Unlikely to shorten lifespan • Mild disease • Lifestyle modifications such as avoidance of caffeine and nicotine • Small amounts of alcohol are effective on occasion (be sure to ask about ETOH abuse) • Propranolol prn • Moderate to severe tremor • Additional medications • Surgery – implantation of thalamic nucleus stimulator • http://www.youtube.com/watch?v=qaHx15M_NRE&NR=1

17. Stepped pharmacologic approach • First line • Primidone • Long acting beta blocker • Second line • Botox has been tried (injecting agonist-antagonist muscles) but results are inconsistent • Anticonvulsants (gabapentin, topiramate) • Benzodiazepines (alprazolam, clonazepam) • CCB (nimodipine) • Investigational drugs • Drugs which have similar effects as ethanol (octanol) and primidone (barbiturate t2000) without associated adverse effects

19. References • Fatta B Nahab, Elizabeth Peckham, Mark Hallett, Essential Tremor, Deceptively Simple…Pract Neurol 2007; 7: 222–233 • Up to date • You Tube (search under Essential Tremor)