> Table of Contents > Essential Tremor Syndrome
Essential Tremor Syndrome
Jonathon M. Firnhaber, MD
image BASICS
DESCRIPTION
  • A postural (occurring with voluntary maintenance of a position against gravity) or kinetic (occurring during voluntary movement) flexion-extension tremor that is slow and rhythmic and primarily affects the hands and forearms, head, and voice with a frequency of 4 to 12 Hz
  • Older patients tend to have lower frequency tremors, whereas younger patients exhibit frequencies in the higher range.
  • May be familial, sporadic, or associated with other movement disorders
  • Can begin at any age but the incidence and prevalence increase with age
  • The tremor can be exacerbated by emotional or physical stresses, fatigue, and caffeine.
  • System(s) affected: neurologic, musculoskeletal, ear/nose/throat (ENT) (voice)
EPIDEMIOLOGY
Essential tremor is the most common pathologic tremor in humans.
Incidence
  • Can occur at any age but bimodal peaks exist in the 2nd and 6th decades
  • Incidence rises significantly after age 49 years.
Prevalence
The overall prevalence for essential tremor has been estimated between 0.4% and 0.9% but is increased in older (65 years) patients to 4.6% and in advanced age (95 years) up to 22% (1)[B].
ETIOLOGY AND PATHOPHYSIOLOGY
  • Suspected to originate from an abnormal oscillation within thalamocortical and cerebello-olivary loops, as lesions in these areas tend to reduce essential tremor
  • Essential tremor is not a homogenous disorder; many patients have other motor manifestations and nonmotor features, including cognitive and psychiatric symptoms.
Genetics
  • Positive family history in 50-70% of patients; autosomal dominant inheritance is demonstrated in many families, but twin studies suggest that environmental factors are also involved.
  • A link to genetic loci exists on chromosomes 2p22-2p25, 3q13, and 6p23. In addition, a Ser9Gly variant in the dopamine D3 receptor gene on 3q13 has been suggested as a risk factor.
COMMONLY ASSOCIATED CONDITIONS
  • Can be present in 10% of patients with Parkinson disease (PD); characteristics of PD that distinguish it from essential tremor include 3- to 5-Hz resting tremor; accompanying rigidity, bradykinesia, or postural instability; and no change with alcohol consumption.
  • Patients with essential tremor have a 4% risk of developing PD. Although action tremors may precede PD, they will be diagnosed as essential tremor as long as the bradykinesia and rigidity of PD are not yet present (1)[B].
  • Resting tremor, typically of the arm, may be seen in up to 20-30% of patients with essential tremor. Although action tremor is the hallmark feature of essential tremor, it is commonly found in patients with PD as well.
image DIAGNOSIS
PHYSICAL EXAM
  • Tremor can affect upper limbs (˜95% of patients).
  • Less commonly, the tremor affects head (˜34%), lower limbs (˜30%), voice (˜12%), tongue (˜7%), face (˜5%), and trunk (˜5%).
DIFFERENTIAL DIAGNOSIS
  • PD
  • Wilson disease
  • Hyperthyroidism
  • Multiple sclerosis
  • Dystonic tremor
  • Cerebellar tremor
  • Asterixis
  • Psychogenic tremor
  • Orthostatic tremor
  • Drug-induced or enhanced physiologic tremor (amiodarone, cimetidine, lamotrigine, itraconazole, valproic acid, SSRIs, steroids, lithium, cyclosporine, &bgr;-adrenergic agonists, ephedrine, theophylline, tricyclic antidepressants [TCAs], antipsychotics) (3)[B].
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • No specific biologic marker or diagnostic test is available.
  • Ceruloplasmin and serum copper to rule out Wilson disease
  • Thyroid-stimulating hormone to rule out thyroid dysfunction
  • Serum electrolytes, BUN, creatinine
  • Brain MRI usually is not necessary or indicated unless Wilson disease is found or exam findings imply central lesion.
Diagnostic Procedures/Other
  • Accelerometry evaluates tremor frequency and amplitude; >95% of PD cases exhibit frequencies in the 4- to 6-Hz range, and 95% of essential tremor cases exhibit frequencies in the 5- to 8-Hz range.
  • Surface electromyography is less helpful in distinguishing essential tremor from PD.
Test Interpretation
Posture-related tremor
image TREATMENT
MEDICATION
Pharmacologic treatment should be considered when tremor interferes with activities of daily living (ADLs) or causes psychological distress.
First Line
  • Propranolol 60 to 320 mg/day in divided doses or in long-acting formulation reduces limb tremor magnitude by ˜50%, and almost 70% of patients experience improvement in clinical rating scales. There is insufficient evidence to recommend propranolol for vocal tremor. Single doses of propranolol, taken before social situations that are likely to exacerbate tremor, are useful for some patients.
  • Primidone 25 mg at bedtime, gradually titrated to 150 to 300 mg at bedtime, improves tremor amplitude by 40-50%. Maximum dose is 750 mg/day, with doses >250 mg/day typically divided to BID or TID. Low-dose therapy (<250 mg/day) is just as effective as high-dose (750 mg/day) therapy.
  • Propranolol and primidone have similar efficacy when used as initial therapy for limb tremor; both carry a level A recommendation (4)[A].
  • 30-50% of patients will not respond to either propranolol or primidone.
P.367

Second Line
  • Topiramate at a mean dose of 292 mg/day demonstrated significantly greater reduction in tremor rating scale (TRS) compared with placebo (7.70 vs. 0.08; p <.005; baseline TRS = 37.0) in a small study combining results of three double-blind, randomized, controlled trials following a common protocol. Use is limited by dropout rates as high as 40% due to appetite suppression, weight loss, paresthesias, and concentration difficulties (5)[B].
  • Gabapentin up to 400 mg TID
  • Sotalol, nadolol, and atenolol are alternative &bgr;-blockers; each has less evidence than propranolol to support use.
  • Clonazepam and alprazolam should be used with caution because of abuse potential.
  • Clozapine has shown efficacy at doses of 6 to 75 mg/day but is recommended only for refractory cases of limb tremor because of a 1% risk of agranulocytosis. The American Academy of Neurology (AAN) indicates that insufficient evidence exists to support or refute the efficacy of clozapine for chronic use (4)[A].
  • Memantine, in a pilot study using doses up to 40 mg/day, showed significant benefit in a small subset of the study group. Adverse events at this dose included dizziness, somnolence, and poor energy (6)[B].
  • Pramipexole, at a dose of 2.1 mg/day, demonstrated moderate efficacy in reducing severity of tremor in a pilot study of 29 patients. Immediate- and extended-release formulations were equally effective (7)[B].
  • Levetiracetam and 3,4-diaminopyridine are probably ineffective at reducing limb tremor and should not be considered according to the AAN (4)[A].
  • Other medications that have been evaluated for treatment of essential tremor, with limited data to support their use, include acetazolamide, clonidine, flunarizine, methazolamide, nimodipine, olanzapine, phenobarbital, pregabalin, quetiapine, sodium oxybate, and zonisamide (4)[A].
  • Alcohol may provide transient improvement in symptoms, but its brief duration of action, subsequent rebound, and associated risk of developing alcohol addiction make it a less attractive option for longer term treatment. Alcohol may be an appropriate option for short-term, situation-specific improvement in symptoms.
  • Botulinum toxin A injections should be offered as a treatment option for cervical dystonia (level A recommendation from AAN) and may be offered for blepharospasm, focal upper extremity dystonia, adductor laryngeal dystonia, and upper extremity essential tremor. Limited data support its use for head and voice tremor (8)[B].
ISSUES FOR REFERRAL
Referral to a neurologist can help to differentiate those with dystonia, neuropathic tremor, PD, or drug-induced tremor.
SURGERY/OTHER PROCEDURES
  • Deep brain stimulation provides a magnitude of benefit that is superior to all available medications and may be used to treat medically refractory limb tremor; it has fewer adverse effects than thalamotomy (9)[B].
  • Bilateral thalamic stimulation is effective in reducing tremor and functional disability; however, dysarthria is a possible complication.
  • Unilateral thalamotomy may be used to treat limb tremor that is refractory to medical management.
  • Bilateral thalamotomy is not recommended because of adverse side effects.
image ONGOING CARE
DIET
Avoid caffeine.
PROGNOSIS
Tremor tends to worsen with age, increasing in amplitude.
REFERENCES
1. Elias WJ, Shah BB. Tremor. JAMA. 2014;311(9): 948-954.
2. Bain P, Brin M, Deuschl G, et al. Criteria for the diagnosis of essential tremor. Neurology. 2000;54 (11 Suppl 4):S7.
3. Zeuner KE, Deuschl G. An update on tremors. Curr Opin Neurol. 2012;25(4):475-482.
4. Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2011;77(19):1752-1755.
5. Connor GS, Edwards K, Tarsy D. Topiramate in essential tremor: findings from double-blind, placebo-controlled, crossover trials. Clin Neuropharmacol. 2008;31(2):97-103.
6. Handforth A, Bordelon Y, Frucht SJ, et al. A pilot efficacy and tolerability trial of memantine for essential tremor. Clin Neuropharmacol. 2010;33(5):223-226.
7. Herceg M, Nagy F, Pál E, et al. Pramipexole may be an effective treatment option in essential tremor. Clin Neuropharmacol. 2012:35(2):73-76.
8. Simpson DM, Blitzer A, Brashear A, et al. Assessment: botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1699-1706.
9. Flora ED, Perera CL, Cameron AL, et al. Deep brain stimulation for essential tremor: a systematic review. Mov Disord. 2010;25(11):1550-1559.
Additional Reading
&NA;
  • Buijink AW, Contarino MF, Koelman JH, et al. How to tackle tremor—systematic review of the literature and diagnostic work-up. Front Neurol. 2012;3:146.
  • Deuschl G, Raethjen J, Hellriegel H, et al. Treatment of patients with essential tremor. Lancet Neurol. 2011;10(2):148-161.
  • Sullivan KL, Hauser RA, Zesiewicz TA. Essential tremor. Epidemiology, diagnosis, and treatment. Neurologist. 2004;10(5):250-258.
  • Thenganatt MA, Louis ED. Distinguishing essential tremor from Parkinson's disease: bedside tests and laboratory evaluations. Expert Rev Neurother. 2012;12(6):687-696.
Codes
&NA;
ICD10
G25.0 Essential tremor
Clinical Pearls
&NA;
  • Core criteria for diagnosis of essential tremor include bilateral action (intention) tremor of the hands, forearm, and/or head without resting component.
  • Beneficial response to alcohol and positive family history help to differentiate essential tremor from PD (PD is characterized by tremor at rest, bradykinesia, and rigidity, and it does not improve with alcohol use).
  • 10% of patients with PD will have both resting tremors of PD and essential (intention) tremors.
  • Wilson disease, thyroid disease, and medication effect should be ruled out.
  • Brain MRI is usually not necessary or indicated.
  • First-line treatments include propranolol and primidone.