Essential Tremor

Aka: Essential Tremor, Benign Essential Tremor

1. Epidemiology
   1. Prevalence: 0.4 to 6%
      1. Most common pathologic Tremor cause in world
   2. Age of onset 20-60 years (bimodal distribution)
      1. Likely has onset for most patients in ages 20-30 years but is mild initially
      2. Later presentation at age 60-70 years coincides with the natural progression in severity
   3. Causes
      1. Genetic (Autosomal Dominant inheritance) in 50% of cases
      2. Sporadic
2. Findings: Symptoms and Signs
   1. Postural Tremor (Subset of Action Tremor)
      1. Initially presents as kinetic distal arm Tremor
      2. Some patients may have a postural component
      3. Usually bilateral (may be unilateral initially)
      4. Slowly progressive
      5. Rest Tremor is typically not present
         1. May progress to Rest Tremor if severe
   2. Frequency at 4-11 Hz
      1. Slower frequencies proximally
      2. Higher frequencies distally
   3. Distribution
      1. Hands (most commonly affected)
         1. Wrist flexion-extension movement
      2. Head
         1. Forward flexion and extension (Nodding 'Yes')
         2. Lateral rotation (Shaking head 'No')
      3. Other regions affected
         1. Can also affect voice, Tongue and legs
   4. Provocative
      1. Not task specific
      2. Stress or Fatigue
      3. CNS Stimulant Medications
      4. Ask patient to hold hands out in front of them
      5. Ask patient to draw spiral
         1. Archimedes Spiral drawn (spiral with wavy hands)
   5. Palliative
      1. Small amounts of Alcohol
      2. Rest
3. Differential Diagnosis
   1. See Tremor
   2. See Postural Tremor
   3. Essential Tremor is a diagnosis of exclusion made on clinical grounds
      1. Second or alternative Tremor diagnosis is identified in up to 30-50% of patients over time
      2. Tremor with other neurologic changes suggests alternative diagnosis
   4. Parkinson's Disease
      1. Rest Tremor affecting extremities
4. Labs: Not indicated unless atypical case
   1. Serum Chemistry Panel including Glucose
   2. Complete Blood Count
   3. Thyroid Stimulating Hormone (TSH)
5. Management: General Measures
   1. Wrist weights
   2. Alternate hand Postures
      1. Incorporate extended arm
   3. Avoid Alcohol as a therapeutic measure
      1. Transient effect with tolerance developing quickly
      2. Tremors may worsen after the Alcohol effect wears off
6. Management: Medications - First line
   1. Effective in only 30-50% of Essential Tremor cases
   2. Beta Blocker (preferred)
      1. Most effective for limb Tremors, but will is also effective in head Tremor
      2. Non-selective Beta Blockers (preferred first-line)
         1. Propranolol (most commonly used)
            1. Daily use: Propranol LA (Inderal) 80-320 mg daily
            2. Prn use: Propranolol 10-40 mg every 6 to 12 hours as needed
         2. Nadolol or Corgard (preferred Beta Blocker for decreased adverse effects, longer duration)
            1. Start: 40 mg once daily
            2. Maximum: 240 mg daily
      3. Selective Beta Blockers (alternative in Obstructive Lung Disease)
         1. Atenolol
         2. Metoprolol (Lopressor)
   3. Primidone (anticonvulsant)
      1. Primidone (Mysoline) 25-750 mg qd
         1. Start with half of a 50 mg tablet in the evening
         2. Increase slowly
      2. More adverse effects than Propranolol
         1. Sedation
         2. Nausea
         3. Dizziness or Vertigo
         4. Clumsiness
   4. Topiramate (anticonvulsant)
      1. Start 25 mg orally daily and titrate to 100 mg orally daily over 2-4 weeks
         1. Leblhuber (2010) Case Rep Neurol 15;2(1):1-4 +PMID: 20689627 [PubMed]
      2. Considered first-line agent in Tremor as of 2020
         1. Ferreira (2019) Mov Disord 34(7): 950-8 [PubMed]
7. Management: Specific Essential Tremor management (not responding to agents above)
   1. Refractory essential hand Tremor
      1. Topirimate starting with 25 mg daily
      2. Benzodiazepines prn
      3. Gabapentin (Neurontin) starting with 300 mg at night
   2. Refractory head and voice Essential Tremor
      1. Medications typically fail for control
      2. Head Tremor
         1. Botulinum Toxin Injection of cervical paraspinal and splenius Muscle
      3. Voice Tremor
         1. Botulinum Toxin Injection of thyroarytenoid Muscles (ENT and EMG guided)
   3. Severe Refractory Essential Tremor
      1. Medications are unlikely to be effective
      2. Bilateral Deep Brain Stimulation
   4. Primary Writing Tremor
      1. Medications tend to be ineffective
   5. Orthostatic Tremor (high frequency Tremor 13 to 18 Hz)
      1. Benzodiazepines may be effective
   6. References
      1. Ahiskog (2012) Mayo POIM Conference, Rochester
8. Management: Medications - Other
   1. Other Agents
      1. Calcium Channel Blockers
      2. Carbonic Anhydrase Inhibitors
      3. Gabapentin (Neurontin)
      4. Benzodiazepines
      5. Botulinum Toxin
   2. Experimental Agents
      1. Nimodipine
      2. Mirtazapine
   3. Surgical management in very severe cases
      1. Thalamic Stimulation (Deep Brain Stimulation)
      2. Thalamotomy
9. Prognosis
   1. Indicators of better medication response
      1. Very low amplitude rapid Tremor
      2. Hand Tremor (contrast with head and voice Tremor)
   2. Morbidity associated with impact on job functioning and social embarrassment, as well as Activities of Daily Living
      1. Up to 25% of patients change career or retire early due to Essential Tremor
10. References
    1. (2012) Presc Lett 19(3): 18 [PubMed]
    2. Hopfner (2020) Neurotherapeutics 17(4):1603-21 +PMID: 32915385 [PubMed]
    3. Louis (2001) N Engl J Med 345(12): 887-91 [PubMed]
    4. Pahwa (2003) Am J Med 115:134-42 [PubMed]