Essential Tremor - Model 5-Mark Answer (Final Year MBBS)

Definition

Epidemiology

• Affects ~1% of the general population and up to 5% of those over 60 years
• Estimated 5-10 million people in the US/Europe
• Frequency increases dramatically after age 70
• Can present in childhood but has a bimodal peak - second decade and after age 35-40

Etiology & Genetics

• ~50% are familial - autosomal dominant inheritance with high penetrance (hence also called "familial tremor" or "hereditary tremor")
• No single confirmed causative gene; expansion of GGC repeat in NOTCH2NLC gene has been associated but not independently confirmed
• Several loci implicated; phenotypic heterogeneity suggests multiple underlying genes

Pathophysiology

1. Olivocerebellar pathway - abnormal oscillatory activity in the inferior olivary nucleus and cerebellar circuits (supported by increased blood flow in cerebellum during tremor, and presence of cerebellar signs in ~10% of ET patients)
2. Thalamo-cerebellar loops - the VIM (ventro-intermediate) nucleus of the thalamus acts as a "tremor pacemaker"; this is supported by the fact that thalamic DBS/ablation relieves tremor

• Loss of Purkinje cells in the cerebellum
• Axonal "torpedoes" (axonal swellings)
• Decreased axonal branching
• These findings suggest a neurodegenerative component, though this remains controversial

Clinical Features

• Postural and action tremor (appears when limb held against gravity or during movement)
• NOT a resting tremor (this helps differentiate from Parkinson's disease)
• Frequency: 4-8 Hz (Adams & Victor) / 6-10 Hz (Harrison's)
• Usually bilateral and symmetric; often begins in the dominant hand

Diagnosis

1. Bilateral postural or kinetic tremor of hands/forearms
2. Duration >3 years
3. No other neurological signs (though mild ataxia/coordination impairment can be present)
4. No secondary cause

Differential Diagnosis (vs. Parkinson's Disease - High Yield!)

Treatment

Non-pharmacological

• Reassurance (mild cases need no treatment)
• Avoid precipitating factors (caffeine, stress)
• Weighted utensils for eating

Pharmacological (First-line)

1. Propranolol (beta-blocker) - 20-120 mg/day in divided doses (up to 80-200 mg/day); reduces tremor in 50-70% of patients. Acts centrally (not just peripheral beta-2 blockade). Contraindicated in asthma and bradycardia. Mainly effective for hand tremor; head tremor is often refractory.
2. Primidone (barbiturate) - 125-250 mg three times daily; start at very low dose (12.5 mg) to avoid initial side effects (drowsiness, nausea, ataxia). Effective when propranolol fails or is not tolerated.

Second-line

• Gabapentin, Topiramate - benefits reported but less widely used
• Botulinum toxin injections - useful for voice tremor or focal limb tremor (can cause muscle weakness)
• Metoprolol, Nadolol - alternative beta-blockers

Surgical (Severe, Drug-Resistant Cases)

• Deep Brain Stimulation (DBS) of VIM nucleus of thalamus - highly effective for drug-resistant ET
• Thalamotomy (VIM) - older surgical approach
• Focused ultrasound thalamotomy - newer, non-surgical approach; proven effective in some ET cases (does not require open surgery)

Key Examination Points (Remember!)

• ET is the commonest movement disorder
• Autosomal dominant inheritance
• Action/postural tremor (not rest tremor)
• Alcohol improves the tremor (a characteristic feature)
• First-line drugs: Propranolol and Primidone
• Surgical target: VIM nucleus of thalamus
• ET tremor disappears during sleep
• Head tremor disappears when the head is supported (postural in nature)