How do I approach a patient with myoclonus (involuntary muscle twitching) and what are the differential diagnoses and investigations to consider?

Approach to Myoclonus: Clinical Evaluation and Management

Initial Clinical Characterization

Begin by determining whether the myoclonus is epileptic or non-epileptic, as this fundamentally changes your diagnostic and therapeutic approach. 1, 2

Key Clinical Features to Document

• Timing and distribution: Note whether jerks occur at rest, with posture maintenance, or during action; document if they are focal, segmental, or generalized 3
• Duration and pattern: Myoclonus consists of sudden, brief, lightning-like jerks lasting only a fraction of a second 4, 5
• Consciousness: Preserved consciousness during episodes distinguishes myoclonus from epileptic events 4
• Triggers: Identify specific precipitants including excitement, frustration, postural changes, sensory stimuli, or specific movements (kinesigenic forms) 4
• Age of onset and family history: Essential for narrowing differential diagnoses 3

Critical Distinction: Myoclonus vs Status Myoclonus

Status myoclonus (continuous, repetitive myoclonic jerks lasting >30 minutes) within 72 hours after cardiac arrest predicts poor neurological outcome with 0% false positive rate, while isolated myoclonus has an unacceptable 5-11% false positive rate and should NOT be used alone for prognostication. 6

Differential Diagnoses by Context

Post-Cardiac Arrest Setting

• Status myoclonus: Continuous generalized jerking within 72-120 hours post-arrest indicates poor prognosis (0% FPR) 6
• Lance-Adams syndrome: Early-onset prolonged myoclonus that evolves into chronic action myoclonus with potential good recovery 6, 1
• Cortical vs subcortical: Distinguish using EEG—cortical has epileptiform correlates, subcortical does not 4

Physiological Classification (Most Clinically Useful)

• Cortical myoclonus: Brief, focal jerks with EEG correlates; commonly occurs with continuous cortical background activity 4, 2
• Subcortical myoclonus: No EEG correlate; key distinguishing feature 4
• Cortical-subcortical: Occurs "in lockstep" with epileptiform abnormalities like burst suppression 4
• Brainstem myoclonus: Requires specific clinical and electrophysiological features 2
• Spinal/segmental myoclonus: Focal, does not respond to antiepileptic drugs 2, 7
• Peripheral myoclonus: Focal involvement 7

Etiological Considerations

• Infectious: Viral encephalitis (measles with 1:1 EEG-jerk relationship), Nipah virus, JC virus/PML 5
• Iatrogenic: Review medications (opiates) and metabolic derangements (hepatic/renal failure) 2
• Epileptic syndromes: Juvenile myoclonic epilepsy, myoclonic seizures 5, 7
• Genetic: Myoclonus-dystonia and other hereditary forms 8
• Functional: Propriospinal myoclonus (controversial etiology, often functional) 2

Movements to Differentiate From Myoclonus

• Tics: More complex pattern, can be temporarily suppressed 4
• Convulsive syncope: Movements occur after loss of consciousness, not as primary symptom 4
• Hyperekplexia: Triggered specifically by sudden noise/touch with excessive startle response 4
• Tonic seizures: Sustained muscle contractions rather than brief jerks 5

Essential Investigations

Electrophysiological Studies (Highest Priority)

EEG is crucial for distinguishing cortical from subcortical myoclonus and identifying epileptic activity. 1, 4

• EEG during episodes: Identifies awareness, reactivity, and epileptic correlates 4
• Continuous EEG monitoring: Recommended for suspected status epilepticus and treatment monitoring 1
• EMG with EEG: Determines cortical vs subcortical vs spinal origin 3
• Timing for post-arrest patients: Evaluate off sedation whenever possible; wait 72+ hours to minimize false positives from residual sedation 6

Additional Diagnostic Tests

• Neuroimaging: MRI to identify structural lesions
• Metabolic workup: Hepatic and renal function, electrolytes 2
• Infectious evaluation: If viral encephalitis suspected (CSF analysis, viral PCR) 5
• Genetic testing: When hereditary forms suspected based on family history 8

Treatment Algorithm Based on Physiology

First-Line Agents by Myoclonus Type

For cortical myoclonus, use levetiracetam, valproic acid, or clonazepam as first-line treatment. 1, 2, 7

• Cortical: Levetiracetam (preferred first-line), valproic acid, or clonazepam 1, 2, 7
• Cortical-subcortical (epileptic): Valproic acid has demonstrated efficacy for myoclonic seizures 7
• Subcortical/brainstem: Clonazepam first-line; levetiracetam and valproic acid as alternatives 2, 7
• Spinal/segmental: Clonazepam first-line; botulinum toxin for focal cases 2, 7
• Peripheral focal: Botulinum toxin 7

Post-Cardiac Arrest Status Myoclonus

Treatment options include sodium valproate, levetiracetam, clonazepam, propofol, benzodiazepines, and barbiturates. 1

• Do NOT use routine seizure prophylaxis in post-arrest patients due to adverse effects and poor response 1
• Subcortical myoclonus without EEG correlate may not require aggressive antiseizure treatment if not interfering with mechanical ventilation 4

Critical Pitfalls to Avoid

• Never use phenytoin or carbamazepine: These may paradoxically worsen myoclonus 2
• Avoid single-agent therapy: Polytherapy with multiple drugs in large dosages is usually required for functional improvement 3, 9
• Don't prognosticate on myoclonus alone: Only status myoclonus within 72 hours has acceptable predictive value; isolated myoclonus has 5-11% false positive rate 6
• Functional myoclonus requires different approach: Multimodal treatment including psychotropic drugs, physical/occupational therapy, and psychiatry collaboration 2

Refractory Cases

• L-5-Hydroxytryptophan and sodium oxybate: For refractory subcortical/brainstem myoclonus 2
• Perampanel: Promising preliminary data for treatment-resistant cases 8
• Deep brain stimulation: Bilateral globus pallidus pars-interna targeting for myoclonus-dystonia when pharmacological treatments exhausted 2