Myoclonus
Myoclonus
What You'll Learn
- Definition: Brief, involuntary, shock-like jerks caused by sudden muscle contraction (positive) or sudden loss of tone (negative/asterixis)
- Classification: By physiology (cortical > subcortical > brainstem > spinal > peripheral); cortical myoclonus is the most common subtype of pathologic myoclonus
- Cortical myoclonus: Action-sensitive, stimulus-sensitive; EEG shows giant SEPs and back-averaged cortical transients; enhanced C-reflex on EMG
- Opsoclonus-myoclonus: In children → neuroblastoma (~50%); in adults → breast, lung, or ovarian cancer. Anti-Ri (ANNA-2) is the classic antibody, but many adult OMS cases are seronegative — the absence of a paraneoplastic antibody does NOT exclude the diagnosis or the need for cancer screening.
- PME syndromes: Unverricht–Lundborg (EPM1, cystatin B), Lafora disease (Lafora bodies, PAS+), NCLs, sialidosis (cherry-red spot)
- Treatment: Levetiracetam, valproate, clonazepam, piracetam; avoid phenytoin and carbamazepine (worsen myoclonus)
HighYield Pearls
- Cortical myoclonus signature: action- & stimulus-sensitive, focal/multifocal, distal > proximal, EMG burst <50 ms, giant SEPs (P25–N33 ≥10 µV), back-averaged cortical transient, enhanced C-reflex
- Lance–Adams (post-hypoxic action myoclonus): emerges after cardiac arrest survivors regain consciousness → clonazepam + levetiracetam + valproate ± piracetam (NOT acute post-anoxic status myoclonus, which is a poor-prognosis cortical-subcortical pattern)
- JME treatment trap: first-line valproate / levetiracetam / lamotrigine—but lamotrigine can WORSEN myoclonus in JME and is contraindicated in Dravet; phenytoin & carbamazepine & gabapentinoids also worsen
- Hyperekplexia: neonate with stiffness + exaggerated startle + apnea → GLRA1 (glycine receptor α1); nose-tap maneuver aborts the spasm; treat with clonazepam
- Opsoclonus–myoclonus–ataxia: child → screen for neuroblastoma (urine HVA/VMA, MIBG, MRI chest–abdomen–pelvis); adult → breast/SCLC, anti-Ri (ANNA-2); many adult cases are seronegative—still hunt for tumor
- Palatal myoclonus: essential = ear click, no lesion; symptomatic = Guillain–Mollaret triangle (dentate–red nucleus–inferior olive) with hypertrophic olivary degeneration on T2/FLAIR; persists in sleep
- Negative myoclonus = asterixis: hepatic, uremic, hypercapnic, or drug encephalopathy (gabapentinoids/opioids in renal failure, valproate-induced hyperammonemia, lithium, bismuth)
- PME triad: progressive action myoclonus + tonic-clonic seizures + cerebellar ataxia/cognitive decline — Unverricht–Lundborg (mildest), Lafora (PAS+ bodies, rapid decline), MERRF (ragged-red fibers), NCL, sialidosis (cherry-red spot)
- CJD: rapidly progressive dementia + startle myoclonus + EEG periodic sharp-wave complexes (PSWCs) at 1–2 Hz; DWI cortical ribboning + pulvinar/hockey-stick sign
- Drug-induced myoclonus in renal failure: opioids (esp. meperidine, morphine), gabapentin/pregabalin, lithium, bismuth, tramadol — dose-reduce or discontinue, do not just add an AED
🔍 Quick ReferenceClinical · EEG / EMG · Etiology / treatment
Clinical phenotype
- Action myoclonus after cardiac arrest survivor → Lance–Adams syndrome
- Stiff neonate, exaggerated startle, nose-tap aborts spasm → Hyperekplexia (GLRA1)
- Rhythmic ear-click audible to examiner → Essential palatal myoclonus
- Dancing eyes, dancing feet in a toddler → Opsoclonus–myoclonus–ataxia / neuroblastoma
- Flapping tremor in liver/renal failure → Asterixis (negative myoclonus)
- Morning jerks of arms dropping coffee cup, GTC on awakening → Juvenile myoclonic epilepsy (JME)
- Progressive action myoclonus + ataxia + cognitive decline in adolescent → Progressive myoclonic epilepsy (PME)
- Segmental rhythmic abdominal/truncal jerks persisting in sleep → Spinal/propriospinal myoclonus
EEG / EMG / imaging
- Giant SEPs (P25–N33 ≥10 µV) + back-averaged cortical transient + enhanced C-reflex → Cortical myoclonus
- EMG burst <50 ms → Cortical origin (vs >100 ms subcortical/spinal)
- Periodic sharp-wave complexes (PSWCs) 1–2 Hz + cortical ribboning on DWI → Creutzfeldt–Jakob disease
- Hypertrophic olivary degeneration (T2/FLAIR hyperintensity, enlarged olive) → Symptomatic palatal myoclonus (Guillain–Mollaret triangle lesion)
- Generalized 4–6 Hz polyspike-and-wave, photoparoxysmal response → JME
- Ragged-red fibers on muscle biopsy + lactic acidosis → MERRF
- PAS-positive intraneuronal inclusions (Lafora bodies) on axillary skin/sweat-duct biopsy → Lafora disease
Etiology / genetics / treatment
- Cherry-red macular spot + myoclonus → Sialidosis type I (NEU1)
- EPM1 / cystatin B (CSTB) dodecamer repeat → Unverricht–Lundborg disease
- EPM2A (laforin) / EPM2B (malin) → Lafora disease
- mtDNA m.8344A>G (MT-TK) → MERRF
- SGCE (paternal imprinting, maternal silencing) → Myoclonus–dystonia (alcohol-responsive)
- Anti-Ri / ANNA-2 → Adult OMS (breast, SCLC)
- Lamotrigine, phenytoin, carbamazepine, gabapentinoids, vigabatrin → WORSEN myoclonus (especially in JME & Dravet)
- Levetiracetam + valproate + clonazepam ± piracetam → Cortical / Lance–Adams myoclonus
- Opioids / gabapentin / pregabalin in renal failure → Drug-induced myoclonus & asterixis
Classification of Myoclonus
By Physiology (Generator Site)
| Type | Generator | Distribution | Key Features |
|---|---|---|---|
| Cortical | Sensorimotor cortex | Focal / multifocal | Action-sensitive, stimulus-sensitive; giant SEPs, back-averaged cortical transient, enhanced C-reflex |
| Cortical–subcortical | Cortex + thalamus/brainstem (loop) | Generalized | Epileptic myoclonus (e.g., JME); bilateral synchronous jerks |
| Subcortical (non-brainstem) | Basal ganglia / thalamus | Generalized / segmental | Myoclonus–dystonia (SGCE); thalamic lesions; no preceding cortical transient |
| Brainstem | Reticular formation, pontomedullary nuclei | Generalized / axial | Reticular reflex myoclonus, hyperekplexia, palatal myoclonus |
| Spinal | Spinal cord segments | Segmental / propriospinal | Rhythmic, may persist in sleep; spinal cord lesions |
| Peripheral | Nerve root / plexus / nerve | Focal | Hemifacial spasm, nerve root compression |
By Distribution
- Focal: Single body region (e.g., one arm, face)
- Multifocal: Multiple non-contiguous regions, asynchronous (classic for cortical myoclonus)
- Segmental: Contiguous body segments (e.g., arm + shoulder); typical of spinal myoclonus
- Generalized: Whole-body jerks; cortical–subcortical or reticular origin
By Etiology
- Physiologic: Hypnic jerks (sleep starts), hiccups, exercise-induced — normal, no treatment needed
- Essential: Isolated myoclonus without other neurological deficits; autosomal dominant or sporadic; benign course
- Epileptic: Myoclonus as the predominant seizure type (JME, PME syndromes, Lennox–Gastaut)
- Symptomatic (secondary): Due to identifiable underlying disease (neurodegenerative, metabolic, toxic, post-hypoxic)
💎 Board Pearl
- Cortical myoclonus is the most common subtype of pathologic myoclonus — action-sensitive + stimulus-sensitive + multifocal = cortical origin
- Boards love the physiologic classification — knowing the generator site determines the EEG/EMG findings and treatment approach
Cortical Myoclonus
Clinical Features
- Most common subtype of pathologic myoclonus
- Action-sensitive: Worsens with voluntary movement (action myoclonus) — highly disabling
- Stimulus-sensitive: Triggered by touch, light, sound (reflex myoclonus)
- Distribution: focal or multifocal, distal predominance (hands > face > feet)
- Brief jerks (<50 ms EMG burst duration) — shorter than subcortical myoclonus
- Often co-occurs with cortical reflex seizures
Electrophysiologic Diagnosis
- EEG back-averaging: Time-locked cortical transient precedes the myoclonic jerk by 15–40 ms (arm) — confirms cortical generator
- Giant somatosensory evoked potentials (SEPs): Enlarged P25–N33 amplitude (≥10 µV) — indicates cortical hyperexcitability
- Enhanced C-reflex (long-loop reflex): Exaggerated late EMG response to peripheral nerve stimulation; cortical loop-mediated
- EMG burst duration: <50 ms (short) — vs. >50 ms in subcortical myoclonus
- EEG may show generalized spike-wave or polyspike-wave discharges in epileptic cortical myoclonus
Treatment
- Levetiracetam: First-line for cortical myoclonus; broad efficacy, well-tolerated
- Valproate: Effective for cortical and cortical–subcortical myoclonus; risk of hepatotoxicity, teratogenicity
- Piracetam: 8–24 g/d; specifically effective for cortical myoclonus; not FDA-approved in the US — LEV is the practical substitute
- Clonazepam: Add-on; sedation limits use; effective for all myoclonus types
- Avoid: Phenytoin, carbamazepine, gabapentin — may worsen cortical myoclonus
💎 Board Pearl
- Back-averaging is the gold-standard technique to confirm cortical origin — shows a cortical transient preceding the jerk
- Giant SEPs + enhanced C-reflex + short EMG bursts (<50 ms) = cortical myoclonus triad on electrophysiology
- Phenytoin and carbamazepine should generally be avoided in cortical myoclonus — they often worsen cortical myoclonus (not a formal contraindication, but a near-universal teaching point)
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