Myoclonic Seizures of Infancy

1. Definition of Myoclonic Epilepsy

Myoclonic epilepsy refers to a group of epileptic syndromes where myoclonic seizures are a prominent or predominant feature.

Myoclonus: A sudden, brief (<100 ms), shock-like involuntary contraction (positive myoclonus) or cessation of contraction (negative myoclonus) of a muscle or group of muscles.
Epileptic: Correlates with an ictal EEG discharge (typically generalized polyspike-and-wave).

2. Characteristic Features of Myoclonic Epilepsies with Onset in Infancy

The differential diagnosis is critical as prognosis varies from benign to devastating.

Syndrome	Age of Onset	Clinical Features	EEG Findings	Prognosis
Benign Myoclonic Epilepsy of Infancy (BMEI)	6 months – 3 years (Peak 1–2 yrs)	• Brief myoclonic jerks of head/arms (nodding/flinging). • Occurs in normal infants. • No other seizure types initially. • Rare reflex triggers (noise/touch).	Interictal: Normal background. Generalized spike/polyspike-and-wave (3 Hz) during sleep/drowsiness. Ictal: Generalized polyspike-wave burst.	Excellent. Seizures respond well to Valproate. Development usually normal. Resolves in childhood.
Dravet Syndrome (Severe Myoclonic Epilepsy of Infancy - SMEI)	< 1 year (Peak 5–8 months)	• Febrile seizures (prolonged/hemiclonic) often first. • Myoclonic seizures appear later (1–4 yrs). • Multiple types: Atypical absence, focal, tonic-clonic. • Triggered by fever/hot bath.	Early: Normal. Later: Generalized/focal spikes, polyspike-waves. Photosensitivity is common.	Poor. High mortality (SUDEP), severe intellectual disability, refractory to treatment.
Myoclonic Astatic Epilepsy (Doose Syndrome)	7 months – 6 years (Peak 2–4 yrs)	• Drop attacks: Myoclonic jerk followed by loss of tone (astatic) $\to$ Falls. • Staring spells, GTCs. • Previous development often normal.	Interictal: Parietal rhythmic theta (4–7 Hz). Ictal: Polyspike-and-wave followed by slow wave (atonia).	Variable. 50% have cognitive impairment. Often resistant to drugs; responsive to Ketogenic Diet.
Infantile Spasms (West Syndrome)	3 – 7 months	• Spasms: Sustained (1–2 sec) flexion/extension clusters. • Not true brief myoclonus, but often confused.	Hypsarrhythmia: Chaotic high voltage slow waves + multifocal spikes.	Poor if not treated early. Risk of LGS and regression.
Early Myoclonic Encephalopathy (EME)	Neonatal / Early Infancy (< 3 mo)	• Erratic, fragmentary myoclonus. • Severe hypotonia, metabolic etiology (e.g., Non-ketotic hyperglycinemia).	Suppression-Burst pattern.	Very Poor. High mortality in infancy.

3. Approach to an Infant with Myoclonic Seizures

A. History

Description: Differentiate from startle (Moro reflex), sleep myoclonus (occurs only in sleep), or shuddering attacks.
Timing: On waking (JME type) or falling asleep?
Triggers: Fever (Dravet), Noise/Touch (Reflex myoclonus), Photic.
Development: Regression suggests epileptic encephalopathy (West/Dravet); Normal suggests BMEI.
Family Hx: Febrile seizures (GEFS+ spectrum/Dravet).

B. Clinical Examination

Neurocutaneous: Ash leaf macules (Tuberous Sclerosis $\to$ Infantile Spasms).
Neurological: Head size, tone, fundoscopy (metabolic storage disorders).
Provocation: Clap test (auditory reflex) or photic stimulation.

C. Investigations

Video-EEG (Gold Standard):
- Capture the event to confirm it is epileptic.
- Assess background (Normal = BMEI; Slow/Chaotic = Encephalopathy).
- Look for photosensitivity.
MRI Brain: Rule out structural causes (tuberous sclerosis, dysplasia). Essential if focal features or delay present.
Genetic/Metabolic Testing:
- SCN1A panel: If history of febrile seizures + myoclonus (Dravet).
- Metabolic: Ammonia, lactate, urine organic acids (if early onset <3mo).

4. Management of Myoclonic Seizures (General & Specific)

A. General Principles

Avoid Aggravating Drugs: Carbamazepine, Oxcarbazepine, Phenytoin, and Vigabatrin (unless West syndrome) can worsen myoclonus.
Safety: Helmets for drop attacks (Doose); water safety.

B. Pharmacotherapy

Drug of Choice (First Line):
- Valproate (VPA): Broad spectrum, highly effective for BMEI and Doose.
  - Dose: 20–40 mg/kg/day.
  - Caution: Hepatotoxicity (avoid in mitochondrial disease/infants <2 yrs with metabolic flags).
Second Line / Add-on:
- Clonazepam / Clobazam: Benzodiazepines are very effective for myoclonus but cause sedation/tolerance.
- Levetiracetam: Safe, broad spectrum.
- Ethosuximide: Specifically for myoclonic-astatic or absence components.
Topiramate / Zonisamide: Broad spectrum adjunctive options.

C. Syndrome-Specific Management

Dravet Syndrome:
- First Line: Valproate + Clobazam.
- Add-on: Stiripentol, Fenfluramine, or Cannabidiol (CBD).
- Contraindicated: Sodium channel blockers (Carbamazepine/Phenytoin).
Doose Syndrome (MAE):
- Ketogenic Diet: Often more effective than medications; considered early if Valproate fails.

D. Treatment of Acute Cluster / Status

Buccal Midazolam or Rectal Diazepam for home rescue.