Myoclonic Epilepsy with Ragged Red Fibres

Myoclonic epilepsy with ragged red fibres (MERRF) is a maternally inherited mitochondrial disease, mostly from the m.8344A>G variant in MT-TK (80%). It features myoclonus, generalised epilepsy, ataxia and myopathy with ragged red fibres on muscle biopsy.

Pathophysiology. Impaired mitochondrial translation reduces oxidative phosphorylation in neurons and muscle, with variable heteroplasmy.

Onset in childhood or adulthood with action myoclonus, generalised tonic clonic seizures, cerebellar ataxia, cognitive decline, myopathy, sensorineural hearing loss, optic atrophy, short stature, multiple symmetric lipomas (neck, shoulders) and neuropathy. Cardiomyopathy and conduction defects may occur.

Serum lactate raised. EEG shows generalised spike and wave with photosensitivity. MRI shows cerebellar and cerebral atrophy, sometimes basal ganglia change. Genetic testing for m.8344A>G (blood or urine, with muscle if needed). Muscle biopsy shows ragged red fibres and cytochrome oxidase negative fibres. ECG, echocardiography, glucose, audiometry and ophthalmology.

Differential diagnosis.

• Progressive myoclonic epilepsies (Unverricht-Lundborg disease, Lafora disease, neuronal ceroid lipofuscinosis, sialidosis).
• MELAS, Leigh syndrome, juvenile myoclonic epilepsy and spinocerebellar ataxia.

Myoclonus and seizures. Levetiracetam 500 mg twice daily, increased to 1500 mg twice daily (adjust to eGFR), and clonazepam 0.5 mg at night, increased to 4 mg daily in divided doses. Piracetam is an alternative for myoclonus: 7.2 g daily in divided doses, increased to 24 g daily (adjust to eGFR). Zonisamide 100 mg daily is an option. Avoid valproate and phenytoin, which can worsen mitochondrial function or ataxia.

Supportive. Coenzyme Q10 and other supplements have limited benefit. Cardiac, endocrine and hearing care. Physiotherapy and occupational therapy.

Avoid valproate, aminoglycosides and prolonged fasting.

Monitoring. Seizure control, ECG, echocardiography, glucose and audiometry yearly.

Referral and escalation. Refer to mitochondrial disease and epilepsy services and genetics.

Special groups. Genetic counselling is complex because of heteroplasmy.