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Progressive myoclonic epilepsy
Progressive Myoclonic Epilepsy (PME)

Progressive myoclonic epilepsy

Progressive Myoclonic Epilepsy (PME)

Progressive Myoclonic Epilepsy (PME) refers to a heterogeneous group of rare epileptic disorders marked by the combination of:

Myoclonus: Sudden, brief, shock-like muscle jerks.
Seizures: Often generalized tonic-clonic.
Progressive neurological deterioration: Cognitive decline, cerebellar ataxia, and sometimes behavioral changes.

🧠 Core Clinical Features

Multifocal myoclonus, often stimulus-sensitive.
Seizures: Generalized tonic-clonic (GTC) most common.
Progressive neurological dysfunction, including:
- Cognitive decline
- Cerebellar signs (ataxia, dysarthria)
- Pyramidal and extrapyramidal features in some cases
Onset usually in childhood or adolescence, but adult-onset forms exist.

🧬 Etiologies

Common genetic and metabolic causes of PME include:

Disorder	Gene(s)	Notes
Unverricht-Lundborg (EPM1)	`CSTB`	Most common in some populations; relatively benign.
Lafora disease	`EPM2A`, `NHLRC1`	Severe, rapidly progressive; Lafora bodies in neurons.
Neuronal ceroid lipofuscinosis (NCLs)	Multiple	Visual loss, seizures, cognitive regression.
MERRF (Myoclonic Epilepsy with Ragged Red Fibers)	Mitochondrial DNA (`MT-TK`)	Myopathy, ataxia, hearing loss, lactic acidosis.
Sialidosis	`NEU1`	Myoclonus, cherry-red macula, coarse facial features.
DRPLA (Dentatorubral-pallidoluysian atrophy)	`ATN1`	Trinucleotide repeat disorder; ataxia, chorea, dementia.

🔍 Diagnosis

Clinical suspicion based on triad: myoclonus + seizures + decline.
EEG: Generalized polyspike-and-wave; background slowing.
MRI: Often shows cerebellar or cortical atrophy.
Genetic testing: Crucial for etiologic diagnosis.
Metabolic workup: Especially in pediatric or atypical cases.

💊 Treatment

Antiepileptic Therapy

Often resistant to standard drugs.
Useful agents:
- Levetiracetam
- Valproate
- Clonazepam
- Zonisamide
- Piracetam
Avoid: Phenytoin, Carbamazepine → can worsen myoclonus.

Supportive and Adjunctive Care

Neurorehabilitation
Cognitive support and education
Nutritional care
Speech and physical therapy

Experimental and Palliative Options

Targeted therapy for specific mutations (still in development).
Corpus callosotomy may help in refractory disabling myoclonus (e.g., in adult DRPLA).

📉 Prognosis

Variable and depends on cause.
- EPM1: slower decline.
- Lafora, NCLs: rapidly fatal.
Most patients eventually suffer severe disability.

🧰 Summary for Clinicians

PME should be suspected in young patients with myoclonus, seizures, and cognitive/neurological regression.
Early genetic confirmation is crucial for prognosis and family counseling.
Multidisciplinary care is essential.