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:
LevetiracetamValproateClonazepamZonisamidePiracetam
- 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.