Progressive myoclonic epilepsy [Neurosurgery Wiki]

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====== 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.