Progressive Myoclonus Epilepsies

Progressive myoclonic epilepsies (PMEs) are rare disorders caused by metabolic, genetic,and neurodegenerative diseases, which have been defined as severe conditions characterized by refractory epilepsy, neurological deterioration, and cognitive impairment with a poor prognosis. PME can present with multiple seizure types, worsening myoclonus, and developmental regression. A wide range of specific etiology contributes to the PME. Mainly there are six types of well-characterized PMEs, namely the UnverrichtLundborg Disease (ULD), Lafora disease (LD), Neuronal ceroid lipofuscinoses (NCLs), Myoclonus epilepsy with ragged red fibers (MERRF),Sialidosis and Dentatorubral pallidoluysian atrophy (DRPLA).Unverricht–Lundborg disease-also called progressive myoclonic epilepsy type 1 (EPM1)-is autosomal-recessively inherited and is characterized by stimulus sensitive myoclonus and tonic-clonic seizures. Some patients may develop cerebellar features after the disease onset. Lafora body disease-also called progressive myoclonic epilepsy type 2 (EPM2)-is an autosomal-recessive form of progressive myoclonus epilepsy.It is characterized by myoclonus, tonic-clonic seizures,visual hallucinations,intellectual decline and progressive neurological deterioration. The neuronal ceroid lipofuscinoses (CLN) comprise a heterogeneous group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive cognitive and motor deterioration, progressive tonic–clonic as well as myoclonic seizures, and early death. Most forms have visual loss. The clinical phenotypes traditionally divide into infantile, late infantile, juvenile and adult, based on age at onset. Dentatorubral-pallidoluysian atrophy (DRPLA), unlike other progressive myoclonus epilepsies, is an autosomal-dominant disorder characterized by epilepsy, cerebellar ataxia, choreoathetosis, myoclonus, dementia and psychiatric symptoms in varying combinations. Myoclonic epilepsy with ragged-red fibers (MERRF) is a multisystem mitochondrial disorder,named after its characteristic muscle biopsy appearances. The onset is usually in childhood, after normal early development. The first symptom is often myoclonus, followed by generalized epilepsy, ataxia, weakness and dementia. Common associated findings are hearing loss, short stature, optic atrophy and cardiomyopathy with Wolff–Parkinson–White syndrome. Sialidosis type 1 (cherry-red spot myoclonus syndrome) also called mucolipidosis type I, is an autosomal-recessive lysosomal storage disease caused by a deficiency of the enzyme α-N-acetyl neuraminidase-1 (coded by the NEU1 gene on chromosome 6p21). It is classified into two main clinical variants: type 1, the milder variant, and type 2, usually more severe and with an earlier onset. The disease is characterized by myoclonic epilepsy, visual problems, hyperreflexia and ataxia that develop in the second or the third decade of life. There are specific treatments for some forms of progressive myoclonus epilepsy. For example, metabolic disorders such as Gaucher’s disease may respond to substrate reduction therapy or enzyme replacement therapy. Valproate is often the first choice to treat myoclonic seizures because of its broad spectrum of antiepileptic action and its good myoclonus suppression potential. It may be less preferable in women owing to its teratogenicity but should not be denied to women who have no plans to conceive, in the face of an incurable disease. Also, in case of MERRF patients VPA should be avoided. Clonazepam (CNZ) is another efficacious first-line AED. As a whole, Drugs useful in progressive myoclonic epilepsies is including Sodium valproate, Levetiracetam ,Topiramate, Clonazepam, Zonisamide and Phenobarbital. Drugs that exacerbate myoclonus including Lamotrigine, Phenytoin, Carbamazepine, Oxcarbazepine, Tiagabine and Vigabatrin.

Keywords:

myoclonus epilepsies , progressive , Etiology , Treatment