Progressive Myoclonus Epilepsies (PMEs) are a group of uncommon clinically and genetically heterogeneous disorders characterised by myoclonus, generalized epilepsy, and neurological deterioration, including dementia and ataxia. PMEs may have infancy, childhood, juvenile or adult onset, but usually present in late childhood or adolescence, at variance from epileptic encephalopathies, which start with polymorphic seizures in early infancy. Neurophysiologic recordings are suited to describe faithfully the time course of the shock-like muscle contractions which characterize myoclonus. A combination of positive and negative myoclonus is typical of PMEs. The gene defects for most PMEs (Unverricht-Lundborg disease, Lafora disease, several forms of neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged-red fibers [MERRF], and type 1 and 2 sialidoses) have been identified. PMEs are uncommon disorders, difficult to diagnose in the absence of extensive experience. Thus, aetiology is undetermined in many patients, despite the advance in molecular medicine. Treatment of PMEs remains essentially symptomaticof seizures and myoclonus, together with palliative, supportive, and rehabilitative measures. The response to therapy may initially be relatively favourable, afterwards however, seizures may become more frequent, and progressive neurologic decline occurs. The prognosis of a PME depends on the specific disease. The history of PMEs revealed that the international collaboration and sharing experience is the right way to proceed. This emerging picture and biological insights will allow us to find ways to provide the patients with meaningful treatment.
The large number of different syndromes and seizure types together with an interindividual variable response to antiepileptic drugs (AEDs) make the treatment of epilepsy challenging. Fortunately, the last few years have been characterized by a huge interest in epilepsy genetics and two methods, genome-wide analyses and next-generation sequencing, have definitely given the possibility to write a new chapter in the book of treatment of epilepsy, the chapter on precision medicine. Epilepsy offers a good opportunity for the personalization of therapy if we consider that at least one third of epileptic patients do not achieve complete seizure control with the currently available pharmacological treatments, treatment is still often empirical and precise therapy, based on the pathogenesis and the mechanism of each AED is not generally possible because this mechanism often remains incompletely known. In addition, new drugs are often not targeted but developed using in vivo seizure models, to be potentially used by the largest number of patients. This method leads to a therapy aimed at treating the symptoms and the seizures rather than the single pathogenic mechanism of each seizure type or syndrome. In this narrative review, we summarize the established evidence regarding pharmacogenomics in epilepsy and discuss the basis of precision medicine.
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