Background: Progressive myoclonus epilepsies (PMEs) are a group of rare inherited diseases featuring
a combination of myoclonus, seizures and variable degree of cognitive impairment. Despite extensive investigations,
a large number of PMEs remain undiagnosed. In this review, we focus on the current pharmacological
approach to PMEs.
Methods: References were mainly identified through PubMed search until February 2017 and backtracking of
references in pertinent studies.
Results: The majority of available data on the efficacy of antiepileptic medications in PMEs are primarily anecdotal
or observational, based on individual responses in small series. Valproic acid is the drug of choice, except for
PMEs due to mitochondrial diseases. Levetiracetam and clonazepam should be considered as the first add-on
treatment. Zonisamide and perampanel represent promising alternatives. Phenobarbital and primidone should be
reserved to patients with resistant disabling myoclonus or seizures. Lamotrigine should be used with caution due
to its unpredictable effect on myoclonus. Avoidance of drugs known to aggravate myoclonus and seizures, such
as carbamazepine and phenytoin, is paramount. Psychiatric (in particular depression) and other comorbidities
need to be adequately managed. Although a 3- to 4-drug regimen is often necessary to control seizures and myoclonus,
particular care should be paid to avoid excessive pharmacological load and neurotoxic side effects. Target
therapy is possible only for a minority of PMEs.
Conclusions: Overall, the treatment of PMEs remains symptomatic (i.e. pharmacological treatment of seizures
and myoclonus). Further dissection of the genetic background of the different PMEs might hopefully help in the
future with individualised treatment options.