Epilepsy and prion diseases: A narrative review

• Published in: Epilepsy & behavior 2021-02, Vol.115, p.107630-107630, Article 107630
• Main Authors: Mbizvo, Gashirai K., Ziso, Besa, Larner, Andrew J.
• Format: Article
• Language: English
• Subjects: Cognitive decline; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome; Epilepsy; Humans; Neurodegenerative disease; Prion Diseases - complications; Prion Diseases - diagnosis; Prions - genetics; Protein misfolding; Seizures; Status epilepticus
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2020.107630

•Epileptic seizures may occur in around 10% of patients with sporadic CJD, and less in other forms.•The usual semiology of seizures in prion diseases is focal motor or nonconvulsive status epilepticus.•Electroencephalography may show periodic lateralized and generalized periodic epileptiform discharges.•Antiepileptic treatment is empirical and palliative as there are no randomized trials.•Loss of prion protein function and its abnormal aggregate toxicity contribute to epileptogenesis. Epileptic seizures have been described as one feature of prion diseases, but are an unusual clinical presentation. The aim of this narrative Review was to summarize current knowledge of epileptic seizures in the various forms of prion diseases, from a clinical perspective. Examination of the published literature identified no systematic studies; the evidence base is largely anecdotal, consisting mainly of case studies and small case series. Hence, uncertainty prevails as to seizure frequency, semiology, treatment, and pathogenesis in prion diseases. Seizures probably occur in around 10% of sporadic cases but less frequently in iatrogenic and familial forms, with the possible exception of the E200K mutation. The literature suggests a predominance of focal motor and nonconvulsive status epilepticus. Electroencephalographic accompaniments include periodic lateralized or generalized periodic epileptiform discharges (PLEDs, GPEDs), sometimes predating the more typical periodic sharp wave complexes. There are no convincing accounts of successful antiepileptic drug therapy. The underlying mechanisms of epileptogenesis in prion diseases may include loss of cellular prion protein function (PrPc) and aggregation of abnormally folded prion protein (PrPSc). The need for systematic studies and clinical trials to expand the evidence base surrounding epilepsy and prion diseases is evident.