3rd Edition of Dementia World Conference 2026

Abstract

Background: Genetic Creutzfeldt-Jakob Disease (gCJD) is a fatal neurodegenerative disorder caused by mutations in the prion protein gene (PRNP). It is characterized by rapidly progressive cognitive decline, cerebellar ataxia, and generalized myoclonus. While seizures occur in fewer than 10% of patients during the disease course, onset presenting as Epilepsia Partialis Continua is extraordinarily rare. This atypical presentation in young patients mimicking acute structural, metabolic, infectious, or autoimmune etiologies represents a diagnostic challenge. Case Description: A 43-year-old woman with no family history of neurodegenerative diseases, and no remarkable medical history, except migraine without aura,  attended the neurology department with subacute-onset of unremitting jerking movements of the right upper limb (limb shaking) with no awareness impairment. This clinical picture along with the video-electroencephalography (vEEG) monitoring confirmed the diagnosis of Epilepsia Partialis Continua. The status epilepticus responded to initial therapeutic lines of antiseizure medications —including intravenous clonazepam, levetiracetam, and lacosamide. The vEEG demonstrated initial focal abundant ictal discharges originating from the left fronto-temporal regions that subsequently degenerated into persistent and lateralized sharpy, rhythmic delta activity (LRDA) over the left hemisphere at 2.5 Hz. Brain Magnetic Resonance Imaging (MRI) on diffusion-weighted imaging (DWI) revealed striking cortical ribboning localized to the left fronto-temporal and insular cortices, alongside corresponding restricted diffusion in both the head of caudate and lenticular nucleus. Extensive serum and cerebrospinal fluid (CSF) panels for metabolic, infectious, paraneoplastic, and autoimmune encephalopathies were completely negative. However, advanced CSF biomarker analysis revealed a positive Real-Time Quaking-Induced Conversion (RT-QuIC) assay and elevated 14-3-3 protein. Given her unusually young age, genetic sequencing of the PRNP gene was performed, confirming a heterozygous V210I mutation coupled with a methionine/valine (MV) polymorphism at codon 129. Despite intensive anti-seizure optimization and empirical high-dose steroids and apheresis, the patient slowly deteriorated into akinetic mutism and subsequenlty a minimal conscious state in an 18 month follow-up period. Discussion: The V210I mutation represents the second most common mutation worldwide and the most prevalent cause of gCJD in the south of Italy (Campania region) yet an initial presentation of Epilepsia Partialis Continua is a profound rarity. This case demonstrates that the focal neurodegenerative process of prion accumulation can cause aggressive, localized cortical hyper-excitation that mimics primary structural epilepsy. Prion disease must be included in the differential diagnosis of an unexplained unremitting focal seizures, even in young patients without a known family history of dementia. Early utilization of advanced diagnostic tools like video-EEG, DWI-MRI and CSF RT-QuIC is crucial to avoiding prolonged, futile intervention and to rapidly reaching the diagnosis.