Epilepsia partialis continua as the presenting manifestation of Creutzfeldt–Jakob disease: A video‐polygraphic clinical vignette

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Epilepsia partialis continua (EPC) is an exceptionally rare presenting feature of Creutzfeldt–Jakob disease (CJD).1 We describe a 48-year-old man with familial CJD (fCJD) who presented with EPC as the initial manifestation. Video-polygraphic recordings demonstrated a temporal correlation between lateralized periodic discharges (LPDs) and the patient's left upper limb jerks, confirming their cortical origin. To our knowledge, this represents the first video-polygraphically documented case of EPC in CJD, highlighting the diagnostic value of detailed neurophysiological assessment. Relevant literature is reviewed in Table 1. Definite sCJD Definite sCJD CJD is a fatal neurodegenerative disorder caused by accumulation of misfolded prion proteins in the central nervous system.2 It primarily affects individuals aged 55–75 years, with an annual incidence of 1–2 cases per million worldwide. CJD occurs in sporadic, genetic (familial) or acquired forms; fCJD accounts for ≈10%–15% and is mostly associated with the E200K PRNP mutation.2 Clinically, CJD is characterized by rapidly progressive dementia, myoclonus, cerebellar ataxia, visual disturbances and pyramidal or extrapyramidal signs. Epileptic seizures are uncommon and rarely represent the initial manifestation.3 EPC is a rare subtype of focal motor status epilepticus, characterized by repetitive, arrhythmic, stereotyped muscle jerks persisting over long periods.4 Its occurrence as the initial manifestation of CJD is exceedingly rare, with only seven cases reported.1, 5-10 Our previously healthy patient presented with involuntary movements of the left upper limb and progressive gait unsteadiness over 2 weeks. His father had died from E200K-related fCJD. Neurological examination showed mild gait ataxia and shock-like involuntary movements of the left upper limb. Neuropsychological evaluation disclosed preserved cognitive functions (MMSE: 26). Blood tests and cerebrospinal fluid analysis were unremarkable. Brain MRI revealed restricted diffusion with corresponding T2/FLAIR hyperintensity involving the right caudate nucleus, anterior lentiform nucleus, cingulate gyrus, insula, and less prominently the right frontal, parietal, and temporal cortices (Figure S1). Video-polygraphy (EEG, EKG and electromyography of left upper limb and facial muscles) revealed LPDs over the right fronto-central-temporal regions. Each spike was time-locked with short-lasting (<50 msec) myoclonic jerks of the left upper limb (Video 1), consistent with EPC. Treatment with multiple antiseizure medications (clonazepam, levetiracetam, brivaracetam) was ineffective. The patient's condition rapidly deteriorated over few weeks, with cognitive decline, severe ataxia, generalized tonic–clonic seizures, akinetic mutism. At this time, EEG showed generalized periodic discharges (GPDs) occurring at 1–2 s intervals. The patient died 45 days after admission. Genetic testing confirmed the E200K mutation; PRNP codon 129 polymorphism was not assessed. Epileptic seizures occur in ≈15% of CJD patients during the disease course, being the presenting symptoms in only 3% of sCJD.2, 3 EPC is even rarer, with only seven reported patients1, 5-10 and only one genetically confirmed fCJD.10 EPC in a previously healthy subject usually prompts investigation for alternative diagnosis, including stroke, Rasmussen encephalitis, tumor.5 In our patient, the characteristic DWI/FLAIR cortical and basal ganglia involvement, together with the positive family history, strongly supported the fCJD suspicion, subsequently confirmed genetically. No prior study has provided video-polygraphic documentation of EPC in CJD. In our patient, polygraphic recordings showed distal left upper limb EMG discharges lasting <100 ms time-locked to right fronto-central-temporal LPDs, providing clear electrophysiological evidence of EPC.4 LPDs are not specific to CJD, with GPDs representing the most characteristic finding reported in intermediate disease stages in sCJD.3, 11 Nevertheless, LPDs have been documented in early CJD2 and in 3/7 of reported patients with EPC, including one with fCJD.1, 5, 8 LPD lateralization typically mirrors cortical MRI abnormalities, correlates with contralateral focal motor signs and frequently evolves into GPDs with disease progression, as prion aggregates spread from restricted cortical areas to diffuse bilateral cortical regions.3 Patients with EPC associated with CJD appear to have a worse prognosis than those with typical presentations.8 Review of reported cases shows survival after EPC onset ranging from a few weeks to a few months, with a median of approximately 2–3 months,1, 6-10 considerably shorter than the usual 6–12 months in sporadic CJD and 5–9 months in E200K-related fCJD. Our patient's rapid clinical course is fully consistent with these observations, supporting evidence that EPC at disease onset may represent a marker of an especially aggressive phenotype, likely reflecting early cortical involvement. Nevertheless, the more aggressive course may be a consequence of epilepsy itself, including potential adverse effects of anti-seizure medications and an increased risk of sudden unexpected death in epilepsy (SUDEP).8 Additionally, the possible influence of PRNP codon 129 polymorphism on the clinical phenotype should be taken into account.12 In conclusion, EPC may represent an early manifestation of CJD. A high index of suspicion is warranted when EPC occurs in the context of rapidly progressive neurological symptoms. Open access publishing facilitated by Universita degli Studi Magna Graecia di Catanzaro, as part of the Wiley - CRUI-CARE agreement. Work supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). The authors have no competing interests to declare that are relevant to the content of this article. The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1 Data S1 Data S2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Which percentage of patients with sporadic CJD present with epileptic seizures as an early manifestation? In CJD, lateralized periodic discharges are most frequently observed: Which is the prognosis of patients with CJD presenting with Epilepsia Partialis Continua (EPC) at disease onset? Answers may be found in the supporting information.

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