Sporadic Creutzfeldt–Jakob Disease (sCJD) is a rare, rapidly progressive, and fatal prion disorder, with limited epidemiological data from India due to diagnostic constraints and under-recognition. We report a cluster of five probable sCJD cases presenting within a short period of two months to a tertiary-care hospital in Eastern India, highlighting important clinical, radiological, and diagnostic considerations. All patients, aged 49–75 years, presented with rapidly progressive cognitive decline accompanied by neuropsychiatric disturbances, myoclonus, rigidity, and cerebellar or extrapyramidal features. Comprehensive evaluation excluded infectious, metabolic, autoimmune, and paraneoplastic etiologies. MRI brain consistently demonstrated characteristic diffusion-weighted cortical ribboning and basal ganglia involvement in patients who underwent imaging. FDG-PET, performed in select cases, showed widespread cortical hypometabolism with relative subcortical hypermetabolism, providing complementary diagnostic value in distinguishing sCJD from autoimmune encephalitis. EEG revealed global cerebral dysfunction, with periodic sharp wave complexes observed in one patient. Notably, cerebrospinal fluid analysis showed 14-3-3 protein positivity in all five patients, with testing performed at a national reference center (NIMHANS). Despite empirical immunotherapy in selected cases, clinical deterioration was relentless, and all patients experienced a fatal course consistent with prion disease.

This series underscores the diagnostic challenges in differentiating sCJD from treatable mimics, particularly autoimmune and paraneoplastic encephalitides. The unusual temporal clustering raises the possibility of under-recognition in the region and highlights the need for strengthened clinical vigilance, improved access to advanced diagnostics such as RT-QuIC, and the establishment of a structured national prion surveillance system in India.

TBA