Sporadic Creutzfeldt–Jakob Disease in the young (50 and below): 10-year review of United Kingdom surveillance

INTRODUCTION: Sporadic Creutzfeldt–Jakob Disease (sCJD) is the commonest human prion disease, with a median age of onset of 68 years. We characterise the clinical, investigation, and neuropathological features in young individuals with sCJD using data from UK national CJD surveillance. METHODS: Referrals between 2011 and 2021 were examined, with definite (post-mortem confirmed) or probable sCJD cases included. Clinical features, MRI, EEG, CSF RT-QuIC, 14-3-3, PRNP sequencing and neuropathological findings were examined. We compared younger (≤ 50 years age of onset) with older individuals. Records of Non-sCJD referrals were also reviewed. RESULTS: 46 (4%) young individuals were identified (age at onset 25–50) from 1178 cases. 15 (33%) were autopsy confirmed. Psychiatric disturbance (37% vs 22%, p = 0.02) and headache (11% vs 3%, p = 0.01) at presentation, and longer disease duration (by 1.45 months, 95% CI 0.43–2.79, logrank p = 0.007) were commoner. CSF RT-QuIC showed lower sensitivity (82% vs 93%, p = 0.02). There was no difference in sensitivity of MR brain or CSF 14-3-3. There were no significant co-pathologies in autopsy-confirmed cases. For non-sCJD referrals, 41 cases were of other CJD subtypes, and 7 non-prion diagnoses. CONCLUSIONS: Young-onset sCJD is more likely to present with neuropsychiatric symptoms and headache, longer disease duration, and lower sensitivity of RT-QuIC. These findings may be driven by the underlying molecular subtypes. Our results guide the evaluation of younger individuals presenting with rapidly progressive cognitive, neuropsychiatric, and motor decline, and emphasise the need for additional vigilance for atypical features by clinicians and CJD surveillance programmes worldwide. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11467-3.