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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Lancet Neurol. 2021 Mar;20(3):235–246. doi: 10.1016/S1474-4422(20)30477-4

Panel 1.

Historical case studies from the German CJD surveillance center

Case A (typical CJD)
A 63-year-old woman complained about language disturbance (mild amnestic aphasia) that had started two weeks before hospital admission.
Neurological and neuropsychiatric examination showed cognitive deficits and ataxia. The EEG showed continuous focal epileptiform patterns but enforced antiepileptic medication showed no clinical benefit. In the CSF, 14-3-3 proteins (64455 AU/mL, cut-off > 20000 AU/mL) and t-Tau (12460 pg/mL, cut-off >1300 pg/mL) were both highly increased and RT-QuIC was positive. No signs of CNS inflammation were present. MRI showed restricted diffusion in frontal, temporal, and parietal regions, as well as in caudate nucleus and left putamen. The clinical condition of the patient worsened within one week. Clinical examination showed severe dementia, pyramidal and extrapyramidal signs, as well as myoclonus. Follow-up EEGs showed CJD-typical PSWCs. PRNP sequencing revealed no pathogenic mutation and homozygosity for Methionine at Codon 129. The patient was diagnosed with probable sCJD according to common criteria,4 supported by positivity of CSF RT-QuIC.
The patient passed after 2 months of disease duration. Brain autopsy revealed PrPSc depositions with neuropathological characteristics of the most frequent MM/MV1 sCJD subtype.
Case B (atypical sCJD)
Family members recognized personality changes and mild cognitive deficits in a 54-year-old woman, and suspected an affective disorder.
After 5 months of symptom duration, a neurology specialist observed rapidly progressive dementia with apraxia. MRI showed restricted diffusion in parietal, occipital, and temporal regions with very subtle involvement of caudate nucleus (no other pathological findings); EEG showed sporadic triphasic complexes but no PSWCs. The CJD surveillance center was consulted and recommended further clinical investigations including CSF analyses. The CSF showed no evidence for inflammatory CNS diseases, positive 14-3-3 proteins at a rather low level (21527 AU/mL, cut-off >20000 AU/mL), and positive RT-QuIC. PRNP sequencing revealed no pathogenic mutation and homozygosity for Methionine at Codon 129. Although clinical diagnostic criteria4 for sCJD were not fulfilled at that time (the patient showed only rapidly progressive dementia), the biomarker signature was highly suggestive and no alternative diagnoses were revealed.
The case was classified as probable sCJD according to amended surveillance center criteria12 based on RT-QuIC positivity. Disease course (rather slow progression), MRI results (predominant cortical involvement), and Codon 129 were suggestive for the rare MM2C (“cortical”) sCJD subtype. The patient passed after 11 months of disease duration. Brain autopsy revealed PrPSc depositions with neuropathological characteristics of the MM/MV2C sCJD subtype.