Multifocal hits for propagation of prion protein in sporadic Creutzfeldt-Jakob disease

Abstract

A 60-year-old woman presented with discomfort during respiration and anxiety. One month later, she developed dysarthria and unsteadiness of gait that gradually progressed over 3 months. She was referred to our affiliated hospital. A neurologist noted muscle rigidity, parkinsonian gait, and bradyphrenia, but her general cognitive function was preserved, with a Mini-Mental State Examination (MMSE) score of 29/30. At this time, diffusion-weighted imaging (DWI) demonstrated multifocal spotty hyperintense signals in the cerebral cortex (figure, A). Six months later, she became unable to stand or walk because of limb and truncal ataxia, and she was admitted to our hospital. On admission, she showed marked cognitive decline (MMSE score of 14/30) and apathy. Neurologic examination revealed cerebellar ataxia and parkinsonism such as rigidity and akinesia, but myoclonus was not present. Laboratory findings were all normal except for those of the serologic tests for syphilis (STS) and the Treponema pallidum latex agglutination (TPLA) test. Both the STS and the TPLA test showed positivity for syphilis with a low titer, whereas the TPLA test of CSF showed negative results, indicating self-limited syphilis. DWI findings were not significantly different from those 5 months ago (figure, B). EEG showed 5-Hz slow waves but not periodic sharp wave complexes. Two months after admission, she developed urinary tract infection and subsequently severe inspiratory stridor with a high-pitched sound. Laryngeal fiberscope showed that the bilateral vocal cords were fixed in the midline position. After tracheostomy, her stridor disappeared. However, her condition deteriorated rapidly. She became mute and subsequently developed myoclonus. At this time, CSF analysis revealed a total tau protein level of 246 pg/mL (cutoff for the diagnosis of sporadic Creutzfeldt-Jakob disease [CJD] >1,300). The 14-3-3 protein was not detected in the CSF. However, RT-QUIC (real-time quaking-induced conversion) assay, which has a sensitivity of 83.3% for CJD,1 showed positivity for CJD. EEG showed 1-Hz periodic sharp wave complexes. DWI revealed hyperintense signals slightly spread (figure, C) and extended throughout the cerebral cortex and basal ganglia 4 months later (figure, D). The diagnosis of sporadic CJD was made on the basis of progressive dementia and myoclonus, EEG findings, and hyperintense lesions detected by DWI. Analysis of the prion protein gene PRNP showed no mutations. The polymorphic codon 129 was homozygous for methionine and codon 219 was homozygous for glutamate. Acknowledgment: The authors thank Dr. Kitamoto for genotyping and Dr. Satoh for analyses of CSF biomarkers.