Case Report: Extremely Early Detection of Preclinical Magnetic Resonance Imaging Abnormality in Creutzfeldt-Jakob Disease With the V180I Mutation.

Ryuichi Koizumi,Katsuo Kimura,Atsushi Mugita,Fumiaki Tanaka,Hitaru Kishida,Naohisa Ueda

doi:10.3389/fneur.2021.751750

Ryuichi Koizumi, Katsuo Kimura + Show 4 more

Open Access

https://doi.org/10.3389/fneur.2021.751750

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Abstract

The diagnosis of presymptomatic Creutzfeldt–Jakob disease (CJD) is challenging. The levels of total tau protein, 14-3-3 protein, and protease-resistant isoform of prion protein (PrPres) in the cerebrospinal fluid; periodic sharp wave complexes on electroencephalography; and diffusion-weighted imaging (DWI) of brain magnetic resonance imaging (MRI) have all been used to diagnose symptomatic CJD, but none of these markers have been established in the diagnosis of presymptomatic CJD. Here, we report a case of genetic CJD with the V180I mutation in which a small punctate cortical hyperintensity was detected on DWI 6 months before symptom onset and 9 months before diagnosis. Presymptomatic CJD is currently impossible to diagnose because of the lack of established early diagnostic markers. However, since MRI is increasingly used in daily clinical practice, the chance detection of such DWI abnormalities would have important implications in terms of providing a clue to examine a highly specific early diagnostic marker to be developed in the future for CJD. This will allow presymptomatic intervention by disease-modifying therapy in the near future.

Highlights

Creutzfeldt–Jakob disease (CJD) is a transmissible spongiform encephalopathy caused by the spread of pathological protease-resistant isoform of prion protein (PrPres) in the central nervous system
Diagnostic markers for CJD have been well-established and include total tau (t-tau) protein, 14-3-3 protein, and PrPres detected by real-time quaking-induced conversion (RT-QuIC) in the cerebrospinal fluid (CSF) as well as periodic sharp wave complexes (PSWCs) on electroencephalography (EEG) and cortical and/or basal ganglia hyperintensity on diffusion-weighted imaging (DWI) of brain magnetic resonance imaging (MRI) [1]
High signal abnormalities on DWI in the cortical regions and/or in the striatum are of significant diagnostic value for CJD

Summary

INTRODUCTION

Creutzfeldt–Jakob disease (CJD) is a transmissible spongiform encephalopathy caused by the spread of pathological protease-resistant isoform of prion protein (PrPres) in the central nervous system. It is clinically characterized by rapidly progressing behavioral changes; psychiatric symptoms; dementia; myoclonus; cerebellar, pyramidal, and extrapyramidal signs; and visual disturbances and is invariably fatal [1]. No abnormalities were detected on MRI performed due to a slight headache 5 years prior (Figure 1A), DWI demonstrated very small hyperintensity in the right parietal cortex (Figure 1B, arrow). Two months later, she developed a mild action tremor in her extremities, which gradually deteriorated.

DISCUSSION

Findings

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