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Published on: April 4, 2018
Reduced cerebral blood flow in genetic prion disease with PRNP D178N-129M mutation: an arterial spin labeling MRI
Shuai Chen1, Min Guan2, Jun-Kui Shang1
1Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
Abstract:
The D178N mutation in the PRNP gene is associated with fatal familial insomnia and Creutzfeldt-Jakob disease (CJD). Typically, the D178N mutation associated with the 129M genotype is related to fatal familial insomnia while the same mutation associated with the 129V genotype is linked to familial CJD. We describe a D178N-129M haplotype in a patient with early, severe dementia and late-onset minor insomnia, mainly presenting as the CJD phenotype. Cerebrospinal fluid 14-3-3 protein was positive. Diffusion weighted imaging demonstrated widespread cortical ribbon-like high signal intensity, which was also seen in the basal ganglia bilaterally. Arterial spin labeling (ASL) MRI showed severe hypoperfusion in the cerebral cortex, basal ganglia and thalami but this was least marked in the thalami. Neuroimaging abnormalities were more prominent in the cerebral cortex than the thalamus, which was in line with the clinical picture of severe dementia rather than insomnia. ASL-MRI seems to be a useful tool for the detection and follow-up of perfusion changes in patients and asymptomatic carriers harboring the PRNP mutation.
Insights
The D178N-129M PRNP mutation typically causes fatal familial insomnia, but can present as Creutzfeldt-Jakob disease (CJD) with severe dementia. Arterial spin labeling MRI effectively detects perfusion changes in PRNP mutation carriers.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- The PRNP gene's D178N mutation is linked to prion diseases, typically Fatal Familial Insomnia (FFI) with the 129M genotype and Creutzfeldt-Jakob Disease (CJD) with the 129V genotype.
- Understanding genotype-phenotype correlations is crucial for diagnosing and managing these rare neurodegenerative disorders.
Observation:
- A patient presented with early-onset severe dementia and late-onset mild insomnia, exhibiting the CJD phenotype despite carrying the D178N-129M haplotype usually associated with FFI.
- Cerebrospinal fluid 14-3-3 protein was positive, and diffusion-weighted imaging revealed widespread cortical and basal ganglia abnormalities.
- Arterial spin labeling (ASL) MRI demonstrated significant hypoperfusion in the cerebral cortex and basal ganglia, with less pronounced changes in the thalami.
Findings:
- Neuroimaging findings, particularly the prominent cortical hypoperfusion on ASL-MRI, correlated with the patient's severe dementia, diverging from the typical insomnia-predominant FFI phenotype.
- This case highlights a phenotypic variability within the D178N-129M PRNP mutation.
Implications:
- ASL-MRI is a valuable tool for detecting and monitoring perfusion deficits in individuals with PRNP mutations, including asymptomatic carriers.
- This study expands the known phenotypic spectrum of the D178N-129M mutation, emphasizing the importance of integrating genetic, clinical, and advanced neuroimaging data for accurate diagnosis.
