Fatal familial insomnia with abnormal signals on routine MRI: a case report and literature review

BACKGROUND Fatal familial insomnia (FFI) is a rare autosomal dominant disease caused by the PRNP D178N/129 M mutation. Routine brain CT and MRI usually reveal non-specific features. We report a patient with FFI presenting with diffuse abnormal signals on MRI, later confirmed as combined with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CASE PRESENTATION The patient was a 58-year-old female, whose main clinical manifestations were insomnia, movement disorders, autonomic hyperactivity and mental deterioration. The patient also suffered a typical episode of transient global amnesia. MRI indicated a diffuse white matter abnormality and microbleeding on the susceptibility-weighted imaging. On biopsy, the brain tissue sections showed spongiform changes with gliosis, neuronal degeneration, and prion protein deposition in a portion of the neurons. In addition, arteriosclerosis was prominent. Transmission electron microscopy showed osmiophilic particle deposition in the matrix of medial smooth muscle cells. Gene sequencing confirmed a diagnosis of FFI with CADASIL. CONCLUSIONS This case is a compelling example that even with evidence of leukoencephalopathy, prion disease should be an important differential diagnosis of rapidly progressive dementia and related diseases. In cases of genetic diseases with atypical manifestations, the coexistence of two or even more diseases should be considered as a possible explanation.