Sporadic fatal insomnia with clinical, laboratory, and genetic findings

A 75-year-old man presented with a three-year history of progressively worsening insomnia and dementia. His mother and older sister had similar disorders. On initial examination, he was awake, apathetic, and disoriented but had no focal neurological deficits. Electroencephalography showed diffuse background slowing with neither periodic discharge nor sleeping activity. A single-photon emission CT scan showed significantly reduced cerebral perfusion in bilateral thalami, basal ganglia, and limbic cortices. In the late stage of his illness, he developed sphincter dysfunction. Laboratory studies showed increased T-lymphocytes and B-lymphocytes and reduced cortisol level. Cerebrospinal fluid 14-3-3 protein was absent. Genetic evaluations failed to show the aspartate to asparagine point mutation at codon 178 but disclosed an asparagine to serine substitution at codon 171 in one allele and a deletion of 24 base pairs in the other allele in the human prion protein gene. These findings led to a diagnosis of sporadic fatal insomnia, which is a recently described prion disease.