Fatal insomnia: The elusive prion disease

Abstract

A previously well 54-year-old woman presented with a short history of diplopia, cognitive decline, hallucinations and hypersomnolence. The patient had progressive deterioration in short-term memory, ocular convergence spasm, tremor, myoclonus, gait apraxia, central fever, dream enactment and seizures. Results of investigations were normal including MRI brain, electroencephalogram, cerebrospinal fluid (CSF, including CSF prion protein markers) and brain biopsy. The patient died from pneumonia and pulmonary embolus. Brain postmortem analysis revealed neuropathological changes in keeping with Fatal familial insomnia (FFI); the diagnosis was confirmed on genetic testing. FFI is caused by an autosomal dominant and highly penetrant pathogenic Prion Protein gene PRNP. Although usually familial, fatal insomnia (FI) also occurs in a rare sporadic form. FI is a rare human prion disease with prominent sleep disturbance, autonomic, motor, cognitive and behavioural involvement. Patient management is with best supportive care and early suspected diagnosis allows for timely palliation.