Fatal familial insomnia (FFI) is a unique hereditary prion disease with 
characteristic disturbances of sleep. We studied the serotonergic system in 8 
FFI-affected subjects by immunohistochemistry for the serotonin-synthesizing 
enzyme, tryptophan hydroxylase (TH). Quantification of neurons in median raphe 
nuclei showed no total neuronal loss in FFI but a substantial increase of TH+ 
neurons (approximately 62%) in FFI subjects compared with controls. Our data 
indicate an alteration of the serotonergic system that might represent the 
functional substrate of some typical symptoms of FFI.