Widespread expression of alpha-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course

Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive disorder cl inically characterized by extrapyramidal signs and progressive dementia. In a typical case, the clinical symptoms become apparent during late childhoo d, and usually the course is protracted over a decade or more. We recently had an opportunity to study the brains of two cases of HSS with a clinical course of over 30 years. Case 1 was a 44-year-old female and case 2 was a 3 7-year-old male. Grossly, the brains showed severe fronto-temporal lobar at rophy with abundant spheroids and mild iron deposits in the globus pallidus , associated with features of motor neuron disease. In addition, there was diffuse sponginess in the atrophic cortex as well as widespread Alzheimer's neurofibrillary tangles (NFTs) and Lewy bodies (LBs) in the cortical and s ubcortical regions, including the spinal cord. Ultrastructurally, NFTs were composed of paired helical filaments, and LBs of central dense cores with radiating fibrils. Discrete immunostaining was demonstrated in NFTs and neu ropil threads with various antibodies against phosphorylated tau, and in LB s with antibody against alpha-synuclein. In addition, diffuse, overlapping immunoreactivity of alpha-synuclein and phosphorylated tau was seen within thr cytoplasm of many neurons. However, when LBs and NFTs coexisted within the same neurons, they were clearly segregated. The findings of our present cases as well as those reported in the literature may indicate that simult aneous and extensive occurrence of abnormal phosphorylation of tau and accu mulation of alpha-synuclein may constitute cardinal pathological features o f HSS with protracted clinical course. (C) 2000 Elsevier Science B.V. All r ights reserved.