A clinical and pathological study of motor neurone disease on Guam

Despite over 40 years of intensive study, the cause of the high incidence o f motor neurone disease (MND) on Guam, and the relationship between this di sease and MND seen in the rest of the world are still uncertain. We present a series of 45 cases of Guamanian MND, which reaffirm the clinical similar ity between this disease and MND seen in other countries. However, the occu rrence of MND among the indigenous Chamorros of Guam is distinguished by fo ur factors: (i) high prevalence; (ii) frequent familial occurrence; (iii) c o-occurrence with the parkinsonism-dementia complex (PDC); and (iv) associa tion with an unusual and distinctive linear retinopathy termed Guam retinal pigment epitheliopathy (GRPE). These distinguishing factors were not prese nt in four non-Chamorros who resided on Guam when their MND symptoms occurr ed. Pathologically, the classical features of MND were seen in Guamanian Ch amorro cases including ubiquitin inclusions. Neurofibrillary tangles were f requently seen. The neurofibrillary tangles appeared in the same distributi on as described in the PDC but, unlike classical PDC, they were not usually associated with cell loss and occurred less frequently. While neurofibrill ary tangle formation and the clinicopathological syndrome of MND may occur in parallel, observations from this series suggest that pathologically clas sical MND on Guam may occur independently of neurofibrillary degeneration a nd the clinical features of PDC.