Springer Semin Immunopathol (1995) 17:17-28 Springer Seminars in Immunopathology (~) Springer-Verlag 1995 Immunological findings in amyotrophic lateral sclerosis Jack P. Antel, Neff R. Cashman Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada Amyotrophic lateral sclerosis (ALS) remains a syndrome defined by clinical and pathological rather than etiological criteria. The definition includes loss of both upper motor neurons (UMNs), i.e., neurons in motor cortex with secondary degeneration of the corticospinal tracts, and lower motor neurons (LMNs), i.e., neurons in brain stem motor nuclei and anterior horns of the spinal cord. Other neuronal populations such as those of the spinocerebellar tract, dorsal column, and intermediolateral cell column may also be involved in some cases, as assessed by pathological more so than by clinical criteria [95]. The mean duration of survival is 3--4 years with extremes in both directions being encountered. The usual sporadic form of the disease occurs in a male:female ratio of 2-3:1 and has a rather even distribution throughout the world except for several discrete foci in the Western Pacific where incidence rates have been increased up to 1000-fold. In these foci, some of which seem to be disappearing, unique putative neuronotoxic environmental factors are postulated to be involved [58]. The peak incidence rate has usually been regarded as being in the 6th and 7th decade of life, although data from Olmstead County, Minnesota, suggest that incidence rates do not decline after this age [40]. A continued increase in incidence rate would be more consistent with a degenerative disorder than a primary autoimmune or infectious etiology. Progressive motor neuron disease (MND) phenotypes are also well described in which the disease distribution exclusively or predominately involves only the UMNs or only the LMNs. The former is referred to as primary lateral sclerosis; the latter as spinal or bulbar muscular atrophy. The heterogeneity of clinical phenotypes associated with the autosomal dominant form of ALS with point mutations in the superoxide dysmutase (SOD) gene indicates that a common etiology can account for multiple MND clinical presentations [65]. The association of sporadic MND cases, particu- Correspondence to: J.P. Antel