The site of disease onset in ALS remains enigmatic, and resolution of this quandary could shed light of ALS pathogenesis and may be of therapeutic significance. Previous studies suggested a contiguous spread of disease, implying a role for local (spinal) factors in ALS pathogenesis. In contrast, Sekiguchi and colleagues report non-contiguous spread, a well observed finding in ALS.<\/p>\n
While the mechanisms underlying such disease propagation remain uncertain, its plausible to argue that corticomotoneuronal (CM) hyperexcitability could contribute to such a disease pattern of spread. For example, the C8\/T1 innervated muscles receive the highest density of CM innervation and would be expected to be affected first.<\/p>\n
Subsequently, if CM neurons innervating the L5 motor neurons were to become hyperexcitable then potentially the muscles innervation by L5 myotomes would be affected and so on. This “river of cortical hyperexcitability<\/em><\/strong>” hypothesis may explain the rapid spread of ALS in a non-contigous fashion. It needs to be proved, but sure would explain a lot!!!<\/p>\n","protected":false},"excerpt":{"rendered":" The site of disease onset in ALS remains enigmatic, and resolution of this quandary could shed light of ALS pathogenesis and may be of therapeutic significance. Previous studies suggested a contiguous spread of disease, implying a role for local (spinal) factors in ALS pathogenesis. In contrast, Sekiguchi and colleagues report non-contiguous spread, a well observed […]<\/p>\n