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.

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.

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” hypothesis may explain the rapid spread of ALS in a non-contigous fashion. It needs to be proved, but sure would explain a lot!!!