The motor cortex and amyotrophic lateral sclerosis

On theoretical grounds, abnormalities of the motor cortex in patients with amyotrophic lateral sclerosis (ALS) could lead to anterograde ("dying-forwa rd") transneuronal degeneration of the anterior horn cells as suggested by Charcot. Conversely, retrograde ("dying-back") degeneration of the corticos pinal tracts could affect the motor cortex. Evidence derived from clinical, neuropathological, static, and functional imaging, and physiological studi es, favors the occurrence of anterograde degeneration. It is hypothesized t hat transneuronal degeneration in ALS is an active excitotoxic process in w hich live but dysfunctional corticomotoneurons, originating in the primary motor cortex, drive the anterior horn cell into metabolic deficit. When thi s is marked, it will result in more rapid and widespread loss of lower moto r neurons, In contrast, slow loss of corticomotoneurons, as occurs in prima ry lateral sclerosis (PLS), precludes excitotoxic drive and is incompatible with anterograde degeneration. Preservation of slow-conducting non-M1 dire ct pathways in PLS is not associated with excitotoxicity, and anterior horn cells survive for long periods of time. (C) 2001 John Wiley & Sons, Inc.