High resting level and weak response of baroreflex-governed sympathetic outflow in amyotrophic lateral sclerosis

Both altered sympathetic function and insulin resistance have been observed in amyotrophic lateral sclerosis (ALS). Insulin is a sympathetic stimulator. We recorded muscle sympathetic nerve activity (MSNA) by microneurography in 9 patients with ALS and 9 healthy controls during rest. We also initiated a number of sympathoexcitatory maneuvers, including intake of 100 g of glucose. Patients showed reduced glucose tolerance and a higher heart rate and higher level of MSNA at rest than controls (61.0 ± 15.2 vs. 41.2 ± 5.8 bursts/min, P = 0.006); baroreflex inhibitory influence was present. In contrast, MSNA in ALS patients responded more weakly to maneuvers. This inverse relationship is interpreted as a "ceiling effect," as ALS patients use nearly maximal MSNA capacity already at rest and do not have sympathetic failure. The increased level of MSNA may be a primary feature of ALS, but insulin stimulation may also contribute. Our findings are assessed in relation to previous, sometimes seemingly contradictory observations.