Corticomotoneuronal integrity and adaptation in spinal muscular atrophy.

OBJECTIVE To gain further insight into disease pathophysiologic process and potential adaptations through investigating whether cortical dysfunction or plasticity is a feature of spinal muscle atrophy (SMA). DESIGN Prospective, double-center study. SETTING Outpatient clinics and research institute. PARTICIPANTS Clinical assessments, combined with threshold-tracking transcranial magnetic stimulation techniques, were completed in 11 genetically characterized patients with SMA. MAIN OUTCOME MEASURES Clinical, functional, and neurophysiologic variables were compared between the 11 patients with SMA types 2 and 3, 24 healthy control participants, and 81 patients with amyotrophic lateral sclerosis (ALS) serving as disease controls. RESULTS Maximal motor-evoked potential amplitude as a percentage of the compound muscle action potential was significantly increased in patients with SMA compared with the healthy controls but was similar to that in ALS (SMA, mean [SE], 39.7% [4.0%]; ALS, 38.8% [2.8%]; controls, 20.3% [2.5%]; F = 10.1; P < .001). In contrast, short-interval intracortical inhibition (SMA, 14.4% [1.6%]; ALS, 4.3% [1.8%]; controls, 17.0% [2.3%]; F = 11.4; P < .001) and cortical silent-period duration (SMA, 204.4 [9.8] milliseconds; ALS, 182.7 [5.2] milliseconds; controls, 208.8 [3.7] milliseconds; F = 4.8; P = .01), similar between SMA patients and healthy controls, were significantly larger when compared with the findings in ALS. Of relevance, peripheral disease burden as measured by the compound muscle action potential amplitude (SMA, 6.3 [0.8] mV; ALS, 5.9 [0.4] mV; controls, 11.8 [0.5] mV; F = 35.5; P < .001) and Neurophysiological Index (SMA, 0.7 [0.2]; ALS, 0.7 [0.1]; controls, 3.1 [0.2]; F = 108.2; P < .001), were significantly reduced in both SMA and ALS patients when compared with healthy controls. CONCLUSIONS Taken together, findings from the present study suggest that despite spinal motoneuron degeneration there remains preservation of corticomotoneuronal function in SMA. The greater corticomotoneuronal projections to surviving spinal motoneurons likely represent an adaptive response to spinal motoneuron degeneration in SMA.