Impairment of sensory-motor integration at spinal level in amyotrophic lateral sclerosis

Objective: Subclinical sensory defect can be detected early in ALS. Its impact on spinal excitability was assessed by testing the effects produced by intrinsic hand muscle afferents in triceps brachii motoneurons of patients with distal motor weakness. Methods: TMS was applied over the motor cortex to produce MEP in contralateral triceps during tonic contraction. The intensity varied to compare the full MEP recruitment curve in ALS patients and controls. Then, median and ulnar nerve stimulations at wrist level were combined to TMS to compare the resulting changes in MEP size in both groups. Results: MEP recruitment curves were similar in both groups but MEP threshold was significantly higher in ALS. At sub-threshold intensity for MEP, TMS depressed more EMG activity in ALS than in controls. Nerve stimuli increased MEP size in both groups with similar temporal characteristics but the level of facilitation was stronger in ALS. Conclusion: Cortical hypo-excitability in ALS was accompanied with stronger intra-cortical inhibition in triceps area. While the corticospinal and peripheral inputs were likely depressed, spinal motoneuron response to combined inputs was particularly enhanced in ALS. Significance: Spinal network properties likely compensate for depression of afferent inputs leading to motoneuron hyper-excitability, which may contribute to excito-toxicity.