Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: Insights from H reflex paradigms

Abstract

Introduction/AimsIn amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre‐ and post‐synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS.MethodsWe evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos).ResultsFifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition.DiscussionSpinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.

Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis

“…In accordance with the results obtained in animal models, spinal inhibition is reduced in human patients as the disease progresses. Observations suggested that recurrent inhibition involving Renshaw cells (see above) is decreased in patients showing spinal symptoms (Howells et al, 2020 ; Ozyurt et al, 2020 ; Sangari et al, 2022 ; Castro et al, 2024 ). Interestingly, an increase in recurrent inhibition was observed in the early phase of the disease in one of these studies, supporting the hypothesis of an initial compensatory mechanism preventing MN decline (Sangari et al, 2022 ).…”