Descending Brainstem Systems Contribute to Ankle Clonus in Humans with Spinal Cord Injury

Abstract

Ankle clonus is a sustained, involuntary, rhythmic muscle contraction frequently observed in humans with spinal cord injury (SCI). Although its pathophysiology remains incompletely understood, converging evidence suggests a role for brainstem systems in its generation. Following SCI, brainstem neuromodulatory inputs partially compensate for the loss of descending motor pathways by regulating motoneuron excitability during involuntary contractions, suggesting their involvement in the generation of clonus. To test this hypothesis, motoneuron excitability in response to Ia synaptic input was quantified using the soleus H-reflex and maximal motor response (H/M ratio). Brainstem involvement was assessed using the long-latency component of the cutaneous reflex (LLR), which is influenced by monoaminergic pathways, and the StartReact response, in which reductions in reaction time to a loud acoustic stimulus are thought to reflect descending drive from the reticular formation, measured in the tibialis anterior and soleus muscles. We studied males and females with chronic SCI, both with and without ankle clonus, using standardized clinical tests across two days. Participants with clonus showed elevated H/M ratios, indicating increased motoneuron excitability, whereas those without clonus exhibited lower values than controls. Additionally, individuals with clonus exhibited longer LLR duration and greater LLR magnitude in both muscles, along with shorter reaction times to startle stimuli, consistent with enhanced monoaminergic and reticulospinal contributions. Notably, LLR duration was positively correlated with both StartReact response and H/M ratio. Together, these findings suggest a potential contribution of descending brainstem systems to the maintenance of clonus after chronic SCI. Significance Statement Ankle clonus is a repetitive, involuntary muscle contraction often seen after spinal cord injury (SCI). Its cause is not fully understood, but brainstem pathways may contribute by increasing the excitability of spinal motoneurons. In this study, we measured reflex responses in leg muscles and reactions to sensory and startling stimuli in people with chronic SCI, with and without clonus. Individuals with clonus showed stronger and longer reflex responses and faster reactions to startling sounds. These findings suggest that brainstem pathways involved in movement control may help maintain ankle clonus after SCI.