Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness and atrophy. A recent study published in Muscle & Nerve sheds light on the role of spinal interneurons in the pathophysiology of ALS, with significant implications for both diagnosis and treatment. This article elaborates on the findings presented in the journal article by Castro, Oliveira Santos, Swash, and de Carvalho (2024).

DOI: 10.1002/mus.28035

Understanding Spinal Interneurons in ALS

Spinal interneurons act as a critical intermediary between motor neurons and sensory input, and their proper functioning is necessary for motor coordination. The new study proposed that in ALS, a form of “interneuronopathy” could be occurring, impairing this essential neural processing and contributing to symptoms like hyperreflexia and muscle rigidity.

The H Reflex as a Diagnostic Tool

The H reflex is an electrical response in a muscle following stimulation of the nerves that supply it, akin to the reflexes tested during a physical examination but measured electrically. By studying the soleus H reflex through various spinal inhibitory mechanisms, researchers can gain insight into the conductivity and integrity of neuronal pathways. Castro and colleagues used these paradigms to assess segmental spinal inhibitory mechanisms in ALS patients and healthy controls.

Highlights of the Study

Fifteen ALS patients with minimal lower motor neuron involvement and ten healthy individuals participated in the research. Three different modulation paradigms were evaluated: homonymous recurrent inhibition (H’ RI Pre), post-activation depression (Pos), and a combination of both (H’ RI Pre Pos). Findings revealed that ALS patients exhibited reduced inhibition in all paradigms when compared to the control group, suggesting an impairment in spinal inhibitory mechanisms.

The Implications for ALS Patients

The discovery that ALS patients show reduced spinal inhibitory responses points to the potential for these mechanisms to be used in the diagnosis and monitoring of the disease. This reduction in spinal inhibition may underlie the hyperreflexia commonly observed in ALS and suggests that altered interneuron function is a central feature of the disease. The data underscore the concept of interneuronopathy in ALS, which could lead to new avenues of treatment focused on preserving or restoring interneuron functionality.

Future Research Directions

In light of these insights, further research could identify specific interneuronal subtypes involved in ALS and evaluate potential neuroprotective strategies. There’s also a clear necessity for longitudinal studies to determine whether these inhibitory patterns can predict disease progression.


This study highlights the importance of spinal interneurons in the pathology of ALS and provides a new perspective on the mechanisms of motor neuron dysfunction. With its focus on the sometimes underrecognized aspect of interneuron involvement, this research moves the scientific community a step closer to unraveling the complexities of ALS.


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