Synaptic dynamics linked to widespread elevation of h-reflex before peripheral denervation in amyotrophic lateral sclerosis

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Sangari, Sina | Lackmy-Vallée, Alexandra | Preuilh, Arnaud | Peyre, Iseline | Pradat, P.-F. | Marchand-Pauvert, Veronique

Edité par CCSD ; American Physiological Society -

International audience. Changes in Hoffmann reflex (H-reflex) exhibit heterogeneity among patients with amyotrophic lateral sclerosis (ALS), likely due to phenotype diversity. Current knowledge primarily focuses on soleus H-reflex, which may demonstrate an initial increase before subsequent decline throughout the disease course. The main objective was to investigate other muscles, to determine whether H-reflex changes could be associated with patient phenotype (onset site, functional disabilities). Additional experiments were performed to elucidate the neurophysiological mechanisms underlying H-reflex modifications. In age- and sex-matched groups of controls and patients, we compared H-reflex recruitment curves in soleus, quadriceps, and forearm flexors. Additionally, we examined H-reflex and motor evoked potential (MEP) recruitment curves in quadriceps. Last, to assess potential changes in monosynaptic excitatory post-synaptic potentials (EPSPs) of both peripheral and cortical origins, we analyzed peri-stimulus time histograms (PSTH) and peristimulus frequencygrams (PSF) of single motor units, along with H-reflex occurrence after paired pulse stimuli. The ratio between maximal amplitudes of H-reflex and direct motor response increased in all muscles, irrespective of disease onset, and was found positively correlated with exaggerated osteotendinous reflexes and spasticity, but depressed in patients on-riluzole. This finding was accompanied by a reduction in MEP size and no changes in PSTH, PSF, and paired-pulse H-reflex probability. It is speculated that spinal interneurons may compensate for potential depression of monosynaptic EPSPs in ALS. From a clinical perspective, while the added value of H-reflex to osteotendinous reflex evaluation may be limited, it can serve as a valuable quantitative biomarker of pyramidal dysfunction in clinical trials.

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