Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability

Abstract

Objective: Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (S_t O₂ ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood.

Methods: We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between S_t O₂ , neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of S_t O₂ measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year.

Results: We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (p > 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, S_t O₂ values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and S_t O₂ . This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired.

Interpretation: The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067-1079.