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

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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 (StO2) 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 StO2, neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of StO2 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, StO2 values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and StO2. 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

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