Nocturnal Hypoxia in ALS Is Related to Cognitive Dysfunction and Can Occur as Clusters of Desaturations

Abstract

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.MethodTwenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night) and their clinical characteristics and cognitive function were compared.ResultsCompared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40%) had poor memory retention (p = 0.039) and retrieval efficiency (p = 0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group.ConclusionsThese results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation–reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.

Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia‐response and RNA processing functions

“…Mutant SOD1 mice which experienced chronic intermittent hypoxia showed reduced performance on the rotarod, reduced ability in the wire hanging test, poorer spatial memory as assessed by the Y-maze, and a greater loss of motor neurones, compared to the SOD1 G93A mice under normoxia conditions [81]. This correlates with data recorded from ALS patients, which compared nocturnal hypoxia with cognitive dysfunction [82]. The results demonstrated that patients who experience nocturnal hypoxia (as defined as the average O2 saturation being <95% for more than 10% of the sleep time) showed a significant decrease in their memory retention and retrieval efficiency abilities.…”

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“…The pyramidal cells of Sommer's sector in the hippocampus and of layers 3 and 5 in the neocortex, and the Purkinje cells in the cerebellum are cell populations in the adult central nervous system particularly vulnerable to hypoxic injury . Park et al identified a significant correlation of the duration of nocturnal hypoxia with impaired memory retention and retrieval efficiency in ALS patients . These additional cognitive deficits likely further compromise the precious remaining quality of life for patients with ALS.…”

“…37 Park et al identified a significant correlation of the duration of nocturnal hypoxia with impaired memory retention and retrieval efficiency in ALS patients. 38 These additional cognitive deficits likely further compromise the precious remaining quality of life for patients with ALS.…”

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