Abstract
ObjectivesHypoxia, or abnormally low blood‐oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored.MethodsWe analyzed high‐resolution T1‐weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic‐clonic seizures (GTCS) recorded during long‐term video‐electroencephalography (VEEG), recruited from two sites (n = 22), together with data from age‐ and sex‐matched healthy controls (n = 43). Subjects were sub‐divided into those with mild/moderate (GTCS‐hypox‐mild/moderate, n = 12) and severe (GTCS‐hypox‐severe, n = 10) hypoxia, measured by peripheral oxygen saturation (SpO2) during VEEG. Whole‐brain voxel‐based morphometry (VBM) and regional volumetry were used to assess group comparisons and correlations between brain structural measurements as well as the duration and extent of hypoxia during GTCS.ResultsMorphometric and volumetric alterations appeared in association with peri‐GTCS hypoxia, including volume loss in the periaqueductal gray (PAG), thalamus, hypothalamus, vermis, cerebellum, parabrachial pons, and medulla. Thalamic and PAG volume was significantly reduced in GTCS patients with severe hypoxia compared with GTCS patients with mild/moderate hypoxia. Brainstem volume loss appeared in both hypoxia groups, although it was more extensive in those with severe hypoxia. Significant negative partial correlations emerged between thalamic and hippocampal volume and extent of hypoxia, whereas vermis and accumbens volumes declined with increasing hypoxia duration.SignificanceBrain structural alterations in patients with GTCS are related to the extent of hypoxia in brain sites that serve vital functions. Although the changes are associative only, they provide evidence of injury to regulatory brain sites related to respiratory manifestations of seizures.
Highlights
Patients with epilepsy who succumb to sudden expected death in epilepsy (SUDEP), and those who are at elevated risk, show extensive regional brain structural changes, especially in gray matter areas responsible for autonomic, respiratory, and sensory regulation.[1,2]
We found here that hypothalamic gray matter (GM) is reduced in generalized tonic-clonic seizures (GTCS) with hypoxia, an outcome not reported previously in those at risk for SUDEP
The extent of hypoxia during seizures in GTCS patients is related to the magnitude of brain morphological and volumetric alterations in sites that serve oxygen sensing or integration, breathing regulation, and cardiovascular recovery
Summary
Patients with epilepsy who succumb to sudden expected death in epilepsy (SUDEP), and those who are at elevated risk, show extensive regional brain structural changes, especially in gray matter areas responsible for autonomic, respiratory, and sensory regulation.[1,2] The processes inducing these alterations, as well as the temporal course of injury and precise relationships with SUDEP, remain poorly understood. Prospective imaging studies investigating links between SUDEP risk factors observed in epilepsy monitoring units (such as physiologic, autonomic, and respiratory alterations) and brain structural changes are lacking. Demonstration of such links may shed light on mechanisms underlying the fatal scenario, reveal markers for early detection of SUDEP risk, and guide the tailoring of appropriate interventions to prevent catastrophic events. The processes include hyperexcitation accompanying neural activation during ictal processes, starving neurons if excitation is maintained without
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