We describe, in Ethiopia, a third successful pattern of human adaptation to high-altitude hypoxia that contrasts with both the Andean “classic” (erythrocytosis with arterial hypoxemia) and the more recently identified Tibetan (normal venous hemoglobin concentration with arterial hypoxemia) patterns. A field survey of 236 Ethiopian native residents at 3,530 m (11,650 feet), 14–86 years of age, without evidence of iron deficiency, hemoglobinopathy, or chronic inflammation, found an average hemoglobin concentration of 15.9 and 15.0 g/dl for males and females, respectively, and an average oxygen saturation of hemoglobin of 95.3%. Thus, Ethiopian highlanders maintain venous hemoglobin concentrations and arterial oxygen saturation within the ranges of sea level populations, despite the unavoidable, universal decrease in the ambient oxygen tension at high altitude.

Summary: Purpose: Mutations in the voltage‐gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition to seizures, patients with SCN1A mutations often experience sleep abnormalities, suggesting that SCN1A may also play a role in the neuronal pathways involved in the regulation of sleep. However, to date, a role for SCN1A in the regulation of sleep architecture has not been directly examined. To fill this gap, we tested the hypothesis that SCN1A contributes to the regulation of sleep architecture, and by extension, that SCN1A dysfunction contributes to the sleep abnormalities observed in patients with SCN1A mutations.Methods: Using immunohistochemistry we first examined the expression of mouse Scn1a in regions of the mouse brain that are known to be involved in seizure generation and sleep regulation. Next, we performed detailed analysis of sleep and wake electroencephalography (EEG) patterns during 48 continuous hours of baseline recordings in a knock‐in mouse line that expresses the human SCN1A GEFS+ mutation R1648H (RH mutants). We also characterized the sleep–wake pattern following 6 h of sleep deprivation.Key Findings: Immunohistochemistry revealed broad expression of Scn1a in the neocortex, hippocampus, hypothalamus, thalamic reticular nuclei, dorsal raphe nuclei, pedunculopontine, and laterodorsal tegmental nuclei. Co‐localization between Scn1a immunoreactivity and critical cell types within these regions was also observed. EEG analysis under baseline conditions revealed increased wakefulness and reduced non–rapid eye movement (NREM) and rapid eye movement (REM) sleep amounts during the dark phase in the RH mutants, suggesting a sleep deficit. Nevertheless, the mutants exhibited levels of NREM and REM sleep that were generally similar to wild‐type littermates during the recovery period following 6 h of sleep deprivation.Significance: These results establish a direct role for SCN1A in the regulation of sleep and suggest that patients with SCN1A mutations may experience chronic alterations in sleep, potentially leading to negative outcomes over time. In addition, the expression of Scn1a in specific cell types/brain regions that are known to play critical roles in seizure generation and sleep now provides a mechanistic basis for the clinical features (seizures and sleep abnormalities) associated with human SCN1A mutations.

During obstructive sleep apnea (OSA), respiratory activation of upper airway muscles, particularly genioglossus, is ineffective during sleep. Functional electrical stimulation (FES) of muscles reportedly reduces the number and length of OSAs. Our goals were to examine the effect of FES on sensation during wakefulness and on OSA events. Studies were performed in 11 subjects: 4 healthy asymptomatic subjects and 7 patients with OSA. Surface electrodes placed on the submental region produced discomfort; however, during sleep, the stimulus intensity producing arousal was significantly greater than that producing barely tolerable discomfort during wakefulness. Additionally, we developed a protocol for placement of fine-wire electrodes into the neurovascular bundle of the hypoglossal nerve, using recognizable radiographic features and computerized axial tomography as guides. In these patients, while awake, optimal wire placement was associated with visible tongue protrusion without discomfort. With both surface stimulation and fine-wire FES, during sleep the stimulus intensity required to produce obvious electroencephalographic arousal was significantly greater than that producing a barely tolerable sensation while awake. During apneic events, the application of surface stimulation had an inconsistent effect, terminating 22% of the apneas, and fine-wire FES also had a limited impact, terminating 23% of the apneic events. We conclude from our studies that subjects tolerate surface and fine-wire FES to higher stimulus parameters during sleep than during wakefulness but that both approaches have an inconsistent effect on apneas during sleep.