Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. Retrospective assessment of a prospectively collected cohort. Academic hospital. Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry–based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and “Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP” (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ≥15 or more events per hour or <15/h, respectively, on the apnea–hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07–4.34], P = 0.031; and 2.35 [1.12–4.93], P = 0.024) and in the PLSC (1.36 [1.13–1.63], P = 0.001; and 1.44 [1.06–1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08–3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73–0.99], P = 0.031; and HR, 0.91 [0.86–0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Background: The relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals.Methods: We studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined.Results: 358 elderly individuals without dementia were included (mean±sdage 71.0±4.2 years; 42.5% males). A lower mean peripheral oxygen saturation (SpO₂) during sleep was associated with a steeper decline in Mini-Mental State Examination (B= −0.12, p=0.004), Stroop test condition 1 (B=0.53, p=0.002) and Free and Cued Selective Reminding Test delayed free recall (B= −0.05, p=0.008). A longer time spent asleep withSpO₂<90% was associated with a steeper decline in Stroop test condition 1 (B=0.47, p=0.006). Moderation analysis showed that apnoea–hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers.Conclusions: Our results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.

Objective: Our aim was to analyze and compare the use of therapeutic coma (TC) for refractory status epilepticus (SE) across different centers and its effect on outcome. Methods: Clinical data for all consecutive adults (>16 years) with SE of all etiologies (except postanoxic) admitted to 4 tertiary care centers belonging to Harvard Affiliated Hospitals (HAH) and the Centre Hospitalier Universitaire Vaudois (CHUV) were prospectively collected and analyzed for TC details, mortality, and duration of hospitalization. Results: Two hundred thirty-six SE episodes in the CHUV and 126 in the HAH were identified. Both groups were homogeneous in demographics, comorbidities, SE characteristics, and Status Epilepticus Severity Score (STESS); TC was used in 25.4% of cases in HAH vs 9.75% in CHUV. After adjustment, TC use was associated with younger age, lower Charlson Comorbidity Index, increasing SE severity, refractory SE, and center (odds ratio 11.3 for HAH vs CHUV, 95% confidence interval 2.47–51.7). Mortality was associated with increasing Charlson Comorbidity Index and STESS, etiology, and refractory SE. Length of stay correlated with STESS, etiology, refractory SE, and use of TC (incidence rate ratio 1.6, 95% confidence interval 1.22–2.11). Conclusions: Use of TC for SE treatment seems markedly different between centers from the United States and Europe, and did not affect mortality considering the whole cohort. However, TC may increase length of hospital stay and related costs. Classification of evidence: This study provides Class III evidence that for patients with SE, TC does not significantly affect mortality. The study lacked the precision to exclude an important effect of TC on mortality.

Objective: There is much controversy about the neurobiological mechanisms underlying the effects of sleep‐disordered breathing on the brain. The aim of this study was to investigate the association between markers of sleep‐related hypoxemia and brain anatomy.Methods: We used data from a large‐scale cohort from the general population (n = 775, 50.6% males, age range = 45–86 years, mean age = 60.3 ± 9.9) that underwent full polysomnography and brain magnetic resonance imaging to correlate respiratory variables with regional brain volume estimates.Results: After adjusting for age, gender, and cardiovascular risk factors, only mean oxygen saturation during sleep was associated with bilateral volume of hippocampus (right: p = 0.001; left: p < 0.001), thalamus (right: p < 0.001; left: p < 0.001), putamen (right: p = 0.001; left: p = 0.001), and angular gyrus (right: p = 0.011; left: p = 0.001). We observed the same relationship in left hemispheric amygdala (p = 0.010), caudate (p = 0.008), inferior frontal gyrus (p = 0.004), and supramarginal gyrus (p = 0.003). The other respiratory variables—lowest oxygen saturation, percentage of sleep time with oxygen saturation < 90%, apnea–hypopnea index, and oxygen desaturation index—did not show any significant association with brain volumes.Interpretation: Lower mean oxygen saturation during sleep was associated with atrophy of cortical and subcortical brain areas known for high sensitivity to oxygen supply. Their vulnerability to hypoxemia may contribute to behavioral phenotype and cognitive decline in patients with sleep‐disordered breathing. ANN NEUROL 2020;87:921–930