Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.

While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled

Status epilepticus: impact of therapeutic coma on outcome.

OBJECTIVES: 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. DESIGN: Retrospective assessment of a prospectively collected cohort. SETTING: Academic hospital. PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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

Therapeutic coma for status epilepticus: Differing practices in a prospective multicenter study.

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. 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. 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). 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. 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

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Abnormal timing of slow wave synchronization processes in non-rapid eye movement sleep parasomnias.

Sleepwalking, confusional arousals, and sleep terrors are parasomnias occurring out of non-rapid eye movement (NREM) sleep. Several previous studies have described EEG changes associated with NREM parasomnia episodes, but it remains unclear whether these changes are specific to parasomnia episodes or whether they are part of the normal awakening process. Here we directly compared regional brain activity, measured with high-density (hd-) EEG, between parasomnia episodes and normal awakenings (without behavioral manifestations of parasomnia). Twenty adult patients with non-rapid eye movement parasomnias underwent a baseline hd-EEG recording (256 electrodes) followed by a recovery sleep recording after 25 h of total sleep deprivation, during which auditory stimuli were administered to provoke parasomnia episodes. Both normal awakenings (n = 25) and parasomnia episodes (n = 96) were preceded by large, steep, and "K-complex-like" slow waves in frontal and central brain regions, and by a concomitant increase in high-frequency EEG (beta) activity. Compared to normal awakenings, parasomnia episodes occurred on a less activated EEG background and displayed higher slow wave activity (SWA) and lower beta activity in frontal and central brain regions after movement onset. Our results suggest that non-rapid eye movement awakenings, irrespective of behavioral manifestations of parasomnia episodes, involve an arousal-related slow wave synchronization process that predominantly recruits frontal and central brain areas. In parasomnia episodes, this synchronization process comes into play abnormally during periods of high SWA and is associated with higher SWA after movement onset. Thus, an abnormal timing of arousal-related slow wave synchronization processes could underlie the occurrence of NREM parasomnias

Age- and sex-specific associations between obstructive sleep apnea risk and cognitive decline in middle-aged and older adults: A 3-year longitudinal analysis of the Canadian longitudinal study on aging.

Whether obstructive sleep apnea (OSA) increases the risk of cognitive decline and how sex and age influence this association is not clear. Here, we characterized the sex- and age-specific associations between OSA risk and 3-year cognitive change in middle-aged and older adults. We included 24,819 participants aged 45-85 (52% women) from the Canadian Longitudinal Study on Aging. OSA risk was measured at baseline using the STOP combined to body mass index (STOP-B). Neuropsychological tests assessed memory, executive functioning, and psychomotor speed at baseline and at 3-year follow-up. We conducted age- and sex-specific linear mixed models to estimate the predictive role of baseline STOP-B score on 3-year cognitive change. Men at high-risk for OSA aged 45-59 years showed a steeper decline in psychomotor speed (+13.2 [95% CI: -1.6, 27.9]) compared to men at low-risk. Men at high-risk for OSA aged 60-69 showed a steeper decline in mental flexibility (-1.2 [-1.9, -0.5]) and processing speed (+0.6 [0.3, 0.9]) than those at low-risk. Women at high-risk for OSA aged 45-59 showed a steeper decline in processing speed (+0.1 [-0.2, 0.4]) than women at low-risk, while women at high-risk ≥70 years had a steeper decline in memory (-0.2 [-0.6, 0.1]) and processing speed (+1.0 [0.4, 1.5]). Associations between OSA risk and cognitive decline over 3 years depend on age and sex. Being at high-risk for OSA is associated with a generalized cognitive decline in attention and processing speed, while a memory decline is specific to older women (≥70 years)

Abnormal brain iron accumulation in obstructive sleep apnea: A quantitative MRI study in the HypnoLaus cohort.

Obstructive sleep apnea syndrome (OSA) may be a risk factor for Alzheimer's disease. One of the hallmarks of Alzheimer's disease is disturbed iron homeostasis leading to abnormal iron deposition in brain tissue. To date, there is no empirical evidence to support the hypothesis of altered brain iron homeostasis in patients with obstructive sleep apnea as well. Data were analysed from 773 participants in the HypnoLaus study (mean age 55.9 ± 10.3 years) who underwent polysomnography and brain MRI. Cross-sectional associations were tested between OSA parameters and the MRI effective transverse relaxation rate (R2*) - indicative of iron content - in 68 grey matter regions, after adjustment for confounders. The group with severe OSA (apnea-hypopnea index ≥30/h) had higher iron levels in the left superior frontal gyrus (F &lt;sub&gt;3,760&lt;/sub&gt; = 4.79, p = 0.003), left orbital gyri (F &lt;sub&gt;3,760&lt;/sub&gt; = 5.13, p = 0.002), right and left middle temporal gyrus (F &lt;sub&gt;3,760&lt;/sub&gt; = 4.41, p = 0.004 and F &lt;sub&gt;3,760&lt;/sub&gt; = 13.08, p &lt; 0.001, respectively), left angular gyrus (F &lt;sub&gt;3,760&lt;/sub&gt; = 6.29, p = 0.001), left supramarginal gyrus (F &lt;sub&gt;3,760&lt;/sub&gt; = 4.98, p = 0.003), and right cuneus (F &lt;sub&gt;3,760&lt;/sub&gt; = 7.09, p &lt; 0.001). The parameters of nocturnal hypoxaemia were all consistently associated with higher iron levels. Measures of sleep fragmentation had less consistent associations with iron content. This study provides the first evidence of increased brain iron levels in obstructive sleep apnea. The observed iron changes could reflect underlying neuropathological processes that appear to be driven primarily by hypoxaemic mechanisms