Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

Impact of timing of continuous intravenous anesthetic drug treatment on outcome in refractory status epilepticus.

BACKGROUND: Patients in refractory status epilepticus (RSE) may require treatment with continuous intravenous anesthetic drugs (cIVADs) for seizure control. The use of cIVADs, however, was recently associated with poor outcome in status epilepticus (SE), raising the question of whether cIVAD therapy should be delayed for attempts to halt seizures with repeated non-anesthetic antiepileptic drugs. In this study, we aimed to determine the impact of differences in therapeutic approaches on RSE outcome using timing of cIVAD therapy as a surrogate for treatment aggressiveness. METHODS: This was a retrospective cohort study over 14 years (n = 77) comparing patients with RSE treated with cIVADs within and after 48 h after RSE onset, and functional status at last follow-up was the primary outcome (good = return to premorbid baseline or modified Rankin Scale score of less than 3). Secondary outcomes included discharge functional status, in-hospital mortality, RSE termination, induction of burst suppression, use of thiopental, duration of RSE after initiation of cIVADs, duration of mechanical ventilation, and occurrence of super-refractory SE. Analysis was performed on the total cohort and on subgroups defined by RSE severity according to the Status Epilepticus Severity Score (STESS) and by the variables contained therein. RESULTS: Fifty-three (68.8%) patients received cIVADs within the first 48 h. Early cIVAD treatment was independently associated with good outcome (adjusted risk ratio [aRR] 3.175, 95% confidence interval [CI] 1.273-7.918; P = 0.013) as well as lower chance of both induction of burst suppression (aRR 0.661, 95% CI 0.507-0.861; P = 0.002) and use of thiopental (aRR 0.446, 95% CI 0.205-0.874; P = 0.043). RSE duration after cIVAD initiation was shorter in the early cIVAD cohort (hazard ratio 1.796, 95% CI 1.047-3.081; P = 0.033). Timing of cIVAD use did not impact the remaining secondary outcomes. Subgroup analysis revealed early cIVAD impact on the primary outcome to be driven by patients with STESS of less than 3. CONCLUSIONS: Patients with RSE treated with cIVADs may benefit from early initiation of such therapy.

Effects of clobazam for treatment of refractory status epilepticus.

BACKGROUND: Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). METHODS: We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination. We assessed the differences between patients with and without CLB and correlated CLB with outcome. Among patients treated with CLB, we studied responders and non-responders and compared our CLB cohort with recently published data. RESULTS: CLB was part of the AED regimen in 24/70 (34.3 %) RSE episodes. In six of these (25.0 %) RSE resolution was attributed to CLB. Baseline characteristics of episodes with and without CLB treatment showed no significant differences and RSE termination rates were very similar (83.3 % vs. 80.4 %). CLB was administered in clinically more complex RSE with longer RSE duration and worse outcome, but CLB was not related independently to outcome. Comparison of our results with previously published data revealed that baseline characteristics as well as CLB maintenance doses and time of treatment initiation were similar in both cohorts. CLB was less frequently the last AED added to RSE therapy in our patients indicating a lower treatment success rate than previously reported. CONCLUSIONS: CLB represents a reasonable AED and promising add-on agent for treatment of RSE. However, rates of successful CLB response were substantially lower than in a recently published study. Differing RSE characteristics and treatment strategies may account for the discrepancy between study results, as RSE etiologies and seizures types associated with unfavorable prognosis were more common in our cohort, while anesthetics tended to be less frequently applied to achieve seizure control.

Comparison of scoring tools for the prediction of in-hospital mortality in status epilepticus.

PURPOSE: Several scoring tools have been developed for the prognostication of outcome after status epilepticus (SE). In this study, we compared the performances of STESS (Status Epilepticus Severity Score), mSTESS (modified STESS), EMSE-EAL (Epidemiology-based Mortality Score in Status Epilepticus- Etiology, Age, Level of Consciousness) and END-IT (Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation) in predicting in-hospital mortality after SE. METHOD: Data collected retrospectively from a cohort of 287 patients with SE were used to calculate STESS, mSTESS, EMSE-EAL, and END-IT scores. The differences between the scores' performances were determined by means of area under the ROC curve (AUC) comparisons and McNemar testing. RESULTS: The in-hospital mortality rate was 11.8%. The AUC of STESS (0.628; 95% confidence interval (CI), 0.529-0.727) was similar to that of mSTESS (0.620; 95% CI, 0.510-0.731), EMSE-EAL (0.556; 95% CI, 0.446-0.665), and END-IT (0.659; 95% CI, 0.550-0.768; p > .05 for each comparison) in predicting in-hospital mortality. STESS with a cutoff of 3 was found to have lowest specificity and number of correctly classified episodes. EMSE-EAL with a cutoff at 40 had highest specificity and showed a trend towards more correctly classified episodes while sensitivity tended to be low. END-IT with a cutoff of 3 had the most balanced sensitivity-specificity ratio. CONCLUSIONS: EMSE-EAL is as easy to calculate as STESS and tended towards higher diagnostic accuracy. Adding information on premorbid functional status to STESS did not enhance outcome prediction. END-IT was not superior to other scores in prediction of in-hospital mortality despite including information of diagnostic work-up and response to initial treatment.

Factors associated with occurrence and outcome of super-refractory status epilepticus.

PURPOSE: Super-refractory status epilepticus (SRSE) represents a challenging medical condition with high morbidity and mortality. In this study, we aimed to establish variables related to SRSE development and outcome. METHODS: We retrospectively screened our databases for refractory SE (RSE) and SRSE episodes between January 2001 and January 2015. Baseline demographics, SE characteristics, and variables reflecting the clinical course were compared in order to identify factors independently associated with SRSE occurrence. Within the SRSE cohort, predictors of in-hospital mortality as well as good functional outcome in survivors to discharge were established through univariate and multivariable analyses. RESULTS: A total of 131 episodes were included, among those 46 (35.1%) meeting the criteria of SRSE. Comparison of RSE and SRSE episodes revealed a lower premorbid mRS score (odds ratio (OR) per mRS point, 0.769; p=0.039) and non-convulsive SE (NCSE) in coma (OR, 4.216; p=0.008) as independent predictors of SRSE. SRSE in-hospital mortality was associated with age (OR, 1.091 per increasing year; p=0.020) and worse premorbid functional status (OR, 1.938 per mRS point; p=0.044). Good functional outcome in survivors was independently related to shorter SRSE duration (OR, 0.714 per day; p=0.038). CONCLUSION: Better premorbid functional status and NCSE in coma as worst seizure type indicate a role of acute underlying etiologies in the development of SRSE. In-hospital mortality in SRSE is determined by nonmodifiable factors, while functional outcome in survivors depends on seizure duration underscoring the need of achieving rapid seizure termination.

Association of seizure duration and outcome in refractory status epilepticus.

The aim of the study was to identify factors influencing long-term outcome and to evaluate the prognostic power of the Status Epilepticus Severity Score (STESS) in refractory status epilepticus (RSE). We retrospectively extracted data on baseline characteristics, RSE details, and hospital course including complications from all patients treated for RSE in our institution between January 2001 and January 2013. Functional outcome was assessed using the modified Rankin Scale (mRS) and was defined as good when either RSE did not lead to functional decline or when the resulting mRS score was 2 or below. Seventy-one episodes in 65 patients were analyzed. The median follow-up time was 12 weeks (IQR 6-35), two patients were lost to follow-up. Poor functional long-term outcome was observed in 42/69 (60.9%) episodes. In-hospital mortality occurred in 13/71 (18.3%) episodes. Multivariable analysis revealed that STESS ≥ 3, longer RSE duration, and sepsis were independently related to poor functional long-term outcome. Receiver operating characteristics (ROC) curve analyses confirmed the cut-off dichotomization into STESS ≥ 3 and STESS < 3 for optimal discrimination between good and poor outcome (AUC = 0.671, p = 0.002, YI = 0.368, NPV = 0.607, PPV = 0.756) and revealed an RSE duration of 10 days as a significant cut-off point associated with outcome (AUC = 0.712, p = 0.012, YI = 0.310; NPV = 0.545, PPV = 0.750). In conclusion, STESS and RSE duration represent relevant scores and parameters impacting long-term outcome after RSE. A shorter RSE duration is associated with better outcome and, therefore, rapid and adequate treatment for seizure termination should be enforced.