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Introduction: Thanks to ever-growing advances in medical science, couples who are in the in vitro fertilisation (IVF) now have more options than ever to encase their chances at a successful pregnancy. One of the options is the use of EmbryoGlue (EG), that creates a bridge between the embryo and the uterus and provides protection to the embryo itself during the transfer process. Aim of this study was to determine whether EG medium is of greater importance for embryo implantation than conventional medium in assisted reproductive technology and compare the rate of embryo implantation with EG and conventional medium in relation to the quality of the embryo, the age of the patients and tobacco smoking. Methods: The retrospective study included 50 patients who used EG medium in embryo transfer (ET) and 50 patients in the control group using conventional medium. All patients underwent ET after stimulation of the cycle according to a short protocol. ETs were done on Day 2, 3, or 5 in the blastocyst stage. Age and smoking status were recorded. Results: Out of a total of 100 patients, 42 patients had successful implantation and positive b-hCG 15 days after ET. In a control group 38 % had positive b-hCG and in the group of patients who used EG 46 %. A higher rate of embryo implantation success was observed on the second day of transfer in the group of patients using EG. In the EG group a significant increase in the embryo implantation rate was observed in patients older than 35. In tobacco smokers the implantation rate was higher if they used EG during ET. Conclusion: EG medium had a positive effect on the second day of ET, patients above the age of 35 and patients who were tobacco smokers.

Mycoplasma pneumoniae, a frequent respiratory pathogen, can cause neurological disease manifestations. We here present a case of M. pneumoniae as cause of meningitis and occurrence of an intracranial abscess as a complication of mastoiditis with septic cerebral venous sinus thrombosis in a patient with multiple sclerosis on anti-CD20 therapy., (© 2024. The Author(s).)

Burst suppression (BS) on EEG induced by intravenous anesthesia (IVAT) is standard therapy for refractory status epilepticus (RSE). If BS has any independent therapeutic effect on RSE is disputed. We aimed to define EEG characteristics of BS predicting termination or recurrence of status after weaning. All RSE patients treated with IVAT while undergoing continuous EEG monitoring on the neurological intensive care unit between 2014 and 2019 were screened for inclusion. A one hour-period of visually preselected BS-EEG was analyzed. Bursts were segmented by a special thresholding technique and underwent power spectral analysis. Out of 48 enrolled patients, 25 (52.1 %) did not develop seizure recurrence (group Non SE) after weaning from IVAT; in 23 patients (47.9 %), SE reestablished (group SE). In group Non SE, bursts contained higher amounts of EEG delta power (91.59 % vs 80.53 %, p < 0.0001), while faster frequencies were more pronounced in bursts in group SE (theta: 11.38 % vs 5.41 %, p = 0.0008; alpha: 4.89 % vs 1.82 %, p < 0.0001; beta: 3.23 % vs 1.21 %, p = 0.0002). Spectral profiles of individual bursts closely resembled preceding seizure patterns in group SE but not in group Non SE. Accordingly, persistence of spectral composition of initial ictal patterns in bursts, suggests ongoing SE, merely interrupted but not altered by BS. Fast oscillations in bursts indicate a high risk of status recurrence after weaning from IVAT. EEG guided individualized sedation regimes might therefore be superior to standardized anesthesia protocols., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [S. Gollwitzer received personal fees from Desitin, UCB, outside the submitted work. J.D. Lang served on the speakers’ bureau of Eisai and Destin. H.M. Hamer has served on the scientific advisory boards of Arvelle, Bial, Corlieve, Eisai, GW, Novartis, Sandoz, UCB Pharma and Zogenix. He has served on the speakers’ bureaus of or received unrestricted grants from Amgen, Ad-Tech, Alnylam, Bracco, Desitin, Eisai, GW, Nihon Kohden, Novartis, Pfizer, and UCB Pharma. The remaining authors have no conflicts of interest]., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients., Methods: We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics., Results: In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases., Conclusion: Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Outside of the work reported in this paper, H.M. Hamer has served on the scientific advisory boards of Arvelle, Bial, Corlieve, Eisai, GW, Novartis, Sandoz, UCB Pharma and Zogenix. He has been part of the speakers’ bureaus of or received unrestricted grants from Amgen, Ad-Tech, Alnylam, Bracco, Desitin, Eisai, GW, Nihon Kohden, Novartis, Pfizer, and UCB Pharma. The remaining authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: Super-refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE., Methods: This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model., Results: Ninety-one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per μg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0-1.2, p < .01). The median length of treatment in the NICU was 33.7 [23.2-56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU-acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in-hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In-hospital mortality was significantly higher in patients in whom seizure control could not be achieved., Significance: We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long-term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Status epilepticus is characterized by persistent or repetitive seizures which, without successful treatment, can lead to neuronal damage, neurological deficits and death of the patient.While status epilepticus with motor symptoms can usually be clinically diagnosed, nonconvulsive status epilepticus is often clinically overlooked due to its ambiguous semiology, so that electroencephalography (EEG) recording is necessary. The treatment of status epilepticus is performed in four treatment steps, whereby a difficult to treat status epilepticus is present from the third step at the latest and intensive medical care of the patient is necessary. Timely initiation of treatment and sufficient dosage of anticonvulsive medication are decisive for the success of treatment. There is little evidence for the "late" stages of treatment. Intensive medical measures pose the risk of complications that worsen the prognosis. Especially in nonconvulsive status epilepticus, the use of anesthetics must be weighed against possible complications of mechanical ventilation., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann-Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients., (© 2022. The Author(s).)

Objective: To determine patients' characteristics and regions in the temporal lobe where resections lead to a decline in picture naming., Methods: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections., Results: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8- 14.4%) and fusiform gyrus (decline range: 12.1-18.4%)., Significance: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction., Methods: We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory., Results: 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I-V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters., Conclusions: There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction., Significance: qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction., Competing Interests: Declaration of Competing Interest Tamara M. Müller, Rüdiger Hopfengärtner, Stephan Rampp, Johannes Lang, Jenny Stritzelberger, Caroline Reindl, Maximilian I. Sprügel, Müjgan Dogan Onugoren, Iris Muehlen, Joji B. Kuramatsu, Stefan Schwab: report no disclosures. Stephanie Gollwitzer reports personal fees from Desitin, Eisai, UCB, outside the submitted work. Dominik Madžar reports grants from UCB Pharma and BayerVitalGmbH, outside submitted work. Hagen B. Huttner reports grants from Novartis, grants and personal fees from Bayer AG, grants and personal fees from Daiichi Sankyo, grants and personal fees from Medtronic, grants and personal fees from Portola Pharmaceuticals, outside the submitted work. Hajo M. Hamer: reports personal fees from UCB, Desitin, Eisai, GW, Novartis, IQWiG, Hexal, facetoface, grants from Amgen, Ad-Tech, Bracco, Pfizer, Micromed, Nihon Kohden, personal fees from Arvelle, outside the submitted work., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The role of neuroinflammation in the pathophysiology of seizures is increasingly recognized, and the evaluation of potential biochemical markers of inflammatory processes in seizures and status epilepticus (SE), such as C-reactive protein (CRP), has gained attention. The present study assessed the first CRP level obtained in an SE episode regarding its value for SE outcome prediction. Among 362 admissions for SE during the study period, 231 episodes satisfied the inclusion criteria. Higher initial CRP concentrations were independently associated with in-hospital mortality and poor functional outcome at discharge in logistic regression models adjusting for SE severity, severity of SE etiology, and development of treatment refractoriness. Therefore, initial CRP levels may add to the prediction of SE prognosis. The pathomechanisms through which CRP is linked with the prognosis of SE, however, remain to be established., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Aims: This study determined the influence of age on bleeding characteristics and clinical outcomes in primary spontaneous (non-OAC), vitamin K antagonist-related (VKA-) and non-vitamin K antagonist oral anticoagulant-related (NOAC-) ICH., Methods: Pooled individual patient data of multicenter cohort studies were analyzed by logistic regression modelling and propensity-score-matching (PSM) to explore the influence of advanced age on clinical outcomes among non-OAC-, VKA-, and NOAC-ICH. Primary outcome measure was functional outcome at three months assessed by the modified Rankin Scale, dichotomized into favorable (mRS = 0-3) and unfavorable (mRS = 4-6) functional outcome. Secondary outcome measures included mortality, hematoma characteristics, and frequency of invasive interventions., Results: In VKA-ICH 33.5% (670/2001), in NOAC-ICH 44.2% (69/156) and in non-OAC-ICH 25.2% (254/1009) of the patients were ≥80 years. After adjustment for treatment interventions and relevant parameters, elderly ICH patients comprised worse functional outcome at three months (adjusted odds ratio (aOR) in VKA-ICH: 1.49 (1.21-1.84); p < 0.001; NOAC-ICH: 2.01 (0.95-4.26); p = 0.069; non-OAC-ICH: 3.54 (2.50-5.03); p < 0.001). Anticoagulation was significantly associated with worse functional outcome below the age of 70 years, (aOR: 2.38 (1.78-3.16); p < 0.001), but not in patients of ≥70 years (aOR: 1.21 (0.89-1.65); p = 0.217). The differences in initial ICH volume and extent of ICH enlargement between OAC-ICH and non-OAC-ICH gradually decreased with increasing patient age., Conclusions: As compared to elderly ICH-patients, in patients <70 years OAC-ICH showed worse clinical outcomes compared to non-OAC-ICH because of larger baseline ICH-volumes and extent of hematoma enlargement. Treatment strategies aiming at neutralizing altered coagulation should be aware of these findings.

Background: Inflammatory response is the hallmark of secondary brain injury in stroke patients. Neutrophil-to-lymphocyte ratio (NLR) emerged as a marker for functional outcome in several diseases., Objectives: To investigate the association between NLR on admission and during hospital stay and functional outcome in acute ischemic stroke (AIS)., Methods: This observational study included all consecutive AIS patients admitted at a German stroke center covering 2011-2013. Patient characteristics and clinical data were retrieved from institutional databases. Multivariate analysis was conducted to investigate parameters associated with functional outcome. Receiver operating characteristic (ROC) analysis was performed to identify the best cutoff for NLR to discriminate between favorable and unfavorable functional outcome. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on functional outcome., Results: A total of 807 patients with AIS were included for analysis. Patients with worse functional outcome at 3 months were older and had worse clinical status on admission, higher rates of infectious complications, and an increased NLR. ROC analysis identified a NLR of 3.3 as best cutoff value to discriminate between favorable and unfavorable functional outcomes (area under the curve 0.693, p < 0.001, Youden's index = 0.318; p < 0.001; sensitivity 68.5%, specificity 63.9%). Propensity-matched analysis still demonstrated a higher rate of unfavorable functional outcome at 3 months in patients with NLR ≥ 3.3 [modified Rankin scale 3-6 at 3 months: NLR ≥ 3.3 51.5% vs. NLR < 3.3 36.4%; p = 0.002]., Conclusions: In AIS patients we identified NLR as an important predictor for unfavorable functional outcome.

Objective: Hematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH., Methods: Pooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome., Results: Occurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17)., Interpretation: HE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Whether time of hospital admission-during or outside regular working hours-affects functional outcome in intracerebral hemorrhage (ICH) is unestablished as previous analyses have focused on mortality only. We here investigate whether on- versus off-hour hospital admission in ICH is associated with levels of invasiveness and clinical outcomes., Methods: Based on the UKER registry (NCT03183167) we grouped ICH-patients according to on- versus off-hour hospital admission. Primary outcome measures was functional outcome after 3 months using the modified Rankin scale (mRS) dichotomized into favorable (mRS = 0-3) and unfavorable (mRS = 4-6). Multivariate regression analyses were used to adjust for baseline imbalances, and subgroup analyses were performed to explore associations of on- versus off-hour admission with invasiveness of therapeutic interventions., Results: A total of 438/1269 (34.5%) of ICH-patients were admitted during regular working hours. Mortality rates were not significantly different among patients with on- versus off-hour admission. On-hour patients showed a significantly larger proportion of patients with favorable outcome (on-hour: mRS = 0-3 after 3 months: 176/416 (42.3%) versus off-hour: 265/784 (33.8%); P = .004). Analysis of invasive therapeutic interventions revealed that likelihood of favorable outcome was significantly increased among on-hour admitted patients who did not require neurosurgical interventions (no external ventricular drain n = 349, OR: 1.67[1.13-2.48], P < .05; no hematoma evacuation surgery n = 423, OR: 1.51[1.07-2.14], P < .05)., Conclusion: This study verified an "off-hour effect" in ICH that relates to functional outcome, rather than mortality, and which may be linked to different levels of invasive therapeutic interventions in patients admitted during off-hour., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: New antiepileptic drugs (AEDs) are increasingly applied in second-line therapy of status epilepticus (SE). In our study, we analyzed the impact of the choice of second-line AEDs on the course and prognosis of SE., Methods: This retrospective single- center study used data of an 8 year cohort of SE in adults from 2007 to 2014. Based on the year of market introduction with a cutoff at 1990, we classified AEDs as traditional or new. Prescription pattern associated differences in prognosis were measured through univariate and multivariable analysis of 3 endpoints: occurrence of refractory SE (RSE), functional outcome in survivors to discharge (good: mRS at discharge <3 or identical to admission mRS; otherwise poor), and in-hospital mortality., Results: From 362 SE episodes during the study period, 222 episodes were included into the study, among those 150 episodes treated with new and 72 with traditional AEDs. Use of new AEDs increased during the study period. After adjustment for confounders, treatment with new AEDs was on the one hand associated with higher rate of RSE occurrence (OR 1.95, 95 % CI 1.05-3.62, p = 0.03), but, on the other hand, also with better functional outcome at discharge (OR 2.64, 95 % CI 1.16-6.00, p = 0.02), while it was not an independent predictor of in- hospital mortality (OR 0.88, 95 % CI 0.33-2.33, p = 0.80)., Conclusion: Our observation that new AEDs may be associated with a higher rate of RSE development and relatively better functional outcome when adjusted for the premorbid mRS needs confirmation in prospective studies., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background/objective: Prognostication is a routine part of the delivery of neurocritical care for most patients with acute neurocritical illnesses. Numerous prognostic models exist for many different conditions. However, there are concerns about significant gaps in knowledge regarding optimal methods of prognostication., Methods: As part of the Arbeitstagung NeuroIntensivMedizin meeting in February 2018 in Würzburg, Germany, a joint session on prognostication was held between the German NeuroIntensive Care Society and the Neurocritical Care Society. The purpose of this session was to provide presentations and open discussion regarding existing prognostic models for eight common neurocritical care conditions (aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, traumatic spinal cord injury, status epilepticus, Guillain-Barré Syndrome, and global cerebral ischemia from cardiac arrest). The goal was to develop a qualitative gap analysis regarding prognostication that could help inform a future framework for clinical studies and guidelines., Results: Prognostic models exist for all of the conditions presented. However, there are significant gaps in prognostication in each condition. Furthermore, several themes emerged that crossed across several or all diseases presented. Specifically, the self-fulfilling prophecy, lack of accounting for medical comorbidities, and absence of integration of in-hospital care parameters were identified as major gaps in most prognostic models., Conclusions: Prognostication in neurocritical care is important, and current prognostic models are limited. This gap analysis provides a summary assessment of issues that could be addressed in future studies and evidence-based guidelines in order to improve the process of prognostication.

Objective: To determine the influence of intracerebral hemorrhage (ICH) location and volume and hematoma surface on perihemorrhagic edema evolution., Methods: Patients with ICH of the prospective Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage (UKER-ICH) cohort study (NCT03183167) between 2010 and 2013 were analyzed. Hematoma and edema volume during hospital stay were volumetrically assessed, and time course of edema evolution and peak edema correlated to hematoma volume, location, and surface to verify the strength of the parameters on edema evolution., Results: Overall, 300 patients with supratentorial ICH were analyzed. Peak edema showed a high correlation with hematoma surface ( R 2 = 0.864, p < 0.001) rather than with hematoma volumes, regardless of hematoma location. Smaller hematomas with a higher ratio of hematoma surface to volume showed exponentially higher relative edema ( R 2 = 0.755, p < 0.001). Multivariable logistic regression analysis revealed a cutoff ICH volume of 30 mL, beyond which an increase of total mass lesion volume (combined volume of hematoma and edema) was not associated with worse functional outcome. Specifically, peak edema was associated with worse functional outcome in ICH <30 mL (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.68-4.12, p < 0.001), contrary to ICH ≥30 mL (OR 1.20, 95% CI 0.88-1.63, p = 0.247). There were no significant differences between patients with lobar and those with deep ICH after adjustment for hematoma volumes., Conclusions: Peak perihemorrhagic edema, although influencing mortality, is not associated with worse functional outcomes in ICH volumes >30 mL. Although hematoma volume correlates with peak edema extent, hematoma surface is the major parameter for edema evolution. The effect of edema on functional outcome is therefore more pronounced in smaller and irregularly shaped hematomas, and these patients may particularly benefit from edema-modifying therapies., (© 2019 American Academy of Neurology.)

Objective: To investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: We analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018-2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature <36°C or >38°C, respiratory rate >20 per minute, heart rate >90 per minute, or white blood cell count <4,000/μL or >12,000/μL in the absence of infection. The primary outcome consisted of the modified Rankin Scale (mRS) at 3 and 12 months investigated by adjusted ordinal shift analyses. Bias and confounding were addressed by propensity score matching and multivariable regression models., Results: Of 780 patients with ICH, 21.8% (n = 170) developed SIRS during hospitalization. Patients with SIRS showed more severe ICH compared with those without; i.e., larger ICH volumes (18.3 cm 3 , interquartile range [IQR 4.6-47.2 cm 3 ] vs 7.4 cm 3 , IQR [2.4-18.6 cm 3 ]; p < 0.01), increased intraventricular hemorrhage (57.6%, n = 98/170 vs 24.8%, n = 79/319; p < 0.01), and poorer neurologic admission status (NIH Stroke Scale score 16, IQR [7-30] vs 6, IQR [3-12]; p < 0.01). ICH severity-adjusted analyses revealed an independent association of SIRS with poorer functional outcome after 3 (OR 1.80, 95% CI [1.08-3.00]; p = 0.025) and 12 months (OR 1.76, 95% CI [1.04-2.96]; p = 0.034). Increased ICH volumes on follow-up imaging (OR 1.38, 95% CI [1.01-1.89]; p = 0.05) and previous liver dysfunction (OR 3.01, 95% CI [1.03-10.19]; p = 0.04) were associated with SIRS., Conclusions: In patients with ICH, we identified SIRS to be predictive of poorer long-term functional outcome over the entire range of mRS estimates. Clinically relevant associations with SIRS were documented for previous liver dysfunction and hematoma enlargement.

Background and Objective: Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished., Methods: We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH -assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0-3) and unfavorable outcome (mRS = 4-6). Secondary outcomes included mortality at 3  months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome., Results: Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0-3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); p = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; p = 0.083). Multivariable analysis revealed that a Graeb score >2 was independently associated with unfavorable outcome (mRS 4-6: OR 3.16 [1.54-6.48]; p = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40-4.74]; p = 0.002) in IVH patients., Conclusions: Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients., (© 2019 S. Karger AG, Basel.)

Purpose: Delayed cerebral ischemia is a major complication after subarachnoid hemorrhage. Our previous study showed that alpha power reduction in continuous quantitative EEG predicts delayed cerebral ischemia. In this prospective cohort, we aimed to determine the prognostic value of alpha power in quantitative EEG for the long-term outcome of patients with subarachnoid hemorrhage., Methods: Adult patients with nontraumatic subarachnoid hemorrhage were included if admitted early enough for EEG to start within 72 hours after symptom onset. Continuous six-channel EEG was applied. Unselected EEG signals underwent automated artifact rejection, power spectral analysis, and detrending. Alpha power decline of ≥40% for ≥5 hours was defined as critical EEG event based on previous findings. Six-month outcome was obtained using the modified Rankin scale., Results: Twenty-two patients were included (14 male; mean age, 59 years; Hunt and Hess grade I-IV; duration of EEG monitoring, median 14 days). Poor outcome (modified Rankin scale, 2-5) was noted in 11 of 16 patients (69%) with critical EEG events. All six patients (100%) without EEG events achieved an excellent outcome (modified Rankin scale 0, 1) (P = 0.0062; sensitivity 100%, specificity 54.5%). Vasospasm detected with transcranial Doppler/Duplex sonography appeared 1.5 days after EEG events and showed weaker association with outcome (P = 0.035; sensitivity 100%, specificity 45.5%). There was no significant association between EEG events and ischemic lesions on imaging (P = 0.1). Also, no association between ischemic lesions and outcome was seen (P = 0.64)., Conclusions: Stable alpha power in quantitative EEG reflects successful therapy and predicts good functional outcome after subarachnoid hemorrhage. Critical alpha power reduction indicates an increased risk of poor functional outcome.

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.

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., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Troponin I is a widely used and reliable marker of myocardial damage and its levels are routinely measured in acute stroke care. So far, the influence of troponin I elevations during hospital stay on functional outcome in patients with atraumatic intracerebral hemorrhage (ICH) is unknown., Methods: Observational single-center study including conservatively treated ICH patients over a 9-year period. Patients were categorized according to peak troponin I level during hospital stay (≤0.040, 0.041-0.500, > 0.500 ng/mL) and compared regarding baseline and hematoma characteristics. Multivariable analyses were performed to investigate independent associations of troponin levels during hospital stay with functional outcome - assessed using the modified Rankin Scale (mRS; favorable 0-3/unfavorable 4-6) - and mortality after 3 and 12 months. To account for possible confounding propensity score (PS)-matching (1: 1; caliper 0.1) was performed accounting for imbalances in baseline characteristics to investigate the impact of troponin I values on outcome., Results: Troponin elevations (> 0.040 ng/mL) during hospital stay were observed in 308 out of 745 (41.3%) patients and associated with poorer status on admission (Glasgow Coma Scale/National Institute of Health Stroke Scale). Multivariable analysis revealed troponin I levels during hospital stay to be independently associated with unfavorable outcome after 12 months (risk ratio [95% CI]: 1.030 [1.009-1.051] per increment of 1.0 ng/mL; p = 0.005), but not with mortality. After PS-matching, patients with troponin I elevation (≥0.040 ng/mL) versus those without had a significant higher rate of -unfavorable outcome after 3 and 12 months (mRS 4-6 at 3 months: < 0.04 ng/mL: 159/265 [60.0%] versus ≥0.04 ng/mL: 199/266 [74.8%]; p < 0.001; at 12 months: < 0.04 ng/mL: 141/248 [56.9%] versus ≥0.04 ng/mL: 179/251 [71.3%]; p = 0.001)., Conclusions: Troponin I elevations during hospital stay occur frequently in ICH patients and are independently associated with functional outcome after 3 and 12 months but not with mortality., (© 2018 S. Karger AG, Basel.)

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., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background There is conflicting evidence about the influence of sex on outcome after spontaneous intracerebral hemorrhage (sICH) and the majority of the research focused on mortality and short-term outcome only. We investigated sex differences in long-term functional outcome after sICH. Methods We used data from a prospective hospital registry and included all consecutive patients with ICH admitted to our institution between January 2006 and July 2014. Functional outcome was assessed by modified Rankin Scale evaluated 3 and 12 months after ICH. We explored the influence of sex on long-term functional outcome using multivariable regression models and additionally by means of propensity score matching. Results We analyzed 823 patients, of whom 380 (46%) women. Women were on average three years older (p < 0.001), men had more often deep hematomas (p = 0.01). Unadjusted mortality rates were significantly increased in women at three months (42% vs. 35%; odds ratio (OR): 1.35; 95% confidence interval (CI): 1.02-1.80). After adjusting for baseline prognostic factors there were no differences between men and women in short- and long-term mortality (OR = 1.01; 95% CI = 0.66-1.54 and OR = 1.04; 95%CI = 0.69-1.57, respectively) and short- and long-term unfavorable outcome (OR = 1.02; 95%CI = 0.67-1.55 and OR = 0.96; 95% CI = 0.62-1.48, respectively). Conclusion We found no sex-related differences in long-term functional outcome in patients with sICH. The apparently worse functional outcome in women can be explained by differences in age.

Background and Purpose: Several studies have reported a better functional outcome in lobar intracerebral hemorrhage (ICH) compared with deep location. However, among lobar ICH, a correlation of hemorrhage site-involving the specific lobes-with functional outcome has not been established., Methods: Conservatively treated patients with supratentorial ICH, admitted to our hospital over a 5-year period (2008-2012), were retrospectively analyzed. Lobar patients were classified as isolated or overlapping ICH according to affected lobes. Demographic, clinical, and radiological characteristics were recorded and compared among lobar ICH patients using above subclassification. Functional outcome-dichotomized into favorable (modified Rankin Scale, 0-3) and unfavorable (modified Rankin Scale, 4-6)-was assessed after 3 and 12 months. Multivariate regression analysis was performed to identify predictors for favorable outcome., Results: Of overall 553 patients, 260 had lobar ICH. In isolated lobar ICH, median hematoma-volume decreased from rostral (frontal, 22.4 mL [7.3-55.5 mL]) to caudal (occipital, 7.1 mL [5.2-16.4 mL]; P =0.045), whereas the proportion of patients with favorable outcome increased (frontal: 23/63 [36.5%] versus occipital: 10/12 [83.3%]; P =0.003). Patients with overlapping lobar ICH had larger ICH volumes than isolated lobar ICH (overlapping, 48.9 mL [22.6-78.5 mL] versus 15.3 mL [5.0-44.6 mL]; P <0.001) and poorer clinical status on admission (Glasgow Coma Scale and National Institutes of Health Stroke Scale). Correlations with anatomic aspects provided evidence of a rostrocaudal gradient with increasing gray/white-matter ratio and decreasing hematoma-volume and rate of hematoma enlargement from frontal to occipital ICH location. Multivariate analysis revealed affection of occipital lobe (odds ratio, 3.75 [1.38-10.22]) and affection of frontal lobe (odds ratio, 0.52 [0.28-0.94]) to be independent predictors for favorable outcome and unfavorable outcome, respectively., Conclusions: Among patients with lobar ICH radiological and outcome characteristics differed according to location. Especially affection of the frontal lobe was frequent and associated with unfavorable outcome after 3 months., (© 2017 American Heart Association, Inc.)

Background: Data on clinical characteristics and outcome of patients with intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very limited., Methods: Nine hundred and seventy three consecutive primary ICH patients were analyzed using our prospective institutional registry over a period of 9 years (2006-2014). We compared clinical and radiological parameters as well as outcome - scored using the modified Rankin Scale (mRS) and analyzed in a dichotomized fashion as favorable outcome (mRS = 0-3) and unfavorable outcome (mRS = 4-6) - of ICH patients with and without cancer. Relevant imbalances in baseline clinical and radiological characteristics were adjusted using propensity score (PS) matching., Results: Prevalence of systemic cancer among patients with ICH was 8.5% (83/973). ICH patients with cancer were older (77 [70-82] vs. 72 [63-80] years; p = 0.002), had more often prior renal dysfunction (19/83 [22.9%] vs.107/890 [12.0%]; p = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3] vs. 15.3 [5.4-42.9] mL; p = 0.017). After PS-matching there were no significant differences neither in mortality nor in functional outcome both at 3 months (mortality: 33/81 [40.7%] vs. 55/158 [34.8%]; p = 0.368; mRS = 0-3: 28/81 [34.6%] vs. 52/158 [32.9%]; p = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150 [46.7%]; p = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; p = 0.620) among patients with and without concomitant systemic cancer. ICH volume tended to be highest in patients with hematooncologic malignancy and smallest in urothelial cancer., Conclusions: Patients with ICH and concomitant systemic cancer on average are older; however, they show smaller ICH volumes compared to patients without cancer. Yet, mortality and functional outcome is not different in ICH patients with and without cancer. Thus, the clinical history or the de novo diagnosis of concomitant malignancies in ICH patients should not lead to unjustified treatment restrictions., (© 2017 S. Karger AG, Basel.)

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.

Background and Purpose: Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients., Methods: This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as <1.0 (10(9)/L) and was correlated with patient's characteristics and outcome., Results: Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10-32] versus 13 [5-24]; P<0.001), larger hematoma volume (18.5 [6.2-46.2] versus 12.8 [4.4-37.8]; P=0.006), and unfavorable outcome (74.7% versus 63.3%; P=0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80-1.53 [10(9)/L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P<0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P=0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029-3.955], P=0.041; LOA: odds ratio, 1.391 [0.795-2.432], P=0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P<0.0001, Youden's index=0.290; LOA: area under the curve=0.513, P=0.676, Youden's index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P=0.198, Youden's index=0.106; volume: area under the curve=0.550, P=0.0898, Youden's index=0.1224)., Conclusions: Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH., (© 2016 American Heart Association, Inc.)

Purpose: The aim of this study was to assess factors associated with the use of topiramate (TPM) in refractory status epilepticus (RSE)., Methods: We retrospectively reviewed RSE episodes over a 12-year period. Episodes treated with and without TPM were compared in terms of demographics, RSE characteristics, clinical course, and outcome in univariate and multivariate analyses. Subgroups defined by type of RSE were studied separately. Functional outcome was assessed with the modified Rankin Scale., Results: Among 71 episodes, 17 (23.9%) were treated with TPM and seizure control was achieved in all of these. The results of unadjusted comparisons suggested a use of TPM in younger and healthier patients who received more perseverant treatment indicated by a higher number of antiepileptic drugs applied. In multivariate analysis adjusting for RSE duration, however, these associations lost significance. Furthermore, TPM was not a predictor of successful RSE termination in neither the overall cohort, nor in the subgroup of complex-partial RSE., Conclusion: After multivariate adjustment, no significant differences were observed between episodes treated with and without TPM in baseline characteristics, treatment, and outcome. Regarding the latter, this study does therefore not yield evidence for a particular efficacy of TPM in RSE., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Streptococcus equi subspecies zooepidemicus (Streptococcus zooepidemicus) is a rare cause of meningitis in humans. Humans mainly get infected by contact with an animal source or by ingestion of unpasteurized dairy products. In rare cases, bacterial meningitis can be complicated by endogenous endophthalmitis which is frequently associated with a poor visual prognosis., Case Presentation: A 73 year old male Caucasian patient presented with clinical signs indicative of bacterial meningitis. Blood and cerebrospinal fluid cultures yielded beta-hemolytic, catalase-negative cocci. The strain was identified as Streptococcus zooepidemicus. The patient was likely infected by contact with a sick horse. Under antibiotic treatment, his general condition improved rapidly. Early after hospital admission, however, he began seeing a black spot in his left eye's central visual field. An ophthalmological examination revealed signs of endogenous endophthalmitis and so the patient underwent vitrectomy. Despite treatment, the visual acuity of his left eye remained severely impaired. He showed no further neurological deficits at hospital discharge., Conclusion: Meningitis caused by Streptococcus zooepidemicus is rare with only 27 previously published adult cases in the literature. Of note, this report constitutes the third description of endogenous endophthalmitis associated with Streptococcus zooepidemicus meningitis. Thus, endogenous endophthalmitis may represent a comparatively common complication of meningitis caused by this microorganism.

Background: Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated., Methods: This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome., Results: Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06)., Conclusion: Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact., (© 2015 S. Karger AG, Basel.)

Background: Seizures are a common complication after intracerebral hemorrhage (ICH) but there is a substantial lack of information on the long-term incidence in ICH survivors and whether post-ICH seizures affect functional long-term outcome., Methods: Over a five-year period 464 consecutive patients with spontaneous ICH were analyzed. Focussing on 1-year ICH survivors, clinical, and radiological parameters were retrieved from institutional prospective databases. The occurrence of seizures was categorized as early (≤7 days) or late (>7 days). Functional outcome was assessed by mailed questionnaires and telephone interviews, and was categorized into good vs. poor (mRS: 0-2 vs. 3-5) and favorable vs. unfavorable (mRS: 0-3 vs. 4-5). Multivariate regression models were calculated to investigate risk factors associated with post-ICH seizures including an a priori defined subgroup analysis of lobar ICH patients., Results: Among 203 long-term ICH survivors, 19.7 % developed seizures of which 55 % occurred late. Factors associated with seizures were lobar location (OR 8.10; 95 % CI 3.04-21.59; p < 0.001), sepsis (OR 4.59; 95 % CI 1.20-17.53; p = 0.026), and history of alcohol abuse (OR 3.36; 95 % CI 1.25-9.06; p = 0.017). Subgroup analysis of lobar ICH patients revealed history of alcohol abuse as the only independent predictor of post-ICH seizures (OR 5.22; 95 % CI 1.25-21.78; p = 0.024). Functional long-term outcome among survivors was slightly worse in patients with post-ICH seizures (p = 0.059). In multivariate regression modeling for prediction of poor outcome, the parameter "post-ICH seizures" again reached a statistical trend (p = 0.065), and established parameters such as age, GCS, and hemorrhage volume were independently related to poor outcome., Conclusions: Post-ICH seizures among long-term ICH survivors are common and may contribute to unfavorable functional outcome. Especially lobar ICH patients with a history of alcohol abuse are at risk to develop post-ICH seizures. Therefore, this subgroup may represent a target population for a prophylactic anticonvulsive treatment approach, preferably investigated in a prospective randomized trial.

We present an unusual constellation of the CSF/serum biomarkers of Guillain-Barré syndrome caused by unsteady-state condition of protein diffusion induced by plasmapheresis. Low blood concentrations of immunoglobulins were accompanied by their normal concentrations in the CSF, and hence the corresponding CSF/serum quotients seemed 'increased' suggesting intrathecal humoral response. This was in contrast to the results of isoelectrofocusing showing identical IgG bands pattern in the CSF and serum. Control lumbar puncture performed 6 weeks after the cessation of plasmapheresis, revealed normalization of the immunoglobulins' quotients. It must be stressed that the results of the CSF/serum analysis performed under non-steady state condition may be easily misinterpreted, and only considering the whole pattern of the CSF/serum biomarkers can assure correct interpretation of the results.