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Background and purpose: Previous studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. Methods: We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. Results: A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. Conclusion: After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment. [ABSTRACT FROM AUTHOR]

Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to re‐evaluate risk factors for post‐ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. Background and purpose: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. Methods: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni‐ and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. Results: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow‐up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025). Conclusions: Post‐ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship. Methods: A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized tonic–clonic seizures], diabetes), origin (German, non‐German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10 km away). Respondents rated their willingness to befriend the person on a 10‐point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment. Results: Participants were 64 PWEs (age = 37.1 ± 14.0 years), 64 relatives of PWEs (age = 45.1 ± 13.6 years), and 98 controls without contact with PWEs (age = 24.4 ± 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (−3.4%) and even more avoided PWEs with severe epilepsy (−11.7%), whereas in PWEs with tonic–clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (−12.3%) and contacts via the internet or telephone (−7.3%). PWEs were also less interested in younger people (−5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (−2.3%). Significance: PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures. [ABSTRACT FROM AUTHOR]

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Objective: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived "fair" pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. Methods: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. Results: Fifty‐seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. Significance: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Whether anti-seizure medication (ASM) increases the risk for cancer has been debated for decades. While for some ASM, a carcinoma-promoting effect has been suspected, carcinoma-protective effects have been shown for other ASM. However, the issue remains unresolved as data from preclinical and clinical studies have been inconsistent and contradictory. Methods: We collected anonymous patient data from practice neurologists throughout Germany between 2009 and 2018 using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy (PWE) with an initial cancer diagnosis and antiepileptic therapy prior to the index date were 1:1 matched with a control group of PWE without cancer according to age, gender, index year, Charlson Comorbidity Index, and treating physician. For both groups, the risk to develop cancer under treatment with different ASMs was analyzed using three different models (ever use vs. never use (I), effect per one (II) and per five therapy years (III). Results: A total of 3152 PWE were included (each group, n = 1,576; age = 67.3 ± 14.0 years). The risk to develop cancer was not significantly elevated for any ASM. Carbamazepine was associated with a decreased cancer risk (OR Model I: 0.699, p <.0001, OR Model II: 0.952, p =.4878, OR Model III: 0.758, p <.0004). Significance: Our findings suggest that ASM use does not increase the risk of cancer in epilepsy patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The proportion of patients with intracerebral hemorrhage (ICH) and concomitant indication for oral anticoagulant (OAC) therapy is increasing. Although recent studies documented a favorable risk-benefit profile of OAC initiation, deciding whether, when, and which OAC should be started remains controversial. We investigated (1) OAC recommendations, its implementation, and adherence and (2) factors associated with OAC initiation after ICH.Methods: This prospective observational study analyzed consecutive ICH patients (n = 246) treated at the neurological and neurosurgical department of the University-Hospital Erlangen, Germany over a 21-month inclusion period (05/2013-01/2015). We analyzed the influence of patient characteristics, in-hospital measures, and functional status on treatment recommendations and on OAC initiation during 12-month follow-up.Results: In-hospital mortality of 24.8% (n = 61/246) left 185 patients discharged alive of which 34.1% (n = 63/185) had OAC indication. In these patients, OAC initiation was clearly recommended in only 49.2% (n = 31/63) and associated with favorable [modified Rankin Scale (mRS) = 0-3] functional discharge status [OR 7.18, CI (1.05-49.13), p = 0.04], less frequent heart failure [OR 0.19, CI (0.05-0.71), p = 0.01], and younger age [OR 0.95, CI (0.90-1.00), p = 0.05]. OAC was more often started if clearly recommended [n = 19/31 (61.3%) versus (no recommendation) n = 4/26 (15.4%), p < 0.001; (clearly not recommended, n = 6)] and associated with younger age [67 (58-74) versus 79 (73-83), p < 0.001], favorable functional outcome [n = 10/23 (43.5%) versus n = 5/40 (12.5%), p = 0.01], decreased mortality [n = 6/23 (26.1%) versus n = 19/40 (47.5%), p = 0.06], and functional improvement [n = 13/17 (76.5%) versus n = 7/21 (33.3%), p = 0.01]. We observed no differences in rates of intracranial complications [thromboembolism, n = 3/23 (13.0%) versus n = 4/40 (10.0%), p = 1.00; hemorrhage, n = 1/23 (4.3%) versus n = 3/40 (7.5%), p = 1.00].Conclusions: Clear treatment recommendations by attending stroke physicians significantly influence OAC initiation after ICH. OAC were more frequently recommended and started in younger patients with better functional recovery independent from intracranial complications. This might represent an important determinant of observed beneficial associations, hinting towards an indication bias which might affect observational analyses. [ABSTRACT FROM AUTHOR]

Objective Trigeminal and cervical afferents converge on neurons of the trigeminocervical complex and may significantly alter the function of these neurons. This interaction may have implications for the pathophysiology and treatment of primary headache disorders. Therefore, the aim of this work was to study pain modulatory mechanisms within the trigeminocervical complex. Subjects We used an electrical pain model challenging pro- and antinociceptive systems in 19 healthy volunteers. Methods Transcutaneous supraorbital noxious electrical low-frequency stimulation (0.5 Hz), known to induce both hyperalgesia due to central sensitization (as a marker of pain facilitation) and habituation (as a marker of pain inhibition), was combined with different noxious stimulation paradigms applied to the innervation territory of upper cervical afferents. We investigated the effects of concurrent stimulation in the cervical/extratrigeminal system on habituation profiles, hyperalgesic area, pain, and detection thresholds in the trigeminal system. Results It was previously shown that conditioning 20-Hz noxious electrical stimuli may provoke centrally mediated sensory decline that possesses heterotopic antihyperalgesic properties. Occipital and forearm costimulation at a frequency of 20 Hz had no significant modulating effect on supraorbital pain adaptation, hyperalgesic area, or pain perception. Effects for trigeminal stimulation were independent of occipital stimulus intensity. Furthermore, for single occipital stimulation at 0.5 and 20 Hz, no somatosensory changes could be demonstrated within the trigeminal system. Conclusion Trigeminal nociception stayed unchanged despite of occipital costimulation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]