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Background Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are applied in epilepsy mostly during presurgical assessment. Nonlesional focal epilepsy is very challenging for presurgical evaluation in cases of refractory epilepsy. Objectives We aimed to investigate the contribution of PET and SPECT to focus localization in nonlesional epilepsy. Methods The basic principles of SPECT and PET including different tracers were reviewed. The literature and the most recent publications are discussed in view of findings in nonlesional epilepsy. Results Ictal SPECT shows a high sensitivity of over 80% for ictal onset zone in nonlesional epilepsy. Postprocessing with subtraction ictal SPECT co-registered with MRI (SISCOM) or statistical parametric mapping are the gold standard. Histopathological findings in nonlesional epilepsies with concordant ictal SPECT imaging show focal cortical dysplasia in up to 75% of cases. Ictal injection is unsuccessful in approximately 20% of cases and the procedure is very time consuming and labor intensive. Fluorodeoxyglucose (FDG)-PET in nonlesional epilepsy shows variable sensitivity of 46–76%. As with ictal SPECT, it benefits from postprocessing of co-registration with magnetic resonance imaging (MRI) or even statistical parametric mapping. Hybrid PET/magnetic resonance imaging (MRI) scanners provide additional benefits for identifying lesions. Other PET tracers (11C‑Flumazenil (FMZ), α-11C‑methyl-L-tryptophane (AMT)) are clinically applied in special cases only. Both procedures contribute complementary information in multimodal imaging diagnostics. Conclusions Ictal SPECT and PET are optional diagnostic tools for presurgical assessment in nonlesional epilepsies. They may reverse nonlesional to lesional epilepsy status and identify nonlesional epileptic foci with a fair chance of seizure freedom after epilepsy surgery.

Temporal lobe epilepsy (TLE) is one of the syndromes linked to antibodies against glutamic acid decarboxylase (GAD). It has been questioned whether ‘limbic encephalitis with GAD antibodies’ is a meaningful diagnostic entity. The immunopathogenesis of GAD-TLE has remained enigmatic. Improvement of immunological treatability is an urgent clinical concern. We retrospectively assessed the clinical, MRI and CSF course as well as brain tissue of 15 adult patients with GAD-TLE who underwent temporal lobe surgery. Brain tissue was studied by means of immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration. In 10 patients, there was a period of mediotemporal swelling and T2 signal increase; in nine cases this occurred within the first 6 years after symptom onset. This resulted in unilateral or bilateral hippocampal sclerosis; three cases developed hippocampal sclerosis within the first 2 years. All CSF studies done within the first year (n = 6) revealed intrathecal synthesis of immunoglobulin G. Temporal lobe surgeries were done after a median disease duration of 9 years (range 3 weeks to 60 years). Only two patients became seizure-free. Brain parenchyma collected during surgery in the first 6 years revealed high numbers of plasma cells but no signs of antibody-mediated tissue damage. Even more dense was the infiltration by CD8+ cytotoxic T lymphocytes (CTLs) that were seen to locally proliferate. Further, a portion of these cells revealed an antigen-specific resident memory T cell phenotype. Finally, CTLs with cytotoxic granzyme B+ granules were also seen in microglial nodules and attached to neurons, suggesting a CTL-mediated destruction of these cells. With longer disease duration, the density of all lymphocytes decreased. Whole transcriptome analysis in early/active cases (but not in late/inactive stages) revealed ‘T cell immunity’ and ‘Regulation of immune processes’ as the largest overrepresented clusters. To a lesser extent, pathways associated with B cells and neuronal degeneration also showed increased representation. Surgically treated patients with GAD-TLE go through an early active inflammatory, ‘encephalitic’ stage (≤6 years) with CTL-mediated, antigen-driven neuronal loss and antibody-producing plasma cells but without signs of complement-mediated cell death. Subsequently, patients enter an apparently immunologically inactive or low-active stage with ongoing seizures, probably caused by the structural damage to the temporal lobe. ‘Limbic encephalitis’ with GAD antibodies should be subsumed under GAD-TLE. The early tissue damage explains why immunotherapy does not usually lead to freedom from seizures.

Background Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. Methods We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. Results We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Conclusions Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.

ImportanceAcute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk.ObjectiveTo compare mortality and risk of epilepsy following different types of acute symptomatic seizures.Design, Setting, and ParticipantsThis cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022.ExposuresType of acute symptomatic seizure.Main Outcomes and MeasuresAll-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke).ResultsA total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy.Conclusions and RelevanceIn this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

ZusammenfassungAkut symptomatische Anfälle sind definiert durch einen engen zeitlichen Zusammenhang zwischen einem akuten Ereignis, welches einen negativen Einfluss auf das Gehirn hat, und dem daraus resultierenden Auftreten von epileptischen Anfällen. Diesem akuten Ereignis können neben einer strukturellen Hirnschädigung (z. B. traumatisch, vaskulär) unter anderem auch Entgleisungen im Rahmen internistischer Erkrankungen oder Einfluss von externen Noxen wie Medikamenten, Alkohol oder Drogen zugrunde liegen. In weiterer Folge beschreiben wir die häufigsten internistischen Ursachen, welche zu akut symptomatischen Anfällen führen können. Das Risiko von Elektrolytentgleisungen, Leber- und Nierenerkrankungen, Darmerkrankungen, Diabetes mellitus und der Einfluss unterschiedlicher Medikamente wird diskutiert.

Accidente cerebrovascular isquémico; Tratamiento de reperfusión; Factores de riesgo Ischemic Stroke; Reperfusion treatment; Risk factors Accident cerebrovascular isquèmic; Tractament de reperfusió; Factor de risc Objective The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. Methods We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. Results In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. Interpretation Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy.

Objectives: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). Methods: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. Results: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. Significance: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

Background and Purpose: Thrombophilic gene alterations are a major risk factor for cerebral sinus vein thrombosis (CSVT). Up to 30% of all patients with cerebral sinus vein thrombosis (CSVT) are found to have thrombophilic defects such as prothrombin mutation (PTM) or factor V Leiden (FVL). Their repercussions on the plasma levels of dabigatran etexilate are unclear. In this prospective case–control study, we aimed to investigate whether thrombophilia in CSVT has an influence on dabigatran peak-plasma levels. Methods: We monitored 10 patients over 12 months with acute CSVT, genetic thrombophilia with off-label use of dabigatran etexilate 150 mg twice a day and measured dabigatran peak-plasma levels and radiological outcome. We also monitored patients without genetic thrombophilia with dabigatran etexilate 150 mg twice a day and compared the efficiency and dabigatran peak-plasma levels. Results: Patients with homozygote PTM had significantly lower dabigatran peak concentration compared to patients with FVL or the control group (23 ± 4.2 vs. 152.3 ± 27.5 and 159.6 ± 63.08; p-value ≤ 0.05) There was no significant difference in dabigatran etexilate plasma levels between the heterozygote PTM group compared to patients with FVL or the control group (p = 0.29). There was no correlation between dabigatran peak concentration and delayed thrombus dissolution. Conclusions: Dabigatran peak concentration was stable in patients with heterozygote FVL and heterozygote PTM, but not in homozygote PTM, compared to controls. Genetic screening for thrombophilia in patients after CSVT may be useful to make patient tailored therapeutic decisions regarding oral anticoagulation and may decrease thrombotic events.

Background For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. Methods We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. Results We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033–0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. Conclusion Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

ZusammenfassungWir berichten über ein 7‑jähriges Mädchen mit therapierefraktärer Okzipitallappenepilepsie, welche zu Beginn als Migräne fehlinterpretiert wurde. In weiterer Folge diskutieren wir die klinische Semiologie, die Elektrophysiologie und die Bildgebung v. a. im Hinblick auf die Differenzialdiagnose zur Parietallappenepilepsie.

Oral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen utilization by tissue and complex with free radicals. Beneficial effects are improved endurance performance and reduction fatigue in humans and animals. This pilot study reports the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters.

Epilepsiechirurgie ist eine hochwirksame Therapie mit kurativem Anspruch. Dies belegen inzwischen 3 Studien mit Klasse-1-Evidenz. Bei pharmakoresistenter fokaler Epilepsie mit einer Krankheitsdauer von fast 20 Jahren, mit kürzerer Krankheitsdauer von durchschnittlich 5 Jahren sowie bei Kindern wurde jeweils unabhängig voneinander gezeigt, dass Epilepsiechirurgie dem „best medical treatment“ hochsignifikant überlegen ist. Mithilfe multimodaler Untersuchungsmethoden (z.B. Langzeit-Video-EEG, hochauflösendes cMRT nach Epilepsieprotokoll, FDG-PET, neuropsychologische Testung, fMRT, ev. iktale SPECT-Untersuchung und Verrechnung mittels SISCOM, Postprocessing des cMRTs, „electric source imaging“ [ESI], Magnetenzephalographie [MEG], invasive Abklärung mittels Stereo-EEG-Elektroden oder subduralen Elektroden und WADA-Test) ist es in der prächirurgischen Epilepsiediagnostik nun möglich, Patienten einen epilepsiechirurgischen Eingriff anzubieten, die früher als schlechte oder aussichtslose Kandidaten für eine Epilepsiechirurgie eingeschätzt wurden. Epilepsy surgery is a highly effective therapy with the aim of long-term seizure control, i.e., to cure the epilepsy. Three different studies with class 1 evidence have shown this. In patients with drug-resistant epilepsy (DRE) lasting for nearly 20 years, shorter disease duration of about 5 years, or in children it has been shown independently that epilepsy surgery is highly superior to best medical treatment. Using multimodal techniques (e.g., long-term video EEG, high-resolution cerebral MRI according to epilepsy protocol, FDG-PET, neuropsychological testing, fMRI, ictal SPECT with SISCOM, MRI postprocessing, electric source imaging [ESI], magnetoencephalography [MEG], invasive recording with stereo-EEG electrodes or subdural electrodes and WADA test), it is possible nowadays to offer epilepsy surgery to patients who were previously not regarded as promising candidates for epilepsy surgery. (VLID)4920089 Version of record

Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.

Many people who have had a stroke have trouble moving, even after therapy with the best experts and methods. New ways to make stroke therapy more effective could help people recover more effectively. Some research groups have developed brain-computer interface (BCI) systems that can measure when a stroke patient imagines hand movement by recording brain waves. We developed a BCI that used each patient’s brain activity to control a muscle stimulator and a monitor during therapy. The patients got rewarding feedback during therapy when they imagined a movement correctly. We tested 51 patients, some of whom had a stroke many years ago. Forty nine patients improved after the therapy, based on the results of standardized tests. Therefore, BCI-based therapy could help some stroke patients. We think there will be further advances in the next several years that will lead to more effective therapies using BCIs.

Immunization by means of vaccination is a global health success story, saving millions of lives every year. In this regard, the epidemiology of measles, rabies, polio, rubella, varicella, influenza and mumps infections, all of which can harm the nervous system, could be contained by global vaccination campaigns. In addition, toxoid vaccines against bacterial toxins such as tetanus and diphtheria are indispensable and effective interventions for toxin-mediated neurologic diseases.

Introduction Adult brainstem gliomas (BSGs) are rare central nervous system tumours characterized by a highly heterogeneous clinical course. Median survival times range from 11 to 84 months. Beyond surgery, no treatment standard has been established. We investigated clinical and radiological data to assess prognostic features providing support for treatment decisions. Methods 34 BSG patients treated between 2000 and 2019 and aged ≥ 18 years at the time of diagnosis were retrospectively identified from the databases of the two largest Austrian Neuro-Oncology centres. Clinical data including baseline characteristics, clinical disease course, applied therapies, the outcome as well as neuroradiological and neuropathological findings were gathered and analysed. The tumour apparent diffusion coefficient (ADC), volumetry of contrast-enhancing and non-contrast-enhancing lesions were determined on magnetic resonance imaging scans performed at diagnosis. Results The median age at diagnosis was 38.5 years (range 18–71 years). Tumour progression occurred in 26/34 (76.5%) patients after a median follow up time of 19 months (range 0.9–236.2). Median overall survival (OS) and progression-free survival (PFS) was 24.1 months (range 0.9–236.2; 95% CI 18.1–30.1) and 14.5 months (range 0.7–178.5; 95% CI 5.1–23.9), respectively. Low-performance status, high body mass index (BMI) at diagnosis and WHO grading were associated with shorter PFS and OS at univariate analysis (p p = 0.018). Conclusion ECOG, BMI, WHO grade and ADC values were associated with the survival prognosis of BSG patients and should be included in the prognostic assessment.

Past research has demonstrated a relationship between déjà vu and the entorhinal cortex in patients with wider medial temporal lobe damage. The aim of the present research was to investigate this crucial link in a patient (MR) with a selective lesion to the left lateral entorhinal cortex to provide a more direct exploration of this relationship. Two experiments investigated the experiences of déjà vécu (using the IDEA questionnaire) and déjà vu (using an adapted DRM paradigm) in MR and a set of matched controls. The results demonstrated that MR had quantitatively more and qualitatively richer recollective experiences of déjà vécu. In addition, under laboratory-based déjà vu conditions designed to elicit both false recollection (critical lures) and false familiarity (weakly-associated lures), MR only revealed greater memory impairments for the latter. The present results are therefore the first to demonstrate a direct relationship between the entorhinal cortex and the experience of both déjà vu and déjà vécu. They furthermore suggest that the entorhinal cortex is involved in both weakly-associative false memory as well as strongly-associative memory under conditions that promote familiarity-based processing.

The first and most important step in establishing diagnosis of epilepsy consists of careful history taking from patients and witnesses. The clinical evaluation of the event will lead the indication for further diagnostic tests including e.g. EEG and MRI. Hence, identifying the paroxysmal event as epileptic or non-epileptic is the very first step in the diagnostic process. Paroxysmal events pose a clinical challenge, as these are unpredictable and do not usually occur in the doctor's office. History taking, hunting for witness reports and home-video recordings are the main tools to conclude whether a paroxysmal event is a seizure or not. In this review, we describe the most common differential diagnoses of epileptic seizures, including syncope, psychogenic non-epileptic seizures, as well as a variety of paroxysmal conditions and behaviours of all age groups. Misdiagnosis of non-epileptic events as epilepsy may not only defer the correct diagnosis and treatment but also poses additional risk by prescribing antiepileptic drugs unnecessarily. Moreover, missing the diagnosis of epilepsy implies risk of additional seizures and therefore possibly injuries, sudden death in people with epilepsy, or status epilepticus. Studies have shown that patient and witness accounts are unreliable in a high percentage of cases. Therefore, the core competency of doctors and medical professionals assessing paroxysmal events is knowledge of the clinical features that help define the different aetiologies, thus empowering them to establish the most accurate appraisal of an event. [Published with video sequences].

Emerging and future applications of robotic systems pose unique self-adaptation challenges. To support the research needed to address these challenges, we provide an extensible repository of robotic mission adaptation exemplars. Co-designed with robotic application stakeholders including researchers, developers, operators, and end-users, our repository captures key sources of uncertainty, adaptation concerns, and other distinguishing characteristics of such applications. An online form enables external parties to supply new exemplars for curation and inclusion into the repository. We envisage that our RoboMAX repository will enable the development, evaluation, and comparison of much-needed self-adaptation approaches for the robotic systems domain.

Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy. Some, such as hypoglycaemia or severe hyponatraemia, can be fatal without prompt identification and treatment. Failure to identify seizures associated with recreational drug or alcohol misuse can lead to inappropriate AED treatment, as well as a missed opportunity for more appropriate intervention. In individuals with established epilepsy on treatment, some laboratory monitoring is desirable at least occasionally, in particular, in relation to bone health, as well as in situations where changes in AED clearance or metabolism are likely (extremes of age, pregnancy, comorbid disorders of renal or hepatic function). For any clinician managing people with epilepsy, awareness of the commoner derangements associated with individual AEDs is essential to guide practice. In this article, we review indications for tests on blood, urine and/or cerebrospinal fluid in patients presenting with new-onset seizures and status epilepticus and in people with established epilepsy presenting acutely or as part of planned monitoring. Important, but rare, neurometabolic and genetic disorders associated with epilepsy are also mentioned.

Background Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called “(auto)immune epilepsy.” The concept of “acute symptomatic seizures” may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. Methods Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. Results Patients had surface antibodies against the N-methyl-d-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P P P P P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. Conclusion Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Neurological disorders in pregnancy (NDPs) pose challenges to both obstetricians and neurologists. These diseases or their treatment may have adverse effects on the health of the fetus or complicate the course of the pregnancy, delivery, and postpartum period. Vice versa, the metabolic and endocrine changes associated with pregnancy may affect the mother’s neurological health. The care for a patient with an NDP is further complicated by the lack of clinical studies in this population, misinformation of patients regarding the risks associated with pregnancy when suffering from a neurological condition, and insecurity on the part of many physicians confronted with this constellation. Three different scenarios regarding the interdependency of pregnancy and neurological disease are possible. Most patients with NDPs suffer from a pre-existing condition such as epilepsy or multiple sclerosis, whose occurrence is unrelated to the pregnancy per se but nonetheless raises specific pregnancy-related concerns. The second group of NDP patients is afflicted with a neurological disorder observed with increased incidence during pregnancy (e.g. cerebrovascular disease and peripheral nerve compression syndromes). The third category comprises patients suffering from conditions exclusively seen in the pregnant, for example (pre-)eclampsia and amniotic fluid embolism. The subdivisions delineated here are reflected in the organization of this chapter. The aim is to provide a practical overview of the most frequent neurological conditions in childbearing women, highlighting the pregnancy-related issues and focusing on the management of these patients, which requires a highly interdisciplinary approach.

Purpose of review Functional neuroimaging with PET and SPECT is a commonly used tool in presurgical evaluation. The following article reviews the literature of PET and SPECT in presurgical assessment of epilepsies published in the last year. Recent findings FDG-PET adds concomitant information in temporal and extratemporal lobe epilepsy in adults and children. The pattern of hypometabolism in FDG-PET is a good additional predictor or seizure outcome in TLE with mesial temporal sclerosis or negative MRI. There is growing evidence that diagnostic value of FDG-PET increases with postprocessing. Although several methods were applied in the reviewed literature, all of them seem to outperform the visual analysis. Imaging of the epileptic focus with ictal SPECT is depending on short injection latencies. It is particularly useful in patients with nonlesional MRI and mostly of extratemporal localization. Areas of hyperperfusion remote of SOZ are reflecting the epileptic network. Combining more concordant investigations including PET and SPECT in MRI-negative evaluation adds to better presurgical stratification and therefore, better postsurgical outcome. FET-PET shows increased uptake in status epilepticus. Summary PET and SPECT are important investigations to localize the epileptic focus in temporal lobe and nonlesional extratemporal epilepsies. Postprocessing for both modalities is important to increase diagnostic value.

Nuklearmedizinische Untersuchungen wie PET und SPECT werden v. a. bei nichtlasionellen Epilepsien in der prachirurgischen Epilepsiediagnostik eingesetzt. Auch bei unauffalliger MRT ist ein Hypometabolismus in der FDG-PET indikativ fur den epileptogenen Fokus, zudem kann sie bei Patienten mit limbischer Enzephalitis einen meist temporalen Hypermetabolismus darstellen. Iktales SPECT hat eine besonders hohe lokalisatorische Wertigkeit, wenn die Anfalle komplex-fokal sind und langer als 15 s dauern. Allerdings ist der Aufwand fur diese Diagnostik mit mehreren Tagen Video-EEG-Monitoring hoch. Sie wird daher bei nichtlasionellen oder diskordanten Fallen angewendet. Die iktale SPECT sollte mittels „post-processing“ vom interiktalen SPECT subtrahiert und auf das MRT koregistriert werden (z. B. SISCOM).

Zusammenfassung Hintergrund Das Manuskript ist eine aktualisierte und stark erweiterte Version der 2012 entstandenen DGN-Leitlinie zum ersten epileptischen Anfall und Epilepsien im Erwachsenenalter. Ziel der Leitlinie ist es, den gegenwärtigen Stand des Wissens zur Diagnostik und Therapie anhand der zur Verfügung stehenden wissenschaftlichen Literatur zusammenzufassen und damit zur Verbesserung der diagnostischen und therapeutischen Abläufe und deren Vereinheitlichung beizutragen.Die Leitlinie behandelt ausschließlich Epilepsien im Erwachsenenalter, Epilepsien bei Kindern werden nicht berücksichtigt. Ebenso werden der Status epilepticus sowie Anfälle infolge von immunvermittelten Erkrankungen des Gehirns nicht behandelt, da hierzu eigene Leitlinien vorliegen. Methodik Das Leitliniengremium wurde durch Experten der Neurologie gebildet, die eine besondere Expertise auf dem Gebiet der Epilepsie besitzen und sowohl aus dem klinischen als auch aus dem niedergelassenen Bereich kommen. Neben der Deutschen Gesellschaft für Neurologie (DGN) sind auch die Deutsche Gesellschaft für Neurochirurgie e. V. (DGNC), die Österreichische Sektion der Internationalen Liga gegen Epilepsie, die Schweizerische Liga gegen Epilepsie sowie die Luxemburgische Gesellschaft für Neurologie beteiligt. Es wurde darauf geachtet, auch Mitglieder der jüngeren Generation in das Redaktionskomitee aufzunehmen. Die seit der letzten Ausgabe der Leitlinie 2012 neu erschienene Literatur wurde gesichtet und in die aktuelle Fassung eingearbeitet. Die Methodik der Leitlinienentwicklung entsprach einem nominalen Gruppenprozess und einem modifizierten Delphi-Verfahren (Vorlage zuvor produzierter Texte oder Tabellen, mehrstufige schriftliche Befragungsmethode, Rückkopplungsprozess, Information der Teilnehmer über die Gruppenantwort, Diskussion aller Kommentare mit ggf. daraus resultierender Überarbeitung des Entwurfes, Gruppenmitglieder haben die Möglichkeit einer Überprüfung bzw. eines Vergleichs ihrer Aussagen). Der Konsensprozess entsprach den Regeln der AWMF und der DGN zum Umgang mit potenziellen Interessenkonflikten. Ergebnis Wichtigste Neuerung ist eine erneuerte Definition der Epilepsie, ein wesentlich neuer Aspekt dieser Definition ist die Frage, ob eine Epilepsie „überwunden“ werden kann. Auch zur Klassifikation von Anfällen und Epilepsien ist eine neue Version erschienen, die im Wesentlichen wieder der Version von 1989 entspricht. Als wichtigste therapeutische Neuerung hat sich seit der letzten Fassung der Leitlinie von 2012 das Spektrum der Antiepileptika deutlich erweitert, neue Medikamente sind zugelassen worden (Perampanel, Brivaracetam) oder haben ihre Zulassung erweitert (Zonisamid, Lacosamid, Eslicarbazepinacetat). Der Einsatz von Valproinsäure bei Frauen und Mädchen wird zunehmend kritisch gesehen, in der Leitlinie wird ausführlich auf diese Problematik und die Behandlung von Frauen mit Epilepsie eingegangen. Neben der medikamentösen Therapie werden operative Therapien und Stimulationsverfahren behandelt.Psychosoziale Aspekte sowie die Bereiche Fahrtauglichkeit, Ausbildung und Beruf sowie die Problematik des Absetzens von Medikamenten bei langjähriger Anfallsfreiheit werden umfangreicher als bisher diskutiert, auch wurden Abschnitte zur Mortalität, zu Erste-Hilfe-Maßnahmen und zu akuten symptomatischen Anfällen (ASA) neu in die Leitlinie aufgenommen. Ein eigenes Kapitel zur Pharmakokinetik befasst sich mit dem Interaktionspotenzial von Antiepileptika mit anderen Medikamenten sowie dem möglichen Einfluss auf Vitamin- und Hormonspiegel. Insbesondere Therapien maligner Erkrankungen können durch Interaktionen kritisch beeinflusst werden.

Depression ist neben der Angsterkrankung die haufigste Komorbiditat bei Menschen mit Epilepsie (MmE). Bei Auftreten dieser Komorbiditat ist die Lebensqualitat signifikant reduziert und das Risiko fur Suizidalitat drastisch erhoht – insbesondere in den ersten 12 Monaten nach Diagnosestellung der Epilepsie. Es kann zu einer Zunahme der Anfallsfrequenz kommen. Depression bei MmE wird haufig nicht erkannt und behandelt. Es ist daher ratsam, Screenings fur Depression durchzufuhren. Der ursachliche Zusammenhang dieser Komorbiditaten ist ungeklart. Therapeutische Optionen sind die Optimierung der Antiepileptikatherapie, Antidepressiva, insbesondere selektive Wiederaufnahmehemmer, kognitive Verhaltenstherapie und Vagus-Nerv-Stimulator. Klinische Studien fur die Wirksamkeit dieser Behandlungen sind unzureichend und werden in Zukunft dringend benotigt.

The objective of this study was to analyse the Neurothrombectomy Network registry of the Neuromed Campus (NMC) of the Kepler University Hospital in Linz (Austria). The data were compared to the results of recently published thrombectomy trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT and THRACE). We retrospectively studied 246 patients with acute ischemic stroke who underwent thrombectomy between January 2012 and December 2015 at the NMC in Upper Austria. The main outcome measures were modified Rankin scale (mRS) score 0–2 at 90 days, all-cause mortality and stroke or thrombectomy-related mortality at discharge, as well as 90 days postdischarge. The median age was 70.4 years (IQR 59.9–76.9) and the median NIHSS at admission 16 (IQR 13–20). The thrombolysis in cerebral infarction (TICI) scale 2b–3 recanalization was achieved in 87.4%, 11.0% of the patients died in hospital and an additional 6.1% within 90 days after discharge. After 90 days, 56.5% had a mRS score 0–2. These data suggest that the positive results of thrombectomy reported in several randomized controlled studies can be achieved in routine clinical practice; therefore, the setting of an organized, regional stroke network proved an effective and appropriate method for delivering regional thrombectomy stroke treatment.

Die Epilepsie ist eine der haufigsten neurologischen Erkrankungen im Erwachsenenalter. Behandlung der ersten Wahl fur fokale Epilepsien ist die medikamentose Therapie. Allerdings sollte bereits nach einem nicht Ansprechen auf zwei First-line-Antikonvulsiva die Zuweisung in ein epilepsiechirurgisches Zentrum zur Evaluierung eines moglichen neurochirurgischen Eingriffs erfolgen. Die nichtinvasive prachirurgische Phase-1-Abklarung beinhaltet Anamnese inklusive Fremdanamnese, klinische Untersuchung, strukturelle und funktionelle Bildgebung, simultanes Video-EEG-Monitoring sowie eine neuropsychologische Untersuchung. Kann die epileptogene Zone nicht ausreichend eingegrenzt werden, kann eine invasive Phase 2 mit Implantation von subduralen Streifen- oder Plattenelektroden sowie stereotaktisch implantierten Tiefenelektroden angeschlossen werden. Wird die Indikation zum epilepsiechirurgischen Eingriff gestellt, ist eine penible Planung der Technik sowie des Resektionsausmases essenziell, um das bestmogliche Ergebnis fur den Patienten zu erzielen. Bei Patienten mit Temporallappenepilepsie kann durch eine Operation in 60–80 % der Falle Anfallsfreiheit erzielt werden.

Purpose A number of studies have suggested that depressed mood is one of the most important predictors of quality of life (QoL) in patients with epilepsy. However, the QoL measure used in previous studies was limited to the Quality of Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of QOLIE with measures of depression is influenced by the properties of the instruments used rather than being a valid effect. By using visual analogue scales, the current study aimed to clarify whether depression and QoL are truly correlated in patients with epilepsy. Methods Data from a sample of 261 outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley Outpatient Department, St George's Hospital in London, were analyzed. Patients were screened using the European Quality-of-Life scale (EQ-5D-3L) which includes an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), the Beck Depression inventory—II (BDI-II), the Hospital Anxiety and Depression scale (HADS), and the Major Depression inventory (MDI). Results Depression was found to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42 to 0.51 and r 2 coefficients ranging between 0.18 and 0.26. In addition, we identified patients who were depressed according to DSM-IV criteria (MD) and those with atypical forms of depression (AD). The EQ-5D-3L scores in these subjects compared with those without depression (ND) showed a different impact of AD and MD on QoL. Conclusions The relationship between depression and QoL in people with epilepsy has been demonstrated to be a robust and valid effect, not a result of potential bias of the specific measures used. However, the strength of the association is influenced by the individual instrument. Atypical or subsyndromic forms of depression are as relevant as DSM-based depression in terms of impact on QoL.

The present research explored the effects of selective impairment to the entorhinal cortex on the processes of familiarity and recollection. To achieve this objective, the performance of patient MR, who has a selective impairment of the left entorhinal cortex, was compared to that of age and IQ-matched controls. Four experiments tested participants’ recognition memory for familiar and unfamiliar faces and words. In all experiments, participants studied lists of items and then completed an old/new recognition test in which they also made remember/know/guess judgements. A fifth experiment tested participants’ priming associated with the familiarity process. MR had intact performance in both face recognition experiments as well as having intact performance in pseudoword recognition. Crucially, however, in the familiar word experiment, whilst MR performed similarly to control participants in terms of recollection, she showed a marked impairment in familiarity. Furthermore, she also demonstrated a reversed conceptual priming effect. MR’s impairment is both material-specific and selective for previously encountered but not new verbal items (pseudowords). These findings provide the first clear evidence that selective impairment of the entorhinal cortex impairs the familiarity process for familiar verbal material whilst leaving recollection intact. These results suggest the entorhinal cortex does not have attributes reflective of both recollection and familiarity as previously assumed, but rather supports context-free long-term familiarity-based recognition memory.

Background: The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. Methods: We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis. The discharge diagnoses served as the reference standard for testing the clinical algorithm for two conditions: use of all the clinical information available on a patient during the first week of hospital admission assuming undefined autoantibody status and microbiological test results (C1) vs. consideration of all the information available on a patient, including the results of serological and microbiological testing (C2). Results: Eighty-four patients (33 autoimmune, 51 infectious encephalitis) were included in the study. Fifty-one (17 autoimmune, 34 infectious) had a definite clinical diagnosis. The two groups differed significantly for the presence of headache, fever, epileptic seizures, and CSF cell-count at presentation. Application of the clinical algorithm resulted in a low sensitivity (58%) and very low specificity (8%) for the diagnosis of possible autoimmune encephalitis. The latter increased considerably in the subgroups of probable and definite autoimmune encephalitis. Whereas the sensitivity of the individual diagnostic categories was clearly time-dependent, the specificity rested foremost on the knowledge of the results of microbiological testing. Anti-CASPR2- and -LGI1-associated autoimmune encephalitis and tick-borne virus encephalitis presented particular diagnostic pitfalls. Conclusions: We define clinical symptoms and paraclinical test results which prove valuable for the differentiation between infectious and autoimmune encephalitis. Sensitivity and specificity of the clinical algorithm clearly depended on the amount of time passed after hospital admission and knowledge of microbiological test results. Accepting this limitation for the acute setting, the algorithm remains a valuable diagnostic aid for antibody-negative autoimmune encephalitis or in resource-poor settings. The initiation of immune therapy however should not be delayed if an autoimmune etiology is considered likely, even if the diagnostic criteria of the algorithm are not (yet) fulfilled.

The present research explored the role of the medial temporal lobes in object memory in the unique patient MR, who has a selective lesion to her left lateral entorhinal cortex. Two experiments explored recognition memory for object identity and object location in MR and matched controls. The results showed that MR had intact performance in an object location task [MR=0.70, controls=0.69, t(6)=0.06, P>0.05], but was impaired in an object identity task [MR=0.62, controls=0.84, t(6)=-4.12, P

The purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression.A consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer.From a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0-17.5; p0.001). Self-reported aggressiveness was reported as "always" a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p0.001) and polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p=0.183).Self-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved.