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New onset temporal seizures are increasingly encountered in adult patients. Many of those fulfill diagnostic criteria for possible or definite limbic encephalitis (LE). LE is associated with autoantibodies (autoABs) against neuronal surface structures ('neuronal' autoABs), 'onconeuronal' or GAD65. AutoABs can emerge in a paraneoplastic setting. However, by far not all patients with possible/definite LE have an oncological history. AutoABs have also found to arise in the context of viral encephalitis. Rare associations between autoAB-positive LE and human herpes virus 6 (HHV-6) infection have been as well reported. Our present analysis was dedicated to learn about potentially different autoAB spectra and HHV-6 detection rates in adult-onset temporal seizure patients with possible LE and largely different time spans between first seizure events and referral to a tertiary epileptological center due to pharmacoresistent seizures. We scrutinized serum/CSF samples obtained from adults with 'early diagnosis' of possible LE (≤ 30 months after first seizure event; n = 94) versus a patient group with 'late diagnosis' of possible LE (≥ 97 months; n = 45) for the presence of autoABs and HHV-6 DNA. AutoABs were detected in CSF and/or serum samples (n = 20) in 21.3 % of the early diagnosis patients with the highest abundance of anti-LGI1 (n = 8), significantly more frequent than in the late diagnosis group (autoAB positive: n = 4 (8.9 %); *p < 0.05, Fisher's Exact Test). Quantitative PCR revealed viral HHV-6 DNA in only one serum sample of the early diagnosis cohort but no evidence in corresponding CSF samples or in any sample of the late diagnosis group. The present data demonstrate a higher incidence of distinct autoABs in adults with early diagnosis of possible LE. The distinct spectra of autoABs have to be taken into account in the differential diagnosis of possible LE patients with short versus more sustained duration of temporal seizure activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Neuroinflammation and disruption of blood brain barrier (BBB) are important players in epileptogenesis, ictogenesis and pharmacoresistance. In this context, we investigated blood levels of HMGB1 and other inflammatory and BBB markers after generalized and focal to bilateral tonic-clonic seizures in serum, summarized under the term generalized convulsive seizures (GCS)., Methods: We included consenting adults who were admitted to the epilepsy monitoring unit. Blood samples were drawn at baseline and immediately after a GCS as well as after 2, 6 and 24 h. We measured leukocytes, c-reactive protein (CRP), the danger-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1) and S100, receptor of advanced glycation end products (RAGE) alongside the BBB markers intercellular adhesion molecule-1 (ICAM1) and matrix metalloproteinase 9 (MMP9). Noradrenaline and lactate measurements were available from a previous study. P-levels <0.05 were regarded as significant., Results: Twenty-eight patients with 28 GCS were included. Leukocytosis occurred immediately after GCS and normalized within two hours (p < 0.001). S100 and HMGB1 both increased by ∼80 % (p < 0.001). MMP9 peaked after six hours with levels at 48.6 % above baseline. RAGE decreased by 17.6 % with a nadir at 24 h. CRP increased by 118 % with a peak at 24 h. ICAM1 remained stable (p = 0.068). Postictal HMGB1 correlated with postictal leukocytosis (r = 0.42; p = 0.025) and with MMP9 levels six hours later (r = 0.374; p = 0.05). Postictal lactate levels correlated with MMP9 at 6 h (r = 0.48; p = 0.01) and CRP at 24 h (r = 0.39; p = 0.04). Postictal noradrenaline correlated with lactate (r = 0.57; p = 0.02) and leukocytes (r = 0.39; p = 0.047)., Discussion: The serum level of the DAMPs HMGB1 and S100 increase immediately after GCS. The hypothetical mechanism includes central nervous processes, such as glutamate toxicity and ROS release from seizing neurons but also muscular tissues. BBB breakdown is marked by the release of MMP9. Further research is needed to understand the complex interactions between electrical and metabolic stress, neuroinflammation and BBB mechanics in seizures and epilepsy., Conclusion: Our study reveals signs of inflammation, neuronal damage and transitory disruption of BBB following single GCS, underscoring the widespread and possibily detrimental effects of recurrent seizures on brain properties. The long term impact on the disease course, however, is unclear., Competing Interests: Declaration of Competing Interest RS has received fees as speaker or consultant from Bial, Cyberonics, Desitin, EISAI, LivaNova, Novartis and UCB Pharma. RDN has received fees as a speaker from EISEI. CW and SH have nothing to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Seizure-related modulation of heart rate (HR) was examined extensively in previous studies. However, the overall effect on HR attributable to epileptic seizures is difficult to determine, given the considerable fluctuations of HR before and during seizures. Here, we developed a semi-automatic procedure allowing quantification of the total impact of seizures on HR and determination of temporal relationships between seizure onset assessed by intracranial EEG (iEEG) and ECG., Methods: ECG and iEEG data of epilepsy patients undergoing video-EEG telemetry for epilepsy surgery with bilateral hippocampal depth electrodes were analysed retrospectively. Consecutive RR intervals and HR profiles were determined using R detection algorithms. Novel features including the normalized ictal area under the curve (niAUC), as well as the time point of ECG onset (HR breakpoint) were calculated. Selected HR features were compared to widely-used manually acquired measures. Data are given as median ± SD., Results: Fifteen patients had a total of 34 seizures with left-hippocampal and 37 seizures with right-hippocampal onset. HR increased by 9 ± 19% during seizures. Latency between iEEG seizure-onset to the HR breakpoint was 23 ± 22 s. No significant difference between left- and right-hippocampal seizures was observed with respect to HR increases, latencies and niAUC. A comparison between results of the semi-automatic and manual approach revealed that ictal HR changes showed a higher correlation (r = 0.6) than niAUC (r = 0.4)., Conclusions: The proposed semi-automatic approach to analyze continuous HR data provides useful tools for estimating the overall effect of seizures on HR in greater detail. Our results suggest that the side of hippocampal seizure onset has no significant effect on the latency and extent of ictal HR changes. The algorithms may be of further use in clinical research and the development of seizure detection devices., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Focal cortical dysplasia (FCD) is a frequent finding in drug resistant epilepsy. The aim of our study was to evaluate an isotropic high-resolution 3-dimensional Fluid-attenuated inversion recovery sequence (3D FLAIR) at 3T in comparison to standard 2D FLAIR in the diagnosis of FCD., Materials and Methods: In a prospective study, 19 epilepsy patients with the MR diagnosis of FCD were examined with a sagittal 3D FLAIR sequence with modulated refocusing flip angle (slice thickness 1.10mm) and a 2D FLAIR in the coronal (thk. 3mm) and axial planes (thk. 2mm). Manually placed regions of interest were used for quantitative analysis. Qualitative image analysis was performed by two neuroradiologists in consensus., Results: Contrast between gray and white matter (p ≤ 0.02), the lesion (p ≤ 0.031) or hyperintense extension to the ventricle (p ≤ 0.021) and white matter was significantly higher in 2D than in 3D FLAIR sequences. In the visual analysis there was no difference between 2D and 3D sequences., Conclusion: Conventional 2D FLAIR sequences yield a higher image contrast compared to the employed 3D FLAIR sequence in patients with FCDs. Potential advantages of 3D imaging using surface rendering or automated techniques for lesion detection have to be further elucidated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Autonomic symptoms during seizures may provide information on seizure onset zone. We investigated whether changes in heart rate (HR) and HR variability (HRV) occur during subclinical electrographic seizure patterns, and whether these have a localising/lateralising value., Methods: EEG and ECG recordings of pharmacoresistant epilepsy patients who underwent intracranial video-EEG telemetry were reviewed. Ultra-short-term HRV expressed as standard deviation of the mean before, during and after the subclinical seizure pattern was determined in 10s epochs. Statistics were done with a linear mixed regression model. Values are expressed as mean+/-SD., Results: 26 patients (38+/-10 years, 13 of either gender) have been included; 7 patients with temporal lobe epilepsy (TLE) of either side as well as 7 (right-sided lesion) and 5 patients (left-sided lesion) with frontal lobe epilepsy (FLE). A total of 74 subclinical events (2-3 per patients) were analysed. Pooled data for HR only weakly increased during and after the subclinical pattern with a mean HR of 80+/-10 bpm before to 82+/-11 bpm during (p=0.03) and 81+/-10 bpm after subclinical patterns (p=0.06). HR was higher in patients with left TLE as compared to right TLE (p=0.001). In FLE patients only, the change in HR was correlated with the spatial extent of electrographic pattern localised (p=0.03). Mean HRV did not change during or after subclinical patterns. HRV was; however, lower in TLE patients with left-sided subclinical patterns as compared to right-sided patterns (pre-event HRV left 13+/-6 ms, right 34+/-16 ms)., Conclusions: Our data revealed only minimal changes in autonomic cardiac function during highly localised electrographic seizure patterns and this had no localising/lateralising value.