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OBJECTIVE: Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and non-surgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique.; METHODS: We retrospectively studied surgical procedures, electro-clinical parameters, MRI results, and follow-up data in all children who had undergone hemispherotomy between 2001 and 2018 at our institution. We used logistic regression models to analyze the influence of different factors on seizure outcome.; RESULTS: 152 patients were eligible for seizure outcome analysis only. Of these, 140 cases had complete follow-up data for ≥24 months and provide the basis for the following results. The median age at surgery was 4.3years (range 0.3-17.9years). Complete disconnection (including the insular tissue) was achieved in 63.6% (89/140). At two-year follow-up, seizure freedom (Engel class IA) was observed in 34.8% (8/23) with incomplete insular disconnection while this was achieved in 88.8% (79/89) with complete surgical disconnection (p

Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear aetiology for a period of less than 24 h. Observed psychological, neuroanatomical and hormonal differences between the sexes in episodic memory suggest sex-specific differences in memory disorders such as TGA. The aim of this study was to determine sex-specific differences in cardiovascular risk profiles, recurrences and magnetic resonance imaging (MRI). In total, 372 hospitalised TGA patients between 01/2011 and 10/2021 were retrospectively analysed. Comparisons were made between female and male TGA patients and compared to 216 patients with acute stroke. In our sample, women were overrepresented (61.8%), especially compared to the general population in the 65–74 age category (χ2 = 10.6, p < 0.02). On admission, female TGA patients had significantly higher systolic blood pressure values and a higher degree of cerebral microangiopathy compared to male TGA patients, whereas acute stroke patients did not. No sex-specific differences were observed with respect to recurrences or hippocampal DWI lesions. Our data demonstrate sex-specific differences in TGA. The higher blood pressure on admission and different degree of cerebral microangiopathy in female TGA patients supports the theory of blood pressure dysregulation as a disease trigger. Distinct precipitating events in female and male patients could lead to differences in the severity and duration of blood pressure abnormalities, possibly explaining the higher incidence in female patients.

OBJECTIVE: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set. METHODS: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years). RESULTS: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%. SIGNIFICANCE: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy. ispartof: EPILEPSIA vol:62 issue:4 pages:1005-1021 ispartof: location:United States status: published

Typische MRT-Veranderungen bei limbischer Enzephalitis (LE) sind FLAIR- bzw. T2-Hyperintensitaten und Volumenzunahmen (Schwellungen) in temporomesialen Strukturen (insbesondere der Amygdala), die sich im Verlauf dynamisch darstellen konnen (bilateral oder seitenwechselnd, zu- bzw. abnehmend). Die Rolle der Bildgebung ist es, den klinischen Verdacht auf eine LE zu verstarken, noch bevor der Antikorperstatus bekannt ist. Dabei geht es auch darum, wesentliche Differenzialdiagnosen (periiktale MRT-Veranderungen, Herpes-simplex-Virus-Enzephalitis oder Tumoren) fruh unwahrscheinlich zu machen. Zwar unterscheidet die Bildgebung nicht zwischen limbischen Autoimmunenzephalitiden (meist mit Antikorpern gegen Antigene auf neuralen Oberflachen, z. B. Anti-LGI1-Enzephalitis) und autoimmun-assoziierten Epilepsien bei LE (oft mit Antikorpern gegen intrazellulare neurale Antigene, z. B. bei LE mit GAD-Antikorpern). Die MRT ist aber in der Lage, Verlaufe zu dokumentieren, seien es rucklaufige temporomesiale Veranderungen (z. B. nach erfolgreicher Therapie) oder die Entwicklung einer Hippocampussklerose.

Purpose Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements. Methods/Results High-resolution 3 Tesla (T) magnetic resonance imaging (MRI) did not reveal clear-cut lesions. Invasive video-electroencephalography (EEG) with depth electrodes along the cingulate sulcus (bilateral; patients 1 and 3), right; patient 2 provided congruent results for a circumscribed seizure onset zone within the medial frontal lobe (right: patients 1 and 2; left: patient 3). Topectomies were performed in all patients. Histopathology revealed a small focal cortical dysplasia in the three cases (focal cortical dysplasia [FCD] IIA: patient 1; FCD IIB: patients 2 and 3). All patients remained completely seizure-free since surgery (Engel 1A; follow-up: 9–28 months). Conclusion Ictal fear associated with hyperkinetic semiology points to a seizure-onset zone within the anteromedial frontal lobe (anterior cingulate gyrus). Ictal semiology is crucial for the placement of depth electrodes, especially in MRI-negative cases. These cases illustrate a clinical advantage to the new International League against Epilepsy (ILAE) seizure classification, emphasizing initial clinical symptoms.

Wir berichten uber 2 Patientinnen mit differenzialdiagnostisch schwieriger Konstellation. In beiden Fallen wurden durch den EEG-Befund bzw. anamnestische Details „falsche Fahrten“ gelegt. Implikationen fur die Praxis werden diskutiert.

Objective Some patients with genetic generalized epilepsy (GGE) may present with ambiguous and atypical findings and even focal brain abnormalities. Correct diagnosis may therefore be difficult. Methods We retrospectively collected six patients investigated on the epilepsy monitoring unit with MRI abnormalities mimicking focal cortical dysplasia (FCD‐like) or heterotopias, but with semiology and EEG features of GGE. We compared them to four additional patients with GGE and nonmigratory abnormalities. Results All six patients presented with frontal MRI lesions: radial (“transmantle,” n = 4), cortical‐subcortical (n = 1), and periventricular heterotopia (n = 1). Five had positive family histories. Semiologic lateralizing signs compatible with the lesion were seen in four. Five patients had 3/s spike‐wave complexes, with an asymmetric appearance in three. Regional EEG changes matched with the side of the abnormality in three patients. Invasive EEG (n = 2) or postoperative outcomes (n = 3) argued against an ictogenic role of the MRI abnormalities. Histology showed mild malformation of cortical development, but no focal cortical dysplasia. The six patients were finally diagnosed with juvenile myoclonic epilepsy (n = 2), juvenile absence epilepsy (n = 2), or GGE not further specified (nfs, n = 2). Compared to these patients, the other four (final diagnoses: childhood absence epilepsy, n = 1; perioral myoclonia with absences, n = 1; and GGE nfs, n = 2) had no lateralizing EEG findings. Significance Patients with GGE may have coincidental MRI abnormalities. These cases are challenging as frontal epilepsy and GGE can present with similar semiologies. GGE with coincidental FCD‐like lesions/heterotopias is in particular difficult to diagnose as patients have more lateralizing features (in semiology and EEG) than those with tumors. A detailed noninvasive presurgical evaluation may be justified. We point out red flags that may help to distinguish GGE from frontal epilepsy, even in the presence of brain abnormalities: 3/s spike waves (even if asymmetric), changing lateralizing signs at different times, and a positive family history hinting at GGE.

BACKGROUND AND OBJECTIVES: The SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate–galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic SLC35A2 gene variants. METHODS: This is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models. RESULTS: Two main phenotypes were associated with brain somatic SLC35A2 variants: (1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability and (2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy in 44/47 patients and was inconclusive in 3. The 47 patients harbored 42 distinct mosaic SLC35A2 variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, 4 (9.5%) in‐frame deletions/duplications, and 1 (2.4%) splicing variant. Variant allele frequencies (VAFs) ranged from 1.4% to 52.6% (mean VAF: 17.3 ± 13.5). At last follow-up (35.5 ± 21.5 months), 30 patients (63.8%) were in Engel Class I, of which 26 (55.3%) were in Class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel Class IA and Class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses. DISCUSSION: Brain somatic SLC35A2 gene variants are associated with 2 main clinical phenotypes, EE and DR-FE, and a histopathologic diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue, and surgical outcomes.

Hypochondroplasia is a skeletal dysplasia syndrome with an autosomal dominant inheritance. It may be associated with temporal lobe epilepsy. We present a series of four patients (two female, two male) with hypochondroplasia who presented at our center with drug refractory epilepsy. Clinical details and EEG and MRI findings led to a diagnosis of temporal lobe epilepsy in all four cases. The MRI findings indicate the epilepsy in hypochondroplasia may be associated with bilateral temporal lobe dysgenesis. Copyright © 2021 Elsevier Inc. All rights reserved.

Anteromedial temporal lobe structures seem to support processing of faces and facial expressions. However, differential effects of unilateral left or right temporal lobe resections (TLR) on face processing, recognition of facial expressions, and on BOLD response to faces in intact brain areas are not yet fully understood. Therefore, we compared 39 patients with unilateral TLR (18 left, 21 right) and 20 healthy controls regarding recognition of facial identity and emotional facial expressions as well as BOLD response to fearful and neutral faces. We found impaired recognition of facial identity following right TLR, which was paralleled by reduced BOLD response to faces irrespective of expression in the right fusiform and lingual gyrus in postsurgical fMRI. Right TLR patients also exhibited subtle impairments of emotion recognition as they needed higher intensity of facial expressions for correct responses in a morphing task. Accuracy of emotion recognition and subjective appraisals of facial expressions did not differ between groups. There was no specific reduction of BOLD response to fearful versus neutral faces in either patient group. Our results underline the specific role of the right anteromedial temporal lobe in processing of faces and facial expressions by showing changes in face processing following right TLR in behavioral as well as imaging data. Copyright © 2022. Published by Elsevier Ltd.

ObjectiveTo validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs).MethodsThe accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (ResultsThirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods.ConclusionsRSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies.SignificanceThe definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy. Objective: To validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs). Methods: The accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (3) using distance to the lesion, concordance with resected area and postoperative outcome. Performance was compared with three conventional methods: voltage maps, equivalent current dipole and a distributed source model. Results: Thirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods. Conclusions: RSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies. Significance: The definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy.

OBJECTIVE: We describe for the first time clinical characteristics in a series of 20 pre-surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning.; METHODS: Data on 20 patients with histologically confirmed MOGHE were retrospectively evaluated as to age at epilepsy onset and operation, seizure semiology, magnetic resonance imaging (MRI) localization, electroencephalography (EEG) patterns, extent of the operative resection, and postoperative seizure outcome.; RESULTS: Epilepsy began mainly in early childhood; however, symptoms did not manifest until adolescence or adulthood in 30% of patients. All patients had pathologic MRI findings. In 45% of patients the lesion was initially overlooked. Most commonly, the lesion was seen in the frontal lobe. Seizure semiology was characterized as follows: (1) epileptic spasms at epilepsy onset were common and (2) nocturnal hyperkinetic seizures during the course of the disease were rare. EEG always showed frequent interictal epileptic discharges. Two peculiar patterns were observed: (1) during sleep stage I-II, sub-continuous repetitive (0.5-1.5/s) unilateral plump spike/polyspike slow waves were seen and (2) during wakefulness, unilateral paroxysms of 2-2.5/s spike-wave complexes occurred. In total, 60% of patients were seizure-free 1year postoperatively. Postoperative seizure outcome was positively correlated with the extent of resection, age at epilepsy onset, and age at operation. Postoperative long-term outcomes remained stable in patients undergoing larger operations.; SIGNIFICANCE: MRI, EEG, and semiology already contribute to the diagnosis of probable MOGHE preoperatively. Because postoperative seizure outcomes depend on the extent of the resection, prior knowledge of a probable MOGHE helps to plan the resection and balance the risks and benefits of such an intervention. In patients undergoing larger operations, epilepsy surgery achieved good postoperative results; the first long-term outcome data were stable in these patients. © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Background: Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear etiology for a period of less than 24 h. TGA occurs as a single event in most cases. Prevalence rates of recurrent TGA vary widely from 5.4 to 27.1%. This retrospective study aimed to determine predictors for TGA recurrence.Methods: Cardiovascular risk profile and magnetic resonance imaging (MRI) of 340 hospitalized TGA patients between 2011 and 2020 were retrospectively analyzed. The median follow-up period amounted to 4.5 ± 2.7 years. Comparisons were made between TGA patients with and without subsequent recurrence.Results: TGA patients with subsequent recurrence were significantly younger (recurrent vs. single episode, 63.6 ± 8.6 years vs. 67.3 ± 10.5 years, p = 0.032) and showed a lower degree of cerebral microangiopathy compared to TGA patients without recurrence. The mean latency to recurrence was 3.0 years ± 2.1 years after the first episode. In a subgroup analysis, patients with at least five years of follow-up (N = 160, median follow-up period 7.0 ± 1.4 years) had a recurrence rate of 11.3%. A 24.5% risk of subsequent TGA recurrence in the following five years was determined for TGA patients up to 70 years of age without microangiopathic changes on MRI (Fazekas' score 0).Conclusion: Younger TGA patients without significant microangiopathy do have an increased recurrence risk. In turn, pre-existing cerebrovascular pathology, in the form of chronic hypertension and cerebral microangiopathy, seems to counteract TGA recurrence.

Background: Emotion dysfunction is a key symptom in patients with borderline personality disorder (BPD) and is considered a consequence of dysfunctional emotion regulation (e.g., reduced emotion acceptance). In the present functional MRI (fMRI) study, we investigated the neural correlates of habitual emotion acceptance in individuals with BPD.; Methods: Female patients with BPD and female healthy controls passively viewed negative and neutral movie clips of faces during fMRI. We assessed emotion acceptance using the Emotion Acceptance Questionnaire (EAQ). To examine brain activation associated with habitual emotional acceptance of negative stimuli, the EAQ score was included as a regressor of interest in brain data analyses of activation intensity during negative compared with neutral movies.; Results: We included 20 women with BPD and 20 heatlhy controls in our analysis. Compared with healthy controls, patients with BPD showed significantly more activation in frontostriatal brain regions (i.e., left superior frontal gyrus, right caudate) as well as in the left precuneus, left precentral gyrus, left posterior cingulate cortex and left hippocampus when confronted with negative (v. neutral) stimuli. Patients with BPD reported decreased emotion acceptance compared with healthy controls, and habitual emotion acceptance was inversely associated with activation of striatal areas (i.e., left putamen, left caudate) in patients with BPD.; Limitations: Causal conclusions are not possible. Comorbid diagnoses were not excluded, and only female participants were investigated. Stimuli were not rated immediately and may not be generalizable to all negative emotions. We cannot make any statements about other emotion-regulation strategies that may have been applied here.; Conclusion: Data indicate that striatal hyperactivation during the processing of negative stimuli in women with BPD is related to their decreased disposition to accept unpleasant emotional states. Thus, individuals with BPD may benefit from therapy approaches that focus on emotion acceptance in order to normalize emotional reactions. © 2019 Joule Inc. or its licensors

BACKGROUND: Emotion dysfunction and anhedonia are main problems in borderline personality disorder (BPD). In the present functional magnetic resonance imaging (fMRI) study, we investigated neural activation during the processing of happy faces and its correlates with habitual emotion acceptance in patients with BPD.; METHODS: 22 women with BPD and 26 female healthy controls watched movie clips of happy and neutral faces during fMRI without any instruction of emotion regulation. To associate neural activation with habitual emotion acceptance, we included individual scores of the Emotion Acceptance Questionnaire (EAQ) as a covariate in brain data analysis.; RESULTS: All participants showed amygdala, temporal and occipital activation during the processing of happy compared to neutral faces. Compared with healthy controls, patients with BPD showed significantly more activation within the bilateral caudate. We did not find significant correlations with emotion acceptance.; CONCLUSIONS: Our results indicate caudate hyperactivation in patients with BPD during the processing of happy faces. Although patients reported significantly less emotion acceptance of positive emotions, an association with neural activation was not detectable. Copyright © 2021 Elsevier Ltd. All rights reserved.

Background and purpose Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. Methods We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. Results Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test). Conclusions In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).

Objective: Presurgical evaluation has no established routine to assess reading competence and to identify essential "not to resect" reading areas. Functional models describe a visual word form area (VWFA) located in the midfusiform gyrus in the dominant ventral occipito-temporal cortex (vOTC) as essential for reading. We demonstrate the relevance and feasibility of invasive VWFA-mapping. Methods: Four patients with epilepsy received invasive VWFA-mapping via left temporo-basal strip electrodes. Co-registration of the results and additional data from the literature led to the definition of a region of interest (ROI) for a retrospective assessment of postoperative reading deficits by a standardized telephone-interview in patients with resections in this ROI between 2004 and 2018. Results: Electrical cortical stimulation disturbed whole word recognition and reading in four patients with structural epilepsy. Stimulation results showed distribution in the basal temporal lobe (dorsal mesencephalon to preoccipital notch). We identified 34 patients with resections in the ROI of the dominant hemisphere. Of these, 15 (44.1%) showed a postoperative reading deficit with a mean duration of 18.2 months (+/-32.4, 0.5-122). Six patients suffered from letter-by-letter (LBL) reading. Two patients had permanent LBL reading after resection in the ROI. Significance: We present evidence on the functional relevance of the vOTC for reading by (1) extra operative cortical stimulation of the VWFA and by (2) a retrospective case study of reading deficits in patients operated in this area. Reading assessments and data concerning essential reading structures should be included in the presurgical evaluation of patients with lesions in the left vOTC. (c) 2021 Elsevier Inc. All rights reserved.

OBJECTIVE: Rasmussen encephalitis (RE) is a progressive and destructive inflammatory disease of one hemisphere. Its cause is unknown. We investigated comorbidity and laterality factors that might predispose to RE.; METHODS: We retrospectively compared the histories of 160 RE patients to those with genetic generalized epilepsy (n=154) and those with focal cortical dysplasia Type II (FCD II; n=148).; RESULTS: The median/mean age at symptom onset in RE was 7/10years (range = 1-53years), and 58.1% of the patients were female. The female sex predominated in RE patients, with age > 7years at disease manifestation. The left hemisphere was affected in 65.6%. Perinatal complications (preterm birth, twin pregnancies, early acquired brain lesions) were more frequent in RE than in control patients. Ipsilateral facial autoimmune conditions (scleroderma en coup de sabre, uveitis, or chorioretinitis) were only observed in RE patients (6.9%). Onset of RE was more frequently associated with fever than that of FCD II. In 33.1% of RE patients, ≥1 potential risk factor was found. Interestingly, 11.9% of patients had one-sided early brain lesions or facial autoimmune lesions ipsilateral to subsequent RE; none had such a lesion contralaterally.; SIGNIFICANCE: Perinatal complications and facial autoimmune conditions may act as predisposing factors for RE. Fever might trigger RE manifestation. Further genetic or infectious contributors may be identified in the future. Single or combined hits may be required to elicit or facilitate the start of the disease. Ipsilateral early comorbid lesions or facial autoimmune processes might in part explain the enigmatic unilaterality of RE. © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration and abnormal cortical lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying PMG development are not yet understood. About 40 genes have been associated with PMG, and small copy number variations have also been described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here, we analyzed 26 PMG patients employing array-based DNA methylation profiling on formalin-fixed paraffin-embedded material. A series of 62 well-characterized non-PMG cortical malformations (focal cortical dysplasia type 2a/b and hemimegalencephaly), temporal lobe epilepsy, and non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction and hierarchical cluster analysis of DNA methylation profiles showed that PMG formed a distinct DNA methylation class. Copy number profiling from DNA methylation data identified a uniform duplication spanning the entire long arm of chromosome 1 in 7 out of 26 PMG patients, which was verified by additional fluorescence in situ hybridization analysis. In respective cases, about 50% of nuclei in the center of the PMG lesion were 1q triploid. No chromosomal imbalance was seen in adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, PMG 1q patients presented with a unilateral frontal or hemispheric PMG without hemimegalencephaly, a severe form of intractable epilepsy with seizure onset in the first months of life, and severe developmental delay. Our results show that PMG can be classified among other structural brain lesions according to their DNA methylation profile. One subset of PMG with distinct clinical features exhibits a duplication of chromosomal arm 1q. Electronic supplementary material The online version of this article (10.1007/s00401-020-02228-5) contains supplementary material, which is available to authorized users.

Objective The number of patients requiring depth electrode implantation for invasive video EEG diagnostics increases in most epilepsy centres. Here we report on our institutional experience with frameless robot-assisted stereotactic placement of intracerebral depth electrodes using the Neuromate® stereotactic robot-system. Methods We identified all patients who had undergone robot-assisted stereotactic placement of intracerebral depth electrodes for invasive extra-operative epilepsy monitoring between September 2013 and March 2020. We studied technical (placement) and diagnostic accuracy of the robot-assisted procedure, associated surgical complications and procedural time requirements. Results We evaluated a total of 464 depth electrodes implanted in 74 patients (mean 6 per patient, range 1–12). There were 27 children and 47 adults (age range: 3.6–64.6 yrs.). The mean entry and target point errors were 1.82±1.15 and 1.98±1.05 mm. Target and entry point errors were significantly higher in paediatric vs. adult patients and for electrodes targeting the temporo-mesial region. There were no clinically relevant haemorrhages and no infectious complications. Mean time for the placement of one electrode was 37±14 min and surgery time per electrode decreased with the number of electrodes placed. 55 patients (74.3%) underwent definitive surgical treatment. 36/51 (70.1%) patients followed for >12 months or until seizure recurrence became seizure-free (ILAE I). Conclusion Frameless robot-guided stereotactic placement of depth electrodes with the Neuromate® stereotactic robot-system is safe and feasible even in very young children, with good in vivo accuracy and high diagnostic precision. The surgical workflow is time-efficient and further improves with increasing numbers of implanted electrodes.

Mit dem Nachweis einer epileptogenen Lasion leistet die MRT ihren Beitrag zum besonderen Ziel der Epilepsietherapie bei Kindern: eine von Anfallen ungestorte (fruh)kindliche Entwicklung. Malformationen kortikaler Entwicklung und hemispharale Pathologien kommen bei Kindern mit pharmakoresistenter Epilepsie haufiger vor. Bis zum 24. Lebensmonat verandert die Hirnreifung/Myelinisierung die Kontraste in MRT-Untersuchungen, was den Lasionsnachweis storen kann.

We describe five patients with frontal lobe epilepsy who underwent electrocortical stimulation (ES) for language localization and language functional magnetic resonance imaging (fMRI) prior to epilepsy surgery. Six months after surgery, three patients suffered from a drop of verbal fluency. In all of them, frontal areas with presurgical language fMRI activity were resected. Our results suggest that resection in regions of areas with presurgical fMRI activation is not without risk for a postsurgical loss of function, even when ES results were negative for language function in these areas. Using fMRI activations might be specifically helpful to plan the resection when ES delivered inconclusive results.

The medial temporal lobes (MTL) play a prominent role in associative memory processing. Still, it is unclear to what extent specific structures within the MTL sub-serve distinct aspects of associative memory. Here, the role of the MTL in forming spontaneous associations in a "naturalistic" setting is investigated applying a word-list memory test not presenting items in an associative fashion. This allows for the differential investigation of item recall and associative binding. Participants included patients with medial temporal lobe epilepsy (mTLE, n = 79) and healthy controls (n = 58). Memory performance in a verbal list-learning paradigm was analyzed by (1) inter-trial repetitions ("binding", i.e., number of word-pairs consistently recalled over two consecutive trials), and (2) single item recall. In patients, behavioral results were correlated with rhinal cortex and hippocampal volumetric data. Results showed that binding was specifically diminished for patients with mTLE during learning and delayed recall. Moreover, binding predicted behavioral differences in item recall. Notably, hippocampal volumes were correlated with item recall during delayed recall, whereas rhinal cortex volumes were correlated with binding during learning. Our results provide evidence that diminished verbal memory in patients with mTLE at least partly can be attributed to functional reductions in spontaneous inter-trial stimulus binding. Moreover, they demonstrate a process-dependent functional dissociation between rhinal cortex and hippocampus for verbal encoding and recall: While the rhinal cortex is mainly engaged in detecting novel associations, the hippocampus primarily subserves consolidation and recall of associations between stimuli. Our study thus advances current models of the sub-specialization of MTL structures and offers novel evidence that memory formation in the MTL is mediated by associative item-processing, even when stimuli are not presented in an associative fashion per se. Thus, our results provide valuable qualitative insights into mechanisms of memory formation and memory failures in patients with MTL dysfunctions. Copyright © 2019 Elsevier Ltd. All rights reserved.

Using fMRI as a clinical tool, for example for lateralizing language, requires that it provides accurate results on the individual level. However, using a single voxel-wise activity map per patient limits how well the uncertainty associated with a decision can be estimated. Here, we explored how using a “volume-wise” analysis, where the lateralization of each time point of a patient’s fMRI session is evaluated independently, could support clinical decision making. Ninety-six patients with epilepsy who performed a language fMRI were analyzed retrospectively. Results from Wada testing were used as an indication of true language lateralization. Each patient’s 200 fMRI volumes were correlated with an independent template of prototypical lateralization. Depending on the strength of correlation with the template, each volume was classified as indicating either left-lateralized, bilateral or right-lateralized language. A decision about the patient’s language lateralization was then made based on how most volumes were classified. The results show that, using a simple majority vote, accuracies of 84% were reached in a sample of 63 patients with high-quality data. When 33 patients with datasets previously deemed inconclusive were added, the same accuracy was reached when more than 43% of a patient’s volumes were in agreement with each other. Increasing this cutoff to 51% volumes with agreeing classifications allowed for excluding all inconclusive cases and reaching accuracies over 90% for the remaining cases. Further increasing the cutoff to 65% agreeing volumes resulted in correct predictions for all remaining patients. The study confirms the usefulness of fMRI for language lateralization in patients with epilepsy, by demonstrating high accuracies. Furthermore, it illustrates how the diagnostic yield of individual volumes of fMRI data can be increased using simple similarity measures. The accuracy of our approach increased with the number of agreeing volumes, and thus allowed estimating the uncertainty associated with each individual diagnosis.

Subkortikal oder subependymal gelegene, periventrikulare nodulare Heterotopien sind ein morphologisches Korrelat pharmakoresistenter Epilepsien, das einer epilepsiechirurgischen Resektion in aller Regel nicht zuganglich ist. Die stereotaktische Thermoablation stellt in dieser Situation eine effektive Behandlungsmoglichkeit mit geringem Risiko interventionsassoziierter Defizite dar. Vorausgehen muss eine bildgebende und elektrophysiologische Diagnostik einschlieslich Ableitung mit Tiefenelektroden, um die Epileptogenizitat der Heterotopie zu belegen. Wir stellen die Behandlung eines Kindes und eines Erwachsenen mit dieser Vorgehensweise bei Nachbeobachtung von mehr als 5 Jahren dar und diskutieren sie auf Basis der Literatur zur Epileptogenizitat von Heterotopien und ihrer Behandlung mittels epilepsiechirurgischer oder thermoablativer Verfahren.

In epilepsy patients, language lateralisation is an important part of the presurgical diagnostic process. Using task-based fMRI, language lateralisation can be determined by visual inspection of activity patterns or by quantifying the difference in left- and right-hemisphere activity using variations of a basic formula [(L-R)/(L+R)]. However, the values of this laterality index (LI) depend on the choice of activity thresholds and regions of interest. The diagnostic utility of the LI also depends on how its continuous values are translated into categorical decisions about a patient's language lateralisation. Here, we analysed fMRI data from 712 epilepsy patients who performed a verbal fluency task. Each fMRI data set was evaluated by a trained human rater as depicting left-sided, right-sided, or bilateral lateralisation or as being inconclusive. We used data-driven methods to define the activity thresholds and regions of interest used for LI computation and to define a classification scheme that allowed us to translate the LI values into categorical decisions. By deconstructing the LI into measures of laterality (L-R) and strength (L+R), we also modelled the relationship between activation strength and conclusiveness of a data set. In a held-out data set, predictions reached 91% correct when using only conclusive data and 82% when inconclusive data were included. Although only trained on human evaluations of fMRIs, the approach generalised to the prediction of language Wada test results, allowing for significant above-chance accuracies. Compared against different existing methods of LI-computation, our approach improved the identification and exclusion of inconclusive cases and ensured that decisions for the remaining data could be made with consistently high accuracies. We discuss how this approach can support clinicians in assessing fMRI data on a single-case level, deciding whether lateralisation can be determined with sufficient certainty or whether additional information is needed.

Developmental and epileptic encephalopathies are characterized by infantile seizures and psychomotor delay. Glycosylphosphatidylinositol biosynthesis defects, resulting in impaired tethering of various proteins to the cell surface, represent the underlying pathology in some patients. One of the genes involved, PIGP, has recently been associated with infantile seizures and developmental delay in two siblings. Here, we report the second family with a markedly overlapping phenotype due to a homozygous frameshift mutation (c.456delA;p.Glu153Asnfs*34) in PIGP. Flow cytometry of patient granulocytes confirmed reduced expression of glycosylphosphatidylinositol‐anchored proteins as functional consequence. Our findings corroborate PIGP as a monogenic disease gene for developmental and epileptic encephalopathy.

PURPOSE: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery.; METHODS: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables.; RESULTS: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results.; CONCLUSION: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE. Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.