Evaluating the Inheritance Risk: Epilepsy Prevalence among Offspring of Adults with Epilepsy in a Tertiary Referral Epilepsy Center.

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring of patients with epilepsy who were treated at a tertiary epilepsy center. Adult patients with confirmed epilepsy (PWE) receiving outpatient care were consecutively enrolled, starting from January 2021 to January 2023. Data were recorded for various variables, including age, gender, epilepsy pathophysiology, cognitive impairment, and family history of epilepsy. Descriptive statistics, various statistical tests, and multivariate logistic regression analyses were employed to analyze the data. A total of 1456 PWE were included. Among them, 463 patients (31.8%) had children. Twenty-five patients had offspring diagnosed with epilepsy, representing a prevalence of 5.4%. Analysis of the offspring with epilepsy revealed older ages, a higher proportion of parents with idiopathic epilepsy, and a greater prevalence of a positive family history of epilepsy. Multivariate logistic regression analysis demonstrated a significant association between a family history of epilepsy and increased epilepsy risk in offspring. Genetic syndrome-immanent predisposition, advanced age, and a family history of epilepsy were identified as significant risk factors for epilepsy in offspring by means of this mono-center study.

Psychiatric assessment prior to and after switch from levetiracetam to brivaracetam.

PURPOSE: Brivaracetam is often used as an alternative to levetiracetam in patients with epilepsy (PWE) encountering efficacy issues or adverse events with levetiracetam. This study evaluated the psychological status of PWE who were switched from levetiracetam to brivaracetam due to psychiatric tolerability concerns in comparison to those who remained on levetiracetam. METHODS: We used various psychological assessments including the Symptom Checklist SCL-90-R, the Beck Depression Inventory-II, and the adverse event profile. Eligible participants completed the questionnaires at baseline and again 8 days later. Psychological changes were assessed using standard statistical methods to show differences between a group that immediately switched from levetiracetam to brivaracetam and another group with unchanged levetiracetam. RESULTS: Between May 2020 and May 2021, 63 patients participated in the study, of whom 34 switched from levetiracetam to brivaracetam. At baseline, participants who switched to brivaracetam had fewer antiseizure medications but experienced more monthly seizures. Baseline scores for anxiety (p = 0.020) and psychoticism (p = 0.046) on SCL-90-R in PWE switched to brivaracetam were higher than in the remaining group. In the subsequent assessment, all psychological scores were reduced and were no longer significantly different between both groups. Using multiple regression, initial treatment with a single antiseizure medication and male gender emerged as predictors of psychological improvement. CONCLUSION: Our study found no increased risk of adverse events or psychiatric symptoms after switching from levetiracetam to brivaracetam. Though statistically non-significant, a trend towards improved psychiatric outcomes in the switch group warrants further investigation in future trials with stronger designs for enhanced statistical power.

Visual illustration supporting patient-physician communication in epilepsy: A validation and reliability study of seizure images.

Seizure manifestations may be difficult to describe in words alone. Thus, initially, 24 seizure images were developed to support communication and gain assistance during obtaining the patient's history. Before being used in clinical practice, these seizure images must be investigated for validity and reliability. We tested the images with untrained participants including patients with epilepsy, persons who had witnessed seizures, and participants who had neither had nor witnessed epileptic seizures. The participants filled in a questionnaire evaluating the images twice within 3 days. The participants were asked to choose one of the 2 written descriptions that best matched each seizure image. The validity was assessed using one-proportion z-test. The reliability was assessed by Gwet's AC1. The first analysis showed that the proportion of correctly identified seizure images was higher than 70%, except for 2 images representing dystonia and myoclonus. The dystonia image was modified, and the myoclonus image was removed. In the final evaluation, the seizure images were identified with an overall correctness ratio of 96%. The final AC1 of the seizure images was classified as very high. The final 23 seizure images are proved to be valid and have a high agreement that can be used in clinical practice.

Effects of hippocampus-sparing resections in the temporal lobe: Hippocampal atrophy is associated with a decline in memory performance.

OBJECTIVE: In patients with temporal lobe epilepsy (TLE) with a nonlesional and nonepileptogenic hippocampus (HC), in order to preserve functionally intact brain tissue, the HC is not resected. However, some patients experience postoperative memory decline, possibly due to disruption of the extrahippocampal memory network and secondary hippocampal volume (HV) loss. The purpose of this study was to determine the extent of hippocampal atrophy ipsilateral and contralateral to the side of the surgery and its relation to memory outcomes. METHODS: Hippocampal volume and verbal as well as visual memory performance were retrospectively examined in 55 patients (mean age ± standard deviation [SD] 30 ± 15 years, 25 female, 31 left) before and 5 months after surgery within the temporal lobe that spared the entire HC. HV was extracted based on prespecified templates, and resection volumes were also determined. RESULTS: HV loss was found both ipsilateral and contralateral to the side of surgery (P < .001). Postoperative left HV loss was a significant predictor of postoperative verbal memory deterioration after left-sided surgery (P < .01). Together with the preoperative verbal memory performance, postoperative left HV explained almost 60% of the variance (P < .0001). However, right HV was not a clear predictor of visual memory performance. Larger resection volumes were associated with smaller postoperative HV, irrespective of side of surgery (left: P < .05, right: P < .01). SIGNIFICANCE: A disruption of the memory network by any resection within the TL, especially within the language-dominant hemisphere, may lead to HC atrophy and memory decline. These findings may further improve the counseling of patients concerning their postoperative memory outcome before TL resections sparing the entire HC.

Functional hemispherectomy is safe and effective in adult patients with epilepsy.

INTRODUCTION: Functional hemispherectomy (FH) is a well-established therapeutic option for children with epilepsy with parenchymal damage confined to one hemisphere, yet its application in adults remains rare. The intention of our study was to investigate postoperative clinical and epileptological outcome in adults who received FH for intractable epilepsy. MATERIALS AND METHODS: We retrospectively analyzed 12 adult patients (18-56years) with intractable epilepsy due to unihemispheric pathology. All patients underwent FH. Postoperative neurological and cognitive outcome as well as seizure status were evaluated with a mean follow-up period of 4.9years. RESULTS: Ten patients (83%) were seizure-free (Engel I), and two (17%) had recurrent seizures at last follow-up. Apart from one patient requiring operative revision for bone flap infection, no perioperative morbidity or mortality occurred. Postoperative functional assessment revealed deterioration of motor function in 7 patients, whereas 5 remained unchanged. Language was unchanged in 8 patients. The absence of background slowing in preoperative electroencephalogram (EEG) as well as ictal and interictal EEG patterns located ipsilateral to the side of surgery was associated with favorable seizure outcome. CONCLUSION: Favorable seizure control and acceptable functional outcome can be achieved by FH in adults with intractable epilepsy. The risk of postoperative deficits is moderate and even older patients are able to manage postoperative motor impairment. Therefore, FH should be considered in case of unihemispheric lesions also in adults.

Surgical Treatment of Mesiotemporal Lobe Epilepsy: Which Approach is Favorable?

BACKGROUND: Mesiotemporal lobe epilepsy is one of the most frequent causes for pharmacoresistant epilepsy. Different surgical approaches to the mesiotemporal area are used. OBJECTIVE: To analyze epileptological and neuropsychological results as well as complications of different surgical strategies. METHODS: This retrospective study is based on a consecutive series of 458 patients all harboring pharmacoresistant mesiotemporal lobe epilepsy. Following procedures were performed: standard anterior temporal lobectomy, anterior temporal or key-hole resection, extended lesionectomy, and transsylvian and subtemporal selective amygdalohippocampectomy. Postoperative outcome was evaluated according to different surgical procedures. RESULTS: Overall, 1 yr after surgery 315 of 432 patients (72.9%) were classified Engel I; in particular, 72.8% were seizure-free after anterior temporal lobectomy, 76.9% after key-hole resection, 84.4% after extended lesionectomy, 70.3% after transylvian selective amygdalohippocampectomy, and 59.1% after subtemporal selective amygdalohippocampectomy. No significant differences in seizure outcome were found between different resective procedures, neither in short-term nor long-term follow-up. There was no perioperative mortality. Permanent morbidity was encountered in 4.4%. There were no significant differences in complications between different resection types. In the majority of patients, selective attention improved following surgery. Patients after left-sided operations performed significantly worse regarding verbal memory as compared to right-sided procedures. However, surgical approach had no significant effect on memory outcome. CONCLUSION: Different surgical approaches for mesiotemporal epilepsy analyzed resulted in similar epileptological, neuropsychological results, and complication rates. Therefore, the approach for the individual patient does not only depend on the specific localization of the epileptogenic area, but also on the experience of the surgeon.

Transsylvian Selective Amygdalohippocampectomy for Mesiotemporal Epilepsy: Experience with 162 Procedures.

Background: Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of epilepsy refractory to medical therapy. Among different surgical approaches, selective amygdalohippocampectomy has gained increasing interest for its rationale of isolated removal of the epileptogenic mesiotemporal area. Objective: To summarize our experience with surgical treatment of MTLE in 162 patients using the transsylvian approach and to analyze possible effects of length of hippocampal resection and postoperative gliosis on seizure and cognitive outcome. Methods: Clinical, radiological, histopathological and neuropsychological findings of 162 patients with MTLE who were operated by the senior author between 1993 and 2012 were retrospectively evaluated. Postoperative follow-up mounted up to 240 months (59 ± 56 months). Seizure outcome was available in 156 patients with minimum follow-up of 3 months. Extent of hippocampal resection was evaluated in 70 and postoperative gliosis in 62 of the 92 patients. Results were then correlated with seizure and cognitive outcome. Results: Of 134 patients with a follow-up of at least 1 year, 85 (63.4%) remained completely seizure free (Engel Ia) and 118 (88.0%) had a worthwhile improvement after surgery (Engel I+II). There was no perioperative death. Permanent morbidity was encountered in 4 patients (2.5%). Neither the extent of hippocampal resection nor postoperative gliosis correlated with seizure outcome or postoperative memory performance. Conclusion: Transsylvian selective amygdalohippocampectomy can be recommended as an adequate procedure for the surgical treatment of mesiotemporal epilepsy with favorable epileptological results and acceptable morbidity.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently.

Quality control of elective surgery for drug-resistant epilepsy in a German reference centre--a long-term outcome study.

PURPOSE: Resective epilepsy surgery is the recommended treatment for a well-defined group of patients with drug-resistant epilepsy. Long-term outcome studies are an appropriate quality control to assess the value of elective surgical procedures ethically and economically. This paper reports the long-term post-surgical follow-up of adult patients of the Kork Epilepsy Centre. METHOD: Data collection was performed by means of a questionnaire to obtain updated information about postsurgical outcome, frequency and postsurgical seizure semiology in case of relapse, postsurgical use of antiepileptic drugs, social issues and satisfaction rates. We classified seizure outcome according to the ILAE surgery outcome scale (OC 1-OC 6). RESULTS: Outcome data of 340 adult patients were obtained. Mean post-operative follow-up was 6.7 years (range 1.0-21.6 years). Seizure remission was 67% if comprising patients with postoperative auras only (OC 1+OC 2). Sixty-two per cent of patients were completely seizure free. The majority of patients (78%) underwent temporal lobe resections. Sixty-four per cent of these and 52% of the patients with extra-temporal resections became completely seizure-free (OC 1). Only 34% of the patients with negative MRI achieved complete seizure-freedom. CONCLUSION: In line with others our huge cohort sample that covers decades of experience with epilepsy surgery revealed satisfying long-term outcome results. Best results were obtained in lesional temporal lobe epilepsy, least favourable results in MRI-negative epilepsy.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.

Visuo-spatial memory tests in right temporal lobe epilepsy foci: clinical validity.

OBJECTIVE: To examine the appropriateness of visual memory tests as an identification method for right mesial temporal lobe dysfunctions in an epilepsy patient group and to study the relationship and possible overlap with non-memory cognitive domains and demographic variables. METHODS: Eighty preoperative candidates with mesial temporal lobe epilepsy (TLE) were examined using the "Corsi Block-Tapping Test", "Diagnosticum für Cerebralschädigung" (DCS), the path subtest of the "Verbaler und Visueller Merkfähigkeitstest" (VVM), and the Rey-Osterrieth Complex Figure Test (ROCF). Factorial analyses were performed on raw scores to determine the effect of epilepsy-related variables, interictal epileptiform discharges (IEDs) and presence of cortical dysgenesis, on visual and verbal memory parameters. Sensitivity, specificity and Receiver Operating Characteristic (ROC) curves were calculated based on normative data. Furthermore, Spearman correlations between memory and non-memory cognitive tasks were performed. RESULTS: The scores for test sensitivity and specificity and the ROC curves illustrate the tests' poor capacity to lateralize the functional deficit zone even when epilepsy-related factors, such as cortical dysgenesis or presence of contralateral IEDs were controlled. Significant correlations were found between the visual memory measures and nonverbal reasoning, processing speed, attentional flexibility, and visual planning. CONCLUSION: These neuropsychological tests are not sensitive enough to lateralize the epileptogenic focus in temporal lobe epilepsy patients since in addition to learning and consolidation processes, they measure additional cognitive domains. These results have implications for clinical neuropsychologists, in terms of test choice and the interpretation in the context of presurgical diagnostics.

Hyperkinetic seizures in patients with temporal lobe epilepsy: clinical features and outcome after temporal lobe resection.

PURPOSE: Temporal lobe epilepsy (TLE) is usually associated with automatisms. Hyperkinetic seizures are supposed to be unusual. Because we witnessed several patients with TLE and ictal hyperkinetic symptoms, we retrospectively assessed the number, clinical findings, and seizure outcome in such patients who had undergone temporal lobe resection. METHODS: We reviewed medical history, video-electroencephalography (EEG) recording and neuroimaging of adult patients who underwent epilepsy surgery for TLE at the Kork Epilepsy Center over the last 20 years with a minimum postoperative follow-up of 12 months. KEY FINDINGS: Among 294 patients who were resected exclusively in the temporal region, we identified 17 (6%) who presented with hyperkinetic semiology such as violent vocalization, complex movements of the proximal segments of the limbs, rotation of the trunk, pelvic thrusting, or early tonic or dystonic posturing. Most of the patients had a preceding aura. Ictal EEG activity was located in the corresponding temporal region, usually with a wide distribution over temporal electrodes with fast spread to unilateral frontal electrodes and to the contralateral side. Neuroimaging revealed extended lesions in the temporal lobe involving mesial and neocortical structures. Most of the patients underwent classical anterior temporal lobe resection including amygdalo-hippocampectomy. Fourteen patients (82%) became completely seizure-free (Engel class Ia). Histopathology showed mainly focal cortical dysplasia plus hippocampal sclerosis. SIGNIFICANCE: Hyperkinetic seizure semiology may occasionally occur in patients with TLE and is, therefore, no contradiction to the hypothesis of TLE if scalp EEG patterns and neuroimaging findings correspond. The postoperative seizure outcome is favorable in such patients and not different from outcome data in classical TLE.

Impact of side of lesion, seizure outcome and interictal epileptiform discharges on attention and memory after surgery in temporal lobe epilepsy.

To determine the impact of side of surgery, seizure outcome and interictal epileptiform discharges (IEDs) on attention and memory in a cohort of patients with temporal lobe epilepsy who had undergone unilateral mesial temporal lobe resection. Ninety-four patients were investigated pre- and postoperatively by means of a standardised neuropsychological battery measuring subcomponents of attention, as well as short-term, working and long-term memory. The side of epilepsy surgery, seizure outcome and the presence of postoperative IEDs, as well as their possible relationship to the neuropsychological changes, were assessed. Statistical data were analysed using a repeated-measures MANOVA. The absence of seizures following surgery had a positive effect on short-term memory and attentional control. The occurrence of IEDs was found in patients with impaired figural learning. In terms of attentional control and working memory, patients who continued to present IEDs had also scored lower in these domains prior to surgery. IEDs had an effect independent of seizure presence, but were found to have a "supplementary negative effect" when the two variables were combined.

Reactive oxygen species (ROS) in the human neocortex: role of aging and cognition.

Reactive oxygen species (ROS), formed during normal aerobic metabolism, are involved in signal transduction and cognitive functions, but highly increased ROS concentrations may also have detrimental effects. The aim of the present study was to investigate whether aging and cognitive functions are associated with ROS generation in human neocortex obtained from neurosurgical patients. ROS formation in mitochondria from fresh and re-thawed neocortical specimens was measured by monitoring ROS-mediated conversion of dihydrorhodamine 123 to fluorescent rhodamine 123. The validity of this technique was characterized in rat brain mitochondria. The increase in the concentration-response curve of the complex I inhibitor rotenone on ROS generation, as measured by rhodamine 123 (Rh123) fluorescence, was much more pronounced than that of rotenone on mitochondrial [(3)H]-choline uptake [which indicates changes in the mitochondrial membrane potential (DeltaPsi(M))]. Thus, mitochondrial ROS generation can be shown by Rh123 fluorescence although this fluorescence may also reflect changes in DeltaPsi(M) to some extent. ROS formation in human brain mitochondria positively correlated with the age of patients. Moreover, an age-corrected positive correlation of ROS formation with presurgical cognitive performance was observed. Our data suggest a mild increase in ROS formation with aging possibly reflecting a physiological compensation of mitochondrial function. Furthermore, higher cognitive performances in tests of executive functions may be paralleled by slightly increased ROS levels.

Short-term impact of the switch from immediate-release to extended-release oxcarbazepine in epilepsy patients on high dosages.

Extended-release oxcarbazepine (OXC) was introduced in Germany in January of 2008. In principle, this formulation should allow a better tolerability due to the less marked serum peak concentration of OXC prior to metabolization to its monohydroxy derivate (MHD) that is the active compound. Twenty-seven in-patients who had been referred to our epilepsy centre because of their difficult-to-treat localization-related epilepsies and had been on immediate-release OXC were abruptly switched to extended-release OXC at identical dosages. The adverse event profile (AEP) and the QOLIE-10 questionnaire were obtained immediately prior to and 5 days after this switch. On both days MHD fasting serum concentrations were also measured. After the switch a significant improvement of tolerability and quality of life was reported according to AEP and QOLIE-10 (p<0.001). Ameliorations were apparent in almost every patient (AEP: 26 of 27 patients, QOLIE-10: 23 of 27 patients). The improvement not explained by a drop of MHD levels. On the contrary and in line with preclinical data, serum levels of MHD rose significantly (p<0.001). We suggest that patients on extended-release OXC experience a lower serum concentration peak of the pro-drug OXC.