Evidence for interictal blood-brain barrier dysfunction in people with epilepsy.

OBJECTIVE: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy. METHODS: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy. RESULTS: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy. SIGNIFICANCE: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.

Normalization and cross-sectional validation of an extended Adverse Event Profile (E AEP) in a large cohort of patients with epilepsy.

PURPOSE: The Liverpool Adverse Event Profile (L AEP) is commonly used in clinical practice and pharmacological trials for the monitoring of side effects of anti-seizure medication (ASM). However potentially unrelated, additional symptoms and normative data should be considered to put patients´ complaints into perspective. METHODS: An extended 32-item AEP (E AEP) was given to 537 healthy subjects and 1,605 patients with epilepsy as part of the Bonn ASM side effect registry. The tool was factor-analyzed, corrected for age, gender, and repeated application, and related to drug load and individual substances (with N> 100) on item and scale level (total E AEP and its subscales cognition, dizziness, energy, mood, bodily symptoms, aggression, and sexuality). RESULTS: Compared to non-normalized results, at item level, between one and two-thirds of responses suggesting impairment were found to be unlikely to be related to ASM treatment after normalization. Binary regression analyses revealed differential effects of medication choice, but also of antidepressants and neuroleptics on complaint domains. The explained variance was better for physical than psychological domains. The results reflect both known drug side effects and indications. Patients´ explicit attribution of problems to their medications barely improved the correlation of the E AEP and treatment parameters. CONCLUSION: Application of a norm-referenced AEP is highly recommended to avoid overestimation of treatment related problems in patients with epilepsy. It allows evaluation on item and scale level for individuals as well as groups in drug trials. Plausible relations to individual drugs and to drug load can be demonstrated. The explanatory power was better for physical than psychological domains. Drug-related complaint patterns reflect known drug side effects (e.g. perampanel and brivaracetam with aggression) as well as drug indications (e.g. lamotrigine for depression). This is likely to be particularly relevant when side effects may have affected treatment decisions. Longitudinal evaluation with repeated application of the E AEP with changes of drug treatment is in progress.

Prevalence of dementia in a level 4 university epilepsy center: how big is the problem?

Background: The relationship between epilepsy and dementia is currently a topic of great interest. Our study aimed to determine the prevalence of dementia diagnoses among patients of a large level 4 university epilepsy center. Methods: In this retrospective monocentric study conducted at the Department of Epileptology of the University Hospital Bonn, we searched for dementia-related terms in a total of 145,501 medical letters from 40,360 adult patients who were seen between 2003 and 2021. Files with at least one hit were selected and analyzed with regard to diagnoses, age, age at epilepsy onset, and the question as to whether epilepsy preceded or followed the dementia diagnosis. Results: Among the medical letters of 513 patients, dementia-related terms were found. The letters of 12.7% of these patients stated a dementia diagnosis, 6.6% were suspected of having dementia, 4.9% had mild cognitive impairment, and 6.6% had other neurodegenerative diseases without dementia. Taking all 40,360 patients into account, the prevalence of diagnosed or suspected dementia was 0.25%. An older age (≥60 years) and late-onset epilepsy (≥60 years), but not a longer epilepsy duration, increased the odds of dementia by 6.1 (CI 3.5-10.7) and 2.9 (CI 1.7-4.7), respectively. Additionally, vascular, metabolic, inflammatory, and behavioral mood-related comorbidities were commonly observed. Epilepsy tended to precede (23.2%) rather than follow (8.1%) the dementia diagnosis. Conclusion: Despite the clear limitations of a selection bias and the potential underdiagnosis of dementia and underestimation of its prevalence when relying on the medical letters from a specialized center which rather focuses on epilepsy-related issues, the findings of this study offer valuable insights from the perspective of an epilepsy center. In this setting, the prevalence of dementia in epilepsy is rather low. However, physicians should be aware that the risk of dementia is higher in the elderly, in late-onset epilepsies, and when comorbid risk factors exist. Seizures can also be an early sign of a neurodegenerative disease. Future research should explicitly screen for dementia in patients with epilepsy and stratify them according to their underlying pathologies and comorbidities.

A novel geometry-based analysis of hippocampal morphometry in mesial temporal lobe epilepsy.

Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry-based tool that enables point-wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point-wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age- and gender-matched healthy subjects. FreeSurfer-based segmentations of hippocampal subfields in 3T-MRI were subjected to a geometry-based analysis that resulted in a coordinate system of the hippocampal mid-surface and allowed for point-wise measurements of hippocampal thickness and other features. Using point-wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS-mTLE). In the contralateral hippocampus of HS-mTLE and the affected hippocampus of MRI-negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS-mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni-corrected p < .05). We show that point-wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.

Mesiotemporal Volumetry, Cortical Thickness, and Neuropsychological Deficits in the Long-term Course of Limbic Encephalitis.

BACKGROUND AND OBJECTIVES: Limbic encephalitis (LE) is an autoimmune disease often associated with temporal lobe epilepsy and subacute memory deficits. It is categorized into serologic subgroups, which differ in clinical progress, therapy response, and prognosis. Using longitudinal MRI analysis, we hypothesized that mesiotemporal and cortical atrophy rates would reveal serotype-specific patterns and reflect disease severity. METHODS: In this longitudinal case-control study, all individuals with antibody-positive (glutamic acid decarboxylase 65 [GAD], leucine-rich glioma-inactivated protein 1 [LGI1], contactin-associated protein 2 [CASPR2], and N-methyl-d-aspartate receptor [NMDAR]) nonparaneoplastic LE according to Graus' diagnostic criteria treated between 2005 and 2019 at the University Hospital Bonn were enrolled. A longitudinal healthy cohort was included as the control group. Subcortical segmentation and cortical reconstruction of T1-weighted MRI were performed using the longitudinal framework in FreeSurfer. We applied linear mixed models to examine mesiotemporal volumes and cortical thickness longitudinally. RESULTS: Two hundred fifty-seven MRI scans from 59 individuals with LE (34 female, age at disease onset [mean ± SD] 42.5 ± 20.4 years; GAD: n = 30, 135 scans; LGI1: n = 15, 55 scans; CASPR2: n = 9, 37 scans; and NMDAR: n = 5, 30 scans) were included. The healthy control group consisted of 128 scans from 41 individuals (22 female, age at first scan [mean ± SD] 37.7 ± 14.6 years). The amygdalar volume at disease onset was significantly higher in individuals with LE (p ≤ 0.048 for all antibody subgroups) compared with that in healthy controls and decreased over time in all antibody subgroups, except in the GAD subgroup. We observed a significantly higher hippocampal atrophy rate in all antibody subgroups compared with that in healthy controls (all p ≤ 0.002), except in the GAD subgroup. Cortical atrophy rates exceeded normal aging in individuals with impaired verbal memory, while those who were not impaired did not differ significantly from healthy controls. DISCUSSION: Our data depict higher mesiotemporal volumes in the early disease stage, most likely due to edematous swelling, followed by volume regression and atrophy/hippocampal sclerosis in the late disease stage. Our study reveals a continuous and pathophysiologically meaningful trajectory of mesiotemporal volumetry across all serogroups and provides evidence that LE should be considered a network disorder in which extratemporal involvement is an important determinant of disease severity.

The multifactorial etiology of cognitive deficits in epilepsy and the neuropathology of mesial temporal lobe epilepsy beyond hyperphosphorylated tau.

In response to the recent review by Zawar and Kapur on the overlap between mesial temporal lobe epilepsy (MTLE) and Alzheimer's disease (AD), we (1) underscore that the bidirectionality between epilepsy and dementia is of high interest, also from the epileptological perspective; (2) outline the multifactorial etiology of cognitive deficits in epilepsy; (3) emphasize that the most prevalent neuropathological findings in MTLE comprise hippocampal sclerosis, dysplastic lesions, and neurodevelopmental neoplasm; and (4) state that anti-seizure medication can also have adverse effects on cognition. We conclude that the neuropsychology and neuropathology of MTLE is actually more complex than implicated in the review by Zawar and Kapur. Their suggested model may be valid for a small specific subgroup of cases. However, more studies are needed to confirm the role of hyperphosphorylated tau in epilepsy patients with and without AD considering age and age at epilepsy onset as potential moderator variables.

How are they doing as adults? Psychosocial and socioeconomic outcomes 11-30 years after pediatric epilepsy surgery.

OBJECTIVE: Pediatric epilepsy surgery yields cure from epilepsy or complete seizure control with continued medication in many patients early in life. This study aimed to evaluate the long-term (>10 years) psychosocial and socioeconomic outcomes of pediatric epilepsy surgery and examine the role of comorbid disability, type of surgery, seizure freedom, and age at surgery. METHODS: A novel ad hoc parent/patient questionnaire was used to assess educational and occupational attainment, marital/familial status, mobility, and other outcomes in patients who underwent unilobar or multilobar surgery for drug-refractory epilepsy during their childhood. The questionnaire also captured information on comorbid disability. RESULTS: Of the 353 eligible patients, 203 could still be contacted and 101 of these (50%) returned appropriately filled-in questionnaires (follow-up intervals: 11-30 [mean: 19.6] years). The cure from epilepsy rate was 53%. Type of surgery was strongly confounded by comorbid disability. Patients with comorbid disabilities had significantly lower rates of regular school degrees, gainful employment, marriage, and driving license (N = 29; 12%, 4%, 0%, 3%) compared with non-disabled patients (N = 69; 89%, 80%, 43%, and 67%, respectively). Patients achieved lower school degrees than their siblings and parents. Non-disabled seizure-free patients had better employment and mobility outcomes compared with non-seizure-free patients. Age at surgery (<10 vs. ≥10 years of age) did not have any effect on any outcome in patients with preschool seizure onset. SIGNIFICANCE: Pediatric epilepsy surgery can lead to permanent relief from epilepsy in many patients, but comorbid disability strongly impacts adult life achievement. In non-disabled patients, favorable outcomes in academic, occupational, marital, and mobility domains were achieved, approaching respective rates in the German population. Complete seizure freedom had additional positive effects on employment and mobility in this group. However, in case of chronic comorbid disability the overall life prospects may be limited despite favorable seizure outcomes.

DBS of the ANT for refractory epilepsy: A single center experience of seizure reduction, side effects and neuropsychological outcomes.

Objective: Evaluation of the antiseizure efficacy, side effects and neuropsychological effects of Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT). ANT-DBS is a treatment option for patients with difficult-to-treat epilepsy. Though several works outline the cognitive and/or mood effects of ANT-DBS for the treatment of epilepsy, data on the intersection between antiseizure efficacy, cognitive and undesired effects are scarce. Methods: We retrospectively analyzed the data of our cohort of 13 patients. Post-implantation seizure frequencies were measured at 6 months, 12 months and last follow-up, as well as averaged throughout follow-up. These values were then compared with mean seizure frequencies in the 6 months before implantation. To address acute cognitive effects of DBS a baseline assessment was performed after implantation and before stimulation, and a follow-up assessment was conducted under DBS. The long-term effects of DBS on cognition were assessed by comparing the preoperative neuropsychological profile with a long-term follow-up under DBS. Results: In the entire cohort, 54.5% of patients were responders, with an average seizure reduction of 73.6%. One of these patients achieved temporary seizure freedom and near-total seizure reduction during the entire follow-up. Seizure reduction of <50% was achieved in 3 patients. Non-responders suffered an average seizure increase of 27.3%. Eight of twenty-two active electrodes (36,4%) were off-target. Two of our patients had both electrodes implanted off-target. When removing these two patients from the analysis and averaging seizure frequency during the entire follow-up period, four patients (44.4%) were responders and three experienced a seizure reduction of <50%. Intolerable side effects arose in 5 patients, mostly psychiatric. Regarding acute cognitive effects of DBS, only one patient showed a significant decline in executive functions. Long-term neuropsychological effects included significant intraindividual changes in verbal learning and memory. Figural memory, attention and executive functions, confrontative naming and mental rotation were mostly unchanged, and improved in few cases. Significance: In our cohort, more than half of patients were responders. Psychiatric side effects seem to have been more prevalent compared to other published cohorts. This may be partially explained by a relatively high occurrence of off-target electrodes.

Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy.

OBJECTIVE: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in-depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes. METHODS: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state-of-the-art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls. RESULTS: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low-grade tumors), indicating (1) a secondary, putatively epilepsy-independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis" without segmental neurodegeneration. In the controls, the matched individual principal epilepsy-associated pathologies were not found in combination with the secondary pathology patterns of the study group. INTERPRETATION: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision-making. ANN NEUROL 2023;93:536-550.

Clinical adult outcome 11-30 years after pediatric epilepsy surgery: Complications and other surgical adverse events, seizure control, and cure of epilepsy.

OBJECTIVE: Pediatric epilepsy surgery promises seizure freedom or even cure of epilepsy. We evaluated the long-term (≥10 years) adult clinical outcome including surgery-related adverse events and complications, which are generally underreported. METHODS: A monocentric, single-arm, questionnaire study in now adult patients who underwent epilepsy surgery during childhood. A novel ad hoc parental/patient questionnaire, which addressed diverse outcome domains was applied. RESULTS: From a total of 353 eligible patients, 203 could be contacted (3 patients died of causes unknown) and 101 (50%) returned appropriately filled-in surveys. No evidence for a survey-response bias was found. The rate of surgical complications according to the patient records was 9%. As regards the survey, half of the parents/patients reported surgical adverse events (expected and unexpected issues) and one-third reported permanent aversive sequels. Two-thirds of the patients were seizure-free during the last year before follow-up; 63% were Engel class 1A; favorable seizure outcomes (including auras only) were obtained in 73%; and 54% were seizure-free and off antiseizure medicine (ASM), that is, cured of epilepsy. In non-seizure-free patients, seizure relapse occurred at any time during the follow-up interval but 87% of those with a seizure-free first postoperative year were seizure-free at follow-up. One patient experienced a seizure relapse during the ASM withdrawal trial but became seizure-free again with ASMs. Eleven patients reported an increased number of ASMs as compared to the time before surgery. Earlier focal surgery did not affect the long-term clinical outcome. SIGNIFICANCE: Pediatric epilepsy surgery was capable of curing epilepsy in about one-half of the children and to significantly control seizures in about three-fourths. Long-term success of focal surgery did not depend on age at surgery or duration of epilepsy. Surgical adverse events including complications may be underreported and must be assessed more thoroughly.

'Hippocampal innate inflammatory gliosis only' in pharmacoresistant temporal lobe epilepsy.

Drug-resistant mesial-temporal lobe epilepsy is a devastating disease with seizure onset in the hippocampal formation. A fraction of hippocampi samples from epilepsy-surgical procedures reveals a peculiar histological pattern referred to as 'gliosis only' with unresolved pathogenesis and enigmatic sequelae. Here, we hypothesize that 'gliosis only' represents a particular syndrome defined by distinct clinical and molecular characteristics. We curated an in-depth multiparameter integration of systematic clinical, neuropsychological as well as neuropathological analysis from a consecutive cohort of 627 patients, who underwent hippocampectomy for drug-resistant temporal lobe epilepsy. All patients underwent either classic anterior temporal lobectomy or selective amygdalohippocampectomy. On the basis of their neuropathological exam, patients with hippocampus sclerosis and 'gliosis only' were characterized and compared within the whole cohort and within a subset of matched pairs. Integrated transcriptional analysis was performed to address molecular differences between both groups. 'Gliosis only' revealed demographics, clinical and neuropsychological outcome fundamentally different from hippocampus sclerosis. 'Gliosis only' patients had a significantly later seizure onset (16.3 versus 12.2 years, P = 0.005) and worse neuropsychological outcome after surgery compared to patients with hippocampus sclerosis. Epilepsy was less amendable by surgery in 'gliosis only' patients, resulting in a significantly worse rate of seizure freedom after surgery in this subgroup (43% versus 68%, P = 0.0001, odds ratio = 2.8, confidence interval 1.7-4.7). This finding remained significant after multivariate and matched-pairs analysis. The 'gliosis only' group demonstrated pronounced astrogliosis and lack of significant neuronal degeneration in contrast to characteristic segmental neuron loss and fibrillary astrogliosis in hippocampus sclerosis. RNA-sequencing of gliosis only patients deciphered a distinct transcriptional programme that resembles an innate inflammatory response of reactive astrocytes. Our data indicate a new temporal lobe epilepsy syndrome for which we suggest the term 'Innate inflammatory gliosis only'. 'Innate inflammatory gliosis only' is characterized by a diffuse gliosis pattern lacking restricted hippocampal focality and is poorly controllable by surgery. Thus, 'innate inflammatory gliosis only' patients need to be clearly identified by presurgical examination paradigms of pharmacoresistant temporal lobe epilepsy patients; surgical treatment of this subgroup should be considered with great precaution. 'Innate inflammatory gliosis only' requires innovative pharmacotreatment strategies.

Evaluation of a Rapid Topiramate Titration Scheme for the Early Detection of Cognitive Side Effects.

BACKGROUND: Topiramate (TPM) is effective for treating epilepsy, but executive dysfunction is a common side effect that could significantly affect everyday life. Additionally, previous studies have suggested that patients might be unaware of these changes. OBJECTIVE: To evaluate a rapid TPM titration scheme for the early detection of adverse cognitive side effects. METHODS: In this retrospective study, we assessed changes in objective cognitive performance (EpiTrack®) after rapidly titrating TPM (50 mg per day during an inpatient stay) in 49 epilepsy patients and compared those results with an outpatient control group that underwent the recommended standard titration (n = 23 with 25-50 mg per week). RESULTS: Using Bayesian statistics, analyses revealed decisive evidence of a negative effect on cognitive performance when TPM was introduced (BF 31480000000) independent of the titration speed (BF 0.739). When using a fast titration rate, deficits in executive function increased from a baseline of 53.1 to 73.5% at follow-up, and 55.1% experienced a statistically significant intraindividual decline. When using the standard titration scheme, impairments increased from 52.2 to 65.2%, with an intraindividual deterioration found in 52.2% of the patients. CONCLUSION: Physicians might be able to detect adverse cognitive side effects sooner in epilepsy patients if TPM is administered using a faster titration rate while applying repeated cognitive assessments within days. This approach might help prevent any unnoticed intolerance and eventual negative consequences for the patient. Therefore, we recommend monitoring early on for adverse changes instead of withholding a potentially effective treatment option because of anticipated side effects.

Increased T- and B-cells associated with the phenotype of autoimmune limbic encephalitis with mainly memory dysfunction.

Background: Our goal is to investigate the autoantibodies' presence and immune cells in the bioprobes of autoimmune encephalitis (AE) patients with distinct phenotypes as a promising target in AE. Methods: We retrospectively analyzed immune cells via flow cytometry, serum and cerebrospinal fluid (CSF) autoantibodies, electroencephalography, magnetic resonance imaging in 94 AE patients with suspected temporal lobe epilepsy and classified neuropsychological phenotypes according to their occurrence. Results: We detected different phenotypes in 94 AE patients [10.6% with isolated memory dysfunction (MEM), 11.7% with mood-dysfunction, 12.7% with mood and memory dysfunction, 13.8% with memory and attention dysfunction, 18.1% with memory, mood and attention disturbances and 20.2% with no mood, memory or attention dysfunction]. We did discern a relevant association of phenotypes and CSF antibody-positivity on CSF CD4+ T-cells, CD8+T-cells and HLADR + CD8+T-cells in our patients with MEM presenting elevated CD8+T-cells and HLADR + CD8+T-cells. Furthermore, CSF CD19+B-cells differed significantly between phenotypes in patients with MEM. Discussion: Taken together, the phenotypes in combination with CSF antibody-positivity are biomarkers for stratifying patients. Furthermore, our results confirm the role of CD4+ T-cells, CD8+T-cells and CD19+B-cells in AE patients with a memory dysfunction, providing insights into AE pathogenesis. Our preliminary results should be confirmed by larger-scale investigations.

Preoperative and postoperative memory in epilepsy patients with 'gliosis only' versus hippocampal sclerosis: a matched case-control study.

BACKGROUND: Gliosis only (GO) and hippocampal sclerosis (HS) are distinct histopathological entities in mesial temporal lobe epilepsy. This study explores whether this distinction also exists on a functional level when evaluating pre- and postoperative memory. METHODS: Using a retrospective matched case-control study design, we analysed verbal and visual memory performance in 49 patients with GO and 49 patients with HS before and one year after elective surgery. RESULTS: Clinical differences were evident with a later age at seizure onset (18±12 vs 12±9 years) and fewer postoperative seizure-free patients in the GO group (63% vs 82%). Preoperatively, group and individual-level data demonstrated that memory impairments were less frequent, less severe and relatively non-specific in patients with GO compared with HS. Postoperatively, verbal memory declined in both groups, particularly after left-sided resections, with more significant losses in patients with GO. Factoring in floor effects, GO was also associated with more significant visual memory loss, particularly after left resections. CONCLUSIONS: Compared with HS, GO is characterised by (1) a later onset of epilepsy, (2) less pronounced and more non-specific memory impairments before surgery, (3) a less successful surgical outcome and (4) a more significant memory decline after surgery. Overall, our results regarding cognition provide further evidence that GO and HS are distinct clinical entities. Functional integrity of the hippocampus appears higher in GO, as indicated by a better preoperative memory performance and worse memory outcome after surgery. The different risk-benefit ratios should be considered during presurgical patient counselling.

All's well that ends well? Long-term course of a patient with anti-amphiphysin associated limbic encephalitis.

Anti-amphiphysin associated limbic encephalitis (LE) is a paraneoplastic autoimmune disorder. The initial clinical presentation features seizures, cognitive and neuropsychiatric symptoms. We present the case of a 25-year-old female patient hospitalized after four consecutive tonic-clonic seizures, followed by confusion, psychotic symptoms, nonconvulsive seizure series, and severe global amnesia. Diagnostic workup revealed anti-amphiphysin associated LE without a tumor. MRI and PET indicated inflammatory processes affecting the bilateral mesial temporal structures more pronounced on the left side. Antiseizure medication, benzodiazepines, and immunotherapy resulted in rapid seizure cessation. Subsequent MRI and PET indicated left hippocampal sclerosis and a left mesial temporal hypometabolism. Executive dysfunction resolved in the following weeks. Global amnesia persisted for almost three months. Two years later, episodic memory was normal with residual visual memory impairments. While this patient's seizure and cognitive outcome has been favorable, behavioral problems persisted long after disease onset. The persisting behavioral problems and subsequent MRI evidence (13 years after onset) of a swollen right amygdala indicated a possible relapse. This case report illustrates the importance of early diagnosis of LE for best clinical management. Antiseizure medication and immunotherapy led to seizure freedom and almost complete recovery of cognition. However, long-lasting neuropsychiatric symptoms and possible recurrent inflammation highlight the need for a multimodal long-term monitoring of such patients to rule out a relapse.

Electrodermal Activity Biofeedback Alters Evolving Functional Brain Networks in People With Epilepsy, but in a Non-specific Manner.

There is evidence that biofeedback of electrodermal activity (EDA) can reduce seizure frequency in people with epilepsy. Prior studies have linked EDA biofeedback to a diffuse brain activation as a potential functional mechanism. Here, we investigated whether short-term EDA biofeedback alters EEG-derived large-scale functional brain networks in people with epilepsy. In this prospective controlled trial, thirty participants were quasi-randomly assigned to one of three biofeedback conditions (arousal, sham, or relaxation) and performed a single, 30-min biofeedback training while undergoing continuous EEG recordings. Based on the EEG, we derived evolving functional brain networks and examined their topological, robustness, and stability properties over time. Potential effects on attentional-executive functions and mood were monitored via a neuropsychological assessment and subjective self-ratings. Participants assigned to the relaxation group seemed to be most successful in meeting the task requirements for this specific control condition (i.e., decreasing EDA). Participants in the sham group were more successful in increasing EDA than participants in the arousal group. However, only the arousal biofeedback training was associated with a prolonged robustness-enhancing effect on networks. Effects on other network properties were mostly unspecific for the different groups. None of the biofeedback conditions affected attentional-executive functions or subjective behavioral measures. Our results suggest that global characteristics of evolving functional brain networks are modified by EDA biofeedback. Some alterations persisted after the single training session; however, the effects were largely unspecific across the different biofeedback protocols. Further research should address changes of local network characteristics and whether multiple training sessions will result in more specific network modifications.

Cognitive reawakening and improved quality of life achieved after discontinuing 16 years of anti-seizure treatment with topiramate.

A 42-year-old female patient with epilepsy and a co-morbid migraine suffered from the severe cognitive side effects of topiramate (TPM) for more than 16 years with detrimental consequences for her daily functioning, career, and social interaction. Even a prodromal stage of dementia was suggested, giving rise to fears of developing a neurodegenerative disease. Recently, cognitive monitoring of attention and executive function before and after withdrawal of TPM revealed a significant recovery from the severe negative cognitive side effects of the long-standing and inefficacious antiseizure medication (ASM). Whereas the side effects were reversible after cessation, their consequences for the patient`s biography were permanent. A considerable increase in quality of life, however, was observed without TPM and family members were impressed by the improvements. This case illustrates the potentially severe consequences of negative cognitive side effects which affect daily functioning, career and social life, thus underscoring the importance of being knowledgeable of the potential cognitive risks when prescribing an ASM. Because cognitive side effects may not depend solely on ASM choice and drug load, but also on individual idiosyncratic intolerances, and patients might stay on their treatment for many years, cognitive monitoring is highly recommended.