Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

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.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

The diagnostic value of ictal SPECT-A retrospective, semiquantitative monocenter study.

OBJECTIVE: Ictal single photon emission computed tomography (SPECT) can be used as an advanced diagnostic modality to detect the seizure onset zone in the presurgical evaluation of people with epilepsy. In addition to visual assessment (VSA) of ictal and interictal SPECT images, postprocessing methods such as ictal-interictal SPECT analysis using SPM (ISAS) can visualize regional ictal blood flow differences. We aimed to evaluate and differentiate the diagnostic value of VSA and ISAS in the Bonn cohort. METHODS: We included 161 people with epilepsy who underwent presurgical evaluation at the University Hospital Bonn between 2008 and 2020 and received ictal and interictal SPECT and ISAS. We retrospectively assigned SPECT findings to one of five categories according to their degree of concordance with the clinical focus hypothesis. RESULTS: Seizure onset zones could be identified more likely on a sublobar concordance level by ISAS than by VSA (31% vs. 19% of cases; OR = 1.88; 95% Cl [1.04, 3.42]; P = 0.03). Both VSA and ISAS more often localized a temporal seizure onset zone than an extratemporal one. Neither VSA nor ISAS findings were predicted by the latency between seizure onset and tracer injection (P = 0.75). In people who underwent successful epilepsy surgery, VSA and ISAS indicated the correct resection site in 54% of individuals, while MRI and EEG showed the correct resection localization in 96% and 33% of individuals, respectively. It was more likely to become seizure-free after epilepsy surgery if ISAS or VSA had been successful. There was no MR-negative case with successful surgery, indicating that ictal SPECT is more useful for confirmation than for localization. SIGNIFICANCE: The results of the most extensive clinical study of ictal SPECT to date allow an assessment of the diagnostic value of this elaborate examination and emphasize the importance of postprocessing routines.

A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies.

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P < 5 × 10-8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10-16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187-0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci (>90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10-4, OR = 2.5, 95%CI = 1.499-4.157) and DRB1*04:01 allele (P = 8.3 × 10-5, OR = 2.4, 95%CI = 1.548-3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.

A Validation Study for SHE Score for Acute Subdural Hematoma in the Elderly.

OBJECTIVE: The aim of this study was the verification of the Subdural Hematoma in the Elderly (SHE) score proposed by Alford et al. as a mortality predictor in patients older than 65 years with nontraumatic/minor trauma acute subdural hematoma (aSDH). Additionally, we evaluated further predictors associated with poor outcome. METHODS: Patients were scored according to age (1 point is given if patients were older than 80 years), GCS by admission (1 point for GCS 5-12, 2 points for GCS 3-4), and SDH volume (1 point for volume 50 mL). The sum of points determines the SHE score. Multivariate logistic regression analysis was performed to identify additional independent risk factors associated with 30-day mortality. RESULTS: We evaluated 131 patients with aSDH who were treated at our institution between 2008 and 2020. We observed the same 30-day mortality rates published by Alford et al.: SHE 0: 4.3% vs. 3.2%, p = 1.0; SHE 1: 12.2% vs. 13.1%, p = 1.0; SHE 2: 36.6% vs. 32.7%, p = 0.8; SHE 3: 97.1% vs. 95.7%, p = 1.0 and SHE 4: 100% vs. 100%, p = 1.0. Additionally, 18 patients who developed status epilepticus (SE) had a mortality of 100 percent regardless of the SHE score. The distribution of SE among the groups was: 1 for SHE 1, 6 for SHE 2, 9 for SHE 3, and 2 for SHE 4. The logistic regression showed the surgical evacuation to be the only significant risk factor for developing the seizure. All patients who developed SE underwent surgery (p = 0.0065). Furthermore, SHE 3 and 4 showed no difference regarding the outcome between surgical and conservative treatment. CONCLUSIONS: SHE score is a reliable mortality predictor for minor trauma acute subdural hematoma in elderly patients. In addition, we identified status epilepticus as a strong life-expectancy-limiting factor in patients undergoing surgical evacuation.

Temporal lobe epilepsy surgery: Piriform cortex resection impacts seizure control in the long-term.

OBJECTIVE: Recently, we showed that resection of at least 27% of the temporal part of piriform cortex (PiC) strongly correlated with seizure freedom 1 year following selective amygdalo-hippocampectomy (tsSAHE) in patients with mesial temporal lobe epilepsy (mTLE). However, the impact of PiC resection on long-term seizure outcome following tsSAHE is currently unknown. The aim of this study was to evaluate the impact of PiC resection on long-term seizure outcome in patients with mTLE treated with tsSAHE. METHODS: Between 2012 and 2017, 64 patients were included in the retrospective analysis. Long-term follow-up (FU) was defined as at least 2 years postoperatively. Seizure outcome was assessed according to the International League against Epilepsy (ILAE). The resected proportions of hippocampus, amygdala, and PiC were volumetrically assessed. RESULTS: The mean FU duration was 3.75 ± 1.61 years. Patients with ILAE class 1 revealed a significantly larger median proportion of resected PiC compared to patients with ILAE class 2-6 [46% (IQR 31-57) vs. 16% (IQR 6-38), p = 0.001]. Resected proportions of hippocampus and amygdala did not significantly differ for these groups. Among those patients with at least 27% resected proportion of PiC, there were significantly more patients with seizure freedom compared to the patients with <27% resected proportion of PiC (83% vs. 39%, p = 0.0007). CONCLUSIONS: Our results show a strong impact of the extent of PiC resection on long-term seizure outcome following tsSAHE in mTLE. The authors suggest the PiC to constitute a key target volume in tsSAHE to achieve seizure freedom in the long term.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n = 15; CASPR2, n = 5) of 32 patients with LGI1 (n = 24) and CASPR2 (n = 8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Histopathologic Characterization and Neurodegenerative Markers in Patients With Limbic Encephalitis Undergoing Epilepsy Surgery.

Purpose: Limbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery. Methods: We investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events. Results: Histopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (ß-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker. Conclusion: Our findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS.

The necessity for routine intensive care unit admission following elective craniotomy for epilepsy surgery: a retrospective single-center observational study.

OBJECTIVE: Traditionally, patients who underwent elective craniotomy for epilepsy surgery are monitored postoperatively in an intensive care unit (ICU) overnight in order to sufficiently respond to potential early postoperative complications. In the present study, the authors investigated the frequency of early postoperative events that entailed ICU monitoring in patients who had undergone elective craniotomy for epilepsy surgery. In a second step, they aimed at identifying pre- and intraoperative risk factors for the development of unfavorable events to distinguish those patients with the need for postoperative ICU monitoring at the earliest possible stage. METHODS: The authors performed a retrospective observational cohort study assessing patients with medically intractable epilepsy (n = 266) who had undergone elective craniotomy for epilepsy surgery between 2012 and 2019 at a tertiary care epilepsy center, excluding those patients who had undergone invasive diagnostic approaches and functional hemispherectomy. Postoperative complications were defined as any unfavorable postoperative surgical and/or anesthesiological event that required further ICU therapy within 48 hours following surgery. A multivariate analysis was performed to reveal preoperatively identifiable risk factors for postoperative adverse events requiring an ICU setting. RESULTS: Thirteen (4.9%) of 266 patients developed early postoperative adverse events that required further postoperative ICU care. The most prevalent event was a return to the operating room because of relevant postoperative intracranial hematoma (5 of 266 patients). Multivariate analysis revealed intraoperative blood loss ≥ 325 ml (OR 6.2, p = 0.012) and diabetes mellitus (OR 9.2, p = 0.029) as risk factors for unfavorable postoperative events requiring ICU therapy. CONCLUSIONS: The present study revealed routinely collectable risk factors that would allow the identification of patients with an elevated risk of postsurgical complications requiring a postoperative ICU stay following epilepsy surgery. These findings may offer guidance for a stepdown unit admission policy following epilepsy surgical interventions after an external validation of the results.

Outcome after resective epilepsy surgery in the elderly.

OBJECTIVE: The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls. METHODS: Charts of 2243 patients were screened for operated patients in the authors' center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics. RESULTS: Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly. CONCLUSIONS: The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.

Post-Surgical Outcome and Its Determining Factors in Patients Operated on With Focal Cortical Dysplasia Type II-A Retrospective Monocenter Study.

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy. Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews. Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic-clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only. Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.

Decision-making and duration to accept device-aided therapy in advanced Parkinson's disease / Döntési szempontok és az eszközös terápia elfogadásához szükséges ido elorehaladott Parkinson-kórban.

Összefoglaló. Bevezetés: Az elorehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követoen, az invazív eszközös terápiák bevezetését. Célkituzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás idotartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történo terápiát. A kezelés elfogadásához szükséges idointervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több ido az elso, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált idoszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb idot, míg 71 betegnél egy hónapnál több idot igényelt. A dyskinesisek átlagos idotartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése elotti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészíto terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off idotartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-idotartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az elorehaladott Parkinson-kóros betegek, akiknek hosszabb idotartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészíto gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839-847. INTRODUCTION: In advanced stages of Parkinson's disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. OBJECTIVE: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. METHOD: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mures, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. RESULTS: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off-time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. CONCLUSION: Device-aided therapy is adopted sooner by patients with advanced Parkinson's disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839-847.

T cell numbers correlate with neuronal loss rather than with seizure activity in medial temporal lobe epilepsy.

OBJECTIVE: Medial temporal lobe epilepsy (MTLE) is a drug-resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration. METHODS: We quantified the numbers of CD3+ T cells and CD8+ cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls. RESULTS: We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3+ as well as CD8+ T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T-cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event. SIGNIFICANCE: We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity.

Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection.

INTRODUCTION: The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures. METHODS: Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6). RESULTS: Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9). CONCLUSIONS: ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

Specific B- and T-cell populations are associated with cognition in patients with epilepsy and antibody positive and negative suspected limbic encephalitis.

OBJECTIVE: Neuropsychological impairments are major symptoms of autoimmune limbic encephalitis (LE) epilepsy patients. In LE epilepsy patients with an autoimmune response against intracellular antigens as well as in antibody-negative patients, the antibody findings and magnetic resonance imaging pathology correspond poorly to the clinical features. Here, we evaluated whether T- and B-cells are linked to cognitive impairment in these groups. METHODS: In this cross-sectional, observational, case-controlled study, we evaluated 106 patients with adult-onset epilepsies with a suspected autoimmune etiology. We assessed verbal and visual memory, executive function, and mood in relation to the presence or absence of known auto-antibodies, and regarding T- and B-cell activity as indicated by flow cytometry (fluorescence-activated cell sorting = FACS, peripheral blood = PB and cerebrospinal fluid = CSF). RESULTS: 56% of the patients were antibody-negative. In the other patients, auto-antibodies were directed against intracellular antigens (GAD65, paraneoplastic: 38%), or cellular surface antigens (LGI1/CASPR2/NMDA-R: 6%). Excluding LGI1/CASPR2/NMDA-R, the groups with and without antibodies did not differ in disease features, cognition, or mood. CD4+ T-cells and CD8+ T-cells in blood and CD4+ T-cells in CSF were prominent in the auto-antibody positive group. Regression analyses indicated the role education, drug load, amygdala and/or hippocampal pathology, and CD4+ T-cells play in verbal memory and executive function. Depressed mood revealed no relation to flow cytometry results. CONCLUSION: Our results indicate a link between T- and B-cell activity and cognition in epilepsy patients with suspected limbic encephalitis, thus suggesting that flow cytometry results can provide an understanding of cognitive impairment in LE patients with autoantibodies against intracellular antigens.