Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Twenty-five years of epilepsy surgery at a Central European comprehensive epilepsy center-Trends in intervention delay and outcomes.

OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.

Memory outcomes of temporal lobe surgery in adults aged over 45 years.

OBJECTIVE: It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45 years of age compared with younger patients. METHODS: We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome. RESULTS: The presurgical MQ (median 88) in ≥45 years age group was significantly lower than in both younger groups (median MQ = 100 for ≤30 years age group, p = 0.002; median MQ = 107 for 31-44 years age group, p = 0.002). Three years after the surgery, the MQ decreased significantly in ≤30 years age group (p = 0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome. CONCLUSION: Higher age at the time of surgery does not significantly increase the risk for postsurgical memory decline; however, older patients are more likely to have lowered presurgical MQ. We did not find significant differences in the impact of surgery on seizure outcome among the age groups. Epilepsy surgery appears to be a safe and effective method in the age over 45 years even though an earlier surgery should be preferred.

Atypical handedness in mesial temporal lobe epilepsy.

OBJECTIVE: The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. METHODS: Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated. RESULTS: We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001). CONCLUSIONS: Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy.

OBJECTIVE: The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). METHODS: According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. RESULTS: Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. CONCLUSIONS: According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.

Long-term approach to patients with postsurgical seizures.

OBJECTIVE: The main purpose of the study was to analyze the long-term outcomes and therapeutic approaches for patients with seizures within the first year after surgery. The secondary aim of the study was to evaluate the relationship between 1-year outcome and long-term outcome and choice of therapy. METHODS: Our study was a retrospective investigation of the long-term outcomes of 95 patients (33.5% of all surgically treated patients) with seizure recurrence in the first year after surgery. The patients had follow-up visits for >5 years. RESULTS: At the 5-year follow-up visit (FU5), 28 (29.5%) of the 95 patients were completely seizure-free (International League Against Epilepsy (ILAE) class 1), 17 (17.9%) had auras only (ILAE class 2), and 21 (22.1%) were unimproved (ILAE classes 5 and 6). Statistically significant factors for these long-term outcomes were the focus localization of the epilepsy, preoperative MRI findings, and postoperative follow-up results in the first year. The patients with <3 seizure days in the first postoperative year (ILAE 3) represented 53.6% of the seizure-free patients at FU5; the patients with auras in the first year constituted 64.7% of the patients with only auras at FU5; and the patients unimproved in the first year represented 76.2% of the unimproved patients at FU5. SIGNIFICANCE: Postoperative outcome depends to a certain extent on the outcome achieved in the first postoperative year. More than one third of the patients with postoperative seizures reached a long-term seizure-free outcome, and more than half of them did not experience disabling seizures in the last outcome year. The most therapeutic options were used in patients who were minimally influenced by the operation; the majority of patients with considerable improvement because of the operation do not use any other add-on antiepileptic drugs or other kinds of therapy.

Long-term outcomes in patients after epilepsy surgery failure.

PURPOSE: The primary aim of this study was to analyze the long-term outcomes of patients who were classified as Engel IV one year after resective epilepsy surgery. The secondary objectives were to evaluate the effectiveness of different treatment options and to examine the reasons that the patients did not undergo resective reoperation. METHODS: Our study was designed as a retrospective open-label investigation of the long-term outcomes of 34 patients (12% of all surgically treated patients) who were classified as Engel IV one year after epilepsy surgery. RESULTS: At the last follow-up visit (average of 7.6 ± 4.2 years after surgery), 12 of the 34 examined patients (35.3%) were still classified as Engel IV; 22 of the 34 patients (64.7%) were improved (Engel I-III). Of the 34 patients, 8 (23.5%) achieved an excellent outcome, classified as Engel I, 3 patients (8.8%) were classified as Engel II, and 11 patients (32.4%) as Engel III. The seizure outcome in the patients classified as Engel I was achieved by resective reoperation in 4; by a change in antiepileptic medication in 3 patients; and by vagus nerve stimulation (VNS) in 1 patient. The seizure outcome of Engel II was achieved by a change in antiepileptic medication in all 3 patients. Of the 34 patients, a total of 6 (17.6%) underwent resective reoperation only. The major reasons for this were the absence of a plausible hypothesis for invasive re-evaluation, the risk of postoperative deficit, and multifocal epilepsy in the rest of patients. CONCLUSION: Although the reoperation rate was relatively low in our series, we can achieve better or even excellent seizure outcomes using other procedures in patients for whom resective surgery initially failed.

Long-term outcome and predictors of resective surgery prognosis in patients with refractory extratemporal epilepsy.

PURPOSE: We analyzed the long-term postoperative outcome and possible predictive factors of the outcome in surgically treated patients with refractory extratemporal epilepsy. METHODS: We retrospectively analyzed 73 patients who had undergone resective surgery at the Epilepsy Center Brno between 1995 and 2010 and who had reached at least 1 year outcome after the surgery. The average age at surgery was 28.3±11.4 years. Magnetic resonance imaging (MRI) did not reveal any lesion in 24 patients (32.9%). Surgical outcome was assessed annually using Engel's modified classification until 5 years after surgery and at the latest follow-up visit. RESULTS: Following the surgery, Engel Class I outcome was found in 52.1% of patients after 1 year, in 55.0% after 5 years, and in 50.7% at the last follow-up visit (average 6.15±3.84 years). Of the patients who reached the 5-year follow-up visit (average of the last follow-up 9.23 years), 37.5% were classified as Engel IA at each follow-up visit. Tumorous etiology and lesions seen in preoperative MRI were associated with significantly better outcome (p=0.035; p<0.01). Postoperatively, 9.6% patients had permanent neurological deficits. CONCLUSION: Surgical treatment of refractory extratemporal epilepsy is an effective procedure. The presence of a visible MRI-detected lesion and tumorous etiology is associated with significantly better outcome than the absence of MRI-detected lesion or other etiology.

"MRI-negative PET-positive" temporal lobe epilepsy: invasive EEG findings, histopathology, and postoperative outcomes.

The aim of this retrospective study was to analyze invasive EEG findings, histopathology, and postoperative outcomes in patients with MRI-negative, PET-positive temporal lobe epilepsy (TLE) (MRI-/PET+TLE) who had undergone epilepsy surgery. We identified 20 patients with MRI-/PET+TLE (8.4% of all patients with TLE who had undergone surgery; 11 men, 9 women). Of the 20 patients, 16 underwent invasive EEG. The temporal pole and hippocampus were involved in the seizure onset zone in 62.5% of the patients. We did not identify a lateral temporal or extratemporal seizure onset in any patient. Of the 20 patients, 17 had follow-up periods >1 year (mean follow-up=3.3 years). At the final follow-up, 70.6% patients were classified as Engel I, 5.8% of patients as Engel II, and 11.8% of patients as Engel III and IV (11.8%). Histopathological evaluation showed no structural pathology in any resected hippocampus in 58% of all evaluated temporal poles. The most common pathology of the temporal pole was focal cortical dysplasia type IA or IB. MRI-/PET+TLE should be delineated from other "nonlesional TLE." The ictal onset in these patients was in each case in the temporal pole or hippocampus, rather than in the lateral temporal neocortex. Standard surgery produced a good postoperative outcome, comparable to that for patients with lesional TLE. Histopathological findings were limited: the most common pathology was focal cortical dysplasia type I.