Focal epilepsies: Update on diagnosis and classification.

Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions-developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy.

EEG-based grading of immune effector cell-associated neurotoxicity syndrome.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

In the pursuit of the epileptogenic zone - listen carefully and look deeply.

We report a 30-year-old right-handed man with a history of drug-resistant, non-lesional, childhood-onset focal epilepsy featuring (i) focal unaware seizures with left upper extremity automatisms and tonic posturing preceded by an aura of a ringing/beeping noise, and (ii) nocturnal hyperkinetic seizures. Non-invasive video-EEG, MEG, and PET were unable to delineate the epileptogenic zone (EZ) warranting an invasive investigation with bilateral depth electrodes (SEEG). SEEG data localized the EZ to the right superior temporal sulcus (STS) and right superior temporal gyrus (STG), wherein the auditory cortex lies, with subsequent ictal spread to anterior topography including the operculo-insular region. This hypothesis explained the patient's semiology consisting of focal aware seizures featuring auditory phenomena and nocturnal hyperkinetic seizures. Our multi-disciplinary team elected to proceed with a resection of the posterior right STG guided by electrocorticography (ECoG). Prior to resection, ECoG identified seizures arising from the peri-sylvian region, seemingly discordant to previous SEEG data. Following resection of the posterior right STG, ECoG continued to show seizures from contacts overlying the parietal operculum. It was not until the cortex was resected, at the depth of the right STS, that ECoG no longer showed epileptiform abnormalities. Pathology revealed focal cortical dysplasia type 1A.

Meningioangiomatosis: Multimodal Analysis and Insights From a Systematic Review.

BACKGROUND: Meningioangiomatosis is a poorly studied, rare, benign, and epileptogenic brain lesion. OBJECTIVE: To demonstrate that surgical resection and a short-time interval to surgery improves epileptic seizure control, we performed a systematic review and meta-analysis of meningioangiomatosis cases. METHODS: Using PRISMA-IPD guidelines, the authors performed a systematic review and meta-analysis of histopathologically-proven meningioangiomatosis cases. Literature search in French and English languages (PubMed, Embase, the Cochrane Library, and the Science Citation Index) including all studies (January 1981 to June 2020) dealing with histopathologically-proven meningioangiomatosis, without age restriction. We assessed clinical, imaging, histomolecular, management, and outcome findings of patients with meningioangiomatosis. RESULTS: Two-hundred and seven cases of meningioangiomatosis from 78 studies were included. Most meningioangiomatosis was sporadic, preferentially concerned male patients, younger than 20 years old, and allowed a functionally independent status. Epileptic seizure was the main symptom, with 81.4% of patients having uncontrolled seizures at the time of surgery. Meningioangiomatosis mainly had frontal (32.3%) or temporal (30.7%) locations. Imaging presentation was heterogeneous, and the diagnosis was often missed preoperatively. The histopathologic pattern was similar whatever the clinical presentation, and immunohistochemistry had limited diagnostic value. On molecular analysis, allelic loss at 22q12 was more frequent in samples of meningioangiomatosis-associated meningioma (37.5%) than in isolated meningioangiomatosis (23.1%). Time interval from diagnosis to surgery (p = 0.011) and lack of surgical resection of the meningioangiomatosis (p = 0.009) were independent predictors of postoperative seizure control. CONCLUSIONS: Owing to low scientific evidence, a multicentric prospective study should help refining the management of meningioangiomatosis.

Blood pressure reduction and outcome after endovascular therapy with successful reperfusion: a multicenter study.

BACKGROUND: Elevated systolic blood pressure (SBP) after mechanical thrombectomy (MT) correlates with worse outcome. However, the association between SBP reduction (SBPr) and outcome after successful reperfusion with MT is not well established. OBJECTIVE: To investigate the association between SBPr in the first 24 hours after successful reperfusion and the functional and safety outcomes of MT. METHODS: A multicenter retrospective study, which included 10 comprehensive stroke centers, was carried out. Patients with acute ischemic stroke and anterior circulation large vessel occlusions who achieved successful reperfusion via MT were included. SBPr was calculated using the formula 100×([admission SBP-mean SBP]/admission SBP). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days. Safety endpoints included symptomatic intracerebral hemorrhage, mortality, and requirement for hemicraniectomy during admission. A generalized mixed linear model was used to study the association between SBPr and outcomes. RESULTS: A total of 1361 patients were included in the final analysis. SBPr as a continuous variable was inversely associated with poor outcome (OR=0.97; 95% CI 0.95 to 0.98; p<0.001) but not with the safety outcomes. Subanalysis based on reperfusion status showed that SBPr was associated with lower odds of poor outcome only in patients with complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI 3)) but not in patients with incomplete reperfusion (mTICI 2b). When SBPr was divided into categories (<1%, 1%-10%, 11%-20%, >20%), the rate of poor outcome was highest in the first group. CONCLUSION: SBPr in the first 24 hours after successful reperfusion was inversely associated with poor outcome. No association between SBPr and safety outcome was found.

Endovascular thrombectomy in pediatric patients with large vessel occlusion.

BACKGROUND: Pediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices. METHODS: We conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017. RESULTS: Nineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred. CONCLUSIONS: Endovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Meta-Analysis and Systematic Review.

BACKGROUND: Chronic subdural hematoma is a very common neurosurgical condition. Although conventional surgical methods, such as burr hole irrigation, have been the mainstay of treatment, middle meningeal artery (MMA) embolization has emerged as a promising adjunctive or alternative treatment. The aim of this article was to present a meta-analysis and systematic review of this topic. METHODS: A literature search using keywords "chronic subdural hematoma," "chronic subdural hemorrhage," "refractory subdural hematoma," "refractory subdural hemorrhage," and "middle meningeal artery embolization" was conducted through October 2018. Outcome variables of hematoma recurrence, surgical complications, and modified Rankin Scale score were analyzed and compared between MMA embolization and conventional surgery cohorts. RESULTS: Three double-arm studies comparing embolization and conventional surgery groups and 6 single-arm case series were identified and analyzed. Hematoma recurrence rate was significantly lower in the embolization group compared with conventional treatment group (2.1% vs. 27.7%; odds ratio = 0.087; 95% confidence interval, 0.026-0.292; P < 0.001; I2 = 0%); surgical complication rates were similar between groups (2.1% vs. 4.4%; odds ratio = 0.563; 95% confidence interval, 0.107-2.96; P = 0.497; I2 = 27.5%). Number of patients with modified Rankin Scale score >2 in the embolization (12.5%) versus conventional treatment (9.1%) group showed no statistical difference (P = 0.689). A composite hematoma recurrence rate of 3.6% was found after summing the 6 case series. Composite recurrence and complication rates in the embolization cohorts of the double-arm studies and the case series were lower than literature values for conventional surgical treatments. CONCLUSIONS: MMA embolization is a promising treatment for chronic subdural hematoma. Future randomized clinical trials are needed.