Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

Predictors and prevalence of COVID-19 vaccination in patients with focal epilepsy following resection surgery.

BACKGROUND AND PURPOSE: In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery. METHOD: To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines. RESULTS: Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018-3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619-4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety. CONCLUSIONS: Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the well-being of individuals with epilepsy.

Excitatory somatostatin interneurons in the dentate gyrus drive a widespread seizure network in cortical dysplasia.

Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous studies have primarily focused on the disruption of dysplastic lesions, rather than remote regions such as the hippocampus. Here, we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia. We further investigated the cellular substrates leading to the epileptic hippocampus, using multiscale tools including calcium imaging, optogenetics, immunohistochemistry and electrophysiology. For the first time, we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures. Somatostatin-positive were recruited during cortical dysplasia-related seizures. Interestingly, optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization. By contrast, parvalbumin-positive interneurons retained an inhibitory role as in controls. Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus. Taken together, our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.

Ictal EEG desynchronization during low-voltage fast activity for prediction of surgical outcomes in focal epilepsy.

OBJECTIVE: The authors investigated alterations in functional connectivity (FC) and EEG power during ictal onset patterns of low-voltage fast activity (LVFA) in drug-resistant focal epilepsy. They hypothesized that such changes would be useful to classify epilepsy surgical outcomes. METHODS: In a cohort of 79 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation as well as resective surgery, FC changes during the peri-LVFA period were measured using nonlinear regression (h2) and power spectral properties within/between three regions: the seizure onset zone (SOZ), early propagation zone (PZ), and noninvolved zone (NIZ). Desynchronization and power desynchronization h2 indices were calculated to assess the degree of EEG desynchronization during LVFA. Multivariate logistic regression was employed to control for confounding factors. Finally, receiver operating characteristic curves were generated to evaluate the performance of desynchronization indices in predicting surgical outcome. RESULTS: Fifty-three patients showed ictal LVFA and distinct zones of the SOZ, PZ, and NIZ. Among them, 39 patients (73.6%) achieved seizure freedom by the final follow-up. EEG desynchronization, measured by h2 analysis, was found in the seizure-free group during LVFA: FC decreased within the SOZ and between regions compared with the pre-LVFA and post-LVFA periods. In contrast, the non-seizure-free group showed no prominent EEG desynchronization. The h2 desynchronization index, but not the power desynchronization index, enabled classification of seizure-free versus non-seizure-free patients after resective surgery. CONCLUSIONS: EEG desynchronization during the peri-LVFA period, measured by within-zone and between-zone h2 analysis, may be helpful for identifying patients with favorable postsurgical outcomes and also may potentially improve epileptogenic zone identification in the future.

Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome: A state-of-the-art review.

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.

Clinical Characteristics and Prognostic Significance of Subclinical Seizures in Focal Epilepsy: A Retrospective Study.

INTRODUCTION: The aim was to evaluate the clinical characteristics and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalogram (VEEG) monitoring with or without intracranial electroencephalogram (IEEG) monitoring in patients who had epilepsy surgery. METHODS: We reviewed 286 epileptic patients who underwent subsequent epilepsy surgery during scalp-VEEG evaluation with or without IEEG monitoring between 2013 and 2020, with a minimum follow-up of 1 year. The prevalence and clinical characteristics of SCSs, as well as their prognostic significance, were analyzed. RESULTS: A total of 286 patients were enrolled for analysis, and 80 patients had IEEG implanted. SCSs were recorded in 9.79% of the patients based on VEEG and 50% based on IEEG. In the VEEG group (n = 286), younger seizure onset (P = 0.004) was associated with the presence of s-SCSs (SCSs detected on scalp VEEG). In the IEEG group (n = 80), temporal lobe epilepsy (P = 0.015) was associated with the presence of i-SCSs (SCSs detected on IEEG). Of 286 patients, 208 (72.73%) were seizure-free in the VEEG group, and 56 0f 80 patients (70%) were seizure-free in the IEEG group through the last follow-up. In the VEEG group, the presence of s-SCSs did not affect seizure outcome; predictors of seizure recurrence were longer epilepsy duration (P = 0.003, OR 1.003, 95% CI 1.001-1.005), history of focal to bilateral tonic-clonic seizure (P = 0.027, OR 1.665, 95% CI 1.060-2.613), nonspecific pathology (P = 0.018, OR 2.184, 95% CI 1.145-4.163), and incomplete resection (P = 0.004, OR 2.705, 95% CI 1.372-5.332). In the IEEG group, i-SCSs were significantly associated with seizure outcome (P = 0.028, OR 0.371, 95% CI 0.153-0.898). CONCLUSION: The rate of SCSs captured on IEEG monitoring was higher than that on VEEG monitoring during presurgical evaluation. SCSs detected on VEEG monitoring were associated with younger seizure onset. SCSs detected on IEEG monitoring were associated with temporal lobe epilepsy and also predicted surgical outcomes in focal epilepsy.

Hippocampal Malrotation Could Be Less Significant in Epilepsy Caused by Focal Cortical Dysplasia Type I and Type II.

OBJECTIVES: Debates over the relationship between hippocampal malrotation (HIMAL) and epilepsy continue without consensus. This study explores the role of HIMAL in a cohort of epilepsy caused by focal cortical dysplasia (FCD). METHODS: In this study, 90 patients with epilepsy caused by FCD type I and type II and 48 healthy adults underwent a 3 Tesla MRI following a dedicated epilepsy protocol for the analysis of the prevalence and morphologic features of HIMAL. In addition, numerous clinical characteristics and hippocampal volumes were evaluated. RESULTS: The cohort included a total of 90 patients (32 were HIMAL, 58 were non-HIMAL). Among these patients, 32 (35.6%) had HIMAL (22 left, four right, and six bilateral), which did not differ from the 48 controls, where 16 (33.3%) had HIMAL (12 left, two right, and two bilateral). Neither the quantitative features of HIMAL (diameter ratio, dominant inferior temporal sulcus height ratio, medial distance ratio, dominant inferior temporal sulcus angle, and parahippocampal angle), nor the accompanying characteristics of HIMAL (vertical dominant inferior temporal sulcus, enlarged temporal horn, and a low position of ipsilateral fornix) showed differences between patients with FCD and controls. No statistical difference in the clinical characteristics between FCD patients with HIMAL and those without was found. Neither the side nor the existence of HIMAL was correlated with the lateralization and location of FCD. As to the hippocampal volume, there was no difference between FCD patients with HIMAL and those without. CONCLUSION: Hippocampal malrotation is a common morphologic variant in healthy controls as well as in patients with epilepsy caused by FCD type I and type II. Hippocampal malrotation could be less significant in epilepsy caused by FCD type I and type II.

Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China.

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

Focal cortical dysplasia links to sleep-related epilepsy in symptomatic focal epilepsy.

OBJECTIVE: In sleep-related epilepsy (SRE), epileptic seizures predominantly occur during sleep, but the clinical characteristics of SRE remain elusive. We aimed to identify the clinical features associated with the occurrence of SRE in a large cohort of symptomatic focal epilepsy. METHODS: We retrospectively included patients with four etiologies, including focal cortical dysplasia (FCD), low-grade tumors (LGT), temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and encephalomalacia. SRE was defined as more than 70% of seizures occurring during sleep according to the seizure diary. The correlation between SRE and other clinical variables, such as etiology of epilepsy, pharmacoresistance, seizure frequency, history of bilateral tonic-clonic seizures, and seizure localization was analyzed. RESULTS: A total of 376 patients were included. Among them 95 (25.3%) were classified as SRE and the other 281(74.7%) as non-SRE. The incidence of SRE was 53.5% in the FCD group, which was significantly higher than the other three groups (LGT: 19.0%; TLE-HS: 9.9%; encephalomalacia: 16.7%; P < 0.001). The etiology of FCD (p < 0.001) was significantly associated with SRE (OR: 9.71, 95% CI: 3.35-28.14) as an independent risk factor. In addition, small lesion size (p = 0.009) of FCD further increased the risk of SRE (OR: 3.18, 95% CI: 1.33-7.62) in the FCD group. SIGNIFICANCE: Our data highlight that FCD markedly increased the risk of sleep-related epilepsy independently of seizure localization. A small lesion of FCD further increased the risk of sleep-related epilepsy by 2.18 times in the FCD group.

7T MRI with post-processing for the presurgical evaluation of pharmacoresistant focal epilepsy.

BACKGROUND: We aimed to evaluate the diagnostic yield of seven-tesla (7T) magnetic resonance imaging (MRI) with post-processing of three-dimensional (3D) T1-weighted (T1W) images by the morphometric analysis program (MAP) in epilepsy surgical candidates whose 3T MRI results were inconclusive or negative. METHODS: We recruited 35 patients with pharmacoresistant focal epilepsy. A multidisciplinary team including an experienced neuroradiologist evaluated their seizure semiology, video-electroencephalography data, 3T MRI and post-processing results, and co-registered FDG-PET. Eleven patients had suspicious lesions on 3T MRI and the other 24 patients were strictly MRI-negative. 7T MRI evaluation was then performed to aid clinical decision. Among patients with pathologically proven focal cortical dysplasia (FCD) type II, signs of FCD were retrospectively evaluated in each MRI sequence (T1W, T2W, and FLAIR), and positive rates were analyzed in each MAP feature map (junction, extension, and thickness). RESULTS: 7T MRI evaluation confirmed the lesion in nine of the 11 (81.8%) patients with suspicious lesions on 3T MRI. It also revealed new lesions in four of the 24 (16.7%) strictly MRI-negative patients. Histopathology showed FCD type II in 11 of the 13 (84.6%) 7T MRI-positive cases. Unexpectedly, three of the four newly identified FCD lesions were located in the posterior quadrant. Blurred gray-white boundary was the most frequently observed sign of FCD, appearing on 7T T1W image in all cases and on T2W and FLAIR images in only about half cases. The 7T junction map successfully detected FCD (10/11) in more cases than the extension (1/11) and thickness (0/11) maps. The 3D T1W images at 7T exhibited superior cerebral gray-white matter contrast, more obviously blurred gray-white boundary of FCD, and larger and brighter positive zones in post-processing than 3T T1W images. CONCLUSION: 7T MRI with post-processing can enhance the detection of subtle epileptogenic lesions for MRI-negative epilepsy and may optimize surgical strategies for patients with focal epilepsy.

Clinical characteristics of low-grade tumor-related epilepsy and its predictors for surgical outcome.

OBJECTIVES: Low-grade tumors are the most common neoplasms inducing focal epilepsy; however, the short- and medium-term efficacy of surgery in epilepsy patients with low-grade tumors remains underappreciated. This study aims to summarize the clinical characteristics of epilepsy patients with low-grade tumors and to identify factors associated with postsurgical seizure-free outcomes. METHODS: We retrospectively reviewed consecutive patients with low-grade tumors who underwent subsequent epilepsy surgery in our epilepsy center, between 2012 and 2018 with a minimum follow-up of 1 year. Using Engel's classification and Kaplan-Meier survival analysis, we assessed postoperative seizure freedom over time. Demographical, electroclinical, and other presurgical evaluations were then evaluated for association with postoperative seizure outcome. RESULTS: The cohort included a total of 132 patients: 79 males and 53 females. Among them, 110 (83.33%) were seizure-free through their last follow-up. The Engel class I outcomes were 90.15%, 87.76%, 85.53%, 82.46%, and 73.17% at the end of the 1st, 2nd, 3rd, 4th, and 5th postoperative years, respectively. Multivariate logistic analysis revealed that longer epilepsy duration (p < 0.001, OR 1.091, 95% CI 1.040-1.144) and incomplete resection (p = 0.009, OR 3.673, 95% CI 1.393-9.684) were independently associated with seizure recurrence through the last follow-up. CONCLUSIONS: Surgical treatment for seizure control in patients with low-grade tumors provides excellent short- and median-term outcomes.

Clinical Relevance of Cerebrospinal Fluid Antibody Titers in Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis. To date, there has been no study on the relationship between antibody (Ab) titers and clinical phenotype. This study aims to clarify the relationship between cerebrospinal fluid Ab titers and clinical manifestations of anti-NMDAR encephalitis at onset. Seventy-six consecutive patients with a definite diagnosis were enrolled. The relationship between Ab titers and different onset symptoms including psychiatric symptoms, seizures, and memory deficits were analyzed. We further investigated the correlation between Ab titers and clinical severity as assessed by the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE), respectively. The Ab titers had a median value of 1:10 (range 1:1-1:100). There was no significant difference in titers among various clinical factors including gender and combination of tumor and other diseases (each p > 0.05). Patients presenting with psychiatric symptoms at onset had higher titers than those with seizures (p = 0.008) and memory deficits (p = 0.003). The mRS scores revealed a significant but weak correlation with Ab titers (r = 0.243, p = 0.034), while CASE scores did not correlate with the titers (p = 0.125). Our findings indicated that the Ab titers were associated with the type of onset symptoms, with a higher level of patients with psychiatric symptoms. Regarding the clinical severity, the titers showed a weak correlation with the mRS, but no correlation with the CASE.

Distinguishing Focal Cortical Dysplasia From Glioneuronal Tumors in Patients With Epilepsy by Machine Learning.

Purpose: We are aiming to build a supervised machine learning-based classifier, in order to preoperatively distinguish focal cortical dysplasia (FCD) from glioneuronal tumors (GNTs) in patients with epilepsy. Methods: This retrospective study was comprised of 96 patients who underwent epilepsy surgery, with the final neuropathologic diagnosis of either an FCD or GNTs. Seven classical machine learning algorithms (i.e., Random Forest, SVM, Decision Tree, Logistic Regression, XGBoost, LightGBM, and CatBoost) were employed and trained by our dataset to get the classification model. Ten features [i.e., Gender, Past history, Age at seizure onset, Course of disease, Seizure type, Seizure frequency, Scalp EEG biomarkers, MRI features, Lesion location, Number of antiepileptic drug (AEDs)] were analyzed in our study. Results: We enrolled 56 patients with FCD and 40 patients with GNTs, which included 29 with gangliogliomas (GGs) and 11 with dysembryoplasic neuroepithelial tumors (DNTs). Our study demonstrated that the Random Forest-based machine learning model offered the best predictive performance on distinguishing the diagnosis of FCD from GNTs, with an F1-score of 0.9180 and AUC value of 0.9340. Furthermore, the most discriminative factor between FCD and GNTs was the feature "age at seizure onset" with the Chi-square value of 1,213.0, suggesting that patients who had a younger age at seizure onset were more likely to be diagnosed as FCD. Conclusion: The Random Forest-based machine learning classifier can accurately differentiate FCD from GNTs in patients with epilepsy before surgery. This might lead to improved clinician confidence in appropriate surgical planning and treatment outcomes.

Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis.

BACKGROUND: Accumulating data have suggested seizures occur frequently in patients with neuronal surface antibody-mediated autoimmune encephalitis. We aimed to evaluate seizure outcomes and potential factors associated with the development of epilepsy in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), and anti-gamma-aminobutyric-acid B receptor (GABAB R) encephalitis. METHODS: Patients with anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis were prospectively recruited from 2014 to June 2019, with a median follow-up period of 30.5 months (range 8-67 months). Seizure outcomes were assessed and risk factors of epilepsy were analyzed. RESULTS: A total of 119 patients with anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis were included, and 83 (69.7%) of them developed new-onset seizures. By the end of follow-up, 17 (21.3%) of 80 patients had seizure relapses after intermittent seizure remission or exhibited uncontrolled seizure episodes, contributing to epilepsy. Immunotherapy delay and interictal epileptic discharges (IEDs) were identified to be associated with the development of epilepsy in patients with anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis, particularly anti-NMDAR encephalitis. Furthermore, multivariate logistic regression analysis demonstrated that immunotherapy delay was an independent predictor for epilepsy. CONCLUSION: Our study suggested that immunotherapy delay and IEDs were associated with the development of epilepsy in patients with anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis. Early diagnosis and treatment were required, and particular consideration should be given to patients with these risk factors.

A Case of Recurrent Painful Ophthalmoplegic Neuropathy.

Ophthalmoplegic migraine (OM) is characterized by recurrent episodes of headache with unilateral ophthalmoplegia due to paresis of cranial nerve III, IV, or VI. The recent revision to the International Headache Classification has reclassified it as recurrent painful ophthalmoplegic neuropathy (RPON). However, it is of note that the presentation of oculomotor nerve tumors may mimic RPON. Here, we report the case of a patient presenting with recurrent migraine and oculomotor palsy with several specific magnetic resonance imaging (MRI) findings. The patient was initially diagnosed with migraine 15 years ago, but since 10 years ago, his symptoms had evolved to include repeated oculomotor paralyzes. Before this attack, the patient did eventually recover completely each time after the initial episode. MRI performed during this attack revealed a nodular enhancing lesion described as schwannoma of the left oculomotor nerve, and on diffusion-weighted imaging (DWI), the nerve was isointense to the midbrain. The nodular enhancement became weaker, and the nerve's signal on DWI disappeared 3 months later as the patient's symptoms resolved mostly. This is the first case of RPON demonstrating an obvious change in signal of the affected nerve on DWI during the attack and remission.

Localization value of subclinical seizures on scalp video-EEG in epilepsy presurgical evaluation.

OBJECTIVE: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. METHODS: We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. RESULTS: Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P = .020) and 2-year follow-up (P = .040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. SIGNIFICANCE: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.

Application of MRI Post-processing in Presurgical Evaluation of Non-lesional Cingulate Epilepsy.

Background and Purpose: Surgical management of patients with cingulate epilepsy (CE) is highly challenging, especially when the MRI is non-lesional. We aimed to use a voxel-based MRI post-processing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle epileptogenic lesions in CE, thereby improving surgical evaluation of patients with CE with non-lesional MRI by visual inspection. Methods: Included in this retrospective study were 9 patients with CE (6 with negative 3T MRI and 3 with subtly lesional 3T MRI) who underwent surgery and became seizure-free or had marked seizure improvement with at least 1-year follow-up. MRI post-processing was applied to pre-surgical T1-weighted volumetric sequence using MAP. The MAP finding was then coregistered and compared with other non-invasive imaging tests (FDG-PET, SPECT and MEG), intracranial EEG ictal onset, surgery location and histopathology. Results: Single MAP+ abnormalities were found in 6 patients, including 3 patients with negative MRI, and 3 patients with subtly lesional MRI. Out of these 6 MAP+ patients, 4 patients became seizure-free after complete resection of the MAP+ abnormalities; 2 patients didn't become seizure-free following laser ablation that only partially overlapped with the MAP+ abnormalities. All MAP+ foci were concordant with intracranial EEG ictal onset (when performed). The localization value of FDG-PET, SPECT and MEG was limited in this cohort. FCD was identified in all patients' surgical pathology except for two cases of laser ablation with no tissue available. Conclusion: MAP provided helpful information for identifying subtle epileptogenic abnormalities in patients with non-lesional cingulate epilepsy. MRI postprocessing should be considered to add to the presurgical evaluation test battery of non-lesional cingulate epilepsy.