Hippocampal malrotation (HIMAL) is an increasingly recognized neuroimaging feature but the clinical correlation and significance in epilepsies remain under debate. It is characterized by rounded hippocampal shape, deep collateral, or occipitotemporal sulcus, and medial localization of the hippocampus. In this review, we describe the embryonic development of the hippocampus and HIMAL, the qualitative and quantitative diagnosis issues, and the pathological findings of HIMAL. HIMAL can be bilateral or unilateral and more on the left side. Furthermore, the relevance of HIMAL diagnosis in clinical practice, including its role in epileptogenesis and the impact on the pre-surgical decision are reviewed. Finally, the relationship between HIMAL and hippocampal sclerosis (HS) and the possible role of genetics in the etiology of HIMAL are discussed. The evidence so far suggested that HIMAL does not have a significant role in epileptogenesis or surgical decision. HIMAL could be a genetic developmental imaging feature that represents a more diffuse but subtle structural error during brain development. Many questions remain to be explored, such as possible cognitive alteration associated with HIMAL and whether HIMAL predisposes to the development of HS. Further studies using high-quality MRI, unified consensus qualitative and quantitative diagnostic criteria, and comprehensive cognitive assessment are recommended.

Objective: Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability and epilepsies. In addition to the brain, VGSCs are also abundant enriched in cardiac tissues and are responsible for normal cardiac rhythm. Theoretically, sodium channel blocking antiseizure medications (SCB-ASMs) may have unwanted cardiac side effects. Lacosamide (LCM) is increasingly used in patients with status epilepticus (SE) due to the availability of intravenous formula. The concerns about the proarrhythmic effect are even higher due to the need for rapid administration of LCM. There were limited data on the cardiac safety of intravenous LCM. Hereby, we performed a study to observe the effect of intravenous loading of LCM in patients with seizures in our Neurological Intensive Care Unit (NICU).Methods: We retrospectively reviewed the patients using parenteral LCM for seizures in NICU. A routine infusion time of 30 min was performed. The electrocardiogram (ECG) and blood pressure were recorded before and after LCM injection.Results: We retrospectively reviewed the clinical data of 38 patients using LCM for treating seizures. Two patients had cardiac side effects after LCM loading, one (3.0%) with new-onset first-degree AV block and the other (3.0%) with atrial premature complex. For the quantitative changes of ECG parameter analysis, there was no change in QRS complex, corrected QT intervals, and heart rate except that the PR interval was mildly increased. A mild decrease in the diastolic blood pressure and mean arterial pressure were also observed. None of the above-mentioned parameter alterations required clinical intervention.Conclusion: We evaluated the cardiac safety concern in real-world epilepsy patients requiring intravenous LCM. Near half of this cohort responded to LCM therapy and there was no life-threatening cardiac adverse effect. Intravenous LCM does have some effects on the ECG parameters and blood pressure but without clinical relevance. Despite the theoretical concern of cardiac adverse effects of LCM, the benefit of seizure control outweighed the risk in patients with status epilepticus or seizure clusters, such as hyperthermia, pulmonary edema, cardiac arrhythmias, or cardiovascular collapse.

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22–71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

Periventricular nodular heterotopia (PVNH) is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. PVNH often cause epilepsy, psychomotor development or cognition problem. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology. Our purpose is to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. We included 21 patients with confirmed PVNH. The detailed clinical information, electroencephalography, and other clinical findings were recorded. Detailed brain MR imaging was assessed. Mutation analysis of the FLNA gene was used Sanger sequencing or a next generation sequencing based assay. FLNA mutations were identified in 9 patients (7 females and 2 males), including two nonsense, two splice site, three frameshift, and two missense mutations. In FLNA-positive group, 8 patients had anterior predominant bilateral symmetric presentation and only one had asymmetrical distribution and dilated ventricles. Extra-cerebral features were more often observed in FLNA-positive group than FLNA-negative group. Genetics of PVNH is heterogenous, and mutations in FLNA gene account for less than half of the patients in our cohort. Our finding between FLNA-positive and FLNA-negative patients could guide the clinicians to select relevant genetic testing.

Introduction: Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and/or synaptic antigens. We previously demonstrated that S100A6 was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood–brain barrier (BBB). In this study, we focused on the epigenetic regulation of S100A6, the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies.Methods: We enrolled and collected serum from 10 patients with AE and 10 healthy control (HC) subjects. Promoter methylation and 5‐azacytidine treatment assays were conducted to observe the methylation process of S100A6. The effect of S100A6 on B lymphocytes was analyzed using an adhesion assay and leukocyte transendothelial migration (LTEM) assay. A LTEM assay was also used to compare the effects of the serum of HCs, serum of AE patients, S100A6 recombinant protein, and S100A6 antibodies on B lymphocytes.Result: The promoter methylation and 5‐azacytidine treatment assays confirmed that S100A6 was regulated by DNA methylation. The adhesion study demonstrated that the addition of S100A6 enhanced adhesion between B lymphocytes and a BBB endothelial cell line in a concentration‐dependent manner. The LTEM assay showed that the serum of AE patients, as well as S100A6, promoted B lymphocyte infiltration and that this effect could be attenuated by S100A6 antibodies.Conclusion: We clarified that S100A6 was under epigenetic regulation in patients with AE and that it helped B lymphocytes to adhere to and infiltrate the BBB endothelial layer, which could be counteracted by S100A6 antibodies. Therefore, the methylation profile of S100A6 could be a marker of the activity of AE, and countering the effect of S100A6 may be a potential treatment target for AE.

Autoimmune encephalitis (AE) is a neurological emergency. We aimed to analyze the application and effectiveness of the currently available prediction tools for AE patients in Taiwan. We retrospectively collected 27 AE patients between January 2008 and December 2019. Antibody Prevalence in Epilepsy (APE) score, Response to Immunotherapy in Epilepsy (RITE) score, and anti-NMDAR Encephalitis One Year Functional Status (NEOS) score were applied to validate their usability. Based on the defined cutoff values, the sensitivity and specificity of each score were calculated. A receiver operating characteristic (ROC) curve and the area under the curve (AUC) were generated for each scoring system. The AUC value of APE was 0.571. The AUC value of RITE was 0.550. The AUC values for the NEOS score at discharge and long-term follow-up were 0.645 and 0.796, respectively. The performance of APE and RITE scores was suboptimal in the Taiwanese cohort, probably due to the limitations of the small sample size and single ethnicity. On the other hand, the NEOS score performed better on long-term follow-up than at discharge.