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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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier B.V.)

Competing Interests: Declaration of Competing Interest We are indebted to the patient and family members for their support and participation in the study.

Peripheral neuropathies, especially those with atypical features, remain a diagnostic challenge. In this case, a 60-year-old patient presented with acute-onset weakness starting in the right hand then sequentially involving the left leg, left hand, and right leg over 5 days. The asymmetric weakness was accompanied by persistent fever and elevated inflammatory markers. Subsequent development of rashes combined with careful review of the history led us to the final diagnosis and targeted treatment. This case highlights clinical pattern recognition with the help of electrophysiologic studies in peripheral neuropathies, which provide shortcuts to narrow the differential diagnosis. We also illustrate the important pitfalls from history taking to ancillary testing in diagnosing the rare but treatable cause of peripheral neuropathy (eFigure 1, links.lww.com/WNL/C541)., (© 2022 American Academy of Neurology.)

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE., Methods: A cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE., Results: This survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest difficulty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management., Conclusion: Our study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication., Competing Interests: Author YG was the board member of ZAAE. M-pD was the president of ZAAE. This survey was supported by ZAAE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Qian, Cai, Ding and Guo.)

Objective: To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China., Methods: Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency., Results: Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP., Conclusion: The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions., (© 2022 International League Against Epilepsy.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the assessment and management of epilepsy with anxiety and depression, and their clinical practice based on a survey., Methods: A cross-sectional survey of epilepsy health professionals was undertaken in Zhejiang Province using the modified International League Against Epilepsy (ILAE) Psychology Task Force questionnaire. We recorded the characteristics of participants and the practice of screening, referral, and treatment for depression and anxiety disorders. A total of 146 participants joined in the survey, of which 76.0% were neurologists, and 69 participants were the member of the Zhejiang Association Against Epilepsy (ZAAE)., Results: This survey revealed that almost all participants (87.7%) agreed that screening for depression and anxiety in patients with epilepsy (PWEs) was very important; however, the frequency of screening was very low (41.1% of participants screened less than 10% of patients, and 34.2% participants screened between 10% and 30% of patients). A higher frequency of screening was reported in the member group and compared with that in the non-member group (P = 0.025). The main barrier to screening was the lack of time during clinic visits: 81.5% participants included screening questions as part of their clinical review. When anxiety/depression was diagnosed, the next step should be to refer patients to a psychiatrist (78.1%). No standardized procedures and lack of mental health specialists trained to assess and/or manage PWEs, were the main barriers to follow-up assessment and management. Lack of appropriately trained mental health specialists was also the main barrier to psychological treatment for depression and anxiety., Conclusion: This survey highlighted that epilepsy healthcare professionals in Zhejiang province agreed on the importance of screening for psychiatric comorbidities in PWEs; however, the screening and management were actually insufficient. Certain barriers to screening, referral, and treatment were presented and improvements were recommended., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. Yi Guo is the member of ZAAE. Mei-Ping Ding is the president of ZAAE. This survey was supported by ZAAE., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Qiao, Lai, Zheng, Yang, Fang, Shen, Zhang and Ding.)

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.

Introduction: A new scale, named the Clinical Assessment Scale for Autoimmune Encephalitis (CASE), has recently been developed for rating the severity of autoimmune encephalitis (AE) with a high level of clinimetric properties. In this study, our primary objective was to validate the performance of CASE through a multicenter study in China., Methods: Between July 2014 and December 2019, 143 consecutive patients with definite neuronal surface antibody-associated AE from three tertiary hospitals were enrolled in the study. We validated the reliability, internal consistency, and validity of CASE. We further compared CASE with the modified Rankin scale (mRS) among different subtypes of AE in terms of its sensitivity to disease dynamics. Statistical analyses were performed using GraphPad Prism and R software., Results: Our analyses showed that CASE had good inter- and intraobserver reliability (intra-class correlation coefficient 0.96/0.98) and internal consistency (Cronbach α = 0.847) at disease onset. The scores of CASE and mRS remained well correlated in patients at admission and at discharge (both r = 0.80, p < 0.001). From admission to discharge, the scores of CASE changed in 81 (56.6%) patients, in comparison to changes in mRS in 48 (33.6%) patients (p = 0.007 and p < 0.001, respectively). The largest changes in scores occurred for non-motor symptoms, including psychiatric, memory, and language dysfunctions (40.6, 26.6, and 23.1% of patients, respectively); in contrast, scores for motor symptoms, such as dyskinesia, weakness and ataxia, changed the least (7.0, 15.4, and 16.1% of patients, respectively)., Conclusion: Based on these results, CASE performed well in assessing the severity of neuronal surface antibody-associated AE. In comparison to mRS, it performed better for non-motor symptoms and was more sensitive to changes in severity., (© 2021. The Author(s).)

Objective: To investigate the therapeutic effects of Biejia Yugan Granule on hepatic fibrosis caused by compound factors in rats and its effect on TGF-β1/Smads signaling pathway. Methods: SD rats were randomly divided into blank control group, model control group, colchicine group, Biejia Yugan Granule low, medium and high dose (1.85, 3.70, 7.40 g/kg) groups ( n = 8 in each group). The rat model of hepatic fibrosis was established by treating with 5% alcohol 15 ml/kg (ig) everyday and injecting with 40% carbon tetrachloride (sc) twice a week for 42 days. The effects of Biejia Yugan Granule on liver function, liver index and water content, serum hepatic fibrosis related indicators, key proteins and gene expression of TGF-β1/Smads signaling pathway in rats were observed. Results: Biejia Yugan Granule at the doses of 1.85, 3.70 and 7.40 g/kg could decrease the serum levels of ALT, AST, ALP and HA, PCⅢ, C-Ⅳ, LN significantly, reduce the water content of liver tissue leads to the decrease of liver index, regulate the liver tissue TGF-β1, Smad3 mRNA and Smad7 mRNA expressions. Conclusion: Biejia Yugan Granule has obvious effects of reducing enzyme and protecting liver and inhibiting hepatic fibrosis, and inhibiting TGF-β1/Smads signaling pathway is one of its mechanisms of anti-hepatic fibrosis.

Objective: To investigate the effects of Butylphthalide (NBP) on airway mucus hypersecretion, interleukin-13 (IL-13) and tumor necrosis factor-α (TNF-α) in asthmatic mice. Methods: The mice were randomly divided into control group, asthma group, DEX group and high, medium and low doses of NBP (100, 50, 25 mg/kg) groups ( n =12). Ovalbumin (OVA) injection was sensitized on the 1st, 8th, and 15th day of the experiment, and OVA was inhaled on the 22nd day to stimulate for 5 weeks to replicate the asthma model, and 20 mg/kg of NBP was given for intervention before the challenge. Finally, the asthma behavior, the secretion of goblet cells and Mucin 5ac (Muc5ac)were observed, and meanwhile the viscosity of bronchoalveolar lavage fluid (BALF) and the levels of Muc5ac, IL-13 and TNF-α in BALF were measured by ELISA. Results: Compared with the control group, the degree of sneezing, nose scratching and asthma, the proliferation of airway epithelial goblet cells and secretion of Muc5ac in the asthma group were increased significantly ( P ＜0.01), meanwhile, the viscosity of BALF and the contents of Muc5ac, IL-13 and TNF-α were also increased significantly ( P ＜0.01). Compared with the asthma group, the above behavioral scores of asthma were decreased significantly ( P ＜0.01) after the intervention of 25, 50 and 100 mg/kg NBP, as well as the proliferation of airway epithelial goblet cells, secretion of Muc5ac, the viscosity of BALF and the contents of Muc5ac, IL-13 and TNF-α were significantly lower than those of the asthma group ( P ＜0.05, 0.01). Conclusion: NBP has the effect of anti-asthma by inhibiting mucus hypersecretion, and one of its mechanisms is to alleviate the abnormal expressions of IL-13 and TNF-α.

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., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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., Competing Interests: Conflict of interest statement: Dr. Y-C. Hsu is a senior research scientist in Siemens Healthcare, Shanghai, China. The other authors report no disclosures relevant to the manuscript., (© The Author(s), 2021.)

Autophagy is a highly conserved degradative process that has been associated with a number of neurological diseases. Autophagy-related protein 5 (ATG5) is one of the key genes for the regulation of the autophagy pathway. In this study, we investigated the potential relationship between ATG5 gene polymorphisms and epilepsy in Han Chinese population. We enrolled 112 patients with epilepsy and 100 healthy controls and detected the genotypic and allelic data of 6 single nucleotide polymorphisms (SNPs) in ATG5 (rs2245214, rs510432, rs548234, rs573775, rs6568431 and rs6937876). The associations of 6 SNPs and epilepsy were evaluated. The results revealed the genotypes of overdominant of rs510432 between controls and patients showed significant differences (P overdominant  = 0.003). Subgroup analysis showed a highly significant association of rs510432 with late-onset epilepsy (P overdominant = 0.006), and rs548234 were associated with the susceptibility to temporal lobe epilepsy (P codominant = 0.002, P overdominant = 0.006). Furthermore, ATG5 was not linked to either early-onset epilepsy or drug-resistant epilepsy (p > 0.0083). These results demonstrated an association of an ATG5 gene variant with epilepsy, and stronger associations with several subgroups of epilepsy were identified. Our study may provide novel evidence for the role of ATG5 in epilepsy, and contribute to our understanding of the molecular mechanisms of this chronic neurological disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To validate the recently proposed imaging criteria in distinguishing aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD) at disease onset in a Chinese population., Methods: We enrolled 241 patients in this retrospective study, including 143 AQP4-ab-seropositive NMOSD, 73 MS, and 25 MOG-AD. Cacciaguerra's criteria were described as fulfillment of at least 2/5 conditions including the absence of the combined juxtacortical/cortical lesions, the presence of longitudinal extensive transverse myelitis (LETM) lesions, the presence of periependymal-lateral ventricles lesions, the absence of Dawson's fingers lesions, and the absence of periventricular lesions., Results: Fulfillment of at least 3/5 conditions was able to differentiate NMOSD from MS with a good diagnostic performance (accuracy = 0.92, sensitivity = 0.91, specificity = 0.93), yet failed to differentiate NMOSD from MOG-AD. LETM lesions showed the highest accuracy (0.78), sensitivity (0.70), and specificity (0.97) for NMSOD., Conclusion: Our research suggested the utility of Cacciaguerra's criteria in a Chinese population at disease onset. A better diagnostic performance in NMOSD could be attained with at least 3/5 conditions fulfilled. Yet their utility in distinguishing NMOSD from MOG-AD was limited.

Objective: The goal of this study was to evaluate the predictive capacity of four scoring tools: the Status Epilepticus Severity Score (STESS), the Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT) score, and two variable combinations of the Epidemiology-based Mortality Score in Status Epilepticus (EMSE) in younger and older adult patients with status epilepticus (SE)., Methods: We present a retrospective hospital-based analysis with a focus on adult patients with SE at three tertiary care hospitals in the Zhejiang province of China. Data were collected from January 2013 to December 2018. The patients were divided into two groups: younger adult patients (18-64 years old) and older adult patients (≥65 years old). Clinical outcomes (dead or alive) were assessed at hospital discharge. The four scoring tools were used to predict in-hospital mortality in both younger and older adult patients., Results: The mortality rate in older adult patients (25.4%) was higher than in younger adult patients (12.9%). Compared with the elderly, the younger adult patients had a higher proportion of encephalitis, while acute cerebrovascular disease and Charlson Complications Index (CCI) were lower. For the younger adult patients, END-IT had the largest area under the curve (AUC) of 0.843 (95% CI, 0.772-0.899), which was higher than the EMSE-EAL value of 0.687 (95% CI, 0.603-0.763, p < 0.05) and EMSE-EAC of 0.646 (95% CI, 0.561-0.725, p < 0.05). For the older adult patients, EMSE-EAL had the largest AUC of 0.843 (95% CI, 0.738-0.919), which was significantly higher than STESS with an AUC of 0.676 (95% CI, 0.554-0.782, p < 0.05). Moreover, the AUC of EMSE-EAL in the elderly was larger than in younger adult patients. The cutoffs in younger adult patients were STESS ≥ 4 (sensitivity 0.444, specificity 0.951), END-IT ≥ 3 (sensitivity 0.833, specificity 0.672), EMSE-EAL ≥ 31 (sensitivity 0.778, specificity 0.566), and EMSE-EAC ≥ 33 (sensitivity 0.833, specificity 0.492). However, the cutoffs in older adult patients were STESS ≥ 5 (sensitivity 0.500, specificity 0.925), END-IT ≥ 2 (sensitivity 0.944, specificity 0.547), EMSE-EAL ≥ 30 (sensitivity 0.944, specificity 0.623), and EMSE-EAC ≥ 31 (sensitivity 0.944, specificity 0.415)., Conclusion: Our results indicated that the STESS, END-IT, EMSE-EAC, and EMSE-EAL scores have excellent capacity to predict in-hospital mortality in both younger and older adult patients with SE. Our study supports the use of END-IT in patients under 65 years of age and suggests that EMSE-EAL is the most suitable scoring tool for patients over 65., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the prevention and treatment effect of Biejia Yugan Granule (BYG) on ethanol-induced hepatic fibrosis (EHF) rats. Methods: SD rats were randomly divided into blank control group, model group, BYG group, colchicine group and BYG low and BYG high dose groups ( n =8). The EHF rat model was established by intragastric edible ethanol with a gradually increased dose. Briefly, the rats of model group, colchicine group and BYG low and high dose groups were given gavage of 5 g/(kg·d) ethanol at week 1～4, 7 g/(kg·d) ethanol at week 5～8, 9 g/(kg·d) ethanol at week 9～12 and 9.5 g/(kg·d) ethanol at week 13～24. And the other two groups were treated with equal volume water. At the same time, the corresponding drugs were administrated daily: BYG group was treated with Biejia Yugan Granules 5.55 g/kg, colchicine group was treated with colchicine 0.1 mg/kg, BYG low-dose and high-group were treated with Biejia Yugan Granules 1.85 and 5.55 g/kg respectively. The blank control group and model control group were given the same amount of purified water. On the 169th day of the experiment, the effects of BYG on the macroscopic changes of rat liver organs, the water content of liver tissue and the pathological changes of fibrosis, the content of hydroxy proline (Hyp) in liver tissue and the expression levels of α-SMA and CREB were observed. Results: BYG at the doses of 1.85 and 5.55 g/kg could significantly improve the macroscopic changes of liver and pathological changes of liver tissue fibrosis in rats with EHF, reduce the contents of water and Hyp in liver tissue, and down-regulate the expressions of α-SMA and CREB. Conclusion: BYG has obvious effect on inhibiting EHF and one of its mechanisms is down-regulate the content of CREB.

Objective: To investigate the preventive and therapeutic effects of Qiwei Yugan Granule (QYG) on hepatic fibrosis in rats based on MMP-13/TIMP-1 imbalance. Methods: The rats were randomly divided into control group, model group, colchicine group (1.0×10 -4 g/kg) and QYG treated groups (3.7, 7.4, 14.8 g/kg) ( n =8). The rat model of hepatic fibrosis was established by injected with carbon tetrachloride subcutaneously for 4 weeks and treated with ethanol by gavage for 6 weeks. The effects of QYG on liver function, histopathology of liver, related indexes of serum liver fibrosis, and MMP-13, TIMP-1 in hepatic tissue were observed. Results: QYG at the doses of 14.8、7.4、3.7 g/kg could significantly decrease the serum levels of ALT, AST, HA, PCⅢ and C-Ⅳ, relieve the pathological changes of hepatic fibrosis, increase the activity of MMP-13, decrease the activity of TIMP-1 and alleviate the imbalance of MMP-13/TIMP-1. Among them, QYG had a certain trend of dose-effect relationship with TIMP-1 and MMP-13/TIMP-1 ( P ＜0.05, 0.01). Conclusion: QYG has the effect of preventing and treating liver fibrosis and one of mechanisms is to promote MMP-13/TIMP-1 to restore balance.

Objective: Early and accurate diagnosis of multiple sclerosis (MS) remains a clinical challenge. The main objective is to evaluate the diagnostic and prognostic value of the routinely performed immunoglobulin G (IgG) index for MS patients in the Asian population. Methods: A retrospective study was conducted among a cohort of clinically isolated syndrome (CIS) patients in China with known oligoclonal band (OCB) status and IgG index at baseline. We first evaluated the predictive value of IgG index for OCB status. Secondly, the diagnostic utility and prognostic value of IgG index alone were tested. Lastly, we incorporated IgG index into the 2017 McDonald criteria by replacing OCB with either "IgG index or OCB" (modified criteria 1), "IgG index and OCB" (modified criteria 2), or "IgG index" (modified criteria 3). The diagnostic utility of different criteria was calculated and compared. Results: In a CIS cohort in China ( n = 105), IgG index > 0.7 forecasted OCB positivity ( X 2 = 22.90, P < 0.001). An elevated IgG index was highly prognostic of more clinical relapses [1-year adjusted odds ratio [OR] = 1.32, P = 0.015; 2-years adjusted OR = 1.69, P = 0.013] and Expanded Disability Status Scale worsening (1-year adjusted OR = 1.76, P = 0.040; 2-years adjusted OR = 1.85, P = 0.032). Under the 2017 McDonald criteria (Positive Likelihood Ratio = 1.54, Negative Likelihood Ratio = 0.56), an IgG index > 0.7 in CIS patients increased the likelihood of developing MS within 2 years, either when OCB status was unknown (Positive Likelihood Ratio = 2.11) or with OCB positivity (Positive Likelihood Ratio = 2.11) at baseline; An IgG index ≤ 0.7, along with a negative OCB, helped rule out the MS diagnosis (Negative Likelihood Ratio = 0.53). Conclusions: IgG index > 0.7 predicts OCB positivity at the initial attack of MS and is prognostic of early disease activity. IgG index serves as an easily-obtainable and accurate OCB surrogate for MS diagnosis in the Asian population., (Copyright © 2020 Zheng, Cai, Yang, Zhou, Fang, Shen, Zhang and Ding.)

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 (GABA B R) encephalitis., Methods: Patients with anti-NMDAR, anti-LGI1, and anti-GABA B 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-GABA B 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-GABA B 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-GABA B R encephalitis. Early diagnosis and treatment were required, and particular consideration should be given to patients with these risk factors., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

A 41-year-old man presented with a 2-year history of recurrent painful ophthalmoplegia. Previous brain magnetic resonance imaging showed isolated enlargement of extraocular muscles with enhancement. A diagnosis of idiopathic orbital myositis (IOM) was given. Though the patient initially responded dramatically to corticosteroid, he began developing steroid resistance from his third attack and experienced frequent relapses. Therefore, tacrolimus was added to his regimen. The patient had full symptom recovery after tacrolimus and reported no relapses in the 1-year follow-up. This is the first case showing the efficacy of tacrolimus in treatment of IOM. Our case illustrates the importance of immunosuppressive agents in IOM patient refractory to steroid for both symptom control and relapse prevention., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Recent reports have suggested that seizures may be a component of the clinical presentation in myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. We aimed to conduct a systematic review and meta-analysis to comprehensively evaluate the occurrence of epileptic seizures in the disease., Methods: We searched PubMed, MEDLINE and EMBASE for studies reporting the occurrence of acute symptomatic seizures in MOG-Ab-associated disease. Fixed or random effects model was used to pool results across studies with a meta-analysis., Results: A total of 14 studies met the inclusion criteria. Overall, acute symptomatic seizures were observed in 20.5% (95% confidence interval [CI] 13.7%-30.7%, I 2 =60.6%) patients with MOG-Ab-associated disease, and in a similar proportion of children respectively (20.0%; 95% CI 14.3%-27.8%, I 2 =7.0%). The pooled probability of seizure occurrence in males was 30.1% (95% CI 17.5%-52%, I 2 =0.0%) while that in females was much lower (12.0%; 95% CI 5.5%-26.4%, I 2 =0.0%). Furthermore, when we focused on those with acute disseminated encephalomyelitis-like phenotype, 37.3% patients experienced seizures (95% CI 21.0%-66.3%, I 2 =55.8%)., Conclusions: Our study suggested that epileptic seizures were common in MOG-Ab-associated disease and offered insight into associated factors that contribute to the occurrence of seizures. Future studies with explicit evaluation are required., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the therapeutic effects of Radix Angelicae Sinensis (RADA) on airway mucus hypersecretion and the tumor necrosis factor-α/ nuclear factor- κB (TNF-α/NF-κB) signaling pathway in Yin-deficiency asthma mice. Methods: KM mice were randomly divided into control group, model group, ambroxol group and RADA low, medium and high dose (2, 4 and 8 g/kg) group( n =12). Ovalbumin and the thyroid gland were used to replicate the model of Yin-deficiency asthma. Asthma symptoms in mice , immune globulin E (IgE) , TNF-α , and the expressions of Mucin 5ac (Muc5ac) and NF- κB in lung tissue were observed under the intervention of RADA. Results: RADA at the doses of 2,4 and 8 g/kg could alleviate the asthma symptoms of Yin-deficiency asthma mice significantly, reduce the levels of IgE in serum and TNF-α in bronchoalveolar lavage fluid (BALF), and inhibite the overexpressions of Muc5ac and NF- κB in lung tissue. Conclusion: RADA has significant anti-asthmatic effect. One of its mechanisms is to inhibit TNF-α/NF- κB signaling pathway and to alleviate airway mucus hypersecretion.

Background: Short segment myelitis (SSM, < 3 vertebral segments) is an under-recognized initial manifestation of neuromyelitis optica spectrum disorders (NMOSD). Though infrequent, failure to recognize SSM in patients with NMOSD would lead to incorrect diagnosis and treatment. Therefore, delineation of features of NMOSD-associated SSM is of paramount importance., Objective: Our study aimed to determine the demographic, clinical and radiological features of NMOSD-associated SSM, and compare those with NMOSD-associated longitudinally extensive transverse myelitis (LETM) and multiple sclerosis (MS)-associated SSM, respectively., Methods: Chinese patients presenting initially only with acute myelitis and diagnosed with NMOSD ( n  = 46) and MS ( n  = 11) were included. Clinical, serological, imaging and disability data were collected. Mann-Whitney U test or two-tailed Fisher's exact tests were used to analyse the data., Results: Of the 46 enrolled NMOSD patients, 34 (74%) collectively had 38 LETM lesions, while 12 (26%) had 14 SSM lesions. When compared with LETM, NMOSD presenting with SSM were more likely to have a delayed diagnosis and a lower level of disability at nadir during the first attack. T1-weighted imaging hypointensity was more prominent in NMOSD-associated LETM lesions than NMOSD-associated SSM lesions. When compared with MS-associated SSM, NMOSD-associated SSM lesions were more likely to be centrally located, grey matter involving and transversally extensive on axial imaging and spanned no less than 2 vertebral segments on sagittal imaging., Conclusion: These findings suggest that SSM does not preclude the possibility of a NMOSD diagnosis. Testing for serum aquaporin-4 immunoglobulin G (AQP4-IgG) and careful study of lesions on spinal cord magnetic resonance imaging could aid in an earlier and correct diagnosis., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Diagnostic criteria for multiple sclerosis have evolved over time, with the most recent being the 2017 McDonald criteria. Evidence is lacking regarding the validity of the 2017 McDonald criteria among the Asian population. Therefore, this study aims to evaluate the diagnostic performance of the 2017 McDonald criteria in Chinese patients with clinically isolated syndrome (CIS)., Methods: A total of 93 patients with initial findings suggestive of CIS in a tertiary hospital in China from 2012 to 2017 were included in this retrospective study. Baseline and follow-up data were reviewed. Diagnostic performance (sensitivity, specificity, accuracy), was assessed and survival analysis was performed for the 2017 and 2010 McDonald criteria respectively., Results: Among the 93 Chinese patients with CIS, 57 were female (61.3%) and the median (interquartile range) age of onset was 37 (31.3-41.8) years. The 2017 McDonald criteria displayed a higher sensitivity (75.0% versus 14.6%, p  < 0.0001), lower specificity (47.1% versus 100.0%, p  < 0.05) but an overall higher accuracy (67.7% versus 36.9%, p  < 0.0001) when compared with the 2010 iteration. The novel criteria allow for a better detection of MS at baseline (40.8% versus 9.9%, p  < 0.0001)., Conclusion: The 2017 McDonald criteria had a higher sensitivity but lower specificity than the 2010 iteration. Overall it facilitated an earlier and more accurate diagnosis of multiple sclerosis in Chinese patients with CIS., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objective: To verify the utility of brain lesion distribution criteria in distinguishing multiple sclerosis (MS) from aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive/-negative neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated encephalomyelitis (MOG-EM) in the Chinese population., Methods: A total of 253 patients with MS (80), NMOSD (129 AQP4-IgG positive, 34 AQP4-IgG negative), and MOG-EM (10) were enrolled. Anonymized magnetic resonance imaging results were scored on the previous reported criteria of "at least one lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion." Chi-squared test (or Fisher's exact test) was used to analyze the data., Results: The distribution criteria were able to distinguish MS with a same sensitivity of 93.8% from all type of NMOSD and MOG-EM, with a specificity of 89.7% from the whole NMOSD cohort, 89.1% from AQP4-IgG-positive NMOSD 91.2% from AQP4-IgG-negative NMOSD, and 70.0% from MOG-EM. Dawson's finger-type lesion was the most sensitive and specific feature, whereas the U-fiber lesion was the least., Conclusion: The brain lesion distribution criteria were helpful in distinguishing MS from NMOSD and MOG-EM in the Chinese population. Dawson's finger-type lesion was highly suggestive of MS., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Purpose: The potential of microRNAs (miRNAs) as biomarkers has been explored in various brain diseases, including epilepsy. In this study, we are aiming to analyze the aberrant expression of miRNA-145-5p in patients with refractory epilepsy, and to further explore the correlation with clinical features., Methods: The study cohort comprised 40 patients with refractory epilepsy and 42 healthy controls. MiRNA-145-5p expression levels in plasma were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Data analysis was performed using IBM SPSS Statistics 22.0., Results: Compared with healthy controls, the expression of miRNA-145-5p in plasma was downregulated significantly in the patients with refractory epilepsy (1.180 ± 1.036 vs. 1.541 ± 0.936, p = 0.033) and mesial temporal lobe epilepsy (MTLE) (0.517 ± 0.483 vs. 1.541 ± 0.936, p = 0.004). ROC analysis showed that the area under the curve (AUC) was 0.632 (95%CI: 0.508-0.755; P = 0.040) in refractory epilepsy and 0.829 (95%CI: 0.702-0.955; P = 0.001) in MTLE. Furthermore, the expression of miRNA-145-5p was positively correlated with earlier age at epilepsy onset, more frequent seizures and past history., Conclusions: We suggested that decreased expression of miRNA-145-5p could be a potential non-invasive biomarker for early detection and clinical evaluation of refractory epilepsy. However, further studies are still required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To clarify the features of callosal lesions on magnetic resonance imaging (MRI) in Multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and acute disseminated encephalomyelitis (ADEM)., Methods: Chinese patients diagnosed with MS (n = 33), NMOSD (n = 31), and ADEM (n = 18) were enrolled. Characteristics of lesions in corpus callosum were evaluated with 1.5 Tesla MRI scanners. Chi-squared test (Fisher's exact test) was used to analyze the data., Results: In corpus callosum, NMOSD and ADEM lesions tend to have a diffuse distribution (p = 0.006, p = 0.033) and blurred margins (p < 0.001, p = 0.017), when compared with MS; lesions in NMOSD were less ovoid (p = 0.006), while fewer lesions in ADEM existed in the rostrum and genu (p = 0.002). NMOSD has the most heterogeneous intensity on post-enhancement sequences (p = 0.016, p = 0.001). Radial-like lesions were more common in MS and NMOSD (p = 0.019, p < 0.001)., Conclusion: MS lesions were most likely focally-localized with clear margins. Radial callosal lesions are characteristic of MS and NMOSD but rarely seen in ADEM. The signal intensities of the lesion were the most heterogeneous in NMOSD. Therefore, the lesion patterns in corpus callosum may serve as a useful clue for correct diagnosis, facilitating early treatment., (Copyright © 2019. Published by Elsevier B.V.)

Benign epilepsy with centrotemporal spikes (BECTS) is a common childhood epilepsy syndrome associated with abnormalities in neurocognitive domains, particularly during interictal epileptiform discharges (IEDs). Here, we investigated the effects of IEDs on brain's intrinsic connectivity networks in 43 BECTS patients and 28 matched healthy controls (HCs). Patients were further divided into IED and non-IED subgroups based on simultaneous EEG-fMRI recordings. Functional connectivity within and between five networks, corresponding to seizure origination and cognitive processes, were analyzed to measure IED effects. We found that patients exhibited increased connectivity within the auditory network (AN) and the somato-motor network (SMN), and decreased connectivity within the basal ganglia network and the dorsal attention network, suggesting that both transient and chronic seizure activity may disturb normal network organization. The IED group showed decreased functional connectivity within the default mode network (DMN) compared with the non-IED group and HCs, implying that the DMN was selectively impaired during epileptiform discharges associated with altered self-referential cognitive functions. Moreover, the IED group exhibited increased positive correlations between the AN and the SMN, which suggests a possible excessive influence of centrotemporal spiking on information processing in the auditory system. The association between epileptic activity and network dysfunctions highlights their importance in investigating the pathological mechanism underlying BECTS.

Purpose: The aim of this study was to explore the expression level of autophagy-related proteins in epileptic patients with glioneuronal tumors (GNTs) and evaluate the association with clinicopathological features., Materials and Methods: We obtained the brain specimens from 33 patients with GNTs, including 22 gangliogliomas (GGs) and 11 dysembryoplastic neuroepithelial tumors (DNTs). The expression of two autophagy-related proteins (LC3B and Beclin-1) was evaluated by immunohistochemistry, and BRAF V600E mutation was examined by DNA sequencing., Results: Among 33 epileptic patients with GNTs, the frequency of high expression of LC3B was 36.4% (12/33), and that of Beclin-1 was 39.4% (13/33). High expression of LC3B and Beclin-1 proteins was significantly associated with BRAF V600E mutation in GNTs (P=0.008; P=0.018), and LC3B overexpression was also correlated with temporal location of GNTs (P=0.002). In GGs alone, high expression of LC3B revealed significant correlation with BRAF V600E mutation and temporal location (P=0.020; P=0.015), while Beclin-1 showed no correlation with them (P>0.05). Furthermore, autophagy-related proteins did not show any association with other studied clinicopathological features, such as gender, age at seizure onset, epilepsy duration and postoperative seizure outcome., Conclusions: Our observations demonstrated that impaired autophagy may be associated with BRAF V600E mutation. However, large sample studies with long-term follow-up were required., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Paroxysmal kinesigenic dyskinesia is associated with macrostructural and microstructural abnormalities in the thalamus., Objectives: To examine functional and structural connectivity of thalamocortical networks in paroxysmal kinesigenic dyskinesia and to further investigate the effect of mutation of the proline-rich transmembrane protein 2 on thalamocortical networks., Methods: Patients with paroxysmal kinesigenic dyskinesia (n = 20), subdivided into proline-rich transmembrane protein 2-mutated (n = 8) and nonmutated patients (n = 12) and healthy controls (n = 20) underwent resting-state functional MRI and diffusion imaging scan. The functional properties of correlations in neural activity (functional connectivity) and the structural properties of white matter probabilistic tractography (structural connectivity) were analyzed to characterize thalamocortical networks. Furthermore, the effect of proline-rich transmembrane protein 2 mutation on functional and structural connectivity of thalamocortical networks were examined using one-way analysis of variance among three groups., Results: Patients had increased functional and structural connectivity between ventral lateral/anterior thalamic nuclei and a lateral motor area, as compared to controls. This functional connectivity positively correlated with disease duration. Interestingly, proline-rich transmembrane protein 2-mutated patients showed decreased functional connectivity and preserved structural connectivity, between mediodorsal nucleus and prefrontal cortex, compared to nonmutated patients and controls., Conclusions: Thalamomotor/premotor hyperconnectivity suggests abnormal communication between thalamus and motor cortex in patients. Furthermore, thalamoprefrontal hypoconnectivity in proline-rich transmembrane protein 2-mutated patients might indicate that proline-rich transmembrane protein 2 mutations result in inefficient thalamoprefrontal integration. Our findings facilitate a deeper understanding of the crucial role of thalamocortical dysconnectivity in the pathophysiological mechanisms of paroxysmal kinesigenic dyskinesia. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Purpose: Glioneuronal tumors (GNTs) are the most common histological type of brain tumors in patients who received epilepsy surgery, and part of them presented with BRAF V600E mutation. We aimed to verify the presence of the BRAF V600E mutation in epilepsy-associated GNTs from Chinese population and evaluate the association with clinical features., Methods: Data from 35 patients diagnosed with GNTs, including 24 gangliogliomas and 11 dysembryoplastic neuroepithelial tumors, were retrospectively collected. DNA was extracted from GNTs tissues and BRAF V600E mutation was examined by DNA sequencing. The correlations between BRAF V600E mutation and clinical features were analyzed., Results: Totally, BRAF V600E mutations were detected in 11 patients with GNTs, the rate of mutation were 33.3% and 27.3% in GGs (8/24) and DNTs (3/11), respectively. The probability of BRAF V600E mutation in females (7/12, 58.3%) was significantly higher than that in males (4/23, 17.4%) (P=0.022). Moreover, patients with BRAF-mutated GNTs had a significantly wider variety of seizure types compared to GNTs with BRAF wild-type status (P=0.027). However, no significant correlation between the BRAF status and certain clinical features, such as age of seizure onset, duration of epilepsy, age at surgery, location of the tumor and postoperative seizure free, were observed., Conclusion: We demonstrated the presence of BRAF V600E mutation in Chinese epileptic patients with GNTs, which was significantly correlated with gender and multiple seizure types. Large sample studies and long-term follow-up are required for further confirmation., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome characterized by reversible vasogenic edema typically at a posterior location of the cerebrum. PRES with prominent brainstem or basal ganglia involvement is defined as central-variant, which is rare. We herein report an atypical case of a 35-year-old man with a 2-year history of untreated hypertension who complained of recurrent dizziness. The patient presented with brainstem and diffuse white matter involvement associated with intracranial hemorrhage and recovered fully after therapy. Recognition of this uncommon benign syndrome as a potentially treatable disorder can be of great importance., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Purpose: The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy., Methods: The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0., Results: There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P<0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response., Conclusions: These results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients., (Copyright © 2016. Published by Elsevier B.V.)

The neurobiological basis of paroxysmal kinesigenic dyskinesia (PKD) is poorly defined due to the lack of reliable neuroimaging differences that can distinguish PKD with dystonia (PKD-D) from PKD with chorea (PKD-C). Consequently, diagnosis of PKD remains largely based on the clinical phenotype. Understanding the pathophysiology of PKD may facilitate discrimination between PKD-D and PKD-C, potentially contributing to more accurate diagnosis. We conducted resting-state functional magnetic resonance imaging on patients with PKD-D (n = 22), PKD-C (n = 10), and healthy controls (n = 32). Local synchronization was measured in all 3 groups via regional homogeneity (ReHo) and evaluated using receiver operator characteristic analysis to distinguish between PKD-C and PKD-D. Cortical-basal ganglia circuitry differed significantly between the 2 groups at a specific frequency. Furthermore, the PKD-D and PKD-C patients were observed to show different spontaneous brain activity in the right precuneus, right putamen, and right angular gyrus at the slow-5 frequency band (0.01-0.027 Hz). The frequency-specific abnormal local synchronization between the 2 types of PKD offers new insights into the pathophysiology of this disorder to some extent., Competing Interests: The authors have no conflicts of interest to disclose.

The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: As antiepileptic drugs (AEDs) are known to be associated with alterations in thyroid profiles, we aimed to carry out a meta-analysis to comprehensively assess the effects of AEDs on thyroid hormones in patients with epilepsy., Methods: We searched the NCBI (PubMed), ISI Web of Science, EMBASE databases, and Cochrane Library to identify studies evaluating the association between AED use and thyroid hormone profiles in patients with epilepsy. Fixed or random effects meta-analysis was used to pool results across studies., Results: In all, 35 studies were included in our analysis. Out of a total of 997 patients in these studies, epileptic patients receiving AEDs showed an overall significant decrease in thyroxin (T4) and free T4 (fT4) and higher levels of thyroid stimulating hormone (TSH) than the controls (T4: standardized mean difference [SMD]=-1.839, 95% confidence interval [CI], -2.063 to -1.614; fT4: SMD=-1.190, 95% CI, -1.687 to -0.692; TSH: SMD=0.445, 95% CI, 0.031-0.858). Notably, the use of carbamazepine (CBZ) suggested a significant decrease in triiodothyronine (T3), T4, and fT4; phenytoin (PHT) use showed a decrease in T4 and fT4; and valproic acid (VPA) use was associated with decreased T4 and increased TSH., Conclusion: Our study suggests that use of AEDs such as CBZ, PHT, and VPA, was associated with alteration of thyroid hormones among patients with epilepsy., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)