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.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

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.

Evaluation of CSF albumin quotient in neuronal surface antibody-associated autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Disruption of brain barriers is considered to be involved in the pathogenesis of neuronal surface antibody-associated autoimmune encephalitis (NSAE), but few studies have focused on their relationship. We aimed to explore the association between the integrity of brain barriers and clinical and paraclinical characteristics in patients with NSAE. METHODS: This retrospective study consecutively recruited patients with NSAE. The cerebrospinal fluid (CSF) / serum albumin quotient (Qalb) was used to evaluate the function of brain barriers. The data on demographic information, clinical manifestations, magnetic resonance imaging (MRI), CSF findings and prognosis were collected and analyzed. RESULTS: Of the 93 patients included, 33 (35.5%) patients were assigned to the elevated Qalb group and 60 (64.5%) patients to the normal Qalb group. Males and prodromal symptoms were more common in elevated Qalb group (both P < 0.05). The CSF white blood cell, protein, immunoglobulin G and albumin were significantly higher in elevated Qalb group (all P < 0.05). Patients with elevated Qalb were more likely to have brain lesions on MRI (60.6% versus 33.3%, P = 0.011). The modified Rankin Scale (mRS) scores at discharge and at last follow-up were significantly higher in patients with elevated Qalb than those with normal Qalb (both P < 0.05). After univariate and multivariate analyses, Qalb elevation (adjusted odds ratio = 3.96, 95% confidence interval = 1.15-13.59, P = 0.029) was demonstrated as the only independent risk factor for a poor prognosis. DISCUSSION: Males, prodromal symptoms, brain lesions on MRI, CSF pleocytosis, and elevated CSF protein were more common in NSAE patients with increased Qalb. Qalb elevation was an independent prognostic indicator for a poor prognosis in NSAE.

Inflammatory markers of hemogram parameters as predictive factors for disease severity in anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: This study aimed to investigate the utility of inflammatory markers of hemogram parameters as objective indicators of disease severity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: A total of 98 patients were retrospectively reviewed. Inflammatory markers of hemogram parameters, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio, were acquired within 24 h of admission. We then analyzed their utility as predictive factors for disease severity at different time points assessing with the modified Rankin Scale (mRS). RESULTS: There were 49 patients in the mild group (mRS ≤ 2) and 49 patients in the moderate-to-severe (mRS > 2) group at admission. The moderate-to-severe group presented more frequently with psychiatric symptoms and central hypoventilation, as well as a lower lymphocyte count, a higher neutrophil count, a higher NLR and a higher MLR (all p < 0.05) when compared with the mild group. NLR and MLR showed similar positive correlations with mRS scores (r = 0.40, r = 0.40, both p < 0.001). Further multivariate logistic regression analyses indicated that NLR > 4.232 was an independent risk factor for moderate-to-severe status at admission. Meanwhile, NLR and MLR were associated with disease severity at different stages of follow-up but showed no independent predictive value. CONCLUSION: Our findings suggested that NLR was an independent risk factor for moderate-to-severe status in the initial stage of anti-NMDAR encephalitis with a cut-off value of > 4.232.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency.

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.

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.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

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.

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.

Managing depression and anxiety in patients with epilepsy in eastern China: A survey of epilepsy health professionals in Zhejiang Province.

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.

Anti-Ma2 Antibody-Associated Paraneoplastic Neurological Syndromes: A Pilot Study.

Paraneoplastic neurologic syndromes (PNSs) are a heterogeneous group of disorders caused by the remote effects of cancer with immune-mediated pathogenesis. Anti-Ma2 antibody was defined as one of the well-characterized onconeural antibodies that could help establish a definite PNS diagnosis. We aimed to report and explore patients with anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) who frequently exhibit sensorimotor neuropathy (SMN) using a new method of factor analysis of mixed data (FAMD). Clinical data from a case series of eight patients with definite diagnoses were retrospectively reviewed. FAMD conducted further analyses with a comprehensive visualization in R software. Our cohort, with a predominance of females (5/8), presented more frequently with SMN (4/8), followed by limbic encephalitis (LE) (3/8). Two patients with LE were found to have a testicular germ-cell tumor and a thymoma, respectively. In addition, a patient who developed chronic SMN was diagnosed with multiple myeloma (MM) involving multiple organs. FAMD exhibited the overall features into a two-dimensional coordinate and located each individual into their corresponding position with high relevance. It provided a clue for determining their potential relationships and predictors. Our findings indicated that Ma2-PNS could frequently involve the peripheral nervous system, MM might be one of its associated cancers with a presentation of chronic SMN, and FAMD might be a clinically valuable tool.

Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody-associated disease: a systematic review and meta-analysis.

BACKGROUND: A considerable number of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will experience a relapse, but the effect of maintenance therapies on re-attack rates is currently unknown. OBJECTIVE: To investigate the efficacy and safety of immunosuppressive therapy for preventing disease relapses in patients with MOGAD, including rituximab (RTX), mycophenolate mofetil (MMF), and azathioprine (AZA). METHODS: English-language studies published prior to August 31, 2020, were searched in the NCBI (PubMed), ISI Web of Science, and the Cochrane Library databases. Patient characteristics, treatment regimens, outcome measures, and adverse effects were retrieved. RESULTS: We enrolled 11 studies in the final meta-analysis, including 346 patients with MOGAD. RTX therapy was demonstrated to result in reduced mean annualized relapse rate (ARR) by 1.35 (95% confidence interval (CI): 0.85-1.85) and reduced mean Expanded Disability Status Scale score by 0.80 (95% CI: 0.53-1.08) in patients with MOGAD. MMF therapy was associated with the mean ARR decreasing by 0.83 (95% CI: 0.31-1.35), and AZA was related to the mean ARR decreasing by 1.71 (95% CI: 0.83-2.58). The reported discontinuation rates of RTX, MMF, and AZA therapy due to adverse effects were 3/197 (1.52%), 3/39 (7.69%), and 4/37 (10.81%), respectively. CONCLUSION: The study provided evidence to support the efficacy of RTX, MMF, and AZA on the preventive treatment in patients with MOGAD. However, large randomized controlled trials are still needed in the future.

Validation of the Clinical Assessment Scale for Autoimmune Encephalitis: A Multicenter Study.

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.

Seasonal variation in autoimmune encephalitis: A multi-center retrospective study.

OBJECTIVE: The aim of this study was to examine the seasonal distribution in clinical onset of autoimmune encephalitis (AE) in a multi-center cohort in China. METHODS: This retrospective study consecutively recruited patients with new-onset definite neuronal surface antibody-associated AE between January 2015 and December 2020 from 3 tertiary hospitals. Demographic and clinical characteristics of the participants were comprehensively collected. Statistical analyses were performed using R. RESULTS: Of the 184 patients of AE in our database, 149 (81.0%) were included in the final analysis. The median age of onset was 40.0 years, and 66 (44.3%) patients were female. AE predominantly started in autumn (47, 31.5%) and summer (43, 28.9%) months. Summer-autumn predominance of the clinical onsets was also present in the anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis group (54, 60.0%) and anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis group (20, 76.9%). No obvious seasonal variations were observed among gender, onset age, disease duration, prodromal symptoms, clinical type of initial symptoms, and disease severity by the time of admission. CONCLUSION: This study suggested summer-autumn predominance of the clinical onsets in patients with AE, especially anti-NMDAR and anti-LGI1 encephalitis. Therefore, clinicians should have a high index of suspicion for AE in encephalopathy patients in summer and autumn period.

Case Report: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder Masquerading as Multiple Sclerosis: An Under-Recognized Entity?

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) covers a wide spectrum of manifestations and is defined by the presence of MOG seropositivity. However, in a proportion of patients, there may be an overlap in some of the clinical and radiological manifestations between MOGAD and multiple sclerosis (MS). Being wary of this entity is critical to ensure appropriate therapy. Herein, we present a case with recurrent episodes of short-segment myelitis typical for multiple sclerosis, but later diagnosed as MOGAD by MOG antibody seropositivity. This case, along with previous reports, highlights an increasingly recognized subgroup in MOGAD with initial clinical phenotypes suggestive of MS, but later showing a disease course and therapeutic response compatible with MOGAD. Given the potential overlap of some clinical phenotypes in patients with MS and those with MOGAD, we recommend MOG antibody testing in all patients with recurrent short-segment myelitis, conus medullaris involvement, and those who demonstrated steroid dependence.

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

Association between autophagy-related protein 5 gene polymorphisms and epilepsy in Chinese patients.

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 (Poverdominant = 0.003). Subgroup analysis showed a highly significant association of rs510432 with late-onset epilepsy (Poverdominant = 0.006), and rs548234 were associated with the susceptibility to temporal lobe epilepsy (Pcodominant = 0.002, Poverdominant = 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.