The diagnostic value of image-enhanced endoscopy system in sinonasal inverted papilloma.

PURPOSE: This study aimed to evaluate the diagnostic value of image-enhanced endoscopy (IEE) in detecting sinonasal inverted papilloma (SNIP). METHODS: Overall, 86 patients with unilateral nasal papillary or lobulated neoplasms were included between July 2018 and June 2019. All patients underwent IEE examinations, and the diagnosis of all neoplasms was confirmed through postoperative pathology. Logistic regression analysis was conducted to screen for independent predictors of various types of vascular patterns of SNIP. Furthermore, a prognostic nomogram was constructed using the independent predictors screened by logistic regression analysis to evaluate its usefulness in distinguishing SNIP from nasal polyp (NP) and papillary mucosa folds (PMF). RESULTS: In total, 86 consecutive cases were observed, including 37 with SNIP, 40 with NP, and 9 with PMF. Logistic regression analysis showed that spot, corkscrew, and multilayered vascular patterns were independent predictors of SNIP diagnosis. Furthermore, a nomogram comprising the three independent risk factors was constructed with scores of 5, 2, and 3. The area under the receiver operating characteristic curve for predicting SNIP was 0.954, 0.66, 0.71, and 0.76 for the nomogram model, spot vascular pattern, corkscrew vascular pattern, and multilayered vascular pattern, respectively. CONCLUSION: The nomogram model based on spot, corkscrew, and multilayered vascular patterns in SNIP observed using IEE can be a useful diagnostic tool for predicting and distinguishing between NP and PMF.

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.

Oxysophoridine protects against cerebral ischemia/reperfusion injury via inhibition of TLR4/p38MAPK­mediated ferroptosis.

Oxysophoridine (OSR) is an alkaloid extracted from Sophora alopecuroides L. and exerts beneficial effects in cerebral ischemia/reperfusion (I/R) injury. However, the molecular mechanism underlying the regulatory effects of OSR in cerebral I/R injury remains unclear. In the present study, a cerebral I/R injury rat model was established by occlusion of the right middle cerebral artery. Hematoxylin and eosin and triphenyltetrazolium chloride staining were performed to assess histopathological changes and the extent of cerebral injury to the brain. A Cell Counting Kit­8 and TUNEL assay and western blotting were performed to assess cell viability and apoptosis. Ferroptosis and oxidative stress were evaluated based on ATP and Fe2+ levels and DCFH­DA staining. The protein expression levels of inflammatory factors were assessed using ELISA. The protein expression levels of members of the toll­like receptor (TLR)4/p38MAPK signaling pathway were evaluated using immunofluorescence staining and western blotting. The results demonstrated that OSR decreased brain injury and neuronal apoptosis in the hippocampus in I/R­induced rats. OSR inhibited reactive oxygen species (ROS) production, decreased levels of ATP, Fe2+ and acyl­CoA synthetase long­chain family member 4 (ACSL4) and transferrin 1 protein and increased the protein expression levels of ferritin 1 and glutathione peroxidase 4. Furthermore, OSR blocked TLR4/p38MAPK signaling in brain tissue in the I/R­induced rat. In vitro experiments demonstrated that TLR4 overexpression induced generation of ROS, ATP and Fe2+, which promoted the expression of ferroptosis­associated proteins in hippocampal HT22 neuronal cells. The ferroptosis inducer erastin decreased the effects of OSR on oxygen­glucose deprivation/reoxygenation (OGD/R)­induced cell viability, oxidative stress and inflammatory response. Together, the results demonstrated that OSR alleviated cerebral I/R injury via inhibition of TLR4/p38MAPK­mediated ferroptosis.

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.

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.

Late-onset neuromyelitis optica spectrum disorder mimicking stroke in an elderly Chinese man: Case report.

Context: Few cases of neuromyelitis optica spectrum disorder (NMOSD) with an onset older than 75 years old have been reported.Finding: Herein, we report an 81-year-old Chinese male initially suspected of acute stroke but was ultimately diagnosed with NMOSD.Conclusion: Even in the elderly, a diagnosis of NMOSD should be considered for patients with myelitis, especially those with longitudinally extensive spinal cord involvement. Testing for aquaporin 4 antibody in this scenario is recommended for further confirmation. Once diagnosed, careful consideration of treatment options and close monitoring of side effects are important to improve prognosis in elderly patients.

Predictive value of clinical characteristics in eosinophilic chronic rhinosinusitis with nasal polyps: A cross-sectional study in the Chinese population.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non-ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice. METHODS: A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non-ECRSwNP group. Participants' demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed. RESULTS: The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non-ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non-eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C-index was 0.808 (95% CI, 0.771 to 0.846). CONCLUSIONS: The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non-ECRSwNP cases in clinical practice.

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.

The Gaps Between the Self and Professional Evaluation in Mental Health Assessment of COVID-19 Cluster Cases.

Objective: To analyze the discrepancy between self-rating and professional evaluation of mental health status in coronavirus disease 2019 (COVID-19) cluster cases. Method: A total of 65 COVID-19 cluster cases admitted to Beijing Ditan Hospital Capital Medical University from June 14, 2020 to June 16, 2020 were included in the study. Mental health assessment was completed by self-rating and professional evaluation. The gaps between self-rating and professional evaluation in different demographic characteristics were compared. Results: The results of self-rating were inconsistent with those of professional evaluation. The gap was statistically different among certain demographic subgroups. As for anxiety, the gaps had remarkable statistics differences in subgroups of sex, monthly income, infection way, and anxiety/depression medical history. Similarly, in the terms of depression, the gaps had significant statistic differences in the subgroups of the medical history of anxiety/depression, history of physical disease, employment status and the insurance type, marriage, education (year), residing in Beijing (year), and the monthly income. Conclusion: Compared to the professional evaluation, patients had a higher self-rating, which may be related to some demographic characteristics. It suggests that screening can be conducted in patients with COVID-19 by self-rating first, and then professional evaluation should be carried out in the patients with suspicious or positive results.

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.

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

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

Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. METHODS: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. RESULTS: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. CONCLUSION: These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.