Clinical Attack Research Articles

Comparison of MRI Brain and Spine Lesions During Clinical Attacks and Remission in MOG Antibody-associated Disease and Multiple Sclerosis

Comparison of MRI Brain and Spine Lesions During Clinical Attacks and Remission in MOG Antibody-associated Disease and Multiple Sclerosis

Antibiotic Therapy in Asthma as One of First Step Treatment, a Phase 3 Randomized Clinical Trial

Background: Focus of this study was on subjects suffering from new onset asthma, but actually, they may involve with an infection. Objectives: The target of this study was to determine the frequency of total control of asthma in new onset asthma. Methods: this is a phase 3 randomized clinical trial. The participants were 50 new onset asthma, who feel suffering from respiratory infection, however the physician diagnosis was asthma according to wheezy chest, spirometry and clear chest roentgenogram. Age less than 18 years and pregnant women were excluded. The subjects were randomly divided into two groups, doxycycline hyclate and the placebo arms. The drugs were repacked in similar in shape container. Primary endpoint was time to first recurrence. Secondary endpoints were frequency of total control of asthma, dyspnea, cough, asthma control test (ACT) score, FEV1, FEV1/FVC, eosinophil and neutrophil in blood and sputum. Results: The difference of clinical findings between two groups before the trial were not significant. Ten percent reported acute attack of asthma during last two months. Treatment with Doxycyline revealed significant improvement of clinical findings, asthma attack and ACT score after two months of treatment, however, complete resolution of clinical findings were significantly higher in Doxycyline group compare to placebo. Clinical findings and FEV1 percent predicted in Doxycyline group T2low asthma group showed significant improvement which were not depicted in T2high group. Eighteen months follow up of the subjects showed complete resolution of asthma symptoms in 12 (48%) on Doxycyline group, which was significantly higher than control group (5 (20%). Time to first exacerbation in doxycycline group was 13.6±5.64 months which was significantly longer than control group (7.49±6.95, P=0.002). Time to first exacerbation in CRP positive was significantly longer (13.64±5.35 months) than CRP negative subjects (9.67±7.76 months, P=0.02). Conclusion: Doxycycline is an effective antibiotic for preventing recurrence of asthma, in selected new subjects who suspicious for respiratory infection.

Neutrophil/lymphocyte ratio as an indicator of radiological disease activity in clinically stable multiple sclerosis

Purpose: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and the most common neurological disorder causing disability in young people. There is no sensitive and specific marker for both diagnosis and follow-up. Neutrophil to lymphocyte ratio is an easily applicable method and in this study we aimed to observe the changes in this ratio in the presence of isolated radiologic activity in MS. Materials and Methods: We compared 20 MS active patients with no clinical attack or neurologic progression and only radiologic activity with 20 age- and sex-matched clinically and radiologically stable MS patients in terms of NLR. Results: Mean NLR value was 2.22±0.87 in radiologically active patient group (Min 1.08-Max 4.28) and mean NLR value was 2.31±1.37 in control group (Min 0.96-Max 5.92). We observed that NLR values in patients with radiologic activity only were not significantly different from NLR values in patients with both clinical and radiologic stability. Conclusion: Marker studies in the diagnosis and follow-up of MS continue rapidly. Prospective studies involving a much larger cohort may be instructive in order to demonstrate the association of simple, easily applicable, non-invasive, inexpensive methods such as NLR with MS disease activity.

Epidemiology of Household Transmission of COVID-19 among Patients Attending Outpatient Clinics of Teaching Hospital in Cairo, Egypt

Abstract Background Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People in closed settings with COVID-19 patients, such as household contacts, were more likely to become infected. Household studies can provide informative data for COVID-19 prevention and control. Aim to identify the epidemiological features of household transmission in a sample of patients attending the family medicine clinic of a tertiary hospital in Egypt, and to calculate the household COVID19 secondary clinical attack rate for the recruited patients. Materials and Methods An observational follow-up study was conducted among a sample of 180 primary probable COVID-19 cases attending a tertiary hospital in Cairo, Egypt and their 395 household contacts. The modified WHO case reporting form was used for follow-up of primary probable COVID-19 cases, and the modified WHO contact reporting form was used for their household contacts follow-up. Follow-up phone calls were conducted after 7, 10, and 14 days after attending to the hospital. Results The mean household Secondary clinical attack rate is 65.3 ± 29.9 (95 CI: 60.5% - 70.1%). There was a significant statistical association between reporting symptoms consistent with COVID-19 and sharing a room with the primary case, being not vaccinated, not using Personal protective equipment (PPE) as well as taking care of a primary case (p < 0.001). Conclusion and Recommendations Secondary clinical attack rate among the household contacts was high; more than the average reported rates globally. Vaccination and using PPE had important roles in lowering the risk of reporting symptoms consistent with COVID-19 among household contacts, yet the overall rate of using PPE was low and vaccination coverage was low compared to the rates reported globally. which necessitates more efforts to increase awareness of household transmission and how to safely care for a home-isolated COVID-19 case. The presence of co-morbidities increased the risk of hospitalization among symptomatic contacts This gives an alert to increase the awareness of cases with comorbidities about warning signs that necessitate early hospitalization for a better prognosis. about using PPE among household contacts with a COVID-19 case and also about the importance of vaccination against COVID- 19.

Related factors of acute symptomatic seizures and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease

Objective: To investigate the risk factors of acute symptomatic seizures (ASS) and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: A ambispective cohort study was used including 74 children with MOGAD who were admitted to the Department of Pediatrics of Peking University First Hospital from January 2013 to June 2023 and were followed up. Demographic information, clinical information, treatment status, ASS and epilepsy status were collected. The clinical phenotypes were classified. According to the presence or absence of ASS in the course of disease, the children and the course of disease were divided into groups with and without ASS. Chi-square test, Fisher exact test and Mann Whitney U test were used to analyze the correlation between symptoms and auxiliary examination characteristics and the occurrence of ASS in the two groups of children. Multivariate Logistic regression analysis was used for multivariate analysis. Results: The onset age of the 74 children with MOGAD was 6.58 (3.80, 9.67) years, including 38 females (51.4%) and 36 males (48.6%). The duration of the final follow-up was 2.67 (1.10, 4.12) years, with a total of 239 times acute clinical episodes. ASS occurred in 39.2% (29/74) children during the course of disease and in 29.3% (70/239) of attacks. The common phenotypes were ADEM (67 times (28.0%)), optic neuritis (37 times (15.4%)) and cerebral cortical encephalitis (31 times (13.0%)) in 239 times acute clinical episodes. The incidence of ASS in ADEM and cerebral cortical encephalitis phenotype was 28.4%(19/67) and 100.0% (31/31), respectively. Multivariate analysis showed that cortical involvement on magnetic resonance imaging during clinical attacks was an independent risk factor for ASS (β=-1.49, OR=0.23) after excluding attacks involving only optic nerve or spinal cord (49 episodes). During the follow-up, 5 children (6.8%) had epilepsy, and all children with epilepsy had multiple clinical attacks of MOGAD and previous ASS. Conclusions: Cortical involvement on magnetic resonance imaging during clinical episodes is an independent risk factor for ASS in children with MOGAD. All MOGAD children with epilepsy had ASS and multiple MOGAD clinical episodes in the past.

Blood-based inflammatory protein biomarker panel for the prediction of relapse and severity in patients with neuromyelitis optica spectrum disorder: A prospective cohort study.

To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD. This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort. The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort. Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

MOG Antibody Disease: Nuances in Presentation, Diagnosis, and Management.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a distinct neuroinflammatory condition characterized by attacks of optic neuritis, transverse myelitis, and other demyelinating events. Though it can mimic multiple sclerosis and neuromyelitis optica spectrum disorder, distinct clinical and radiologic features which can discriminate these conditions are now recognized. This review highlights recent advances in our understanding of clinical manifestations, diagnosis, and treatment of MOGAD. Studies have identified subtleties of common clinical attacks and identified more rare phenotypes, including cerebral cortical encephalitis, which have broadened our understanding of the clinicoradiologic spectrum of MOGAD and culminated in the recent publication of proposed diagnostic criteria with a familiar construction to those diagnosing other neuroinflammatory conditions. These criteria, in combination with advances in antibody testing, should simultaneously lead to wider recognition and reduced incidence of misdiagnosis. In addition, recent observational studies have raised new questions about when to treat MOGAD chronically, and with which agent. MOGAD pathophysiology informs some of the relatively unique clinical and radiologic features which have come to define this condition, and similarly has implications for diagnosis and management. Further prospective studies and the first clinical trials of therapeutic options will answer several remaining questions about the peculiarities of this condition.

Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Background and objectivesPatients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). MethodsWe evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. ResultsOur cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p < 0.001) and compared to all other groups (p < 0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. DiscussionSome blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities.

Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) as a compensatory protease inhibitor in hereditary angioedema

BackgroundHereditary angioedema (HAE) is a genetic disorder that manifests as recurrent angioedema attacks, most frequently due to absent or reduced C1 inhibitor (C1-INH) activity. C1-INH is a crucial regulator of enzymatic cascades in the complement, fibrinolytic, and contact systems. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is an abundant plasma protease inhibitor that can inhibit enzymes in the proteolytic pathways associated with HAE. Nothing is known about its role in HAE. ObjectiveInvestigate ITIH4 activation in HAE, establish it as a potential biomarker, and explore its involvement in HAE-associated proteolytic pathways. MethodsSpecific immunoassays for non-cleaved ITIH4 (Intact ITIH4) and an assay detecting both intact and cleaved ITIH4 (Total ITIH4) were developed. We initially tested serum samples from HAE patients (n=20), ACEI-induced edema patients (ACEI) (n=20), and unknown HAE patients (U-HAE) (n=20). Validation involved an extended cohort of 80 HAE patients (60 type I, 20 type II), including samples taken at attack and quiescent disease periods, as well as 100 healthy controls. ResultsIn 63% of HAE patients, the Intact ITIH4 assay showed lower signals than the Total ITIH4 assay. This difference was not observed in ACEI and U-HAE patients. Western blotting confirmed cleaved ITIH4 in low-Intact ITIH4 samples. In serum samples lacking intact endogenous ITIH4, we observed immediate cleavage of added recombinant ITIH4 suggesting continuous enzymatic activity in the serum. Confirmatory HAE cohort analysis revealed significantly lower intact ITIH4 levels in both HAE type 1 and type 2 patients compared to controls, with consistently low Intact/Total ITIH4 ratios during clinical HAE attacks. ConclusionThe disease-specific low intact ITIH4 levels highlight its unique nature in HAE. The results suggest that ITIH4 may exhibit compensatory mechanisms in HAE, suggesting its utility as a diagnostic and prognostic biomarker. The variations during quiescent and active disease periods raise intriguing questions about the dynamics of proteolytic pathways in HAE.

Real-world outcomes in patients with hereditary angioedema prescribed lanadelumab versus other prophylaxis.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by painful, debilitating, and potentiallyfatal swelling attacks. Lanadelumab is approved as long-term prophylaxis (LTP) in patients with HAE. However, realworld data on LTP use in patients with HAE are limited. To describe clinical characteristics, attack history, and quality of life (QoL) of patients with HAE type I/II whowere receiving lanadelumab or other LTPs. Data were drawn from the Adelphi HAE Disease Specific Program, a cross-sectional survey of HAE physicians conducted in the United States from July to November 2021. Physician-reported disease characteristics, HAE attack frequency, and QoL were compared among patients receiving lanadelumab or other LTPs for at least 12 months. Physicians reported data for 144 patients, of whom 29 had received lanadelumab and 115 had received another prophylaxis for at least 12 months. The mean +/- standard deviation number of attacks in the previous 12 months was loweramong patients receiving lanadelumab than other LTPs (2.3 +/- 3.1 versus 3.4 +/- 2.8, respectively; p = 0.075). Although bothgroups had similar current disease activity and severity, more patients receiving lanadelumab versus other LTPs had high disease activity (51.7% versus 12.5%, respectively; p < 0.0001) and disease severity rated as severe (51.7% versus 16.1%, respectively; p = 0.0001) at diagnosis. Physicians reported that more patients who received lanadelumab had good or very good QoL(72.4%) than those receiving other LTPs (36.5%) (p = 0.003). Analysis of these findings suggests lower attack frequency, lower symptomatic impact, and better QoL inpatients treated with lanadelumab than another prophylaxis in a real-world setting.

Serum Biomarker Profiles Discriminate AQP4 Seropositive and Double Seronegative Neuromyelitis Optica Spectrum Disorder.

Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) serum levels are useful to define disease activity in different neurologic conditions. These biomarkers are increased in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) during clinical attacks suggesting a concomitant axonal and glial damage. However, there are contradictory results in double seronegative NMOSD (DS-NMOSD). The aim of this study was to characterize the neuronal, axonal, and glial damage of DS-NMOSD in comparison with AQP4+NMOSD. Patients with DS-NMOSD (i.e., for AQP4 and myelin oligodendrocyte glycoprotein antibodies-MOG-Abs) and age-matched AQP4+NMOSD diagnosed according to the latest diagnostic criteria and with available serum samples obtained within 3 months from onset/relapse were retrospectively enrolled from 14 international centers. Clinical and radiologic data were collected. Serum NfL, GFAP, tau, and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based ELISA (SIMOA). Statistical analysis was performed using nonparametric tests and receiver-operating characteristic (ROC) curve analysis. We included 25 patients with AQP4+NMOSD and 26 with DS-NMOSD. The median age at disease onset (p = 0.611) and female sex predominance (p = 0.072) were similar in the 2 groups. The most common syndromes at sampling in both AQP4+NMOSD and DS-NMOSD were myelitis (56% vs 38.5%) and optic neuritis (34.6% vs 32%), with no statistical differences (p = 0.716). Median EDSS at sampling was 3.2 (interquartile range [IQR] 2-7.7) in the AQP4+NMOSD group and 4 (IQR [3-6]) in the DS-NMOSD group (p = 0.974). Serum GFAP, tau, and UCH-L1 levels were higher in patients with AQP4+NMOSD compared with those with DS-NMOSD (median 308.3 vs 103.4 pg/mL p = 0.001; median 1.2 vs 0.5 pg/mL, p = 0.001; and median 61.4 vs 35 pg/mL, p = 0.006, respectively). The ROC curve analysis showed that GFAP, tau, and UCH-L1, but not NfL, values were able to discriminate between AQP4+ and DS-NMOSD (area under the curve (AUC) tau: 0.782, p = 0.001, AUC GFAP: 0.762, p = 0.001, AUC UCH-L1: 0.723, p = 0.006). NfL levels were associated with EDSS at nadir only in patients with AQP4+NMOSD. Serum GFAP, tau, and UCH-L1 levels discriminate between AQP4+NMOSD and DS-NMOSD. The different biomarker profile of AQP4+NMOSD vs DS-NMOSD suggests heterogeneity of diseases within the latter category and provides useful data to improve our understanding of this disease.

Patterns of neuromyelitis optica spectrum disorder attacks in different age groups and sexes depending on the status of immunosuppressive therapy: A retrospective cohort study.

The association between onset age and sex with relapse risk in neuromyelitis optica spectrum disorder (NMOSD) remains inconclusive. We aimed to describe the clinical features of patients with NMOSD in different age groups and sexes and to analyse relapse characteristics pre- and post-immunosuppressive therapy (IST). Patients with NMOSD were retrospectively reviewed from our clinical centre's database. Demographic and clinical data, attack presentation, and disease course pre- and post-IST were investigated. We also analysed the effect of onset age on the annualized relapse rate and relapse risk according to sex and IST status. Interactions on the additive scale between onset age and sex were analysed. A restricted cubic spline was used to analyse potential nonlinear correlations. Longitudinal changes in the Expanded Disability Status Scale score across NMOSD attacks were analysed using linear mixed-effect models. In total, 533 patients experienced 1394 attacks pre-IST and 753 relapses post-IST. Older age at onset was correlated with more myelitis attacks but fewer optic neuritis attacks, with no sex-related differences in attack presentation. Pre-IST, relapse risk increased with age at onset in women, while a U-shaped correlation between onset age and relapse risk was found in men. Post-IST, an inverted U-shaped association between the predicted relapse risk and onset age was observed in women. Conversely, a negative correlation between the predicted relapse risk and onset age was found in men. Overall, a higher ratio of myelitis attacks was found post-IST. Patients of different onset ages and sexes had different relapse patterns before and after IST.

Clinical and radiological features, treatment responses and prognosis in pediatric patients with co-existing anti-N-methyl-D-aspartate receptor and myelin oligodendrocyte glycoprotein antibody-associated encephalitis: A single center study

To characterize the clinical and radiological features, treatment responses and outcomes of children with co-existing anti-N-methyl-D-aspartate receptor(NMDAR) and myelin oligodendrocyte glycoprotein(MOG) antibody-associated encephalitis. Clinical manifestations, imaging features, effectiveness of treatment and outcomes of patients who were cerebral spinal fluid(CSF)-positive for NMDAR-antibody(NMDAR-ab) and seropositive for MOG-antibody(MOG-ab) were analyzed. Twelve patients including 8 females and 4 males were enrolled. The median onset age was 9 years, ranging from 2.2 to 12.8 years. Behavioral changes and/or psychiatric symptoms (n=8/12), seizures (n=8/12), encephalopathy (n=7/12) were 3 of the most common symptoms. Brain magnetic resonance imaging(MRI) of all the patients showed T2/fluid attenuation inversion recovery(FLAIR) abnormal signal in the cerebral white matter at least once in the courses of disease, 2 of whom developed new brain lesions which were asymptomatic. All of the patients had supratentorial lesions. Spinal cord MRI was performed in 7 patients. Only 1 patient showed related abnormalities with increased T2 signal in the spinal cord C1-5. Nine patients underwent optic nerve MRI; 5 patients demonstrated abnormal results, among whom 4 exhibited T2 abnormal signal (2 were symptom-free) and 1 showed a little effusion in bilateral optic nerve sheats. Intravenous immunoglobulin (IVIG) and intravenous methylprednisolone (IVMP) were the most common used therapies in those patients. Nine patients were treated with second-line therapy to prevent relapses. For total 29 clinical attacks, the median modified Rankin Scale (mRS) before treatment and after therapy of acute stage was 1 and 0, respectively. Seven of 12 patients(58.3%) experienced clinical relapses. In terms of outcome, all of the patients' mRS of last follow-up (≥6 months) was ≤2. Behavioral changes and/or psychiatric symptoms, seizures and encephalopathy were common in children with co-existing anti-NMDAR and MOG antibody-associated encephalitis. A minority of subjects may develop asymptomatic lesions on brain and optic nerve MRI. The relapse rate of this disease is relatively high. The majority of patients responded well to the immunotherapies and had a good outcome(mRS of last follow-up≤2).

Household transmission investigation for Corona Virus Disease 2019 (COVID-19) in a rural and urban population of north India.

Transmissibility within closed settings, such as households, can provide a strategic way to characterize the virus transmission patterns because the denominator can be well defined. We aimed to characterize the household transmission of Severe Acute Respiratory Syndrome Coronavirus (SARS CoV-2) and its associated risk factors. This prospective case-ascertained study was conducted among the household contacts of laboratory-confirmed SARS CoV-2 cases residing in Ballabgarh, Haryana. We enrolled 148 index cases and their 645 household contacts between December 16, 2020 and June 24, 2021. We defined household contact as any person who had resided in the same household as a confirmed COVID-19 case. Baseline data collection and sample collection for real time- reverse transcriptase polymerase chain reaction (RT-PCR) and IgM/IgG against SARS CoV-2 were done on day 1 visit, and followed for a period of 28 days. RT-PCR was repeated on day 14 or whenever the contact is symptomatic and blood sample for serology was repeated on day 28. We estimated household secondary infection rate (SIR) and other epidemiological indicators-median incubation period and serial interval. We employed binomial logistic regression to quantify risk factors associated with infection. The household SIR was 30.5% (95% CI: 27.1-34.1%). The secondary clinical attack rate was 9.3% (95% CI: 7.2-11.8). The risk factors that showed higher susceptibility to infection were household contacts who were the primary care giver of the case, whose index cases were symptomatic, those with underlying medical conditions, those living in overcrowded households, who were sharing toilet with the index cases and also who were not wearing a mask when coming in contact with the case. The median (IQR) incubation period was 4 days (4, 5), mean (SD) serial interval 6.4 (±2.2) days, and median (IQR) serial interval 5 days (5, 7). Households favour secondary transmission of SARS CoV- 2, hence, index cases are recommended to self-isolate and wear masks; and household contacts to follow strict COVID infection control measures within households when a family member is infected.

Distinct features of B cell receptors in neuromyelitis optica spectrum disorder among CNS inflammatory demyelinating diseases

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing.MethodsFrom a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups.ResultsBlood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups.ConclusionsNMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual’s lifetime.

Multiple Sclerosis Presenting as Intracranial Hypertension in the Setting of COVID-19 Infection

Background: Multiple sclerosis (MS) and idiopathic intracranial hypertension (IIH) occur more commonly in women of childbearing age. There are altered cerebrospinal fluid dynamics in both diseases, causing them to have similar presentations at times. Coronavirus disease 19 (COVID-19) has also been reported to affect the central nervous system (CNS) of any age. Case Presentation: We report a19 year old male who initially presented with headaches and fever, and was diagnosed with COVID-19 infection. A few days later, he developed acute severe left eye pain, blurred vision, diplopia, and left ear tinnitus. The patient was found to have reduced visual acuity, left sixth nerve palsy, esotropia and asymmetric bilateral papilledema. Later, he developed left facial nerve palsy. MRI of the brain showed extensive demyelinating lesions. Lumbar puncture revealed significantly increased intracranial pressure (ICP) and positive oligoclonal bands. Conclusion: This is a unique case of MS presenting with intracranial hypertension (IH) in the setting of COVID-19 infection that could have been the trigger for the MS clinical attack.

Kappa Free Light Chain Index Predicts Disease Course in Clinically and Radiologically Isolated Syndromes.

To evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). All consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index. One hundred and eighty two patients (146 CIS and 36 RIS, median age 39 [30; 48] y-o, 70% females) were included with a median follow-up of 21 [13, 33] months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve [AUC] ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB. This study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker.

Brain Mechanisms Underlying Panic Attack and Panic Disorder.

Panic disorder is a psychiatric disorder characterized by recurrent panic attacks, with a prevalence of ~ 4% in the general population, causing heavy personal and socioeconomic burdens. The similarities of animal defense responses to clinical panic attack symptoms in humans make it possible to translate neuroanatomical pathways identified in animal studies to panic disorder in humans. Therefore, in this review we first present a basic overview of panic disorder in humans including the main subtypes, models commonly used to trigger panic attacks, related hypotheses, the neurotransmitter systems that may be involved, and the current clinical treatments to give the reader a comprehensive understanding of panic disorder. The animal section introduces the models that trigger panic-like behavior in animals and the brain regions that may be involved, providing insights for future elucidation of the neural circuit mechanisms behind panic attacks.

Alterations in Aquaporin-4-IgG Serostatus in 986 Patients: A Laboratory-Based Longitudinal Analysis.

This study was undertaken to investigate factors associated with aquaporin-4 (AQP4)-IgG serostatus change using a large serological database. This retrospective study utilizes Mayo Clinic Neuroimmunology Laboratory data from 2007 to 2021. We included all patients with ≥2 AQP4-IgG tests (by cell-based assay). The frequency and clinical factors associated with serostatus change were evaluated. Multivariable logistic regression analysis examined whether age, sex, or initial titer was associated with serostatus change. There were 933 patients who had ≥2 AQP4-IgG tests with an initial positive result. Of those, 830 (89%) remained seropositive and 103 (11%) seroreverted to negative. Median interval to seroreversion was 1.2 years (interquartile range [IQR] = 0.4-3.5). Of those with sustained seropositivity, titers were stable in 92%. Seroreversion was associated with age ≤ 20 years (odds ratio [OR] = 2.25; 95% confidence interval [CI] = 1.09-4.63; p = 0.028) and low initial titer of ≤1:100 (OR = 11.44, 95% CI = 3.17-41.26, p < 0.001), and 5 had clinical attacks despite seroreversion. Among 62 retested after seroreversion, 50% returned to seropositive (median = 224 days, IQR = 160-371). An initial negative AQP4-IgG test occurred in 9,308 patients. Of those, 99% remained seronegative and 53 (0.3%) seroconverted at a median interval of 0.76 years (IQR = 0.37-1.68). AQP4-IgG seropositivity usually persists over time with little change in titer. Seroreversion to negative is uncommon (11%) and associated with lower titers and younger age. Seroreversion was often transient, and attacks occasionally occurred despite prior seroreversion, suggesting it may not reliably reflect disease activity. Seroconversion to positive is rare (<1%), limiting the utility of repeat testing in seronegative patients unless clinical suspicion is high. ANN NEUROL 2023;94:727-735.