Prevalence and incidence of multiple sclerosis in Turkey: A nationwide epidemiologic study.

BACKGROUND: Many studies on multiple sclerosis (MS) reveal different prevalence and epidemiologic results. OBJECTIVES: In this study, we aimed to determine the epidemiologic profile of MS using official health records in Turkey. METHODS: Patients diagnosed with MS from the official health data of the Ministry of Health, representing the entire population of Turkey, were included in the study. Prevalence and incidence calculations were performed using the data on gender, age, year of birth, city of residence, and year of diagnosis. RESULTS: As a result of the study, the number of patients with the ICD code G35 was determined as 201,061 and the number of patients with this code entered at least three times was determined as 82,225. The prevalence of MS in Turkey was calculated as 96.4 per 100,000 and the female/male ratio as 2.1/1. The incidence of MS in 2022 was 6.2 per 100,000 and the mean patient age was 43.1 ± 13.3 years (female: 43.0 ± 13.1 vs male: 43.2 ± 13.7) while the mean age at first diagnosis was 34.0 ± 13.0 (female: 33.6 ± 12.6 vs male: 34.9 ± 13.7). CONCLUSION: The research was conducted via Official Database of Turkey, which includes population of 85 million and provides valuable insights into the prevalence and incidence rates of this chronic disease.

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

BACKGROUND: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. OBJECTIVE: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. METHODS: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). RESULTS: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03). CONCLUSIONS: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

Impact of COVID-19 on pregnancy and fetal outcomes in women with multiple sclerosis.

BACKGROUND: In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with multiple sclerosis (MS), but there are no data about maternal and fetal outcomes. OBJECTIVES: In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection. METHODS: We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020-2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score-based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders. RESULTS: In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32-3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations. CONCLUSION: Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes.

The diagnostic value of the central vein sign in radiologically isolated syndrome.

OBJECTIVE: The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS. METHODS: Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions. RESULTS: 180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis. INTERPRETATION: This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS.

Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Radiologically isolated syndrome.

Individuals can be deemed to have radiologically isolated syndrome (RIS) if they have incidental demyelinating-appearing lesions in their brain or spinal cord that are highly suggestive of multiple sclerosis but their clinical history does not include symptoms consistent with multiple sclerosis. Data from international longitudinal cohorts indicate that around half of people with RIS will develop relapsing or progressive symptoms of multiple sclerosis within 10 years, suggesting that in some individuals, RIS is a presymptomatic stage of multiple sclerosis. Risk factors for progression from RIS to clinical multiple sclerosis include younger age (ie, <35 years), male sex, CSF-restricted oligoclonal bands, spinal cord or infratentorial lesions, and gadolinium-enhancing lesions. Other imaging, biological, genetic, and digital biomarkers that might be of value in identifying individuals who are at the highest risk of developing multiple sclerosis need further investigation. Two 2-year randomised clinical trials showed the efficacy of approved multiple sclerosis immunomodulatory medications in preventing the clinical conversion to multiple sclerosis in some individuals with RIS. If substantiated in longer-term studies, these data have the potential to transform our approach to care for the people with RIS who are at the greatest risk of diagnosis with multiple sclerosis.

The Prevalence of Headache Disorders in Children and Adolescents in Istanbul: A School-Based Study.

BACKGROUND: Headache among children and adolescents is an important health problem. In this school-based epidemiological study conducted in Istanbul, we aimed to reveal the frequency of headaches in this population, define the risk factors associated with headaches, and establish the effect of headaches on the quality of life in this population. METHODS: The child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation structured questionnaire were conducted in 30 schools in Istanbul. The diagnosis was made based on the International Classification of Headache Disorders III-(ICHD-3) beta version. Risk factors associated with headaches were analyzed in a binary logistic regression model. RESULTS: Among the 5944 students (boys = 3011 [50.7%], girls 2933 [49.3%]) who completed the survey and were enrolled in this study, 3354 (56.4%) reported a headache ever. The prevalence of headaches was significantly higher in girls (62.6% vs. 50.4%, P < 0.001). Migraine prevalence was found to be 5.2%, whereas tension-type headache (TTH) prevalence was 26.1%. Being a female, age, living on the European side, and headache history in the family were found to be associated with an increased risk of having a headache. Pupils with headaches reported that they missed an average of 0.5 ± 1.5 school days due to headaches. CONCLUSION: TTH was found to be the most common headache syndrome in Istanbul metropolitan area. Considering the effect of headaches on school success and quality of life in childhood, it is clear that the correct diagnosis of headaches and careful handling of risk factors are crucial for this population.

Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune, inflammatory disease of the central nervous system affecting the optic nerves and spinal cord. Most NMOSD patients have autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). Eculizumab treatment is used effectively and safely in AQP4-IgG+ NMOSD. Our study evaluated the prognosis and outcomes of all clinical trial (PREVENT) patients from Turkey who received eculizumab treatment for AQP4-IgG+ NMOSD. METHOD: Clinical and demographic data of all patients enrolled in the PREVENT and OLE clinical trial in Turkey were analyzed during the study period and after the study ended. Clinical follow-up results were recorded in detail in patients who had to discontinue eculizumab treatment. RESULTS: The study included 10 patients who participated in PREVENT and OLE. Seven patients completed the studies, three patients did not continue the study and were switched to other treatments. Only one of the seven patients was able to continue treatment after eculizumab was approved in AQP4-IgG+NMOSD. The other six patients could not continue treatment due to reimbursement conditions. Four of the six patients who could not continue eculizumab treatment experienced early relapse (within the first three months after stopping the drug). All of these patients had high disease activity before eculizumab and had never relapsed under eculizumab treatment over the long term. CONCLUSION: Eculizumab was used effectively and safely in Turkish AQP4-IgG+NMOSD patients with high disease activity. Disease reactivation and relapse may occur after discontinuation of eculizumab treatment in patients with a long-term stable course. In these cases, close monitoring for disease reactivation is recommended.

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial.

Importance: Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. Objective: To determine the time to onset of symptoms consistent with MS. Design, Setting, and Participants: From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Interventions: Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Main outcomes: Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Results: Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Conclusion and Relevance: Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. Trial Registration: ClinicalTrials.gov Identifier: NCT03122652.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.

ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. OBJECTIVE: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND AND PURPOSE: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation. METHODS: A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow-up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non-rebound group. Clinical and demographic data and 5-year clinical outcomes of both groups were prospectively examined. RESULTS: At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non-rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5-year follow-up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non-rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow-up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non-rebound group (52.4%, p = 0.05). CONCLUSION: When rebound activity is well-monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long-term follow-up.

Infliximab for vascular involvement in Behçet's syndrome.

OBJECTIVE: Vascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. METHODS: Charts of all BS patients who used IFX for vascular involvement between 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. RESULTS: Among the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). CONCLUSION: Infliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

Impact of COVID-19 vaccination or infection on disease activity in a radiologically isolated syndrome cohort: The VaxiRIS study.

BACKGROUND: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised. OBJECTIVES: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS). METHODS: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection. RESULTS: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients. CONCLUSION: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

BACKGROUND: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. OBJECTIVE: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. METHODS: Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. RESULTS: CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. CONCLUSION: The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.

Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

Auto brewery syndrome from the perspective of the neurologist.

BACKGROUND AND PURPOSE: Auto-brewery syndrome (ABS) is a rare condition that causes the digestive system to produce intoxicating amounts of alcohol due to abnormal growth of the gut microbiota. Medicolegal inferences of ABS have two distinct edges. First, malingering in drunk-driving and abusing the syndrome as a factitious disorder may occur. Second, patients suffering from the syndrome may face medicolegal and social problems. Moreover, chronic exposure to alcohol due to undiagnosed ABS might result in cognitive and behavioral disturbances. Here, we present a patient with recurrent encephalopathy episodes and chronic cognitive disturbances, who was diagnosed with the auto-brewery syndrome, to emphasize the neurocognitive consequences of the syndrome. CASE PRESENTATION: A 58 years old female presented with mild cognitive impairment, behavioral disturbances, and recurrent encephalopathy episodes. The history of hemicolectomy, an odd smell on her breath, and cravings for high carbohydrate meals during the paroxysmal episodes raised the suspicion of ABS. Her blood ethanol concentration reached 315 mg/dL following an oral glucose tolerance test (OGTT), and stool analysis revealed increased colonization with C. krusei and C. parapsilosis. She was free of the acute episodes, cognitive and behavioral disturbances improved, and C. krusei and C. parapsilosis were eliminated from the intestinal flora with dietary recommendations and nystatin treatment. CONCLUSION: The auto brewery syndrome is a rare disorder of dysbiosis leading to a disturbed gut-brain axis. Being a treatable and relatively benign diagnosis, presentation of the ABS with neurocognitive disturbances necessitates highlighting.