Span of spleen is associated with disability status in multiple sclerosis: a cross-sectional abdominopelvic ultrasonography study.

Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability status. To test the hypothesis "the gross anatomical features of livers and spleens, are not similar between pwMS with different disease characteristics" a cross-sectional study was conducted on pwMS seen at the Isfahan MS clinic, Iran, from February until December 2023. Definitive, otherwise-healthy, pwMS were enrolled after an initial laboratory evaluation. Presence/absence and grading of non-alcoholic fatty liver disease (NAFLD) and the span of spleen were determined by a radiologist using high-resolution abdominopelvic ultrasonography. 193 pwMS (160 women) were enrolled. Of whom, 143 (74.1%) were receiving first-line disease-modifying therapies (DMTs), 24 (12.4%) fingolimod, and 26 (13.5%) rituximab. The span of spleen was negatively associated with EDSS (adjusted ß [SE] - 4.08 [1.52], p < 0.01), as well as 6 m-CDW (adjusted ß [SE] - 6.94 [3.56], p = 0.05), unlike age, DMTs, and MS duration (all with p > 0.05). Receiver operating characteristic analysis showed, spleen span performs significant but poor in discrimination of EDSS > 1 from EDSS = 1 (area under curve [AUC] 0.62, SE 0.05, p < 0.01), yet, significant and fair in discrimination of presence from absence of 6 m-CDW (AUC 0.72, SE 0.06, p < 0.01). Other findings were unremarkable. Further longitudinal, prospective studies are warranted to confirm whether smaller spleens are predictive of higher disability accrual rate in pwMS. Particularly, findings require further validation in untreated/treatment-naïve pwMS, and ones with higher EDSS scores.

A Randomized Controlled Clinical Trial Comparing Clinical and Radiographic Success Rates of MTA and rhBMP2 in Pulpotomy of Primary Teeth.

Objectives: In an ideal pulpotomy, the radicular pulp remains vital, healthy, and fully encased within an odontoblastic layer. Mineral trioxide aggregate (MTA) and bone morphogenetic proteins (BMPs) have been suggested to facilitate this outcome. We aimed to compare the clinical and radiographic failure and success rates of MTA and rhBMP2 as pulpotomy medicaments. Materials and Methods: Sixty-eight teeth from 3-6-year-old children were randomly assigned to two groups using a split-mouth design. Cervical pulpotomy was performed using MTA in one group and rhBMP2 in the other. Subsequently, the teeth were restored with stainless-steel crowns. Clinical and radiographic assessments were performed at 3, 6, 9, and 12-month follow-up intervals to evaluate success and failure rates. Data were analyzed using Chi-square test and Kaplan-Meier survival analysis (P<0.05) Results: At six and nine months, one tooth in the BMP2 group and one tooth in the MTA group showed internal resorption, respectively. After 12 months, one tooth in the BMP2 group exhibited PDL widening. The radiographic success rate was 100% for the MTA- and 97.1% for the BMP2-group at six months, 96.7% for both groups at nine months, and 96.7% and 93.3%, respectively, at 12 months. No clinical failure criteria were observed in any of the teeth. Survival analysis revealed no significant difference between the two groups. Conclusion: The study reveals comparable outcomes between rhBMP2 and MTA, suggesting rhBMP2 as a viable alternative for pulpotomy in primary teeth. With minimal incidences of complications and no significant differences noted, rhBMP2 demonstrates potential for clinical use.

Effect of enteral probiotics on prognostic scores and C-reactive protein levels in critically ill multiple trauma patients: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND AND AIMS: To evaluate the effect of a one-week LactoCare® oral probiotic supplementation on prognostic scores (APACHE II: acute physiology and chronic health evaluation II; SAPS II: simplified acute physiology score II; SOFA: sequential organ failure assessment), C-reactive protein (CRP) levels, and other outcomes in multiple trauma (MT) patients requiring intensive care compared to placebo. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial. The population included MT patients admitted to ICUs of two referral centers in Isfahan, Iran, from December 2021 to November 2022 (registered under IRCT. ir identifier no. IRCT20211006052684N1). LactoCare® and placebo were administered twice daily for one week. Prognostic scores and CRP levels were calculated/measured before and after the dedicated intervention. RESULTS: There was not a significant difference in APACHE II (p-value = 0.62), SAPS II (p-value = 0.70), SOFA (p-value = 0.71) scores, CRP levels (p-value = 0.25), median hospital days [LactoCare® vs. placebo] (28.00 vs. 22.50, p-value = 0.06), median ICU days (21.00 vs. 18.00, p-value = 0.16), and median days under mechanical ventilation (14.00 vs. 14.50, p-value = 0.74) between the LactoCare® and placebo groups. Also, 28-day mortality and time to discharge did not significantly differ between the two groups. CONCLUSION: Evidence from this trial does not support the use of oral probiotic supplementation for MT patients who are admitted to the ICU.

Third COVID-19 vaccine dose for people with multiple sclerosis who did not seroconvert following two doses of BBIBP-CorV (Sinopharm) inactivated vaccine: A pilot study on safety and immunogenicity.

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines. Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine. Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine. Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year ß: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 ß: -8.36, P <0.01; fingolimod ß: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated ß: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose. Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used.

Effect of multiple sclerosis disease-modifying therapies on the real-world effectiveness of two doses of BBIBP-CorV (Sinopharm) vaccine.

BACKGROUND: Immunogenicity data shows blunted responses to COVID-19 vaccination among people with MS (pwMS) on certain disease-modifying therapies (DMTs). Still, it is uncertain how this data translates into the clinic. OBJECTIVE: To assess the effect of DMTs and other factors on the effectiveness of inactivated vaccination in pwMS. METHODS: This cohort study was conducted in a period in which Iran experienced two COVID-19 peaks caused by the Delta variant. We used multivariable cox regression to compare COVID-19-free survivals, and an ordinal logistic model to compare COVID-19 severity between vaccinated pwMS on different DMTs. RESULTS: A total of 617 pwMS were included in the final analysis, with a mean [SD] follow-up of 25.59 weeks [5.48] after their second dose. Laboratory/imaging-confirmed breakthrough COVID-19 occurred in 15/277 (5.41%) of injectable-treated (reference), 10/61 (16.39%) of fingolimod-treated (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 2.80 [1.24, 6.29]; P = 0.01), 9/128 (7.03%) of other oral-treated (aHR [95%CI]: 1.16 [0.50, 2.68]; P = 0.73), 19/145 (13.10%) of anti-CD20-treated (aHR [95%CI]: 2.11 [1.05, 4.22]; P = 0.04), and 6/56 (10.71%) of non-treated pwMS (aHR [95%CI]: 1.52 [0.57, 4.04]; P = 0.40). Age (adjusted Odds Ratio [aOR] [95%CI]: 1.05 [1.00, 1.10], P = 0.05) number of comorbidities (aOR [95%CI]: 2.05 [1.06, 3.96], P = 0.03), fingolimod therapy (aOR [95%CI]: 10.39 [2.47, 43.62], P < 0.01), and anti-CD20 therapy (aOR [95%CI]: 4.44 [1.49, 13.23], P < 0.01) were independently associated with a more severe COVID-19 course. CONCLUSION: The observed results stress the importance of developing personalized vaccination schedules and reservation of COVID-19 treatment resources for older pwMS with comorbidities receiving fingolimod or anti-CD20 therapies.

Neuro-mucormycosis: Lessons from COVID-19-associated cases.

Background: Scarce data are available on the neurological presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) and COVID-19-unrelated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to compare the neurological presentations and their associated outcomes in patients with CAM and COVID-19-unrelated ROCM. Methods: In December 2021, a case-control analysis was conducted on the CAM (case group) and COVID-19-unrelated ROCM (control group) referrals of one center in Isfahan, Iran. Confirmed CAM patients from January 2020 to December 2021 constituted the case group, and patients with COVID-19-unrelated ROCM from 2016-2019 constituted the control group. Their data were then analyzed using proper (non) parametric tests and generalized linear models (GLM), therein P-value below 0.05 was considered as the criterion of statistical significance, and the SPSS software was used. Results: After retrieving data on 177 patients with mucormycosis, 78 patients with CAM were included as the case group and 72 patients with COVID-19-unrelated ROCM were included as the control group. Neurological presentations suggestive of second, third, and eighth cranial nerve involvement were more prevalent in the CAM group (all with P < 0.05). The mortality rate in the CAM group was 1.9 times that of the controls (P = 0.01), being explained by higher extent of corticosteroid administration among them. Higher age and presentation with gait ataxia, ptosis, and mydriasis were considered to be predictive of poor prognosis in patients with CAM (all with P < 0.05). Conclusion: The neurological manifestations of CAM differ from COVID-19-unrelated ROCM based on the presented results, some of which are associated with poor prognosis. Further replication is warranted to confirm our retrospective analyses.

Immunomodulatory drug fingolimod (FTY720) restricts the growth of opportunistic yeast Candida albicans in vitro and in a mouse candidiasis model.

Fingolimod (FTY720) is a drug derived from the fungicidal compound myriocin. As it was unclear whether FTY720 has antifungal effects as well, we aimed to characterize its effect on Candida albicans in vitro and in a mouse candidiasis model. First, antifungal susceptibility testing was performed in vitro. Then, a randomized, six-arm, parallel, open-label trial was conducted on 48 mice receiving oral FTY720 (0.3 mg/kg/day), intraperitoneal C. albicans inoculation, or placebo with different combinations and chorological patterns. The outcome measures of the trial included serum concentrations of interleukin-10 and interferon-gamma, absolute lymphocyte counts, and fungal burden values in the mice's livers, kidneys, and vaginas. Broth microdilution assay revealed FTY720's minimum inhibitory concentration (MIC99) to be 0.25 mg/mL for C. albicans. The infected mice treated with FTY720 showed lower fungal burden values than the ones not treated with FTY720 (p<0.05). As expected, the mice treated with FTY720 showed a less-inflammatory immune profile compared to the ones not treated with FTY720. We hypothesize that FTY720 synergizes the host's innate immune functions by inducing the production of reactive oxygen species. Further studies are warranted to unveil the mechanistic explanations of our observations and clarify further aspects of repurposing FTY720 for clinical antifungal usage.

Endoscopic clipping of a complicated esophageal perforation following pneumatic dilation for achalasia: A case study and literature review.

A transmural esophageal tear complicated by large size and unusual location was diagnosed in a 59-year-old man after undergoing pneumatic balloon dilation for achalasia. It was closed with six endo-clips. The patient recovered and was discharged with ordinary diet 8 days later, after receiving supportive care for a week.

Multiple sclerosis in sarcoidosis patients: Two case reports.

Two cases of sarcoidosis referred to our clinic with neurological symptoms. They were diagnosed with multiple sclerosis using non-invasive studies. The first patient refused treatment and died of myocardial infarction 6 months after visiting our clinic. The second received interferon-beta and methotrexate with a favorable outcome after 3 years. Since the possible similar presentation of the two conditions could appear indistinct for certain diagnosis, accurate evaluation of symptoms and paraclinical data can provide the best approach to each condition.

Revisiting the antiviral theory to explain interferon-beta's effectiveness for relapsing multiple sclerosis.

Treatments with interferon-beta (IFNß) - a cytokine with established antiviral effects - were initially considered for multiple sclerosis (MS), as epidemiological data pointed towards a viral etiological agent for it. Later, when no specific agent was found for MS, theories explaining IFNß's mechanism of action (MOA) relied on anti-inflammatory mechanisms, which did not explain its ineffectiveness for disease progression independent of relapse activity (PIRA) in progressive forms of MS. Now, with new evidence backing the Epstein-Barr virus (EBV) as a conditional agent in MS etiopathogenesis as well as linking the reactivation of a wide range of other Herpesviridae with MS onset/relapse, it may be time to revisit the antiviral theory to explain IFNß's MOA, look at the evidence from the past two decades from that perspective, and address the paucity of knowledge with new direct studies and discussions.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis.

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

Detection of anti-NMDA receptor antibodies following BBIBP-CorV COVID-19 vaccination in a rituximab-treated person with multiple sclerosis presenting with manifestations of an acute relapse.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a relatively unknown autoimmune entity. Scant reports of post-infection/vaccination anti-NMDAR encephalitis exist. We, hereby, reviewed the relevant cases and added to the literature a possible case of anti-NMDAR encephalitis following COVID-19 vaccination with BBIBP-CorV (Sinopharm). A 50-year-old Persian woman with previously known rituximab-treated MS presented complaining of worsening neurological symptoms all gradually starting and worsening after receiving the second dose of BBVIP-CorV 2 weeks before. Notable findings in her physical examination included ataxic gait and Babinski sign. Considering an acute MS relapse, corticosteroid pulse therapy was initiated, and she was referred for MRI, which revealed multiple new plaques. Her serum sample interestingly tested positive for anti-NMDAR antibodies. CSF analysis was unfortunately not performed. She responded well to the corticosteroid pulse therapy and showed substantial resolution of the symptoms. Considering its relatively low cost of workup and the benefits of correct early diagnosis, clinicians are advised to consider autoimmune encephalitis encountering patients with progressive neurological symptoms after the administration of vaccines, including the ones for COVID-19 which are currently being used extensively.

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study.

BACKGROUND: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated. OBJECTIVE: To detect possible changes in MS clinical disease activity after COVID-19. METHODS: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS). RESULTS: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved. CONCLUSION: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS.

Self-Reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis.

To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective vaccine-related at-risk periods (ARP) - a period from the first dose until two weeks after the second dose of the vaccine. In a multivariable logistic regression model, the presence of comorbidities (P = 0.01), use of natalizumab (P = 0.03), and experiencing post-vaccination myalgia (P < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first dose, and four MS relapses after the second dose of the vaccine were the only reported serious adverse events during the ARPs. To show if the vaccine provoked MS relapses, we compared the relapse rate of vaccinated pwMS in the vaccine-related ARP with the annualized relapse rate of unvaccinated pwMS in the prior year-a measure of baseline MS relapsing activity in the respective time-using a multivariable Poisson regression model accounting for possible confounders, which failed to show any statistically significant increase (P = 0.78). Hence, subject to replication-as the vaccinated and unvaccinated pwMS differed in baseline characteristics-the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of evidence-based consultations to pwMS is encouraged. Limitations of our study briefly included lack of data for self-controlled analysis of relapse rates, possible presence of recall bias, and lack of on-site validations regarding the clinical outcomes due to the remote nature.

Inducing chimeric antigen receptor (CAR) regulatory T cells in-vivo: A novel concept for a potential feasible cure of demyelinating diseases.

Chimeric antigen receptor (CAR) regulatory T cell (Treg) therapy has approved promising in murine experiments. It comprises from ex-vivo introduction of CARs to the Tregs of the recipient, and infusing them back thereafter. This process requires enormous amounts of equipment and expertise and therefore, cannot be considered feasible for people with demyelinating diseases, even if it proves to be effective and safe in the future. The presented novel concept introduces feasibility to CAR Treg therapy, by shifting most of the ex-vivo processes in-vivo. Inter-disciplinary discussions on such concepts is encouraged among experts in different fields.

Atherosclerosis and multiple sclerosis: An overview on the prevalence of risk factors.

BACKGROUND: Atherosclerosis is the leading cause of ischemic heart disease and coronary artery disease. The process of atherosclerosis develops over a period of years and is mainly immune-mediated. Data regarding the prevalence of vascular disease and atherosclerosis among people with multiple sclerosis (pwMS) is inconsistent, therefore, we aimed to provide an overview of the prevalence of atherosclerotic risk factors in pwMS. METHODS: This is a cross-sectional study over a period of one year among pwMS visiting the Isfahan MS center. Study data have been extracted using participants' files and a checklist that was completed by the observers. Only people with relapsing-remitting (RRMS) and secondary progressive (SPMS) forms of MS were included in the study. Participants with primary progressive (PPMS) disease are only described and have been excluded from analyses. RESULTS: Of the 396 pwMS (343 with RRMS and 53 with SPMS), in descending order, the reported risk factors were tobacco smoking (18.4%), dyslipidemia (10%), hypertension (8.8%), and diabetes mellitus (4.5%). In people with RRMS, 17.4% were smokers, 9.9% had dyslipidemia, 8.1% had hypertension, and 4.3% had diabetes mellitus. In SPMS patients 24.5% reported a history of smoking, 13.2% had hypertension, 9.4% had dyslipidemia, and 3.7% had diabetes mellitus. Smoking was insignificantly associated with higher expanded disability status scale (Z: 1.70, p-value = 0.090). Male sex (RR [95%CI]: 1.628 [1.172, 2.261], p-value = 0.004) and increasing age (RR [95%CI]: 1.024 [1.008, 1.040], p-value = 0.003) were associated with a higher number of risk factors. CONCLUSION: The highest observed atherosclerosis risk factor among pwMS was smoking. Diabetes mellitus was the least reported risk factor in our population as a whole. Overall, and in participants with RRMS, dyslipidemia and hypertension were the second and third most commonly reported risk factors, however, hypertension exceeded dyslipidemia in participants with SPMS. Male sex and increasing age were associated with a higher number of atherosclerosis risk factors.

Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial.

BACKGROUND: Nowadays, minimizing the surgical complications of rhinoplasty has gained more importance. Results from previous trials show that Tranexamic acid (TXA) reduces intraoperative bleeding, one of the major complicating factors during rhinoplasty. OBJECTIVE: To contribute to previous evidence by re-evaluating the efficacy of TXA, specifically in reducing intraoperative blood loss and increasing surgical field quality in rhinoplasty. STUDY DESIGN AND METHODS: A randomized placebo-controlled trial was conducted (IRCT20111219008458N2). The outcomes included total intraoperative blood loss, measured by the total volume of fluid collected by suction and gauzes, subtracted by volume of used irrigation fluids, and the quality of surgical field, measured by surgeon's satisfaction on a 5-point Likert scale. Demographics, blood coagulation measures, and clinical data were also collected and were held as covariates in analysis. After blinding, randomization, and group allocations, the intervention group received TXA 10mg/kg and the placebo group normal saline in equal volumes. RESULTS: Data of a total of 80 patients were gathered and analyzed. The total intraoperative blood loss was insignificantly lower (mean difference [95% CI]: - 3.6 ( - 19.19, 11.99), P = 0.65) and surgeon's satisfaction was insignificantly higher (mean difference [95% CI]: 0.18 ( - 0.11, 0.46), P = 0.22) in TXA group. Results were confirmed by multivariable analysis. CONCLUSION: In contrast to most of the previous studies, this study showed only a statistically insignificant decrease in total intraoperative blood loss in patients receiving TXA compared to placebo. Further studies are required to more precisely estimate the efficacy of TXA in reducing blood loss during rhinoplasty. LEVEL OF EVIDENCE: LEVEL I, RANDOMIZED CONTROLLED TRIAL.: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

SARS-CoV-2 serology among people with multiple sclerosis on disease-modifying therapies after BBIBP-CorV (Sinopharm) inactivated virus vaccination: Same story, different vaccine.

BACKGROUND: Various studies indicated blunted humoral responses to COVID-19 mRNA and viral vector vaccines among people with multiple sclerosis (pwMS) on sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20); however, limited evidence was found regarding SARS-CoV-2 serology after inactivated virus vaccination. OBJECTIVE: To provide evidence regarding humoral response to COVID-19 inactivated virus vaccination among pwMS on disease-modifying therapies (DMTs). METHODS: A cohort study was carried out in Isfahan, Iran, enrolling DMT-exposed pwMS and unexposed (UX) healthy participants. Post-vaccination anti-SARS-CoV-2 Spike IgG serology testing was carried out among the participants and compared between participants based on their DMT exposure, using proper statistical tests. A multivariable logistic regression model was used to control for confounding. Association between the second vaccine dose-to-phlebotomy (vac2phleb) and the humoral response was investigated in each DMT-exposed cohort, using linear regression. Among the aCD20 cohort, the association of the last aCD20 infusion-to-first vaccine dose period with serostatus was investigated using an unpaired t-test. RESULTS: After enrolling 358 participants (144 pwMS and 214 healthy), blunted humoral responses were only observed in fingolimod (Log10 mean diff. [SE]: 0.72 [0.18], P = 0.001) and aCD20 (Log10 mean diff. [SE]: 0.75 [0.15], P < 0.001) cohorts compared to the UX cohort. Multivariable analysis confirmed the results. The study did not achieve enough statistical power to detect a significant association between the vac2phleb period and humoral responses. The last aCD20 infusion to first vaccination dose period was longer in the seroconverted pwMS on aCD20 (mean diff. [SE]: 8.43 weeks [2.57], P = 0.005). CONCLUSION: The results of this study mirrored the results of previous studies among mRNA- or viral vector-vaccinated pwMS on DMTs. Therefore, it can be concluded that mode of action contributes less than timing, to the efficiency of vaccination strategies among pwMS on DMTs - especially the ones on S1PR modulators and aCD20. Meanwhile, the mentioned pwMS should be advised to receive early boosters and remain vigilant until further data becomes available and more efficient vaccination strategies are crafted.

Outcome of COVID-19 infection in multiple sclerosis patients receiving disease-modifying therapies.

BACKGROUND: With the spread of COVID-19, treatment of diseases such as multiple sclerosis (MS) should be resumed with caution due to the disease-modifying therapies (DMTs) used in this subset of patients and the immunoregulatory effects of these drugs. We aim to assess the outcome of COVID-19 infection in MS patients receiving DMTs. MATERIALS AND METHODS: This is a cross-sectional study involving 45 COVID-19-infected patients previously diagnosed with MS. The data regarding their MS status and the type of DMT taken by the patients were extracted from the Isfahan MS Institute registry and were summarized. Diagnosis of MS was based on the 2017 McDonald Criteria, and the diagnosis of COVID-19 was based on computed tomography scan and polymerase chain reaction of nasopharyngeal swabs. RESULTS: Out of the 45 MS patients infected with COVID-19, 5 had unfavorable outcomes. Two patients deceased and the other three had persistent respiratory complications on the 4-week follow-up visit. Hypertension, diabetes, seizures, and rheumatoid arthritis were among the comorbidities that the patients reported. Both patients who died received rituximab as part of their MS treatment. All other patients recovered completely. CONCLUSION: Each different drug category may possess a distinct risk for infection, therefore until robust evidence are available, the safest drug should be utilized or the therapy should be postponed, if possible, to minimize patient risk. Disease-modifying therapy use in MS patients should be cautiously applied as their effect on COVID-19 infection prognosis is not yet studied.

Movement Disorders Associated with COVID-19.

As neurological complications associated with COVID-19 keep unfolding, the number of cases with COVID-19-associated de novo movement disorders is rising. Although no clear pathomechanistic explanation is provided yet, the growing number of these cases is somewhat alarming. This review gathers information from 64 reports of de novo movement disorders developing after/during infection with SARS-CoV-2. Three new cases with myoclonus occurring shortly after a COVID-19 infection are also presented. Treatment resulted in partial to complete recovery in all three cases. Although the overall percentage of COVID-19 patients who develop movement disorders is marginal, explanations on a probable causal link have been suggested by numerous reports; most commonly involving immune-mediated and postinfectious and less frequently hypoxic-associated and ischemic-related pathways. The current body of evidence points myoclonus and ataxia out as the most frequent movement disorders occurring in COVID-19 patients. Some cases of tremor, chorea, and hypokinetic-rigid syndrome have also been observed in association with COVID-19. In particular, parkinsonism may be of dual concern in the setting of COVID-19; some have linked viral infections with Parkinson's disease (PD) based on results from cerebrospinal fluid analyses, and PD is speculated to impact the outcome of COVID-19 in patients negatively. In conclusion, the present paper reviewed the demographic, clinical, and treatment-associated information on de novo movement disorders in COVID-19 patients in detail; it also underlined the higher incidence of myoclonus and ataxia associated with COVID-19 than other movement disorders.