Good manufacturing practices production of human placental derived mesenchymal stem cells for therapeutic applications: focus on multiple sclerosis.

BACKGROUND: Among neurological diseases, multiple sclerosis (MS) affects mostly young adults and can cause long-term disability. While most medications with approval from regulatory agencies are very effective in treating MS disease, they are unable to repair the tissue damage found in the central nervous system (CNS). Consequently, Cell-based therapy particularly using mesenchymal stem/stromal cells (MSCs), holds promise for neuroprotection and tissue repair in MS treatment. Furthermore, placenta-derived MSCs (PLMSCs) have shown the potential to treat MS due to their abundance, noninvasive isolation from discarded tissues, no ethical problems, anti-inflammatory, and reparative properties. Accordingly, good manufacturing practices (GMPs) plays a crucial part in clinical SCs manufacturing. The purpose of our article is to discuss GMP-grade PLMSC protocols for treating MS as well as other clinical applications. METHODS AND RESULTS: Placental tissue obtained of a healthy donor during the caesarean delivery and PLMSCs isolated by GMP standards. Flow cytometry was used to assess the expression of the CD markers CD34, CD105, CD90, and CD73 in the MSCs and the mesodermal differentiation ability was evaluated. Furthermore, Genetic evaluation of PLMSCs was done by G-banded karyotyping and revealed no chromosomal instability. In spite of the anatomical origin of the starting material, PLMSCs using this method of culture were maternal in origin. CONCLUSIONS: We hope that our protocol for clinical manufacturing of PLMSCs according to GMP standards will assist researchers in isolating MSCs from placental tissue for clinical and pre-clinical applications.

Effect of ginseng on fatigue related to neuromyelitis optica spectrum disorder: A double-blinded randomized controlled clinical trial.

Background: The effects of ginseng on fatigue have been proven in patients with multiple sclerosis (MS), which have several similar manifestations to neuromyelitis optica spectrum disorder (NMOSD) patients. This study was designed to evaluate the effects of ginseng on fatigue in NMOSD patients. Methods: In this double-blinded randomized controlled clinical trial, 64 patients were recruited and were allocated into two study groups (ginseng or placebo) via block randomization. The participants received either 250-mg ginseng or placebo twice daily for a 3-month period. Also, the measurement of outcome was performed using the valid and reliable Persian version of fatigue severity scale (FSS) questionnaire, which was filled by patients once after enrollment in the study and once at the end of the study post-intervention. Results: In total, 58 patients finished the study with no major side effects. There were no significant differences in demographic, clinical, as well as FSS between two study groups (p>0.05). Ginseng supplementation significantly reduced fatigue (40.21±13.51 vs. 28.97±14.18; p˂0.01), while patients in the placebo group showed significantly higher fatigue score after 3 months post-intervention (35.03±13.51 vs. 38.79±12.27; P: 0.02). The extent of changes in the fatigue score in the ginseng group was significantly greater than in the placebo group (p ˂0.01). Conclusion: This study revealed positive effects of ginseng on reducing fatigue in NMOSD patients with no major side effects. In this regard, further studies are warranted to evaluate and clarify the effects of ginseng on fatigue in NMOSD.

Focal central neurological disorder in patients with autoimmune thyroid disease without encephalopathy.

The report underscores the necessity for a comprehensive evaluation in patients with suggestive laboratory findings or AITD history. Prompt diagnosis and appropriate management are imperative in averting long-term complications.

Effects of non-pharmacological interventions on gait and balance of persons with Multiple Sclerosis: A narrative review.

BACKGROUND: Multiple Sclerosis (MS) is among the most common reasons for disability in young adults. Mobility impairment, primarily related to gait and balance, is ranked as the preeminent concern among persons with MS (PwMS). Gait and balance dysfunction can directly affect the quality of life and activities of daily life in PwMS, hence the importance of effective treatment strategies. Previous studies have demonstrated the positive effect of various non-pharmacological rehabilitation methods, including physiotherapy and electrical stimulation, on gait and mobility in PwMS. Non-pharmacological methods can be tailored to the individual needs and abilities of each patient, allowing healthcare providers to create personalized training programs. Furthermore, these methods typically result in minimal or no side effects. PURPOSE: This review provides a comprehensive overview of an array of non-pharmacological treatment approaches aimed at enhancing ambulatory performance in PwMS. METHODS: We performed a narrative review of the original papers available in PubMed, investigating the effects of different nonmedical approaches on the gait and balance performance of the PwMS. Reviewed treatment approaches include "exercise, physical rehabilitation, dual-task (DT) rehabilitation, robot-assisted rehabilitation, virtual reality-assisted rehabilitation, game training, electrical stimulation devices, auditory stimulation, visual feedback, and shoe insoles". RESULTS AND CONCLUSIONS: Eighty articles were meticulously reviewed. Our study highlights the positive effects of non-pharmacological interventions on patients' quality of life, reducing disability, fatigue, and muscle spasticity. While some methods, including exercise and physiotherapy, showed substantial promise, further research is needed to evaluate whether visual biofeedback and auditory stimulation are preferable over conventional approaches. Additionally, approaches such as functional electrical stimulation, non-invasive brain stimulation, and shoe insoles demonstrate substantial short-term benefits, prompting further investigation into their long-term effects. Non-pharmacological interventions can serve as a valuable complement to medication-based approaches.

The association of upper respiratory infections with neuro-radiological course and attack rate of multiple sclerosis: Results from a large prospective cohort.

Background: Although upper respiratory infections (URIs) are linked to multiple sclerosis (MS) attacks, SARS-COV2 has not been compared to URIs for attack rates. Objectives: This study aimed to evaluate the attack rate and the results of neuroimaging in MS patients with URIs caused by COVID-19 and non-COVID-19 infections (NC-URI). Methods: From May 2020 to April 2021, we followed 362 patients with relapsing-remitting MS in a prospective cohort design. Patients were monitored regularly every 12 weeks; an magnetic resonance imaging (MRI) scan was performed at enrollment and every time a relapse occurred. Poisson analysis was used to determine exacerbation rate ratios (RR) and the MRI parameters were tested using chi-square analysis. Results: 347 patients with an average age of 38 and a female ratio of 86% were included. A RR of 2.24 (p < 0.001) was observed for exacerbations during the at-risk period (ARP). Attacks related to COVID-19 (RR = 2.13, p = 0.001) and NC-URIs (RR = 2.39, p < 0.001) were comparable regarding the increased risk of exacerbation (p = 0.62). Exacerbations within or outside the ARP did not significantly alter the number of baseline GAD-enhancing lesions (p > 0.05 for both). Conclusion: COVID-19 has been shown to increase the risk of MS exacerbations, like other viral URIs.

Higher Dietary Acid Load Might Be a Potent Derivative Factor for Multiple Sclerosis: The Results from a Case-Control Study.

This study aimed to investigate the association between dietary acid load (DAL) and multiple sclerosis (MS), through the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. In a hospital-based case-control study of 109 patients with MS and 130 healthy individuals, a validated 168-item semi-quantitative food frequency questionnaire and a logistic regression model were used to evaluate the association between the DAL and MS. After adjusting for age (years), gender (male/female), body mass index (Kg/m2), and total calories (Kcal), the MS odds were 92% lower for those in the highest tertile of total plant-based protein (OR: 0.08, 95%CI: 0.03, 0.23; p-value < 0.001) and about four times higher for those in the highest tertile of the PRAL (OR: 4.16, 95%CI: 1.94, 8.91; p-value < 0.001) and NEAP scores (OR: 3.57, 95%CI: 1.69, 7.53; p-value < 0.001), compared to those in the lowest tertile. After further adjusting for sodium, saturated fatty acid, and fiber intake, the results remained significant for total plant-based protein intake (OR: 0.07, 95%CI: 0.01, 0.38; p-value = 0.002). In conclusion, a higher NEAP or PRAL score may be associated with increased odds of MS, while a higher intake of plant-based protein instead of animal-based protein may be protective.

Radiological features of late-onset multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Late-onset multiple sclerosis (LOMS) is most commonly defined as the onset of the disease's presentations at age 50 or older. There is still much to discover about the radiological features of LOMS. The current study aims to assess the imaging features of LOMS, as well as the correlation between these findings and the clinical characteristics of these patients. METHOD: This study was conducted following the PRISMA statement. A systematic search was conducted through PubMed, Scopus, and EMBASE databases to identify the studies that have applied magnetic-resonance imaging (MRI) or other imaging methods to investigate the radiological findings, as well as the relationship between them and clinical findings of LOMS patients. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklists. Meta-analysis was conducted using the third version of the compressive meta-analysis software (CMA3). RESULTS: Our search identified 753 unique titles. Among them, 15 studies, including seven case-control, five case-series, and three cross-sectional studies, met the eligibility criteria. According to the quantitative synthesis, brain lesions were detected among 72.2% of LOMS patients (4 studies; 95% CI: 67.0% - 93.1%). In the context of spinal lesions, overall spinal cord involvement was 64.0% (8 studies; 95% CI: 42.5% - 81.1%). Based on the available evidence, supratentorial involvement was found in 82.7% of cases (3 studies; 95% CI: 17.4% - 99.1%), juxtacortical involvement in 34.1% (3 studies; 95% CI: 26.4% - 42.7%), infratentorial involvement in 51.3% (4 studies; 95% CI: 32.1% - 70.1%), and cerebellar involvement in 18.5% (3 studies; 95% CI: 13.9% - 24.1%). CONCLUSION: Based on the neuroimaging findings, we found that, given the heterogeneity of MS, LOMS patients have a high rate of spinal cord lesions and supratentorial involvement. The limited available evidence suggests that Barkhof criteria are the best compromise for the diagnosis of LOMS. There is still a need for future studies.

Psychometric properties of the Persian version of emotions and attitudes towards MRI" (MRI-EMA).

Background: Patients with multiple sclerosis (MS) should have magnetic resonance imaging evaluation regularly. They will experience anxiety before this examination. We conducted this study to evaluate the validity and reliability of emotions and attitudes towards MRI" (MRI-EMA). Methods: One hundred-nine patients with MS were asked to fill the valid and reliable Persian version of Beck Anxiety Inventory (BAI), and MRI-EMA, questionnaires. Two weeks later, twenty cases were asked to fill the questionnaire again to assess reliability. The intra-class correlation coefficient (ICC) and Cronbach's alpha analysis were used. The correlation coefficient between BAI and MRI-EMA was calculated. Five neurologists assessed content validity by content validity ratio (CVR) and content validity index (CVI). Results: The mean age was 37.2±1.2 years and 77% were females. CVI and CVR for all questions were 100%. The correlation coefficient between BAI and MRI-EMA was r=0.1, P=0.1 and only fear of MRI subscale was significantly correlated with BAI. The ICC of all questions was between 0.79 and 0.98. Conclusion: Patients with MS have to be routinely screened with MRI which provides anxiety for them. Considering MRI related anxiety is crucial for these cases. The Persian version of the MRI-EMA questionnaire is a valid and reliable instrument for measuring MRI related anxiety in patients with multiple sclerosis.

Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis.

Introduction: Depression, fatigue, and anxiety are three common clinical comorbidities of multiple sclerosis (MS). We investigated the role of physical activity (PA) level and body mass index (BMI) as modifiable lifestyle factors in these three comorbidities. Methods: A cross-sectional study was conducted in the MS specialist clinic of Sina Hospital, Tehran, Iran. Demographic and clinical data were collected. BMI was categorized in accordance with the WHO's standard classification. Physical activity (PA) level and sitting time per day were obtained using the short form of the International Physical Activity Questionnaire (IPAQ-SF). Fatigue, anxiety, and depression scores were measured using the Persian version of the Fatigue Severity Scale (FSS), Beck Anxiety Inventory (BAI), and Beck's Depression Inventory II (BDI-II) questionnaires, respectively. The correlation between the metabolic equivalent of tasks (MET), BMI, and daily sitting hours with depression, anxiety, and fatigue were checked using the linear regression test. The normal BMI group was considered a reference, and the difference in quantitative variables between the reference and the other groups was assessed using an independent sample t-test. Physical activity was classified with tertiles, and the difference in depression, anxiety, and fatigue between the PA groups was evaluated by a one-way ANOVA test. Results: In total, 85 MS patients were recruited for the study. The mean ± SD age of the participants was 39.07 ± 8.84 years, and 72.9% (n: 62) of them were female. The fatigue score was directly correlated with BMI (P: 0.03; r: 0.23) and sitting hours per day (P: 0.01; r: 0.26) and indirectly correlated with PA level (P < 0.01; r: -0.33). Higher depression scores were significantly correlated with elevated daily sitting hours (P: 0.01; r: 0.27). However, the correlation between depression with PA and BMI was not meaningful (p > 0.05). Higher anxiety scores were correlated with BMI (P: 0.01; r: 0.27) and lower PA (P: 0.01; r: -0.26). The correlation between anxiety and sitting hours per day was not significant (p > 0.05). Patients in the type I obesity group had significantly higher depression scores than the normal weight group (23.67 ± 2.30 vs. 14.05 ± 9.12; P: 0.001). Fatigue (32.61 ± 14.18 vs. 52.40 ± 12.42; P: <0.01) and anxiety (14.66 ± 9.68 vs. 27.80 ± 15.48; P: 0.01) scores were significantly greater among participants in the type II obesity group in comparison with the normal weight group. Fatigue (P: 0.01) and anxiety (P: 0.03) scores were significantly different in the three levels of PA, but no significant difference was found in the depression score (P: 0.17). Conclusion: Our data suggest that a physically active lifestyle and being in the normal weight category are possible factors that lead to lower depression, fatigue, and anxiety in patients with MS.

Efficacy and safety of "Jollab Monzej" as a traditional persian compound medicine for the treatment of multiple sclerosis-related fatigue: A randomized placebo-controlled trial.

Background: The purpose of this study was to investigate the efficacy and safety of Jollab monzej (JMZ), a Traditional Persian compound medicine, on multiple sclerosis-related fatigue (MSRF). Methods: We did a double-blind randomized controlled phase3 clinical trial on the JMZ syrup in fifty-six relapsing-remitting MS (RRMS) patients aged 18-55 years with moderate to severe fatigue using the Expanded Disability Status Scale (EDSS) score ≤ 6. We randomly assigned (1;1) participants to the JMZ syrup or placebo syrup groups treated for one month. Participants, investigators, and assessors were unaware of the assignments. The primary outcome was changes in the fatigue score on the Fatigue Severity Scale (FSS), at baseline and one month after treatment using the intention-to-treat (ITT) analysis. The secondary outcomes were changes in the score of Visual Analogue Scale (VAS), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). Outcomes were measured at baseline, one month after treatment, and 2-week follow-up. Safety was detected in all participants. Results: We randomly assigned 56 participants to the JMZ group (n=28) and placebo group (n=28). Fatigue scores significantly changed in both groups; however, the JMZ group had a greater reduction in FSS score in the ITT analysis. The adjusted mean difference was 8.80 (Confidence interval (CI) 95%, 2.90-14.70, P = 0.00). The mean difference of VAS, BDI, and global PSQI scores were statistically significant (P=0.01, P₌0.00, P₌0.01; respectively). Regarding safety, mild adverse events (AEs) were reported. Conclusion: The results of our study revealed that the administration of JMZ syrup alleviated MSRF and also could improve depression and sleep disorders.

Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients.

T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor ß (TGF-ß), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-ß and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

Effectiveness and safety of switching from fingolimod and natalizumab to rituximab in patients with relapsing remitting multiple sclerosis.

INTRODUCTION: Natalizumab and fingolimod are well-established, sequestrating disease-modifying treatments (DMTs), widely used as a second-line treatment in patients with relapse remitting multiple sclerosis (RRMS). However, there is no standard strategy for managing treatment failure on these agents. The present study aimed to evaluate the effectiveness of rituximab after natalizumab and fingolimod withdrawal. METHODS: A retrospective cohort was accomplished on RRMS patients treated with natalizumab and fingolimod who were switched to rituximab. RESULTS: 100 patients (50 cases in each group) were analyzed. After six months of follow-up, a substantial decline in clinical relapse and disability progression was observed in both groups. However, no significant change was demonstrated in the pattern of MRI activity (P = 1.000) in natalizumab pretreated patients. After adjusting for the baseline characteristics, a head-to-head comparison found a non-significant trend of lower EDSS in the pretreated fingolimod group compared to those previously treated with natalizumab(P = 0.057). However, in terms of clinical relapse and MRI activity, the clinical outcomes were comparable in both groups ((P = 0.194), (P = 0.957). Moreover, rituximab was well-tolerated, and no serious adverse events were reported. CONCLUSION: The present study revealed the effectiveness of rituximab as an appropriate alternative option for escalation therapy after fingolimod and natalizumab discontinuation.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case–control study / COVID-19 y sus implicaciones en el curso clínico-radiológico de la esclerosis múltiple: un estudio de casos y controles

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity.MethodsIn a case–control study, we recruited patients with relapsing–remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later.ResultsThree hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54–26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018).ConclusionCOVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up. (AU)

Antecedentes: La esclerosis múltiple (EM) es una enfermedad inmunomediada que se ha relacionado con varios factores de riesgo, como diversas infecciones virales. Realizamos este estudio para establecer una relación entre la infección por COVID-19 y la gravedad de la EM.MétodosEn un estudio de casos y controles, reclutamos pacientes con esclerosis múltiple remitente-recurrente (EMRR). Los pacientes se dividieron en dos grupos según la PCR positiva para COVID-19 al final de la fase de inscripción. Cada paciente fue seguido prospectivamente durante 12 meses. Los antecedentes demográficos, clínicos y médicos anteriores se recogieron durante la práctica clínica habitual. Las evaluaciones se realizaron cada 6 meses. La resonancia magnética se realizó en el momento de la inscripción y 12 meses después.ResultadosTrescientos sesenta y dos pacientes participaron en este estudio. Los pacientes con EM con infección por COVID-19 tuvieron aumentos significativamente más altos en el número de lesiones de resonancia magnética (p=0,019; OR=6,37 [IC 95%: 1,54-26,34]) y puntajes EDSS (p=0,017), pero no se encontraron diferencias en el total de recaídas anuales o en las tasas de recaída. Las infecciones por COVID-19 se correlacionaron positivamente con la progresión de EDSS (p=0,02) y la cantidad de nuevas lesiones en la resonancia magnética (p=0,004) y predijeron la probabilidad de la cantidad de nuevas lesiones en la resonancia magnética con una probabilidad de 5,92 (p=0,018).ConclusiónCOVID-19 puede conducir a puntajes de discapacidad más altos en la población de EMRR y está asociado con el desarrollo de nuevas lesiones realzadas con Gd en imágenes de resonancia magnética. Sin embargo, no se observó diferencia entre los grupos en cuanto al número de recaídas durante el seguimiento. (AU)

Effect of vitamin A on recovery from the acute phase of multiple sclerosis-related optic neuritis, double-blind, randomized, placebo-controlled trial.

Background: Optic neuritis (ON) is one of the main neuro-ophthalmic presentations of multiple sclerosis (MS), and it causes optic nerve atrophy and axonal loss. However, so far, there is no effective treatment to improve long-term outcomes. Methods: In a double-blind placebo-controlled randomized clinical trial, 50 patients with MS-related ON were allocated into two arms (24 in the control group and 26 in the intervention group) receiving either 25000IU retinyl palmitate or an identical placebo for six months. Visual evoked potential (VEP), visual acuity, and the retinal nerve fiber layer (RNFL) thickness were evaluated and compared before and after the treatment. Results: RNFL thickness reduction in the affected eyes at sixth month compared to the baseline were 14.81 and 19.46 µm, in the intervention and control groups, respectively (P=0.017). However, VitA therapy did not affect visual acuity and VEP. Conclusion: Vitamin A supplementation in the patients with acute ON in MS could lessen optic nerve axonal loss.

Effectiveness of acupuncture for fatigue in patients with relapsing-remitting multiple sclerosis: a randomized controlled trial.

BACKGROUND: Fatigue is experienced by more than 65% of individuals with multiple sclerosis (MS). Some studies have supported the effectiveness of acupuncture in improving the symptoms of MS. OBJECTIVE: The present research was intended to investigate the effectiveness of acupuncture plus amantadine compared with amantadine alone on fatigue in patients with relapsing-remitting MS (RRMS) in the remission stage of the disease. METHODS: In this randomized controlled trial, 60 participants with RRMS suffering from fatigue were recruited and randomized equally to acupuncture (n = 30) and control (n = 30) groups. The acupuncture group received treatment 2 to 3 times per week for 10 sessions over 4 weeks. Both the acupuncture and control groups received amantadine 100 mg daily and routine treatment with immuno-modulators. The primary outcome was the fatigue severity scale (FSS) score, which was evaluated at baseline, and after 2 and 4 weeks. The secondary outcome was the Multiple Sclerosis Quality of Life 54 (MSQOL-54) questionnaire score, measured at baseline and the end of the 4-week treatment period. RESULTS: The severity of fatigue was reduced in both groups. However, after 4 weeks of treatment, the reduction of fatigue in the acupuncture group was more significant than in the control group (P < 0.01, mean difference (MD) = -1.14, 95% confidence interval (CI): -1.83 to -0.45). Quality of life, including mental and physical status, was significantly improved in the acupuncture group compared with the control group (P < 0.05, MD = 9.09, 95% CI: 0.46 to 17.73). No adverse events occurred in any of the participants. CONCLUSIONS: Acupuncture combined with amantadine and routine care compared with amantadine and routine care alone appears to be an effective short-term treatment for reducing fatigue and enhancing quality of life, including physical function and mental status, in patients with RRMS.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

BACKGROUND: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). METHODS: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. RESULTS: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. DISCUSSION: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. CONCLUSION: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.

Characteristics and management of multiple sclerosis patients during the Omicron era: is there a concern about the MS course in the face of the new variant of COVID-19?

INTRODUCTION: The Omicron variant of COVID-19 is highly transmissible, triggering unprecedented infection rates. The present study aimed to investigate the course of multiple sclerosis (MS) in the Omicron era among Iranian patients with MS. METHODS: This observational study was designed on MS patients of the national MS registry of Iran through a self-designed online questionnaire. A questionnaire was prepared as a Google Form for MS patients during the Omicron outbreak from 1 March to 30 April 2022. RESULTS: One hundred seventy-four patients with a mean age of 37.3 ± 9.04 were enrolled. Of the patients, 95.97% used DMT, the most common of which were rituximab and fingolimod. Of the patients, 77.58% were fully vaccinated for COVID-19. Regardless of the COVID-19 vaccination status, 76 patients developed COVID-19, which was mild to moderate. Except for recent corticosteroid therapy and secondary progressive MS (SPMS), other demographic and MS characteristics were not significantly associated with the severity of COVID-19. There was also a marginal association between the Expanded Disability Status Scale (EDSS) and the severity of COVID-19. In addition, 17.10% of patients reported MS relapse following COVID-19 leading to escalation therapy in eight patients. CONCLUSION: Our study demonstrated that in the Omicron era, most patients developed mild COVID-19. Although the predominant COVID-19 variant in this period was Omicron, we could not separate the pathogenic variants. The risk factors for COVID-19 during the Omicron era were not different from other pandemic waves. Our preliminary results revealed that the MS relapse following COVID-19 was higher than in previous waves.