Multiple Sclerosis Exacerbations Research Articles

Application of Glucocorticoids in Therapy of Multiple Sclerosis

Multiple sclerosis is an autoimmune disease affecting the central nervous system that causes significant disability and healthcare burden. Pulse-dosaged glucocorticoids therapy remains the mainstay of treatment of exacerbations of multiple sclerosis. A total of 98 patients were examined, including 28 patients with relapsing-remitting multiple sclerosis (24 women and 4 men) and 70 patients with secondary progressive multiple sclerosis (57 women and 13 men). The number of glucocorticoids therapy courses in 98 patients at all disease stages totalled 536: 98 in relapsing-remitting multiple sclerosis (9 at debuts and 89 at relapsing-remitting stage) and 438 in secondary progredient multiple sclerosis (11 at debuts, 178 at relapsing-remitting stage, and 249 at secondary progression stage). The efficacy of repeated courses of glucocorticoids therapy in patients with RR and secondary progredient multiple sclerosis was evaluated at different stages of the disease progression: debut in relapsing-remitting and secondary progredient multiple sclerosis, relapsing-remitting stage in relapsing-remitting and secondary progredient multiple sclerosis, and secondary progression stage in secondary progredient multiple sclerosis, including retrospective analysis. Important conclusions have been made about complex systemic reorganisation at different stages of relapsing-remitting and secondary-progredient types of multiple sclerosis, efficiency of glucocorticoids therapy in different types of multiple sclerosis and stages of pathological process and about influence of glucocorticoids therapy on the prognosis of the disease.

The Experience of Living with Multiple Sclerosis during the COVID-19 Pandemic

Background: Many studies have shown that psychological distress such as worries and anxiety is one of the causes of the development, recurrence, or exacerbation of multiple sclerosis (MS). This study aimed to explore the lived experiences of patients with MS during the COVID-19 pandemic. Methods: This qualitative study was conducted using an interpretive phenomenological approach. The participants were selected from patients with MS in Tehran, Iran who were members of the Iranian MS Society in 2021. The research sample included 19 patients with MS who were selected using purposive sampling. The data were collected using semi-structured interviews until the data were saturated. The collected data were analyzed using Van Manen’s phenomenological approach, and the validity and truthfulness of the data were confirmed using the four criteria proposed by Lincoln and Guba. Results: Explication of the data revealed 22 subthemes and 5 main themes. The main themes identified were: Feeling of helplessness and fear of inadequacy in self-care, Economic concerns and financial problems, Ineffective interaction with family members, preoccupations and obsessions with the pandemic, and ambivalent and conflicting beliefs about others. Conclusion: The experiences of those affected by the pandemic were linked to personal and familial concerns, health issues, feelings of inadequacy in self-care, and economic difficulties. Additionally, participants were preoccupied with the pandemic and the social problems they faced. Gaining an understanding of these experiences can offer valuable insights to medical professionals, families of patients, and relevant organizations regarding the lived experiences of individuals with MS.

Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis.

Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation. This French multicentric study collected retrospective and prospective data on patients with MS treated with ICIs after a cancer diagnosis. We identified 18 patients with a median age of 48 years. Three of them (17%), all aged 50 years or younger, with a relapsing-remitting course, showed clinical and/or radiologic signs of MS activity 3 to 6 months after ICI initiation. They had stopped disease-modifying treatment (DMT) several months earlier, at the time of cancer diagnosis. Only one had both clinical and MRI activity, with mild severity and complete recovery. Our study suggests that the overall risk of MS activity under ICI is low and could be mainly driven by DMT discontinuation, as in MS in general. Although larger studies are needed for better risk assessment in younger patients with more active disease, ICI should be considered when needed in patients with MS.

Risk of multiple sclerosis in patients with psoriasis receiving anti-IL-17 agents: A case-based review.

Biologics approved for psoriasis exhibit favorable safety profiles, and serious adverse events have rarely been reported. In this report, we present the case of a patient treated with ixekizumab, an anti-interleukin (IL)-17 agent, who 8 months later developed multiple sclerosis (MS). We also review the available literature regarding the use of anti-IL-17 agents in the context of psoriasis and pre-existing or new-onset demyelination. Eight case reports were evaluated as relevant and are presented in our report. In most of the cases secukinumab or ixekizumab administration adequately controlled both skin and pre-existing neurological clinical manifestations. However, there has been a report of MS exacerbation under secukinumab treatment and the occurrence of myelitis in a patient receiving ixekizumab. While the anti-IL-17-biologic-mediated induction of inflammatory events in the central nervous system has not been proven and a causal relationship is lacking, such a probability should be considered in extremely rare cases.

Levels of circulating cytokines in children with multiple sclerosis with different effectiveness of interferon therapy

Multiple sclerosis (MS) is a chronic, demyelinating disease that leads to disability. Understanding the etiology of MS contributes to the development of pathogenetic methods of treatment, and the search for informative biomarkers of the effectiveness of treatment will allow the patient to adjust therapy in time. The aim of this work was to determine informative cytokines and cytokine profiles to predict the effectiveness of IFN-β1a therapy in children with MS.Materials and methods. 66 children with MS aged 16 [14.2–17.5] years who are on INFß-1a therapy were examined: group 1 — patients with exacerbation of MS (with active foci of demyelination by MRI), n = 34; group 2 — patients in remission of MS (without active foci), n = 32. The content of cytokines in the blood serum of patients was assessed using the multiplex panel Human Th17 Magnetic Bead Panel.Results: There was a significant increase in cytokine concentrations in patients with exacerbation of MS compared with children in remission: IL5, IL6, IL9, IL12p70, IL17E/IL25, IL21, IL28A, GM-CSF, TNFß. Threshold values for IL9 (AUC = 0,785), IL6 (AUC = 0,750), TNFß (0,740), IL28A (AUC = 0,744) were obtained above which it is possible to predict an exacerbation of MS in patients: IL9 — 3.9 pg/ml (Sn — 70.6, Sp — 71.9), IL6 — 4.0 pg/ml (Sn — 70.6, Sp — 68.8), TNFß — 6.6 pg/ml (Sn — 70.6, Sp — 71.9), IL28A — 243.0 pg/ml (Sn — 70.6, Sp — 71.9). Cytokine profiles associated with T-lymphocytes and their functions were evaluated using z-score.Conclusions. For the first time, an increase in cytokine levels was demonstrated in children with active foci of demyelination compared to patients in remission of MS. An increase in proinflammatory cytokines and cytokine profiles associated with Th1 and Th17, as well as with Th2 and Th22 has been shown. The use of threshold values for IL9, IL6, TNFβ, IL28A will help predict the development of exacerbation in patients with MS.

Sergančiųjų išsėtine skleroze požiūris į Covid-19 vakcinaciją

Introduction. During the pandemic, vaccination against COVID-19 has become one of the most important ways to prevent severe infection. However, a lack of trust in vaccines among the population, including people with multiple sclerosis (MS) has been identified. In Lithuania, the specific reasons for vaccine hesitancy among people with MS have not been described. We conducted a survey to determine the attitude of people with MS towards vaccination against COVID-19 infection.
 Methods. An original anonymous questionnaire was created. The survey included the following aspects: patient demographics, MS exacerbation, COVID-19 vaccination status, and attitudes towards the vaccination process. The survey was conducted between November 2021 and February 2022. Data were analyzed using IBM SPSS Statistics 27.0 with Chi-square and Mann-Whitney U tests and p-value (statistically significant at <0.05) for each hypothesis.
 Results. Of the 80 MS patients, 82.5% (n=66) were vaccinated and only 17.5% (n=14) were not vaccinated. The most popular positive opinions about vaccination were: “COVID-19 vaccines have more benefits than harm” (71.6%) and “the desire to prevent severe symptoms/hospitalization caused by COVID-19 infection” (79.1%), while mostly agreed negative opinion was “fear of side effects of the vaccine” (84.6%). Intended uptake of COVID-19 vaccines was strongly associated with younger age (p=0.021), higher education level (p=0.008), and employment status (p=0.028). There was no further link between other demographic factors such as gender, residency, and even exacerbation of MS between January 1, 2020 and February 1, 2022 (p>0.05).
 Conclusion. Although there was some hesitancy about the COVID-19 vaccination, people with MS were more likely to take the COVID-19 vaccine due to their positive attitude towards the process.

Association between course of multiple sclerosis and polymorphisms of calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)

Objective. To evaluate the relationship between the frequency of exacerbations and the rate of progression of multiple sclerosis (MS) and polymorphisms of the calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).Material and methods. Ninety patients with relapsing-remitting MS took part in the study. All patients are Caucasians, were born and lived in the Altai region of the Russian Federation. Genotyping was performed by TaqMan probes.Results. A protective effect of the TT genotype VDR FokI (rs2228570) on the risk of increasing disability of more than 0.75 points per year according to the expanded disability scale was found (p = 0.034). The protective effect of the TT genotype of the TaqI polymorphism (rs731236) on exacerbations of MS more than once a year (p = 0.041) was also revealed. Associations of the MS course with other studied polymorphisms were not found.Conclusions. It can be assumed that the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms may influence the course of relapsing-remitting MS. The mechanisms of these influences may include the modulation of immune-inflammatory responses in the central nervous system, which are a key link in the MS pathogenesis.

Content of myeloid-derived suppressor cells in autoimmune diseases in children

Myeloid-derived suppressor cells (MDSCs) play an important role in regulation of immune response. An increase in their number in adult patients with autoimmune diseases has been reported. G-MDSCs, M-MDSCs, and MDSCs(M-G-) at different stages of autoimmune disease may both activate T cell proliferation, leading to disease progression, or inhibit it, thus promoting Treg differentiation. Arginase-1 (Arg- 1) is an enzyme in MDSCs that reduces the concentration of arginine required for T lymphocyte proliferation. Our aim was to evaluate the content of MDSCs populations and functional activity of MDSCs in children with autoimmune diseases. 75 children with inflammatory bowel diseases (IBD), 60 children with multiple sclerosis (MS), 69 children with psoriasis (PS), 62 healthy age-matched children were included into the study. The content of MDSCs ((CD3, CD19, CD56, HLA-DR)-, CD11b+ and CD33+), subpopulations of MDSCs (M-MDSCs, G-MDSCs expressing CD14 and CD15), assessment of Arg-1 activity were performed by flow cytometry techniques. The content of MDSCs in patients with IBD, MS and PS was significantly higher than in the comparison group and depended on the state of exacerbation/remission. In exacerbation and remission of IBD, MS and PS, a significant increase of MDSCs was revealed when compared with healthy children; the highest values were found in children in exacerbation of MS (Me-3.5 (2.5-5.6) % MNC against Me-1.6 (0.9-2.5) % MNC, p 0.001). In patients with MS, the content of G-MDSC, M-MDSC was significantly higher, and MDSC(M-G-) was lower than in healthy children. An increase in absolute amounts of G-MDSCs was shown in MS exacerbation compared to the disease remission state (p = 0.022). For patients with IBD, a significant increase in percentage of MDSCs and M-MDSCs (p = 0.014 and p = 0.045, respectively) was obtained in exacerbation of the disease relative to remission state. In patients with IBD, MS, and PS, a significant increase in Arg-1 activity in MDSCs was found, with a decreased number of MDSCs in patients in remission compared to exacerbation phase of the disease. In children with autoimmune diseases, an increase in the MDSC populations was found. The activity of arginase-1 in MDSCs is increased in remission, along with a decrease in their numbers.

Клиническое значение определения цитокинов у пациентов с рассеянным склерозом и взаимосвязь с герпетической инфекцией

There are persistent infections that contribute to the emergence and development of multiple sclerosis (MS) exacerbations; they are triggered by the Epstein–Barr, herpes type 6, herpes simplex types 1 and 2, varicella-zoster viruses. Cytokines are crucial to arresting the spread of a herpes infection in a body. If their production is out of balance, MS can progress faster. This study aimed at determining the level of cytokines in the blood serum of MS patients, assessing their clinical significance and how they affect reactivation of herpes infection. We examined 36 patients (12 male and 24 female) with confirmed MS (McDonald criteria) in remission. In 18 of them, we diagnosed reactivation of peripheral herpes virus. Serum levels of 15 cytokines (IL1ß, IL4, IL6, TNF-a, INF-γ, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, sCD40L) were determined with the help of xMAP multiplexing. Compared to the control group, MS patients had increased levels of IL10, IL33 (p < 0.001), with high IL33 identified most often (20 patients; 52.8%). During exacerbations, the average level of IL10 grew up (p < 0.01), as did that of IL31, the high levels of which were detected significantly more often (42.8 and 6.9%, respectively; p = 0.04). In addition, a prevailing scenario was the increased levels of IL33 and other cytokines (IL17A, IL17F, IL21, IL31) (57.1 and 6.9% of cases, respectively; p = 0.008). Reactivation of herpes translated into higher levels of IL1ß, IL23 and IL33 compared to cases without reactivation (p < 0.05 and p < 0.01, respectively). High levels of IL33 were significantly more frequently recorded in this group of patients (77.7 and 33.3%; p = 0.008). We discuss involvement of IL10, IL31, IL33 and other cytokines in the pathogenesis of herpes-associated MS.

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

Although upper respiratory infections (URIs) are linked to multiple sclerosis (MS) attacks, SARS-COV2 has not been compared to URIs for attack rates. 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). 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. 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). COVID-19 has been shown to increase the risk of MS exacerbations, like other viral URIs.

Mycobacterium avium subsp. paratuberculosis Antigens Elicit a Strong IgG4 Response in Patients with Multiple Sclerosis and Exacerbate Experimental Autoimmune Encephalomyelitis.

Neuroinflammation can be triggered by microbial products disrupting immune regulation. In this study, we investigated the levels of IgG1, IgG2, IgG3, and IgG4 subclasses against the heat shock protein (HSP)70533-545 peptide and lipopentapeptide (MAP_Lp5) derived from Mycobacterium avium subsp. paratuberculosis (MAP) in the blood samples of Japanese and Italian individuals with relapsing remitting multiple sclerosis (MS). Additionally, we examined the impact of this peptide on MOG-induced experimental autoimmune encephalomyelitis (EAE). A total of 130 Japanese and 130 Italian subjects were retrospectively analyzed using the indirect ELISA method. Furthermore, a group of C57BL/6J mice received immunization with the MAP_HSP70533-545 peptide two weeks prior to the active induction of MOG35-55 EAE. The results revealed a significantly robust antibody response against MAP_HSP70533-545 in serum of both Japanese and Italian MS patients compared to their respective control groups. Moreover, heightened levels of serum IgG4 antibodies specific to MAP antigens were correlated with the severity of the disease. Additionally, EAE mice that were immunized with MAP_HSP70533-545 peptide exhibited more severe disease symptoms and increased reactivity of MOG35-55-specific T-cell compared to untreated mice. These findings provide evidence suggesting a potential link between MAP and the development or exacerbation of MS, particularly in a subgroup of MS patients with elevated serum IgG4 levels.

SARS-CoV-2 pandemic as a model to assess the relationship between intercurrent viral infections and disease activity in Multiple Sclerosis: A propensity score matched case-control study.

An association between intercurrent viral respiratory infections and exacerbations of Multiple Sclerosis (MS) disease activity has been proposed by several studies. Considering the rapid spread of SARS-CoV2 worldwide and the systematic effort to immediately detect all incident cases with specific diagnostic tests, the pandemic can represent an interesting experimental model to assess the relationship between viral respiratory infections and MS disease activity. In this study, we have performed a propensity score matched case-control study with a prospective clinical/MRI follow-up, on a cohort of relapsing-remitting MS (RRMS) patients who tested positive for SARS-CoV2 in the period 2020-2022, with the aim to evaluate if the SARS-CoV2 infection influences the short-term risk of disease activity. Controls (RRMS patients not exposed to SARS-CoV-2, using 2019 as the reference period) were matched 1:1 with cases for age, EDSS, sex and disease-modifying treatment (DMT) (moderate efficacy vs high efficacy). Differences in relapses, MRI disease activity and confirmed disabilty worsening (CDW) between cases in the 6 months following the SARS-CoV-2 infection, and controls in a similar 6 months reference period in 2019 were compared. We identified 150 cases of SARS-CoV2 infection in the period March 2020 - March 2022, out of a total population of approximately 1500 MS patients, matched with 150 MS patients not exposed to SARS-CoV2 (controls). Mean age was 40.9±12.0 years in cases and 42.0±10.9 years in controls, mean EDSS was 2.54±1.36 in cases and 2.60±1.32 in controls. All patients were treated with a DMT, and a considerable proportion with a high efficacy DMT (65.3% in cases and 66% in controls), reflecting a typical real world RRMS population. 52.8% of patients in this cohort had been vaccinated with a mRNA Covid-19 vaccine. We did not observe a significant difference in relapses (4.0% cases, 5.3% controls; p=0.774), MRI disease activity (9.3% cases, 8.0% controls; p=0.838), CDW (5.3% cases, 6.7% controls; p=0.782) in the 6 months after SARS-CoV-2 infection between cases and controls. Using a propensity score matching design and including both clinical and MRI data, this study does not suggest an increased risk of MS disease activity following SARS-CoV-2 infection. All MS patients in this cohort were treated with a DMT, and a considerable number with a high efficacy DMT. These results therefore may not be applicable to untreated patients, for which the risk of increased MS disease activity after SARS-CoV-2 infection may not be excluded. A possible hypothesis explaining these results could be that SARS-CoV2 is less prone, compared to other viruses, to induce exacerbations of MS disease activity; another possible interpretation of these data might be that DMT is able to effectively suppress the increase of disease activity triggered by SARS-CoV2 infection.

Effect of Metabolic and Bariatric Surgery on the Clinical Course of Multiple Sclerosis in Patients with Severe Obesity: a Systematic Review.

Multiple sclerosis (MS) is an autoimmune inflammatory condition affecting the central nervous system (CNS). A systematic review following the PRISMA guidelines was performed to explore the effect of metabolic and bariatric surgery (MBS) on the clinical course and outcomes in patients with multiple sclerosis. Eleven articles examining 394 patients were included in the final analysis. The mean MS duration at the time of surgery was 7.6 ± 4.6 years, and the mean postoperative follow-up was 35.5 ± 5.3 months. MBS leads to the same weight loss with the same complication rate as in patients without MS. Most of patients experienced improvement in clinical course of MS after MBS, compared to non-surgical group. However, there is a risk for MS exacerbation in a number of patients after MBS; they should not be disadvantaged from having MBS, since surgery leads to the same weight loss outcomes with the same complication rate as in patients without MS.

Pregnancy and visual pathology associated with an examination of multiple sclerosis

Introduction. The problem of pregnancy management in women with extragenital pathology is multidisciplinary and requires the participation of various specialists. It is known that pregnancy does not adversely affect the course of multiple sclerosis, and the incidence of pregnancy and delivery complications in multiple sclerosis does not exceed the general population. Nevertheless, multiple sclerosis exacerbations with different clinical presentation are possible during pregnancy, which may require correction of tactical and therapeutic measures. The purpose of the work was to demonstrate the role of a multidisciplinary team for favorable maternal and perinatal outcomes in visual pathology associated with worsening multiple sclerosis in pregnancy through a clinical example. Materials and methods. We retrospectively reviewed the patient's medical records: individual pregnancy and maternity records, labor and delivery history, and medical records of patients receiving care in outpatient settings. Results. A patient with multiple sclerosis had an exacerbation of the disease in the form of optic neuritis on the right side with temporary loss of vision in the first trimester of pregnancy. This required multiple consultations with an ophthalmologist and surgical treatment in the ophthalmology department of the hospital, followed by delivery by cesarean section. Discussion. Multiple sclerosis and its exacerbation in the form of optic neuritis did not affect the development of pregnancy, its favorable outcome was registered, which corresponds to the data of other researchers. Conclusions. A favorable outcome of pregnancy and delivery in a patient with multiple sclerosis and ophthalmopathology associated with its exacerbation during pregnancy was possible due to coordinated teamwork of specialists in various fields and timely correction of complications using a comprehensive approach and modern surgical techniques.

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis

Background Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). Objective To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. Methods Systematic review and meta-analysis of pharmacovigilance registries and observational studies. Results Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40–46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9–89.8), 12.6% (95% CI: 6.3–20.8), 6.7% (95% CI: 4.2–9.9), and 2.9% (95% CI: 1–5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12–28.2) from vaccination was 1.9% (95% CI: 1.3%–2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%–8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%–58.8%) and 0.1% (95% CI: 0%–0.2%) of vaccinations, respectively. Conclusion COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Safety Comparison of Conventional Versus Extended Infusion of Pulse Methylprednisolone in Multiple Sclerosis Exacerbation

Safety Comparison of Conventional Versus Extended Infusion of Pulse Methylprednisolone in Multiple Sclerosis Exacerbation

RADT-42. EFFECTS OF RADIOTHERAPY FOR CNS NEOPLASMS IN PEOPLE WITH MULTIPLE SCLEROSIS

Abstract INTRODUCTION Patients with multiple sclerosis (MS) may be at higher risk of brain tumors (Khalil 2012, London 2020, etc.). However, MS patients have been reported to have adverse effects from radiotherapy, a mainstay of CNS treatment. In the last ten years, radiation techniques have improved. We submit a case report of an MS patient with demyelinating CNS lesions shortly after radiation therapy for an astrocytoma and review the literature. Case description: A 40-year-old woman with a history of MS treated with Siponimod underwent resection of a right frontotemporal grade 2 astrocytoma, IDH mutant. She received adjuvant proton radiotherapy (54 Gy(RBE) over 30 fractions) followed by temozolomide chemotherapy. She tolerated radiotherapy well and only experienced grade 1 dermatitis, fatigue, and hair loss within the field of treatment. 1-month post radiation MRI was stable. 4 months post radiation there was an asymptomatic new typical demyelinating lesion on FLAIR without T1 or contrast changes. This was outside the high dose radiation field (i.e. received ~30 Gy(RBE)). Her Siponimod had been held for concerns of interactions with radiation or chemotherapy. DISCUSSION Cases have been reported of people with MS experiencing adverse effects from radiotherapy. Murphy, et al., reported a 30-year-old woman with MS experiencing an attack of demyelination 2 months after radiotherapy (50 Gy over 25 fractions), and Borges, et al. presents a 28-year-old patient who experienced radiotherapy-induced inflammatory demyelination after receiving whole-ventricular irradiation (24 Gy over 15 fractions). Miller, et al., reported 6 patients without exacerbations of MS but had developed grade 4 neurotoxicity in a median of 1 year; most of those patients were treated with older radiation techniques, however. Radiotherapy effects in people with MS is a topic that should be revisited in the era of more conformal RT techniques, effective MS therapies, and cancer treatment including immunotherapy.

Epstein–Barr virus antibody in newly diagnosed multiple sclerosis patients and its association with relapse severity and lesion location

BackgroundEpstein–Barr virus is considered a risk factor for the development of multiple sclerosis, and recent findings reveal infected plasma -cells in meningeal ectopic lymphoid deposits. Activation of the dormant virus could be responsible for the multiple sclerosis exacerbation AimsTo compare Epstein–Barr nuclear IgG (EBNA IgG) titer in newly diagnosed treatment-naive multiple sclerosis patients regarding the diagnoses date, clinical and radiological activity. MethodsTreatment-naive multiple sclerosis patients were divided into two groups according to Poser (late group) and McDonald2017(early group) diagnostic criteria. EBNA IgG, EDSS, physical (Timed 25 Foot Walk test, Nine-hole Peg test), and cognitive tests (Brief International Cognitive Assessment for Multiple Sclerosis) were done before the methylprednisolone infusion. The lesion location was evaluated by an MRI. Myelitis was considered a severe attack, and optic neuritis a mild relapse. ResultsIn total, 69 patients were enrolled. 44 (63.8%) of them were diagnosed by McDonald2017, and 25 (36.2%) were diagnosed with Poser criteria. There was a significant difference (p = 0.049) between the EBNA IgG titer of the late (median:238 U/ml, IQR: 154–362) and early (median: 154 U/ml, IQR:100.25–293.25). Severe relapse, having a spinal cord lesion, and not being treated with methylprednisolone was associated with higher EBNA IgG titer. ConclusionStudy results show that EBNA IgG was significantly associated with disease activity regarding relapse severity and lesion location and could be a potential biomarker for predicting disease exacerbation.

Presentations and Treatment of Multiple Sclerosis in Pakistan: A Retrospective Review of 188 Cases.

Approximately 10 out of every 100,000 people in Pakistan have multiple sclerosis (MS), yet there is a dearth of research on MS in the country, with most prior studies limited by small sample sizes. We wish to report on the largest study of MS patients from Pakistan. The objectives of this study were to identify demographic characteristics, disease characteristics, hospitalization causes, and past and current treatments of patients with MS in Pakistan. A retrospective review of patient records of all patients diagnosed with MS was carried out at the Department of Medicine at the Aga Khan University Hospital in Karachi and the Pakistan Institute of Medical Sciences in Islamabad. Medical records were used to generate a list of patients who were admitted at participating centers with a diagnosis of MS between December 2019 and September 2020. The diagnosis of MS was based on McDonald criteria. The study was approved by the ethics review committees of both participating centers.The study included 188 patients (mean age, 31.1 ± 11.22 years), with 37.2% men and 62.8% women. Relapsing-remitting MS was the most common type (81%), followed by primary progressive (10%) and secondary progressive (9%). The most common finding on T2-weighted fluid-attenuated inversion recovery MRI sequences was the presence of multiple foci (69.2%), most seen in the periventricular region (52.1%), followed by the juxtacortical region (49.3%). A single focus of gadolinium enhancement was observed in 20% of patients, most seen in the spinal cord (23.9%), followed by the periventricular area (18.1%).Medication infusion was the most common reason for hospitalization, reported in 16% of cases, followed by exacerbation of MS in 13.8% cases, and infection in 4.3% cases. Ocrelizumab (5.3%), steroids (3.8%), and rituximab (3.2%) were the most common treatments prescribed. Patients had been treated previously with oral and intravenous steroids, azathioprine, and mitoxantrone, as shown in TABLE 1.A detailed study of MRI lesions found multiple foci to be the most prevalent (69.2%), with periventricular and juxtacortical lesions the most common sites (52.1% and 49.3%, respectively). Incidental MS was reported in less than 1% of MRI scans.1 Disease characteristics and MRI findings in our group of MS patients were consistent with publications from other parts of the world.2 We explored reasons for hospitalization, the most common of which were MS exacerbation and medication infusions. Most patients (83%) were not taking any medications at their most recent evaluation. A prior study stated that 95% of patients received pulse steroids.3,4 Other treatments mentioned in literature include interferon beta, methotrexate, mitoxantrone,4,5 ocrelizumab, teriflunomide, alemtuzumab, and, per informal reports from neurologists, rituximab and azathioprine.3 Wasay et al found that less than one-fourth of all patients received disease-modifying therapies, of which 11% received methotrexate, 10% received mitoxantrone, and 1% received interferon beta therapy.4 However, recent years have seen a rise in the use of disease-modifying therapies due to an aggressive disease course or secondary progressive MS.6

Safety of pathogenetic therapy for multiple sclerosis during the COVID-19 pandemic

The safety of pathogenetic therapy for multiple sclerosis (MS) is a crucial aspect of the therapeutic strategy during the COVID-19 pandemic.&#x0D; Based on our own data, obtained during the study of MS pathogenesis and safety analysis of MS disease-modifying therapies (DMTs), we hereby suggest a classification of DMTs side effects, based on their type, development, and direction of action. There is a need to thoroughly analyse adverse events caused by pathogenetic therapy, with a balanced assessment of the direct vs. adverse effects of immunosuppressive drugs.&#x0D; Based on available literature, in the article, data on the effect of DMTs with various mechanisms of action on severe coronavirus infection are systematized.&#x0D; Interferon- and glatiramer acetate are the safest drugs to use during the COVID-19 pandemic. Teriflunomide, dimethyl fumarate, natalizumab, ocrelizumab, fingolimod, alemtuzumab, and cladribine should be used with caution. Drugs with a minor systemic immunosuppressant effect (e.g. natalizumab) and selective immunosuppressants (e.g. ocrelizumab) are safer than drugs that cause non-selective depletion of T and B cells.&#x0D; It must be stressed that the risk of MS exacerbation and progression due to untimely prescription or cessation of pathogenetic therapy can significantly exceed the potential risk of COVID-19.&#x0D; Long-term safety monitoring is required for DMTs during the COVID-19 pandemic and when the epidemiological situation stabilizes.