Clinical implications for the association of psoriasis and multiple sclerosis: an observational study.

BACKGROUND: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions. METHODS: 316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI). RESULTS: Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms. DISCUSSION AND CONCLUSION: The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions.

Identifying definite patterns of unmet needs in patients with multiple sclerosis using unsupervised machine learning.

INTRODUCTION: People with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants. METHODS: We conducted a cross-sectional multicentre study. Data were collected through an anonymous, self-administered online form. To cluster PwMS according to their main unmet needs, we performed agglomerative hierarchical clustering algorithm. Principal component analysis (PCA) was applied to visualize cluster distribution. Pairwise comparisons were used to evaluate demographics and clinical distribution among clusters. RESULTS: Out of 1764 mailed questionnaires, we received 690 responses. Access to primary care was the main contributor to the overall unmet need burden. Four patterns were identified: cluster C1, 'information-seekers with few unmet needs'; cluster C2, 'high unmet needs'; cluster C3, 'socially and assistance-dependent'; cluster C4, 'self-sufficient with few unmet needs'. PCA identified two main components in determining the patterns: the 'public sphere' (access to information and care) and the 'private sphere' (need for assistance and social life). Older age, lower education, longer disease duration and higher disability characterized clusters with more unmet needs in the private sphere. However, demographic and clinical factors failed in explaining the four identified patterns. CONCLUSION: Our study identified four unmet need patterns among PwMS, emphasizing the importance of personalized care. While clinical and demographic factors provide some insight, additional variables warrant further investigation to fully understand unmet needs in PwMS.

The role of sex hormones in women with multiple sclerosis: From puberty to assisted reproductive techniques.

BACKGROUND: Multiple Sclerosis is a multifactorial chronic autoimmune disease, affecting predominantly females in the fertile age. Sex hormones changes during a woman's life, from puberty to menopause, including pregnancy and puerperium, may influence the onset and course of Multiple Sclerosis. The effect of estrogen levels on immune, clinical and radiological aspects of Multiple Sclerosis, also stimulated investigation on the effect of sexual hormones therapies, such as oral contraceptives and assisted reproductive technique, on the Multiple Sclerosis course. SEARCH STRATEGY AND SELECTION CRITERIA: A literature search for original articles and reviews was conducted in the databases, including PubMed, Scopus, and ClinicalTrials.gov of the U.S. National Library of Medicine site from 1988 to 2020. RESULTS AND CONCLUSION: This review reports the effects of the physiological and iatrogenic hormonal changes either on immune or clinical or paraclinical features in the different life stages of women affected by Multiple Sclerosis.

Association between relapses, stress, and depression in people with multiple sclerosis during the COVID-19 pandemic.

BACKGROUND: Stress is a potential trigger for clinical and radiological activity in Multiple Sclerosis (MS). COVID-19 pandemic has been a relevant source of mental distress in people with MS (pwMS) and deeply impacted on disease management. OBJECTIVE: To investigate the association between stress, anxiety, depression, and risk of relapse during the COVID-19 pandemic. METHODS: From an electronic database used for clinical practice, we extracted data of relapsing-remitting (RR) or relapsing-progressive (RP) MS patients and calculated the annualized relapse rate (ARR) during 2019 and 2020. From 01/12/2020 to 30/12/2020, enrolled patients were invited to fill in a Google Forms survey to investigate depression, anxiety, stress, and Post-Traumatic Stress Disorder (PTSD). RESULTS: We selected 216 patients with RR or RP-MS to calculate ARR: compared to 2019, in 2020 there was a significant increase in ARR (p = 0.0142). Over 216 selected pwMS, 154 completed the survey. Matching the survey responses and incidence of relapses in 2020, there was a significant association between relapses and stress (p = 0.030) and relapses and depression (p = 0.011), but not between relapses and anxiety (p = 0.130) or PTSD (p = 0.279). CONCLUSIONS: Our results support the hypothesis that pandemic-related stress is associated to clinical exacerbations, both as a possible consequence of the COVID-19 impact on MS care.

Pain, quality of life, and religiosity in people with multiple sclerosis.

PURPOSE: To investigate in multiple sclerosis (MS) patients, the relationship between pain and religiosity and to determine whether distinct dimensions of religiosity were associated with quality of life. METHODS: MS patients during clinical follow-up filled out the visual analogue scale for pain (VAS), the Mc Gill questionnaire (McGQ), the 36-Item Short Form Health Survey (SF-36), and the religious attitude scale (RAS), and expanded disability status scale (EDSS) was assessed. RESULTS: Ninety-two MS patients were enrolled, only two declined. There was a negative correlation between religious practice and faith and some domains of the SF-36 and a positive correlation between sensory, affective, and evaluative aspects of pain (at McGQ) and religious practices, and between evaluative aspects of pain (at McGQ) and faith. EDSS was significantly higher in practitioner believers compared to not practitioners. CONCLUSIONS: More disabled MS patients, with worse quality of life, also due to physical pain, find a source of comfort in faith and religious practices. Pain is not relieved by prayer; therefore, we may guess that in MS the poor beneficial effect of religiosity and practice on pain perception may be linked to a structural/functional damage of neural circuits involved in reducing pain during prayer.

Multiple sclerosis and genetic polymorphisms in fibrinogen-mediated hemostatic pathways: a case-control study.

INTRODUCTION: Blood coagulation constituents might exert immunomodulatory functions in the CNS and may trigger neuroinflammation and demyelination. We evaluated whether particular single-nucleotide polymorphisms (SNPs), thought to be involved in fibrinogen-mediated hemostatic pathways, are overrepresented in patients with MS compared with controls. METHODS: The case-control study consisted of 119 MS patients recruited consecutively at our clinic, and 68 healthy controls. Afterwards, we created a cumulative genetic risk score (CGRS) which included the 5 selected hemostatic risk alleles (Beta-Fibrinogen 455G/A, Glycoprotein IIIa P1A2, Factor V Leiden, Factor V H2R, and Prothrombin 20210G/A). Multivariate ordinal logistic regression and multivariate multinomial logistic regression were applied to evaluate the effect of CGRS on MS susceptibility. RESULTS: The FGB 455 G/A and Factor V H1299R variants might be associated with MS status, in the recessive and dominant model, respectively. A cumulative association of the five SNPs investigated with the disease was observed. DISCUSSION: We found that MS patients carried more pro-hemostatic variants than healthy controls. An increasing number of unfavorable alleles might increase the likelihood of being in the MS group, in the cumulative analysis. Our findings encourage to evaluating these variants in a larger population-based cohort.

Telemedicine application to headache: a critical review.

BACKGROUND: Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic. OBJECTIVE: This review aims to propose a practical approach for the virtual management of these patients. METHODS: To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review. RESULTS: The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientific reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches finds an application in specific communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps. CONCLUSION: Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

Perceived stress and social support in a large population of people with multiple sclerosis recruited online through the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The COVID-19 emergency may cause post-traumatic stress disorder (PTSD), and with regard to people with MS (pwMS) chronic exposure to a wide range of challenging life events has been shown to be correlated with worsening of neurological symptoms, increased lesion burden on brain magnetic resonance imaging and relapses. The aim was to investigate perceived stress, depression, perceived social support, habits and behaviour changes in pwMS through COVID-19 in comparison to a control group. METHODS: A web-based survey was posted on SMsocialnetwork.com to investigate perceived stress (using the Perceived Stress Scale), depression (with Patient Health Questionnaire 2) and perceived social support (using Social Provision Scale 10 item) in pwMS and a control group through the COVID-19 pandemic. A secondary group of people with migraine was investigated. RESULTS: In all, 1286 answers from 612 pwMS and 674 control people were included in the final analysis. The answers from 318 people with migraine were included for a secondary analysis. A higher proportion of pwMS were depressed (43.1% vs. 23.1%; p < 0.001), had a high level of perceived stress (58% vs. 39.8%; p < 0.001) and felt significantly less social support (median 33 vs. 35; Q1-Q3 28-36 vs. 32-37; p < 0.001) compared to the control group. A higher percentage of people with migraine were depressed (50% vs. 43%, p = 0.04) compared to pwMS. CONCLUSIONS: Considering the negative impact that prolonged stress may have on clinical and radiological disease activity of pwMS, and bearing in mind that a beneficial effect has been demonstrated and achieved with stress management, it is suggested to promote stress control in these patients during the COVID-19 pandemic.

Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis.

INTRODUCTION: Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population. MATERIALS AND METHODS: This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the 'Italian MS Register'. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment. RESULTS: Out of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups. DISCUSSION: The use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.

The role of diet in multiple sclerosis: A review.

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.

Dilated perivascular spaces and fatigue: is there a link? Magnetic resonance retrospective 3Tesla study.

INTRODUCTION: Fatigue (F) is a common, inexplicable, and disabling symptom in multiple sclerosis (MS) patients. The purpose of this study was to evaluate a possible correlation between fatigue and morpho-volumetric features and site of dilated perivascular spaces (dPS), visible on 3T magnetic resonance (MR) in fatigued multiple sclerosis patients (FMS). METHODS: We studied 82 relapsing remitting (RR) FMS patients and 43 HC, matched for age, sex, and education. F was assessed by the Fatigue Severity Scale (FSS). To evaluate a possible correlation between degree of F and characteristics of dPS, patients were divided in two groups: more (mFMS) (FSS ≥ 5; n = 30) and less fatigued (lFMS) (FSS ≥ 4; n = 52), compared to a matched healthy control (HC) subject group. The MR study was performed with 3T scanner by SpinEcho T1, Fast-SpinEcho DP-T2, FLAIR, and 3D FSPGR T1 sequences. dPS volumes were measured with Medical Image Processing Analysis and Visualization (MIPAV); Global Cerebral Atrophy (GCA), expressed as Brain Parenchymal Fraction (BPF), was assessed by FSL SIENAX. RESULTS: The t test showed significantly increased dPS number (p = 0.021) in FMS patients (mFMS p = 0.0024 and lFMS p = 0.033) compared to HC. Pearson correlation revealed a significant correlation between dPS number and FSS (r = 0.208 p = 0.051). Furthermore, the chi-squared test confirms the intragroup (HC, mFMS, lFMS) differences about dPS location (p = 0.01) and size (p = 0.0001). CONCLUSION: Our study confirms that PS in MS patients presents with different volumetric and site characteristics as compared to HC; moreover, F severity significantly correlates with dPS number, site, and size.

Vitamin D Supplementation: Effect on Cytokine Profile in Multiple Sclerosis.

Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-ß1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-ß1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation.

Validation of the swallowing disturbance questionnaire in people with multiple sclerosis.

BACKGROUND: The DYSPHAGIA IN MULTIPLE SCLEROSIS (DYMUS) questionnaire is the only specific tool developed to screen for dysphagia in people with Multiple Sclerosis (pwMS). However, some limitations of DYMUS could potentially be addressed by the SWALLOWING DISTURBANCE QUESTIONNAIRE (SDQ), which has not yet been validated in pwMS. The objective of this study was to translate and validate the SDQ into the Italian language for use in pwMS to detect swallowing disturbances. METHODS: We translated the SDQ into Italian and adapted it for use in Italian pwMS. PwMS aged > 18 years, assessed for disability using the Expanded Disability Status Scale (EDSS), completed the SDQ and DYMUS questionnaires and performed the 3-OUNCE WATER SWALLOW TEST (WST). Clinical and demographic data were collected for each patient. The Italian version of the SDQ was retested after 30 days. RESULTS: A total of 84 pwMS were recruited for the study, consisting of 73.8 % women and 48.8 % with a relapsing-remitting form of MS. The mean age of participants was 44.5 years (SD: ±12.46), with a mean disease duration of 17 years (SD: ±10.27), and a median EDSS of 4 (range 1.5-7.5). The Cronbach's alpha for SDQ (to assess internal consistency) was 0.902, which increased to 0.908 after the elimination of item 15, resulting in the SDQ composed of 14 items. ROC analysis demonstrated good accuracy of the 14-item SDQ in pwMS (AUC: 0.811). By dividing the 14-item SDQ score into quartiles, three risk levels for dysphagia were identified: low (score 1-3), intermediate (score 4-8), and high (score ≥9). 14-item SDQ scores significantly correlated with DYMUS (r = 0.820; p<0.0001) and with EDSS (r = 0.541; p<0.0001). PwMS who reported dysphagia had a significantly higher mean 14-item SDQ score (8.27 ± SD 8.15) compared to those without swallowing problems (2.77 ± SD 4.25; p = 0.003). Additionally, pwMS with a positive WST had a significantly higher mean 14-item SDQ score (10.17 ± SD 8.96) than those with a negative WST (2.96 ± SD 3.93; p = 0.02). The Intraclass Correlation Coefficient for the retest, calculated on 48 pwMS in a stable phase of the disease, was 0.91 (95 % CI 0.84-0.95). CONCLUSION: The 14-item SDQ has demonstrated high internal consistency, good accuracy, and reliability in pwMS, making it a readily applicable tool for investigating dysphagia in MS.

Dermatological Neoplastic Diseases Complicating Treatment with Monoclonal Antibodies for Multiple Sclerosis.

Background: Over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed, and an ever-increasing number of disease-modifying treatments has emerged. Among high-efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in a MS patient's treatment due to their targeted mechanism, high efficacy, and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptor inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: The aim of this review is to investigate cases of cutaneous malignancy during mAb therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-ups in pwMS treated with mAbs. Methods: A literature search for original articles and reviews in PubMed was conducted with no date restrictions. Results: A total of 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2024 that met the objectives of this review were selected and reported. Conclusions: The available data do not show a clear link between monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is advisable before starting mAb treatment in pwMS, and subsequent follow-ups should be individualized according to each patient's risk profile.

ChatGPT vs. neurologists: a cross-sectional study investigating preference, satisfaction ratings and perceived empathy in responses among people living with multiple sclerosis.

BACKGROUND: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. METHODS: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1-5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. RESULTS: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = - 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). CONCLUSIONS: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.

Clinically Manifest Infections Do Not Increase the Relapse Risk in People with Multiple Sclerosis Treated with Disease-Modifying Therapies: A Prospective Study.

BACKGROUND: Many factors are believed to be positively associated with the incidence of relapses in people with multiple sclerosis (MS), including infections. However, their role is still controversial. We aimed to investigate whether symptomatic infections in people with MS increase the risk of relapse in the short, medium, or long term. MATERIALS AND METHODS: We enrolled consecutive patients with relapsing MS (RMS) from October to December 2018. From enrolment up to September 2020, an online questionnaire investigating the occurrence of infections was sent via WhatsApp® monthly to the enrolled patients, while in-person visits were performed every six months. When patients complained of symptoms compatible with relapses, they attended an extra in-person visit. RESULTS: We enrolled 155 patients with RMS, and 88.38% of patients were treated with disease-modifying therapies. In the dataset, 126,381 total patient days, 78 relapses, and 1202 infections were recorded over a period of about 2 years. No increased risk of relapse after clinically manifest infections was found in the short-, medium-, or long-term period. No correlation was found between all infections and the number of relapses (p = 0.212). The main analyses were repeated considering only those infections that had at least two of the following characteristics: duration of infection ≥ 4 days, body temperature > 37° Celsius, and the use of drugs (antibiotics and/or antivirals), and no significant associations were observed. CONCLUSIONS: No associations between infections and relapses were observed, likely suggesting that disease-modifying therapies may protect against the risk of relapse potentially triggered by infections.