Pregnancy characteristics in Egyptian female patients with NMOSD.

Background: Neuromyelitis optica spectrum disorder (NMOSD) primarily affects women of childbearing age. Objectives: Studying the potential relationship between NMOSD and pregnancy characteristics and outcomes. Subjects and methods: This is a retrospective cohort study that was conducted on 66 married female patients diagnosed with NMOSD. All patients underwent a thorough review of their demographic and clinical history through their medical records and personal interviews. Additionally, a complete neurological examination was performed, along with the expanded disability status scale (EDSS) and a pregnancy registry questionnaire. Results: After comparing married patients before and after disease onset, there was a significant increase in the number of abortions and the percentage of cesarean sections, as well as a decrease in the percentage of breastfeeding after disease onset. The p values were .02, <.001, and <.001, respectively, with odds ratios of 2.03, 5.13, and 6.17. Additionally, there was a rise in the occurrence of postpartum relapses, which accounted for 66% of all relapses after the disease onset. Most of these relapses (88.7%) occurred within the first 3 months postpartum. Conclusion: Presence of NMOSD increased the percentage of miscarriage, delivery by cesarean section, and decreased the chance of breastfeeding. In addition, pregnancy increases NMOSD relapse and subsequent disability.

Relapses in canine leishmaniosis: risk factors identified through mixed-effects logistic regression.

BACKGROUND: Canine leishmaniosis (CanL), caused by Leishmania infantum, is an important vector-borne parasitic disease in dogs with implications for human health. Despite advancements, managing CanL remains challenging due to its complexity, especially in chronic, relapsing cases. Mathematical modeling has emerged as a powerful tool in various medical fields, but its application in understanding CanL relapses remains unexplored. METHODS: This retrospective study aimed to investigate risk factors associated with disease relapse in a cohort of dogs naturally infected with L. infantum. Data from 291 repeated measures of 54 dogs meeting the inclusion criteria were included. Two logistic mixed-effects models were created to identify clinicopathological variables associated with an increased risk of clinical relapses requiring a leishmanicidal treatment in CanL. A backward elimination approach was employed, starting with a full model comprising all potential predictors. Variables were iteratively eliminated on the basis of their impact on the model, considering both statistical significance and model complexity. All analyses were conducted using R software, primarily employing the lme4 package, and applying a significance level of 5% (P < 0.05). RESULTS: This study identified clinicopathological variables associated with an increased risk of relapses requiring a leishmanicidal treatment. Model 1 revealed that for each 0.1 increase in the albumin/globulin ratio (A/G) ratio, the odds of requiring treatment decreased by 45%. Conversely, for each unit increase in the total clinical score (CS), the odds of requiring treatment increase by 22-30%. Indirect immunofluorescence antibody test (IFAT) was not a significant risk factor in model 1. Model 2, incorporating individual albumin and globulins values, showed that dogs with high IFAT titers, hyper beta-globulinemia, hypoalbuminemia, anemia, and high CS were at increased risk of relapse. Both models demonstrated a good fit and explained a substantial amount of variability in treatment decisions. CONCLUSIONS: Dogs exhibiting higher CS, dysproteinemia, anemia, and high IFAT titers are at increased risk of requiring leishmanicidal treatment upon clinical relapse in CanL. Regular monitoring and assessment of risk factors prove essential for early detection of relapses and effective intervention in CanL cases. The contrasting findings between the two models highlight the complexity of aspects influencing treatment decisions in this disease and the importance of tailored management strategies to improve outcomes for affected dogs.

Impact of sex on clinical outcome in early Multiple Sclerosis.

BACKGROUND: Previous evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS. METHODS: Utilizing prospective cohort data, we assessed the impact of biological sex on time-to-relapse, disability progression (Expanded Disability Status Scale [EDSS]), extremity function (Nine-Hole Peg Test, Timed-25-food walk test), cognition (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test), quality-of-life (Hamburg Quality of Life Questionnaire in Multiple Sclerosis, Short-Form-36), fatigue (Fatigue Severity Scale, Fatigue Scale for Motor and Cognitive functions), and depression (Beck Depression Inventory-II) in clinically isolated syndrome (CIS) or RRMS patients. Inclusion was within 12 months of symptom onset. Linear, negative binomial, mixed, and Cox models estimated male vs. female effects at the four-year follow-up including baseline-to-follow-up course. RESULTS: We included 149 patients (65.1 % female). Eighty-five completed four-year follow-up. No sex differences in time-to-relapse emerged (HR = 0.91;95 %CI = 0.53-1.58). Males had no increased risk of EDSS worsening (OR = 0.75;95 %CI = 0.21-2.35) compared to females. Similarly, minor/no sex differences emerged in other outcomes. CONCLUSIONS: Four years after first manifestation, neither disease activity (disability progression and relapse rate) nor patient-reported outcomes showed sex-related disparities in this early-MS-cohort. GOV IDENTIFIER: NCT01371071.

Treatment strategies and responses for attacks of neuromyelitis optica spectrum disorder: A real-world retrospective cohort study.

We aimed to assess the treatment strategies utilized in patients with neuromyelitis optica spectrum disorder (NMOSD) experiencing relapses, including their frequency, types, and response after 6 months based on the Expanded Disability Status Scale (EDSS) score. METHODS: We conducted a retrospective study involving NMOSD patients from the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). Treatment response at 6 months was categorized as "good" if the EDSS score decreased by ≥1 point after a nadir EDSS score ≤ 3, or by ≥2 points after a nadir EDSS score > 3, "poor" if the EDSS score decrease was slighter, and as "absent" if the EDSS score remained unchanged or worsened. RESULTS: We included 120 NMOSD patients (seropositive N = 75), who experienced 250 NMOSD-related relapses and received 248 treatments. At 6 months, complete recovery was achieved in 70/98 (71.4%) and 15/19 (79%) patients, respectively. Predictors of a "good" response in our regression model were a younger age at disease onset (OR:3.54, CI95% 2.45-5.01, p < 0.0001) and a short delay from onset of relapse to treatment initiation (OR:1.56, CI95% 1.22-2.13, p = 0.004). CONCLUSIONS: Approximately two-thirds of patients experienced complete recovery, and younger age and a short delay to start treatment were independent predictors of a "good" response.

Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer.

BACKGROUND: Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers. PURPOSE: Evaluation of the changes in the methylation level of LINE-1 elements and SEPTIN9 and IKZF1 genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up. METHODS: Blood samples were obtained from RC patients (n = 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10-15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1, SEPTIN9, and IKZF1 in the csb-cfDNA was evaluated by quantitative methyl-specific PCR. RESULTS: The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The SEPTIN9 gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The IKZF1 gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (n = 5) showed an increase in methylation level for the SEPTIN9 and IKZF1 genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10-15 days after surgery. There were no changes in the circulating SEPTIN9, IKZF1, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (n = 20) without relapses. CONCLUSION: The results indicate that SEPTIN9, IKZF1, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.

A Self-Reported Study on Explanatory Variables of Stress in Multiple Sclerosis Patients: Exploring the Effect of Physical Conditions and Emotion Regulation Processes.

BACKGROUND: Multiple sclerosis (MS)-linked stress is frequent, multidetermined and facilitates the onset/exacerbation of MS. However, few explanatory models of stress analysed the joint explanatory effect of emotion regulation and clinical outcomes of MS in those patients. OBJECTIVE: This study explored whether self-reported MS-related conditions (number of relapses, fatigue and global disability) and specific emotion regulation processes (experiential avoidance and self-compassion) explain stress symptoms in MS patients. METHODS: The MS sample comprised 101 patients with MS diagnosis receiving treatment in hospitals and recruited through the Portuguese MS Society. The no-MS sample included 134 age-, sex- and years of education-matched adults without MS recruited from the general Portuguese population. Both samples did not report other neurological disorders. Data were collected using self-response measures. RESULTS: All potential explanatory variables differed significantly between samples, with higher scores found in MS patients. In MS clinical sample, those variables and years of education correlated with stress symptoms and predicted stress symptoms in simple linear regression models. These results allowed their selection as covariates in a multiple linear regression model. Years of education, the number of relapses, fatigue and experiential avoidance significantly predicted 51% of stress symptoms' total variance. CONCLUSIONS: This study provides preliminary evidence on the importance of clinicians and researchers considering the simultaneous contribution of years of education, the number of perceived relapses, fatigue and experiential avoidance as factors that can increase vulnerability to stress in MS patients. Psychological intervention programmes that tackle these factors and associated stress symptomatology should be implemented.

Epidemiology and management of transient ischemic attack in Trieste district, how day hospital assessment improves outcomes: a five-year retrospective study.

BACKGROUND: Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction, without acute infarction or tissue injury lasting less than 24 h. Previous data suggest TIA precedes 15% of ischemic strokes, with a higher risk in the first week. Current practice guidelines advise evaluation through rapid neurological visit or admission to hospital. We provide data on TIA incidence in Trieste, and we compare three different types of assessment: day hospital (DH), stroke unit (SU), and emergency department/outpatients (ED). METHODS: This is a 5-year retrospective study of transient cerebrovascular events admitted in the University Hospital of Trieste (230.623 inhabitants), between 2016 and 2020. We calculated TIA prevalence in Trieste district's general population. Our primary endpoint is ischemic recurrences within 90 days, and we evaluate the possible association between different types of management. RESULTS: TIA incidence rate was 0.54/1000 inhabitants. In the multivariate analysis remained significantly associated with primary endpoint: ABCD2 (OR 1.625, CI 95% 1.114-2.369, p = 0.012) and DH evaluation (OR 0.260, CI 95% 0.082-0.819, p = 0.021). CONCLUSIONS: Incidence of TIA in Trieste district is in line with previous data. We demonstrate the crucial role of DH evaluation over the outpatient/ED in reducing overall mortality and recurrence rate. Prompt recognition of patients at high risk for cerebrovascular events and specialist follow-up may reduce the incidence of major vascular events and death.

Long-Term Low-Dose Pyrimethamine Use for the Prevention of Ocular Toxoplasmosis Recurrences: A Cohort Study.

PURPOSE: To describe the effect of long-term, low-dose pyrimethamine for the prevention of ocular toxoplasmosis (OT) recurrences. METHODS: Sixty-three consecutive patients with inactive ocular toxoplasmosis and positive toxoplasma IgG serology were included. Pyrimethamine (25 mg) + folinic acid (15 mg) were administered every other day (three times weekly) for 12 months. Eighteen patients received the treatment for an additional six months as part of an extension study. RESULTS: Thirty-eight patients (60.3%, n = 63) were female; 38 (60.3%) had a previous history of recurrence and 37 (58.7%) had active OT within the preceding 12 months. Three (4.8%) patients had unilateral recurrences at 8, 12 and 18 months after starting intermittent pyrimethamine treatment. Five patients (7.9%) were discontinued due to hematological, renal and hepatic changes. Treatment was considered successful in 42 patients (84%). CONCLUSION: Long-term, low-dose pyrimethamine can be considered as a treatment option for the prevention of ocular toxoplasmosis recurrence in selected patients, with only a few, mild and reversible systemic adverse events.

IPM Strategy to Control EFB in Apis mellifera: Oxytetracycline Treatment Combined with Partial Shook Swarm and Queen Caging.

We tested an integrated pest management (IPM) strategy to control European foulbrood (EFB) in honey bees. Colonies affected by EFB were assigned to two homogenous groups: an oxytetracycline-treated group (1.5 g OTC/hive) that underwent partial shook swarm (PSS) in combination with queen caging (QC) and an untreated group where only two beekeeping techniques, PSS and QC, were applied. The consumption of sucrose solution, the strength of the colonies, side effects of the mentioned techniques, clinical as well as subclinical relapses of EFB, and the amount of OTC residues in the honey were assessed over a 7-month-long monitoring period. Regarding the consumption of the sucrose solution, there was no significant difference between the OTC-treated and untreated groups. The strength of the untreated colonies was consistently but not significantly higher than those treated with OTC. PSS combined with QC resulted in various side effects in both groups: queen loss (52%), absconding (8%), and drone-laying queen (4%). Untreated colonies (16.7%) showed clinical EFB relapses 4 months after the application of PSS along with QC, while 15.4% of the OTC-treated colonies were confirmed EFB-positive by PCR. OTC residues were detected in the honey yielded in the cases of both groups. Two months after the PSS, the amount of OTC residues in the untreated group was 0.6 ± 0.2 µg/kg, while that in the OTC-treated group amounted to 5.8 ± 11.6 µg/kg; both results are below the maximum residue limit (MRL) of 100 ppb considered in the EU for cascade use.

Risks and outcomes of pregnancy in neuromyelitis optica spectrum disorder: A comprehensive review.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system autoimmune disease. Aquaporin-4 antibody (AQP4-IgG) is present in over 75% of cases and criteria also exist for the diagnosis of seronegative NMOSD. AQP4-IgG NMOSD has a strong female predominance (9:1 ratio), with a median onset age of 40 years. Pregnancy in those with NMOSD is therefore an important topic. Fecundity in NMOSD is likely impaired, and for females who conceive, obstetric complications including miscarriages and pre-eclampsia are significantly higher in NMOSD compared to the general population and in related conditions such as multiple sclerosis (MS). In contrast to MS, NMOSD disease activity does not subside during pregnancy. Also, relapse risk substantially rises above pre-pregnancy rates in the early postpartum period. In view of the evolving landscape of NMOSD, we provide a contemporary update of the impacts of pregnancy in NMOSD.

An update on combination therapies for multiple sclerosis: where are we now?

INTRODUCTION: In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in therapeutic effect. Combination therapies have proven particularly effective against infections such as HIV, cancer, and also chronic autoimmune diseases such as rheumatoid arthritis. AREAS COVERED: The authors review the literature, searching for randomized placebo-controlled or comparative, double-blind or investigator-blinded clinical trials, not including open label clinical trials, of treatment of multiple sclerosis (MS) with combination therapy or add-on therapy, including trials of induction therapy, trials for prevention of disease activity or worsening, amelioration of adverse effects, and treatment of relapses, and trials to increase remyelination. EXPERT OPINION: Combination of two platform therapies (Interferon-beta or glatiramer acetate) was without additional effect. Clinical trials with add-on, often applying repurposed drugs (e.g. simvastatin, atorvastatin, minocycline, estriol, cyclophosphamide, azathioprine, albuterol, vitamin D), have been negative, apart from monthly methylprednisolone that, however, had low tolerability. Combination therapy for neuroprotection/remyelination showed some interesting results, though we are still awaiting results of phase III trials. The results of combination of anti-inflammatory therapies have in general been disappointing. In the future, combination of new effective neuroprotective/remyelinating drugs and highly effective anti-inflammatory treatments may benefit people with MS.

Effectiveness of Rituximab and Its Biosimilar in Treating Adult Steroid-Dependent Minimal Change Disease and Relapse.

Minimal change disease (MCD) is an important cause of nephrotic syndrome in adults. Its course is often complicated by frequent relapses and steroid dependence. Most of the treatment experience of MCD comes from management of pediatric patients rather than adult patients. In this report, the author describes successful experience of using rituximab (RTX) and its biosimilar, RTX-pvvr (ruxience), to treat steroid-dependent MCD and relapses in adult patients. This is the first report of using a RTX biosimilar to treat MCD. This case series demonstrates that RTX and ruxience are well-tolerated, efficacious treatment for managing adult patients with steroid-dependent MCD and relapses.

Características clínicas de pacientes con Lupus Eritematoso Sistémico, al debut y en recaídas

Introducción. Las formas clínicas de presentación del lupus eritematoso sistémico (LES) son variadas, así como las recaídas que ocurren en el curso de la enfermedad. Objetivo. Describir las formas de presentación del debut y las recaídas de pacientes con LES. Metodología. Estudio observacional, descriptivo, de corte transversal, de pacientes con LES, que acudieron al Hospital Nacional, durante el periodo 2022 a 2023. Las variables analizadas fueron las variables sociodemográficas, clínicas y de laboratorio, al debut y durante las recaídas. Resultados. Se incluyeron 47 pacientes, entre 14 y 68 años de edad (media: 29,6 ±12 años), 91,5% del sexo femenino, 59,5% del interior del país, con educación secundaria (68,1%) y ocupación ama de casa (55,3%). El tiempo de enfermedad fue en promedio 48,7 ±37.1 meses. La forma más frecuente de debut fue la poli-artralgia (55,3%), seguido de nefritis (27,7%). En la recaída, la nefritis fue más frecuente (44,7%), seguida de dolor poliarticular (40,4%). La causa de recaída más frecuente fue el abandono del tratamiento (34,0%). Conclusión. La mayoría de las pacientes eran mujeres jóvenes que debutaron la enfermedad con artralgias, seguida de la afectación renal. Las recaídas se presentaron con nefritis. La causa principal de las recaídas fue el abandono del tratamiento.

Introduction: The clinical forms of presentation of systemic lupus erythematosus (SLE) are varied, as well are the relapses that occur in the course of the disease. Objective: To describe the onset and relapses in a cohort of patients with SLE. Methodology. Observational, descriptive, cross-sectional study of patients with SLE who attended the National Hospital, during the period 2022 to 2023. The variables analyzed were sociodemographic, forms of onset and relapses. Results: 47 patients between 14 and 68 years of age (mean: 29.6 ±12 years) were included in the study, 91.5% female, 59.5% from the interior of the country, with secondary education (68.1%) and housewife occupation (55.3%). The duration of illness was on average 48.7 ±37.1 months. The most common form of onset was polyarthralgia (55.3%), followed by nephritis (27.7%). In relapse, nephritis was more frequent (44.7%), followed by polyarticular pain (40.4%). The most frequent cause of relapse was treatment abandonment (34.0%). Conclusion: The majority of patients were young women who presented the disease with arthralgia, followed by kidney involvement. Relapses presented with nephritis. The main cause of relapses were treatment abandonment.

Impact of adherence to disease-modifying drugs in multiple sclerosis: A study on Italian real-world data.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring complex diagnostic and therapeutic management. Treatment with Disease Modifying Drugs (DMDs) is aimed at reducing relapse rate and disease disability. Few real-world, population-based data are available on the impact of adherence on relapse rate. The objective of this study was to assess the impact of adherence to DMDs on relapses in a real-world Italian setting. METHODS: Population-based cohort study. People with MS (PwMS) older than 18 years and residing in the Emilia-Romagna region, Northern Italy, were identified through administrative databases using a validated algorithm. A Cox regression model with a time-varying exposure was performed to assess the association between level of adherence to DMDs and relapses over a 5-year period. RESULTS: A total of 2,528 PwMS receiving a first prescription of DMDs between 2015 and 2019 were included (average age of 42, two-thirds female). Highly adherent PwMS had a 25 % lower hazard of experiencing moderate or severe relapses than non-adherent PwMS (Hazard Ratio 0.75, 95 % CI 0.58 to 0.98), after adjusting for age and sex. Several sensitivity analyses supported the main result. CONCLUSION: The results of our study support the hypothesis that a high level of DMD adherence in MS is associated with a lower risk of moderate or severe relapse. Therefore, choosing the DMD with which to start drug treatment and recommending adherence to treatment appear to be crucial aspects involving both physicians and patients.

IMRT in the treatment of locally advanced or inoperable NSCLC in the pre-durvalumab era: clinical outcomes and pattern of relapses, experience from the Oscar Lambret Center.

Background: Intensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation. Objective: The objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses. Methods: Patients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan-Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test. Results: Seventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity. Conclusion: The use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.

Relapses in Illicit Drug Use Among Probationers: Results in a Risk Group of Public Health Services in Bavaria.

Objective: We aimed to identify in this study time trends of relapses in the illicit consumption of narcotics in a special at-risk population of former drug users under a public health perspective. Methods: In a pooled dataset of 14 consecutive calendar years (2006-2019), the use of seven different narcotic substances was studied in 380 persons with a total of 2,928 urine samples which were analyzed using a valid marker system for narcotic residues. Results: During the entire observation period, the relapse rate for cannabinoids and opiates was the highest despite abstinence requirements. It was noticeable that the relapses across all narcotics groups occurred primarily during the first 3 years of the probation period (90%) with a decrease in illegal consumption during the following years of the observation period. Conclusion: Special attention should be paid to probationers at the beginning of the probation period to develop more effective prevention strategies for substance abstinence by all involved actors in public health services.

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: A study from the RelevarEM registry.

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients.

Detecting isolated cognitive relapses in persons with MS.

BACKGROUND: The existence of isolated cognitive relapses (ICRs) in persons with MS (PwMS) has been debated. OBJECTIVE: To examine relapses with decline on Symbol Digit Modalities Test (SDMT) but no change on Expanded Disability Status Scale (EDSS). METHODS: This 3-year prospective cohort study identified PwMS experiencing a relapse with decrease on SDMT. Participants with SDMT decline/stable EDSS were labeled "ICR," while those with a corresponding decrease on EDSS were classified "Relapse with Cognitive Decline (RCD)." Two definitions of SDMT decline were explored: (1) ⩾ 8 points, and (2) ⩾ 4 points. Logistic regression was used to analyze the relationship between ICR and RCD. RESULTS: The full cohort had 592 participants: 83 experienced relapses; 22 (26.5%) had an SDMT decrease of ⩾ 8 points; 14 (63.6%) met ICR criteria. Logistic regression (X2(1) = 5.112, p = 0.024) using demographics and disease characteristics explained 28.4% of the variance in ICR versus RCD. Only the MS Neuropsychological Questionnaire was associated with ICR (odds ratio (OR): 8.6; 95% confidence interval (CI): 1.1-16.4) 40 relapsing participants with SDMT decrease of ⩾ 4 points were identified: 26 (65%) had a stable EDSS (ICR). Logistic regression did not find any variable predictive of ICR. CONCLUSION: This prospective study demonstrates evidence of ICR in PwMS.

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community.

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles.