Search

Background and purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence‐based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients–Intervention–Comparator–Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home‐based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs. [ABSTRACT FROM AUTHOR]

Background and purpose: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. Methods: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. Results: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre‐specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre‐specified topics, 227 (40%) on additional topics (16 guideline‐pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient‐important outcomes and of taxing issues. Conclusions: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient‐important outcomes. [ABSTRACT FROM AUTHOR]

Background: The 15-deoxi delta prostaglandin J2 (15d-PGJ2) is a peroxisome proliferator-activated receptor-gamma agonist with potent anti-inflammatory properties. It has been suggested that 15d-PGJ2 may modulate multiple sclerosis (MS). Methods: Here, we investigated the plasma levels of 15d-PGJ2 by enzyme-linked immunoassay in 28 healthy controls and 140 MS patients [30 patients with primary-progressive MS, 28 patients with secondary-progressive MS, and 82 patients with relapsing-remitting MS (28 patients during clinical remission, 25 patients during relapse, and 29 treated with interferon-beta – IFN-β)]. Results: Levels of 15d-PGJ2 were similar between healthy controls and untreated MS patients with different clinical courses of the disease. Treatment with IFN-β had no effect on levels of 15d-PGJ2. Conclusions: Although these findings suggest that 15d-PGJ2 is not involved in the acute or chronic phases of the disease, further studies measuring 15d-PGJ2 in cerebrospinal fluid samples are needed before excluding a role of 15d-PGJ2 in MS. [ABSTRACT FROM AUTHOR]

Background and Purpose: To evaluate the effect of menopause on disability accumulation in women followed from their clinically isolated syndrome (CIS)., Methods: We examined the longitudinal changes in Expanded Disability Status Scale (EDSS) scores from CIS until the last follow-up in women belonging to the Barcelona CIS prospective cohort, followed through their menopausal transition. The analysis is based on 13,718 EDSS measurements, with an average of 28 EDSS measurements per patient. Differences in EDSS trajectories between menopausal and nonmenopausal women, controlling for age and disease duration, were evaluated. We performed two sensitivity analyses in women with confirmed MS and in those experiencing early menopause., Results: From 764 eligible women, 496 (65%) responded to the questionnaire, and 74 (14.9%) reached menopause over the follow-up. We did not find a significant inflection point in EDSS trajectories around menopause (slope change -0.009; 95% CI -0.066; 0.046). The annual increase in EDSS over the complete course of the disease was significantly higher in menopausal women (0.049; 95% CI, 0.026-0.074) versus nonmenopausal (0.019; 95% CI, 0.008-0.031; interaction p value 0.025). This difference was lost when controlling for age and disease duration (EDSS annual increase of 0.059; 95% CI, 0.025-0.094 vs. 0.038; 95% CI, 0.021-0.057, respectively; interaction p value 0.321). No inflection point was detected when the analysis was restricted to women with confirmed MS or with earlier menopause., Conclusions: Menopause is not associated with an increased risk of disability in a CIS population, considering EDSS trajectories throughout the course of the disease together with age and disease duration., (© 2021 European Academy of Neurology.)

Background and Purpose: Comorbidities are common in multiple sclerosis (MS), and have been associated with worse outcomes and increased health care resource usage. We studied the frequency of comorbidities and adverse health behaviors (AHBs) in MS patients in the Mediterranean region of Catalonia., Methods: This population-based, case-control study used primary health care information covering 80% of Catalonia's population. Cases were matched by age/sex with randomly chosen controls (ratio = 1:5). Demographic information, comorbidities, AHBs, annual visits, sick leave days, and medication dispensing were studied. The association of comorbidities with MS and the profile of comorbidities according to sex within MS cases were assessed with multivariate logistic regression models, after adjusting for confounding variables. Health care resource usage was analyzed in MS cases compared to controls, and within MS cases in those with compared to those without comorbidities., Results: Five thousand five hundred forty-eight MS cases and 27,710 controls (70% female, mean age = 48.3 years) were included. Stroke (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.17-1.99), epilepsy (OR = 2.46, 95% CI = 1.94-3.10), bipolar disorder (OR = 1.67, 95% CI = 1.17-2.36), and depression (OR = 1.83, 95% CI = 1.70-1.98) were more frequent in MS. Cases were more prone to smoking but less to alcohol intake. Among cases, psychiatric comorbidities were more frequent in women, whereas cardiovascular diseases and AHBs were more frequent in men. MS patients, particularly with comorbidities, had higher health care resource usage than controls., Conclusions: Psychiatric comorbidities, stroke, epilepsy, and AHBs are more common in MS patients than in the general population in the western Mediterranean region of Catalonia. The presence of comorbidities increases the health care resource usage in MS patients., (© 2021 European Academy of Neurology.)

Background and Purpose: Information regarding multiple sclerosis (MS) patients with the 2019 novel coronavirus disease (COVID-19) is scarce. The study objective was to describe the incidence and characteristics of MS patients with COVID-19, to identify susceptibility and severity risk factors and to assess the proportion of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologies according to disease-modifying treatments., Methods: This was a retrospective study of an MS cohort analysing data collected between February and May 2020. Cases were identified through an email survey and clinical visits. The relationship of demographic and MS characteristics with COVID-19 and of the disease-modifying treatments with SARS-CoV-2 serostatus were examined., Results: Data from 48 suspected cases out of 758 valid respondents and from 45 COVID-19 cases identified through clinical visits were collected. Incidence was 6.3%. Nineteen (20.3%) patients were hospitalized and two (2.2%) died. Multivariable models determined that age (odds ratio [OR] per 10 years 0.53, 95% confidence interval [CI] 0.34-0.85), contact with a confirmed case (OR 197.02, 95% CI 56.36-688.79), residence in Barcelona (OR 2.23, 95% CI 1.03-4.80), MS duration (OR per 5 years 1.41, 95% CI 1.09-1.83) and time on anti-CD20 treatment (OR per 2 years 3.48, 95% CI 1.44-8.45) were independent factors for presenting COVID-19 and age (OR per 10 years 2.71, 95% CI 1.13-6.53) for a severe COVID-19. Out of the 79 (84.9%) with serological test, 45.6% generated antibodies, but only 17.6% of those on anti-CD20 therapies. Lymphopaenia or immunoglobulin levels did not relate to COVID-19., Conclusions: Multiple sclerosis patients present similar incidence, risk factors and outcomes for COVID-19 as the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be at a higher risk of COVID-19 and less than 20% generate an antibody response. Only age was related to severity., (© 2020 European Academy of Neurology.)

Background and Purpose: Both baseline prognostic factors and short-term predictors of treatment response can influence the long-term risk of disability accumulation in patients with relapsing-remitting multiple sclerosis (RRMS). The objective was to develop and validate a scoring system combining baseline prognostic factors and 1-year variables of treatment response into a single numeric score predicting the long-term risk of disability., Methods: We analysed two independent datasets of patients with RRMS who started interferon beta or glatiramer acetate, had an Expanded Disability Status Scale (EDSS) score <4.0 at treatment start and were followed for at least 10 years. The first dataset ('training set') included patients attending three MS centres in Italy and served as a framework to create the so-called RoAD score (Risk of Ambulatory Disability). The second ('validation set') included a cohort of patients followed in Barcelona, Spain, to explore the performance of the RoAD score in predicting the risk of reaching an EDSS score ≥6.0., Results: The RoAD score (ranging from 0 to 8) derived from the training set (n = 1225), was based on demographic (age), clinical baseline prognostic factors (disease duration, EDSS) and 1-year predictors of treatment response (number of relapses, presence of gadolinium enhancement and new T2 lesions). The best cut-off score for discriminating patients at higher risk of reaching the disability milestone was ≥4. When applied to the validation set (n = 296), patients with a RoAD score ≥4 had an approximately 4-fold increased risk for reaching the disability milestone (p < 0.001)., Discussion: The RoAD score is proposed as an useful tool to predict individual prognosis and optimize treatment strategy of patients with RRMS., (© 2021 European Academy of Neurology.)

Background and Purpose: Foveal changes were reported in aquaporin-4 antibody (AQP4-Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients; however, it is unclear whether they are independent of optic neuritis (ON), stem from subclinical ON or crossover from ON in fellow eyes. Fovea morphometry and a statistical classification approach were used to investigate if foveal changes in NMOSD are independent of ON and progressive., Methods: This was a retrospective longitudinal study of 27 AQP4-IgG + NMOSD patients (49 eyes; 15 ON eyes and 34 eyes without a history of ON [NON eyes]), follow-up median (first and third quartile) 2.32 (1.33-3.28), and 38 healthy controls (HCs) (76 eyes), follow-up median (first and third quartile) 1.95 (1.83-2.54). The peripapillary retinal nerve fibre layer thickness and the volume of combined ganglion cell and inner plexiform layer as measures of neuroaxonal damage from ON were determined by optical coherence tomography. Nineteen foveal morphometry parameters were extracted from macular optical coherence tomography volume scans. Data were analysed using orthogonal partial least squares discriminant analysis and linear mixed effects models., Results: At baseline, foveal shape was significantly altered in ON eyes and NON eyes compared to HCs. Discriminatory analysis showed 81% accuracy distinguishing ON vs. HCs and 68% accuracy in NON vs. HCs. NON eyes were distinguished from HCs by foveal shape parameters indicating widening. Orthogonal partial least squares discriminant analysis discriminated ON vs. NON with 76% accuracy. In a follow-up of 2.4 (20.85) years, no significant time-dependent foveal changes were found., Conclusion: The parafoveal area is altered in AQP4-Ab seropositive NMOSD patients suggesting independent neuroaxonal damage from subclinical ON. Longer follow-ups are needed to confirm the stability of the parafoveal structure over time., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)