Worse Disability Research Articles

Association of Residential Greenness Exposures on Disability: Findings from the Cohort Study on Global AGEing and Adult Health (SAGE) in China.

With the accelerating population ageing globally, disability has become a major public concern. Residential greenness may be one of the influencing factors of disability, but epidemiological evidence in the associations of residential greenness exposures with disability is limited. We aimed to investigate the associations of residential greenness exposures with the risk of disability in the elderly. Data of 8,408 residents were obtained from the World Health Organization Study on Global AGEing and Adult Health (WHO SAGE) implemented in China during 2007-2018. Participants were matched to the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) at their residential address. Disability was measured by the 12-item Chinese version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0). The associations were examined using a generalized linear mixed model with stratified analyses by the covariates. We observed significantly negative associations of greenness exposures with the summary WHODAS score [NDVI500m: -0.290, 95% Confidence Intervals (95%CI): -0.510, -0.070; EVI500m: -0.453, 95%CI: -0.757, -0.149], and with the score of cognition (EVI500m: -0.472, 95%CI: -0.881, -0.063), mobility (NDVI500m: -0.632, 95%CI: -0.965, -0.299; EVI500m: -0.739, 95%CI: -1.199, -0.280), and participation (NDVI500m: -0.388, 95%CI: -0.651, -0.125; EVI500m: -0.530, 95%CI: -0.893, -0.166). People living alone had a more pronounced association in cognition (NDVI500m: -1.546, 95%CI: -2.471, -0.621). The associations with summary WHODAS score were stronger among participants living in rural areas (NDVI500m: -0.420, -0.683, 95%CI: -0.157), having less education level (NDVI500m: β= -0.618, 95%CI: -0.982, -0.253), and living in northern China (NDVI500m: β= -0.381, 95%CI: -0.776, 0.013). Residential greenness may reduce the onset and worsening of disability, particularly for domains of cognition, mobility, and social participation. Because of its stronger influence among people with low socioeconomic status, increasing greenness levels in areas with lower socioeconomic status may promote health equity.

Assessment of disability and disease burden in neuromyelitis optica spectrum disorders in the CIRCLES Cohort

Neuromyelitis optica spectrum disorders (NMOSD) comprise autoimmune diseases imposing substantial disability. We compared an NMOSD-targeted disability assessment of mobility, vision, and self-care domains (individually and composite) with the multiple sclerosis-targeted Expanded Disability Status Scale (EDSS) to assess NMOSD disease burden. An overall cohort (n = 505) and a subset of these patients with an enriched dataset (n = 198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG–seropositive or –seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61–5.90), vision (OR, 3.99; 95% CI: 2.03–7.86), self-care disability (OR, 1.90; 95% CI: 1.07–3.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71–10.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG–seropositive status in patients ≥ 18 years (p < 0.05). Disease onset phenotype and sex correlated with pain interference (p < 0.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.

A Mouse Model of Temporal Lobe Contusion.

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography-positive," that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.

Complex Regional Pain Syndrome: a cross-sectional study of physical symptoms, disability, and psychological health in long term.

Knowledge about long-time residual symptoms, disabilities, and psychological health in complex regional pain syndrome (CRPS) is limited. The aim was to evaluate outcome, focusing on physical symptoms, disability, and psychological health, in individuals with CRPS through a cross-sectional survey study. Individuals with a confirmed diagnosis of CRPS were identified through medical charts and sent validated survey forms (Disabilities of the Arm, Shoulder and Hand-Quick version, Specific Hand Surgery Questionnaire-8 questions, EuroQol 5 Dimensions 3 levels, Life Satisfaction Questionnaire-11, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Sense of Coherence-29) and complementary questions. Responders (response rate: 99/238, 42%; CRPS type 1: 72%; CRPS type 2: 28%; time since diagnosis median: 59 [34-94] months) reported remaining symptoms and disability (Disabilities of the Arm, Shoulder and Hand-Quick version score: 45 [20-70]) and more improvement in type 1 than in type 2. Only 9% of individuals with CRPS reported no residual pain or discomfort. Approximately 60% had problems in daily activities, 49% had sleeping problems, and 90% experienced moderate-extreme pain with 23% still on sick leave. The Hospital Anxiety and Depression Scale survey revealed significantly higher scores than a Swedish reference population. Individuals with a low Sense of Coherence and high pain catastrophizing had worse disability and were less satisfied with their lives and physical and psychological health. A lower level of education and more anxiety were associated with worsened disability over time. Individuals with CRPS suffer in the long term from pain, sleeping problems, and limitations in daily activities with occurrence of anxiety and depression, resulting in dissatisfaction with many aspects of their lives. A low Sense of Coherence and high pain catastrophizing are associated with a worse outcome. Biopsychosocial aspects should be addressed in clinical practice.

Prognostic factors for worsening and improvement in multiple sclerosis using a multistate model.

The long-term disease trajectory of people living with multiple sclerosis (MS) can be improved by initiating efficacious treatment early. More quantitative evidence is needed on factors that affect a patient's risk of disability worsening or possibility of improvement to inform timely treatment decisions. We developed a multistate model to quantify the influence of demographic, clinical, and imaging factors on disability worsening and disability improvement simultaneously across the disability spectrum as measured by the Expanded Disability Status Scale (EDSS). We used clinical trial data from the Novartis-Oxford MS database including ~130,000 EDSS assessments from ~8000 patients, spanning all MS phenotypes. Higher brain volume was positively associated with disability improvement at all disability levels (hazard ratio (HR) = 1.09-1.19; 95% credible interval (CI) = 1.02-1.27). Higher T2 lesion volume was negatively associated with disability improvement up to EDSS 6 (HR = 0.80-0.89; 95% CI = 0.75-0.94). Older age, time since first symptoms, and the number of relapses in the past year were confirmed as predictors of future disability worsening. Brain damage was identified as the most consistent factor limiting the patient's probability for improvements from the earliest stages and across the whole course of MS. Protecting brain integrity early in MS should have greater weight in clinical decision-making.

Comorbidity and Disease Activity in Multiple Sclerosis

Multiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists. To evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS. A 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024. Comorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders. The main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging. A total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14). In this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

Lived experiences of diabetes self-management among persons with disabilities in rural Tamil Nadu – a case study approach

BackgroundPeople with disabilities have numerous challenges in diabetes self-management. Poor self-management leads to the worsening of disability and secondary complications of diabetes. This study was conducted to explore the challenges in diabetes self-management and the factors influencing diabetes self-management among people with disabilities.MethodsWe conducted 16 case studies among people with physical, neurological, visual, hearing, and multiple disabilities who were affected by diabetes. We adopted a thematic content analysis approach to analyse the data.ResultsPeople with disabilities have challenges in adopting healthy diets as they are unable to purchase and consume fruits and vegetables which are costly, unavailable, and inaccessible. They have difficulty in doing physical activity due to lack of inclusive public spaces which are inaccessible, lack of motivation, and dependence on others for their mobility. Irregular drug supply in the public health system and unaffordable cost of drugs hamper adherence to medications. Laboratories are inaccessible to people with disabilities thus preventing monitoring of blood sugars. They have poor quality of life, life with pain and mental health issues, which prevent adoption of self-management behaviors. The intersectionality of age and gender with disability worsens self-management behaviors. Inaccessible health system, poor quality of health care and insensitive health care providers further complicate self-management.ConclusionThis study documents the challenges faced by persons with disabilities in practicing diabetes self management. There is a need for public health policy and planning that is inclusive of persons with disabilities to make access to diabetes care universal.

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.e., brain atrophy, and retinal layer thinning). MethodsWe designed an observational prospective mono-center study in RRMS patients initiating ALZ treatment. Patients were assessed at baseline (month 0) and thereafter annually for five years with clinical measures, synthetic magnetic resonance imaging (SyMRI) and optical coherence tomography (OCT), with a re-baseline SyMRI scan and an OCT exam 24 months after initiating ALZ. Persons with neurological symptoms but without evidence of neurological disease served as symptomatic controls (SCs, n = 27). ResultsForty-nine RRMS patients were included. Baseline median expanded disability status scale [2.0 (IQR 1.5)] was unchanged during follow-up, 71 % were progression-free, 33 % achieved no evidence of disease activity-3 (NEDA-3). Between baseline and month 60, SyMRI showed a reduction of brain parenchymal fraction (BPF) and grey matter (GM) volume in patients. The BPF reduction was greater in RRMS patients than in SCs (p < 0.05), and more pronounced in patients with high pre-baseline disease activity than in those without (p < 0.01). OCT showed significant thinning of macular ganglion cell and inner plexiform layers (mGCIPL) and in peripapillary retinal nerve fiber layer (pRNFL) in patients. In contrast, absolute values of white matter (WM) volume and myelin content (MyC) quantified by SyMRI, were stable or increased after re-baseline (month 24) and up to month 60, and this increase appeared limited to patients without high pre-baseline disease activity and to patients with NEDA-3 or disability worsening during follow-up. A strong positive correlation between WM volume and GM volume at baseline was lost after ALZ intervention for their delta values, i.e., change from re-baseline (month 24) to month 60. While the positive baseline correlation between WM volume and MyC increased for their delta values, the positive baseline correlation between GM volume and MyC changed to negative for their delta values. ConclusionWe showed that neurodegeneration continued in RRMS patients under ALZ treatment, but it appeared to be limited to BPF and GM, and more pronounced in patients with disease activity. Our data suggest that patients who respond to ALZ treatment show signs of remyelination. OCT and SyMRI have potential to quantify measures of neurodegeneration that is affected by treatment intervention in RRMS.

MultiSCRIPT-Cycle 1—a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial

BackgroundTreatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone.MethodsPragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures.DiscussionMultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice.Trial registrationClinicalTrials.gov NCT06095271. Registered on October 23, 2023

Assessment of treatment expectations in people with suspected endometriosis: A psychometric analysis.

Treatment expectations influence clinical outcomes in various physical and psychological conditions; however, no studies have explored their role in endometriosis treatment. It is necessary to understand how these expectations can be measured to study treatment expectations and their effects in clinical practice. This study aimed to psychometrically analyze and compare different treatment expectation measurements and describe treatment expectations in women with suspected endometriosis. Analysis of cross-sectional baseline data of a mixed-method clinical observational study of N=699 patients undergoing laparoscopy in Germany. Descriptives, bivariate associations, convergent and discriminant validity of four expectation measurements (Treatment Expectation Questionnaire (TEX-Q); Generic rating scale for previous treatment experiences, treatment expectations, and treatment effects (GEEE); numerical rating scales (NRS) assessing improvement and worsening of endometriosis symptoms, expected Pain Disability Index (PDI); range: 0 to 10) were estimated. A cluster analysis was performed on the three GEEE items. Most participants expected high improvement ( M=6.68 to 7.20, SD=1.90 to 2.09) and low worsening ( M=1.09 to 2.52, SD=1.80 to 2.25) of disability from laparoscopy. Participants who expected greater worsening expected more side effects ( r=.31 to .60, p<.001). Associations between the positive and negative expectation dimensions, including side effects, were small to non-significant ( r =|.24| to .00, p<.001 to.978). Four distinct clusters, described as'positive', 'no pain, no gain', 'diminished', and 'uniform' were found, with a total PVE of 62.2%. Women with suspected endometriosis reported positive expectations concerning laparoscopy, but wide ranges indicated interindividual differences. Treatment expectations seem to be a multidimensional construct in this patient group. The investigated measurements did not correlate to the extent that they measured exactly the same construct. The selection of measurements should be carefully considered and adapted for the study purposes. Clusters provide initial indications for individualized interventions that target expectation manipulation. ID NCT05019612 ( ClinicalTrials.gov).

The effects of the MTHFR 677C>T (rs1801133) genetic variant on susceptibility and disability worsening in multiple sclerosis patients are mediated by homocysteine

BackgroundInteractions between genetic and environmental variables contribute to the autoimmune inflammatory process in multiple sclerosis (MS). Elevated homocysteine levels, and vitamin D, vitamin B12, and folate deficiencies are some of the environmental factors associated with the pathogenesis of MS. Considering that the relationship between MTHFR 677C>T (rs1801133) genetic variant, homocysteine, and folate in patients with MS remains unclear and that their role were not extensively explored in the clinical course of the disease, we investigated whether this variant and plasma homocysteine and folate levels are associated with MS susceptibility, disability, disability progression, and inflammatory biomarkers. MethodsThe case-control study included 163 patients with MS categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls (HC). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T variant was genotyped using real time polymerase chain reaction. The plasma levels of some inflammatory biomarkers were determined. Two new composed scores were proposed: the first, namely as inflammatory activity index (IAI), was entered as a latent vector extracted from the macrophage M1 + T helper (Th)1 + Th17 + Th2 + T regulatory (Treg) cytokines, + tumor necrosis factor (TNF)-α+ soluble TNF receptor (sTNFR)-1 + sTNFR2. The second score, namely MS-severity index was entered as a latent vector extracted from the EDSS + MSSS scores + MS diagnosis. ResultsPatients with MS showed higher homocysteine and folate than controls (p < 0.001); homocysteine, and the M1, Th1, Th17, and Th2 Treg cytokine values were different between the three study groups and increased from HC to MS patients with mild disability and to MS patients with moderate/high disability (p < 0.0001). The levels of TNF-α and their soluble receptors sTNFR1 and sTNFR2 were higher in MS patients with EDSS≥3 than in the two other groups (EDSS<3 and HC) (p < 0.001). There was no association between the MTHFR 677 C > T genotypes and MS susceptibility, disability and disability progression (p > 0.05). Moreover, 21.8 % of the disability variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9 % of the disability progression variance was predicted by IAI and CRP (both positively) and 25-hydroxyvitamin D (negatively), whereas 54.4 % of the severity index (MS-EDSS-MSSS) was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively), and adiponectin, body mass index, and 25-hydroxyvitamin D (all negatively), female sex, and the MTHFR 677 TT genotype. In patients and controls, 16.6 % of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. ConclusionThe MTHFR 677C>T variant has an indirect effect on the increase in disability in patients with MS, which also depends on factors such as age, sex, ad folate status.

The Prevalence of Comorbidities and Their Association With Disability Progression in Individuals With Multiple Sclerosis: A Study From Brazil.

Comorbidities negatively impact the course of multiple sclerosis (MS). Identifying them is essential, as they represent potentially modifiable prognostic factors that can adversely influence the disease course. However, comorbidity prevalence remains underexplored in certain populations, including in individuals in Brazil. In this cross-sectional study, we describe the frequency of comorbidities and their correlation with MS disability progression in a Brazilian population by reviewing the medical records of patients from a single MS center in Brazil. Preexisting comorbidities and those present at the time of MS diagnosis were screened. We assessed the prevalence of comorbidities, their prevalence ratios (PR) and the association between them, their number, and the confirmed disability worsening (CDW) that emerged during the follow-up visits. Comorbidities were present in 68.9% of individuals. The most prevalent comorbidities included cardiovascular diseases (19.3%), migraine (13.3%), psychiatric disorders (12.4%), smoking (12.4%), autoimmune diseases (12.0%), respiratory diseases (10.3%), and neoplasms (5.6%). Patients with 1 comorbidity and those with multiple comorbidities (≥ 3) had a significant PR for CDW (2.67, P = .01; 1.25, P = .03, respectively). Cardiovascular and autoimmune diseases presented significant PR for CDW (2.28, P = .03; 4.2, P = .004, respectively). Comorbidities are more prevalent among Brazilian individuals with MS than in the general population and are associated with disease progression. Identifying and managing them may mitigate their adverse effects on disease course.

Long-term disability trajectories in multiple sclerosis: a group-based trajectory analysis of the AusLong cohort

BackgroundPrevious natural history studies highlighted a consistent heterogeneity of disability trajectories among individuals with primary or secondary progressive multiple sclerosis (MS). However, evidence on disability progression in relapsing onset MS...

Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.

To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS). CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs. The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model. These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.

Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness z Scores

Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness <i>z</i> Scores

Association Between Alcohol Consumption and Disability Accumulation in Multiple Sclerosis.

Previous studies have indicated that alcohol consumption is associated with multiple sclerosis (MS) disease progression. We aimed to study the influence of alcohol consumption habits on disease progression and health-related quality of life in MS. We categorized patients from 2 population-based case-control studies by alcohol consumption habits at diagnosis and followed them up to 15 years after diagnosis through the Swedish MS registry regarding changes in the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale 29 (MSIS-29). We used Cox regression models with 95% confidence intervals (CIs) using 24-week confirmed disability worsening, EDSS 3, EDSS 4, and physical and psychological worsening from the patient's perspective as end points. Our study comprised 9,051 patients with MS, with a mean age of 37.5 years at baseline/diagnosis. Compared with nondrinking, low and moderate alcohol consumption was associated with reduced risk of EDSS-related unfavorable outcomes (hazard ratios between 0.81 and 0.90) and with reduced risk of physical worsening. The inverse association was confined to relapsing-remitting MS and was more pronounced among women. High alcohol consumption did not significantly affect disease progression. The inverse relationship between low-moderate alcohol consumption and disability progression became stronger when we only included those who had not changed their alcohol consumption during follow-up (hazard ratios between 0.63 and 0.71). There were no differences in measures of disability at baseline between drinkers who continued drinking alcohol after diagnosis and those who later discontinued. Our findings speak against bias due to reverse causation. Low and moderate alcohol consumption was associated with more favorable outcomes in relapsing-remitting MS, compared with nondrinking, while there was no significant influence of high alcohol consumption on disease outcomes.

Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

Retinal layer thinning for monitoring disease-modifying treatment in relapsing multiple sclerosis—Evidence for applying a rebaselining concept

Background: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). Methods: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6–12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression models. Results: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFLrebaseline (by 0.31%, p < 0.001) and aLGCIPLrebaseline (0.25%, p < 0.001) compared with M-DMT. Conclusions: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.

Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis

Background: Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking. Objectives: To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS. Methods: Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab were identified in the global MSBase cohort and two additional UK centres. Patients were followed for ⩾6/12 and had ⩾3 in-person disability assessments. Patients were matched using propensity score. Four pairwise analyses compared annualised relapse rates (ARRs) and disability outcomes. Results: The eligible cohorts consisted of 853 (fingolimod), 464 (natalizumab), 1131 (ocrelizumab), 123 (alemtuzumab) or 493 (cladribine) patients. Cladribine was associated with a lower ARR than fingolimod (0.07 vs. 0.12, p = 0.006) and a higher ARR than natalizumab (0.10 vs. 0.06, p = 0.03), ocrelizumab (0.09 vs. 0.05, p = 0.008) and alemtuzumab (0.17 vs. 0.04, p < 0.001). Compared to cladribine, the risk of disability worsening did not differ in patients treated with fingolimod (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.47–2.47) or alemtuzumab (HR 0.73, 95% CI 0.26–2.07), but was lower for patients treated with natalizumab (HR 0.35, 95% CI 0.13–0.94) and ocrelizumab (HR 0.45, 95% CI 0.26–0.78). There was no evidence for a difference in disability improvement. Conclusion: Cladribine is an effective therapy that can be viewed as a step up in effectiveness from fingolimod, but is less effective than the most potent intravenous MS therapies.

Ocrelizumab in people with primary progressive multiple sclerosis: A real-world multicentric study

BackgroundOcrelizumab is the only disease-modifying therapy (DMT) approved for the treatment of people with primary progressive multiple sclerosis (pwPPMS). ObjectivesTo provide real-world evidence of ocrelizumab effectiveness and safety in pwPPMS in Croatian MS centers. MethodsA retrospective observational multi-center study of pwPPMS who were started on ocrelizumab in 7 MS centers in Croatia. ResultsWe identified 230 pwPPMS of whom 176 fulfilled the inclusion criteria. The median follow-up of the cohort was 2.73 (0.51–5.77) years. During the follow-up, 50 (28.4%) pwPPMS experienced confirmed disability worsening (CDW) and 19 (10.8%) stopped treatment with ocrelizumab. Baseline EDSS >5 was a statistically significant positive predictor for the development of CDW and/or stop of the treatment due to any cause (OR 2.482, 95% C.I. 1.192–5.166, p = 0.015). However, there was no significant difference in the development of CDW and/or stop of the treatment due to any cause if stratifying the patients based on active PPMS, age at treatment start (≤55 years vs >55 years), disease duration at treatment start (≤10 years vs >10 years), or EDSS at treatment start (≤5.0 vs >5.0). During the follow-up, 26 (14.8%) pwPPMS experienced infusion reactions, 64 (36.4%) had an infection and 4 (2.3%) developed a tumor. The percentage of pwPPMS with low levels of IgG was persistently above 10% and with low levels of IgM was persistently above 20% after cycle 4. ConclusionOur real-world data support the use of ocrelizumab in a much broader pwPPMS population than in the original randomized controlled trial.