Diffusion tensor imaging metrics as natural markers of multiple sclerosis-induced brain disorders with a low Expanded Disability Status Scale score.

Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1-3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics.

Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years.

BACKGROUND: Paramagnetic rim lesions (PRLs) have been linked to higher clinical disease severity and relapse frequency. However, it remains unclear whether PRLs predict future, long-term disease progression. OBJECTIVES: The study aimed to assess whether baseline PRLs were associated with subsequent long-term (10 years) Expanded Disability Status Scale (EDSS) increase and relapse frequency and, if so, whether PRL-associated EDSS increase was mediated by relapse. METHODS: This retrospective analysis included 172 people with multiple sclerosis (pwMS) with 1868 yearly clinical visits over a mean follow-up time of 10.2 years. 3T magnetic resonance imaging (MRI) was acquired at baseline and PRLs were assessed on quantitative susceptibility mapping (QSM) images. The associations between PRLs, relapse, and rate of EDSS change were assessed using linear models. RESULTS: PRL+ pwMS had greater overall annual relapse rate (ß = 0.068; p = 0.010), three times greater overall odds of relapse (exp(ß) = 3.472; p = 0.009), and greater rate of yearly EDSS change (ß = 0.045; p = 0.010) than PRL- pwMS. Greater PRL number was associated with greater odds of at least one progression independent of relapse activity (PIRA) episode over follow-up (exp(ß) = 1.171, p = 0.009). Mediation analysis showed that the association between PRL presence (yes/no) and EDSS increase was 96.7% independent of relapse number. CONCLUSION: PRLs are a marker of aggressive ongoing disease inflammatory activity, including more frequent future clinical relapses and greater long-term, relapse-independent disability progression.

The absence of antibodies in longitudinally extensive transverse myelitis may predict a more favourable prognosis.

BACKGROUND: Isolated first episodes of longitudinally extensive transverse myelitis (LETM) have typically been associated with neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, in some cases, serological testing and screening for other aetiologies are negative, a condition referred to as double seronegative longitudinally extensive transverse myelitis (dsLETM). OBJECTIVE: The objective of this study was to evaluate comparative outcomes of dsLETM, MOGAD-LETM and NMOSD-LETM. METHODS: Cohort study of LETM cases seen in the UK NMOSD Highly Specialised Service between January 2008 and March 2022. RESULTS: LETM = 87 cases were identified (median onset age = 46 years (15-85); median follow-up = 46 months (1-144); 47% NMOSD-LETM = 41 (aquaporin-4 antibodies (AQP4-IgG) positive = 36), 20% MOGAD-LETM = 17 and 33% dsLETM = 29). Despite similar Expanded Disability Status Scale (EDSS) at nadir, last EDSS was higher in AQP4-IgG and seronegative NMOSD-LETM (sNMOSD) (p = 0.006). Relapses were less common in dsLETM compared to AQP4-IgG NMOSD-LETM and sNMOSD-LETM (19% vs 60% vs 100%; p = 0.001). Poor prognosis could be predicted by AQP4-IgG (odds ratio (OR) = 38.86 (95% confidence interval (CI) = 1.36-1112.86); p = 0.03) and EDSS 3 months after onset (OR = 65.85 (95% CI = 3.65-1188.60); p = 0.005). CONCLUSION: dsLETM remains clinically challenging and difficult to classify with existing nosological terminology. Despite a similar EDSS at nadir, patients with dsLETM relapsed less and had a better long-term prognosis than NMOSD-LETM.

Association between sun exposure habits and disease progression in multiple sclerosis.

BACKGROUND AND PURPOSE: Higher latitude has been associated with increased occurrence of multiple sclerosis (MS) and with more severe disease. The aim was to study the impact of sun exposure habits on MS disease progression and health-related quality of life. METHODS: Patients from a population-based case-control study were categorized based on sun exposure habits at diagnosis and were followed up to 15 years post-diagnosis through the Swedish MS registry (n = 3314) with regard to changes in Expanded Disability Status Scale (EDSS). Linear mixed models were used to analyse long-term changes, while Cox regression models, with 95% confidence intervals, were used to investigate outcomes, including 24-week confirmed diasability worsening, EDSS3, EDSS4, and physical worsening as measured by the physical component of the Multiple Sclerosis Impact Scale 29. RESULTS: Compared to average sun exposure (median value), low exposure to sunlight was associated with faster EDSS progression, increased risk of confirmed disability worsening (hazard ratio [HR] 1.48, 95% CI 1.21-1.81), increased risk of reaching EDSS 3 (HR 1.35, 95% CI 1.02-1.79), EDSS 4 (HR 1.47, 95% CI 1.01-2.20) and self-reported physical worsening (HR 1.27, 95% CI 1.00-1.62). Significant trends revealed a lower risk of unfavourable outcomes with increasing sun exposure. CONCLUSIONS: Very low levels of sun exposure are associated with worse disease progression and health-related quality of life in patients with MS.

The Patient-Determined Disease Steps scale is not interchangeable with the Expanded Disease Status Scale in mild to moderate multiple sclerosis.

BACKGROUND AND PURPOSE: The validity, reliability, and longitudinal performance of the Patient-Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS. METHODS: We included relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4. Validity and test-retest reliability was examined. Longitudinal data were analysed with mixed-effect modelling and Cohen's kappa for concordance in confirmed disability progression (CDP). RESULTS: We recruited a total of 1093 participants, of whom 904 had complete baseline data. The baseline correlation between PDDS and EDSS was weak (ρ = 0.45, p < 0.001). PDDS had stronger correlations with patient-reported outcomes (PROs). Conversely, EDSS had stronger correlations with age, disease duration, Kurtzke's functional systems and processing speed test. PDDS test-retest reliability was good to excellent (concordance correlation coefficient = 0.73-0.89). Longitudinally, PDDS was associated with EDSS, age and depression. A higher EDSS score was associated with greater PDSS progression. The magnitude of these associations was small. There was no concordance in CDP as assessed by PDDS and EDSS. CONCLUSION: The PDDS has greater correlation with other PROs but less correlation with other MS-related outcome measures compared to the EDSS. There was little correlation between PDDS and EDSS longitudinally. Our findings suggest that the PDDS scale is not interchangeable with the EDSS.

Comparison of efficacy of plasma exchange versus intravenous immunoglobulin as an add-on therapy in acute attacks of neuromyelitis optica spectrum disorder.

INTRODUCTION: Plasma exchange (PE) is considered a Category II option for the treatment of acute attacks and relapse cases of neuromyelitis optica spectrum disorder (NMOSD). However, neurologists are also considering intravenous immunoglobulins (IVIg) as an add-on therapy for this disorder. AIMS: The aim of this study is to evaluate the efficacy of PE in acute attacks of NMOSD when compared with IVIg, in terms of improvement in the Expanded disability status scale (EDSS) and activities of daily living (ADL) scale score and levels of anti-Aquaporin P4 (AQP4) antibody in seropositive patients. METHODS: We enrolled 43 NMOSD patients in two groups: Group 1 (n = 29) received steroids and PE, and Group 2 (n = 14) received steroids with IVIg. The baseline EDSS and ADL scores were recorded and compared with scores at the end of therapy, 4 weeks, and 3 months after. Also, anti-AQP4 antibody was measured at baseline and post-therapy in seropositive patients of both groups. RESULTS: We observed a significant difference in EDSS (p = 0.00) and ADL score (p = 0.00) at day 10 and 3 months in both groups. However, no significant difference in EDSS, as well as ADL score from baseline (p = 0.83; p = 0.25) to 3 months (p = 0.85; p = 0.19), was observed when delta change of score at 3 months was compared across the two groups (p = 0.39; p = 0.52). We observed improved visual acuity in both groups with mild improvement in findings of magnetic resonance imaging at 3 months. We observed a significant decline in AQP4 antibody concentration (at day 10) in group 1 seropositive patients (p = 0.013) with improved EDSS (p = 0.027) and ADL scores (p = 0.026) of these patients. CONCLUSIONS: PE should be considered as a choice of an add-on therapy in anti-AQP4 antibody-positive NMOSD patients compared with IVIg as it is more effective in reducing antibody concentrations.

[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS: An ambispective study.

BACKGROUND: CLASSIC-MS evaluated the long-term efficacy of cladribine tablets in patients with relapsing multiple sclerosis. OBJECTIVE: Report long-term mobility and disability beyond treatment courses received in CLARITY/CLARITY Extension. METHODS: This analysis represents CLASSIC-MS patients who participated in CLARITY with/without participation in CLARITY Extension, and received ⩾1 course of cladribine tablets or placebo (N = 435). Primary objective includes evaluation of long-term mobility (no wheelchair use in the 3 months prior to first visit in CLASSIC-MS and not bedridden at any time since last parent study dose (LPSD), i.e. Expanded Disability Status Scale (EDSS) score <7). Secondary objective includes long-term disability status (no use of an ambulatory device (EDSS < 6) at any time since LPSD). RESULTS: At CLASSIC-MS baseline, mean ± standard deviation EDSS score was 3.9 ± 2.1 and the median time since LPSD was 10.9 (range = 9.3-14.9) years. Cladribine tablets-exposed population: 90.6% (N = 394), including 160 patients who received a cumulative dose of 3.5 mg/kg over 2 years. Patients not using a wheelchair and not bedridden: exposed, 90.0%; unexposed, 77.8%. Patients with no use of an ambulatory device: exposed, 81.2%; unexposed, 75.6%. CONCLUSION: With a median 10.9 years' follow-up after CLARITY/CLARITY Extension, findings suggest the sustained long-term mobility and disability benefits of cladribine tablets.

Sexual dysfunction in female and male people with multiple sclerosis: disability, depression and hormonal status matter.

BACKGROUND AND PURPOSE: Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) is common and an often underestimated issue in the care of pwMS. The objective of the study was to evaluate risk factors for SD in pwMS, correlate its prevalence with patient-reported measures (quality of life and physical activity) and analyse its association with hormonal status. METHODS: Sexual dysfunction was determined in 152 pwMS using the Multiple Sclerosis Intimacy and Sexuality Questionnaire 19. A logistical regression model was used to identify independent risk factors for SD. RESULTS: The prevalence of SD in pwMS was 47%. Independent risk factors for the development of SD were ever-smoking (odds ratio [OR] 3.4, p = 0.023), disability as measured by the Expanded Disability Status Scale (OR 2.0, p < 0.001), depression (OR 4.3, p = 0.047) and bladder and bowel dysfunction (OR 8.8, p < 0.001); the use of disease-modifying treatment was associated with a lower risk for SD (OR 0.32, p = 0.043). SD was associated with worse quality of life (Multiple Sclerosis Impact Scale 29: physical score 6.3 vs. 40.0; psychological score 8.3 vs. 33.3; both p < 0.001) and lower physical activity (Baecke questionnaire, p < 0.001). Laboratory analysis revealed significantly higher luteinizing hormone and follicle-stimulating hormone levels and lower 17-beta oestradiol, androstenedione, dehydroepiandrosterone sulfate, oestrone and anti-Mullerian hormone levels in female pwMS with SD. In male pwMS and SD, there was a significant decrease in inhibin B levels. CONCLUSIONS: Our findings highlight the requirement of a holistic approach to SD in MS including physical, neurourological and psychosocial factors. Active screening for SD, especially in patients with disability, depression or bladder and bowel dysfunction, is recommended.

Predicting multiple sclerosis severity with multimodal deep neural networks.

Multiple Sclerosis (MS) is a chronic disease developed in the human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale, composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) create opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to data insufficiency or model simplicity. In this paper, we proposed the idea of using patients' multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity in the future. Our contribution has two main facets. First, we describe a pioneering effort to integrate structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict patient's MS severity. The proposed pipeline demonstrates up to 19% increase in terms of the area under the Area Under the Receiver Operating Characteristic curve (AUROC) compared to models using single-modal data. Second, the study also provides valuable insights regarding the amount useful signal embedded in each data modality with respect to MS disease prediction, which may improve data collection processes.

Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. METHODS: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. RESULTS: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. CONCLUSION: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

Oligoclonal Band Status and Features of Radiological and Clinical Findings in Patients with Multiple Sclerosis in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a widely spread and debilitating disease with 2.8 million people worldwide currently affected. However, the exact pathogenesis of the disease and its progression remains incompletely understood. According to the revised McDonald criteria, cerebrospinal fluid oligoclonal bands (CSF OCBs) magnetic resonance imaging (MRI) results, in conjunction with clinical presentation, remain the gold standard of MS diagnostics. Therefore, this study aims to evaluate the association between CSF OCB status and features of radiological and clinical findings in patients with multiple sclerosis in Lithuania. Materials and Methods: The selection of 200 MS patients was performed in order to find associations between CSF OCB status, MRI data and various disease features. The data were acquired from outpatient records and a retrospective analysis was performed. Results: OCB positive patients were diagnosed with MS earlier and had spinal cord lesions more frequently than OCB negative patients. Patients with lesions in the corpus callosum had a greater increase in the Expanded Disability Status Scale (EDSS) score between their first and last visit. Patients with brainstem lesions had higher EDSS scores during their first and last visit. Even so, the progression of the EDSS score was not greater. The time between the first symptoms and diagnosis was shorter for patients who had juxtacortical lesions than patients who did not. Conclusions: CSF OCBs and MRI data remain irreplaceable tools when diagnosing multiple sclerosis as well as prognosing the development of the disease and disability.

The timed 25-foot walk in a large cohort of multiple sclerosis patients.

BACKGROUND: The timed 25-foot walk (T25FW) is a key clinical outcome measure in multiple sclerosis patient management and clinical research. OBJECTIVES: To evaluate T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database (n = 2465). METHODS: We created confirmed disability progression (CDP) variables for T25FW and Expanded Disability Status Scale (EDSS) outcomes. We used intraclass correlation coefficients (ICCs) and Bland Altman plots to evaluate reliability. We evaluated T25FW changes and predictive validity using a mixed-effects model, survival analysis, and nested case-control analysis. RESULTS: The mean baseline score for the T25FW in this study population was 9.2 seconds, median = 6.1 (standard deviation = 11.0, interquartile range (IQR) = 4.8, 9.0). The T25FW measure demonstrated excellent test-retest reliability (ICC = 0.98). Walk times increased with age, disability, disease type, and disease duration; relapses were not associated with an increase. Patients with T25FW progression had a faster time to EDSS-CDP compared to those without (hazards ratio (HR): 2.6; confidence interval (CI): 2.2, 3.1). Changes in the T25FW were more likely to precede changes in EDSS. CONCLUSION: This research confirms the association of the T25FW with disability and provides some evidence of predictive validity. Our findings support the continued use of the T25FW in clinical practice and clinical trials.

MicroRNA-22 Level in Patients with Multiple Sclerosis and Its Relationship with Vitamin D and Vitamin D Receptor Levels.

INTRODUCTION: Multiple sclerosis (MS) is known to be a multifactorial disorder. Numerous observational studies have suggested the implication of multiple genetic and environmental factors in the pathogenesis of MS. The aim of this work was to evaluate expression of the microRNA-22 (miRNA-22) level, in relation to vitamin D (VD) and VD receptor (VDR) levels in patients with MS during remission state. METHODS: This case-control study was conducted in 50 patients with clinically definite MS and 50 age- and sex-matched healthy controls. miRNA-22 expression was assessed in both MS patients and controls using quantitative RT-PCR. The serum level of VD and VDR was assessed in both MS patients and controls using ELISA techniques. RESULTS: The miRNA-22 level was significantly downregulated in MS patients in comparison to controls (p value <0.001). MS patients had also significantly lower VD and VDR levels in comparison to controls (p value <0.001 and <0.001, respectively). Patients with secondary progressive MS (SPMS) have a significantly higher miRNA-22 level than patients with relapsing remitting MS (RRMS) (p value = 0.042). There was a statistically significant positive correlation between the miRNA-22 level and EDSS (p value = 0.033). There was also a statistically significant positive correlation between the miRNA-22 level and VDR level (p value = 0.002). CONCLUSION: The miRNA-22 level was significantly downregulated in MS patients, but it had a positive correlation with disability status. Patients with SPMS have a significantly higher miRNA-22 level than patients with RRMS. VD and VDR levels were significantly lower in MS patients than controls. The miRNA-22 level was positively correlated with the VDR level.

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis.

INTRODUCTION: We aimed to develop and validate an Expanded Disability Status Scale (EDSS) model through clinical, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) measures. METHODS: Sixty-four multiple sclerosis (MS) patients underwent peripapillary retinal nerve fiber layer and segmented macular layers evaluation through OCT (Spectralis, Heidelberg Engineering). Brain parenchymal fraction was quantified through Freesurfer, while cervical spinal cord (SC) volume was assessed manually guided by Spinal Cord Toolbox software analysis. EDSS, neuroradiological, and OCT assessment were carried out within 3 months. OCT parameters were calculated as the average of both nonoptic neuritis (ON) eyes, and in case the patient had previous ON, the value of the fellow non-ON eye was taken. Brain lesion volume, sex, age, disease duration, and history of disease-modifying treatment (1st or 2nd line disease-modifying treatments) were tested as covariables of the EDSS score. RESULTS: EDSS values correlated with patient's age (r = 0.543, p = 0.001), SC volume (r = -0.301, p = 0.034), and ganglion cell layer (GCL, r = -0.354, p = 0.012). Using these correlations, an ordinal regression model to express probability of diverse EDSS scores were designed, the highest of which was the most probable (Nagelkerke R2 = 43.3%). Using EDSS cutoff point of 4.0 in a dichotomous model, compared to a cutoff of 2.0, permits the inclusion of GCL as a disability predictor, in addition to age and SC. CONCLUSIONS: MS disability measured through EDSS is an age-dependent magnitude that is partly conditioned by SC and GCL. Further studies assessing paraclinical disability predictors are needed.

Conjunctival impression cytology and tear film parameters in patients with multiple sclerosis.

PURPOSE: To evaluate conjunctival impression cytology (CIC) findings and tear film parameters in patients with multiple sclerosis (MS) compared with controls. METHODS: Thirty-three patients with MS (MS group) and 33 age- and sex-matched healthy subjects (control group) were included in this cross-sectional comparative study. CIC grades, tear break-up time (TBUT), Schirmer 1 test results, and Ocular Surface Disease Index (OSDI) scores were compared between the two groups, and correlations between CIC grade, TBUT, Schirmer 1 test result, OSDI score, Expanded Disability Status Scale score, and disease duration were analyzed. RESULTS: Mean CIC grade was higher in the MS group than in the control group (1.48 ± 0.71 and 0.39 ± 0.56, respectively; p < 0.001). In the MS group, CIC of the 14 participants (42.4%) was grade 2-3. In the control group, CIC of the only one participant (3.3%) was grade 2, and none of them was grade 3. TBUT (8.12 ± 3.16, 13.06 ± 4.23 s in MS and control groups, respectively; p < 0.001) and Schirmer 1 test results (8.45 ± 5.75, 17.36 ± 10.89 mm in MS and control groups, respectively; p < 0.001) were lower, and OSDI score (36.36 ± 19.19, 13.70 ± 15.36 in MS and control groups, respectively; p < 0.001) was higher in the MS group compared to the control group. CONCLUSION: In patients with MS, objective findings of dry eye, subjective symptoms related to dry eye, and CIC abnormalities, including high grades of conjunctival squamous metaplasia and goblet cell loss, are more common. Patients with MS should be monitored for ocular surface alterations and dry eye disease.

CLINICAL CASE OF NEUROMYELITIS OPTICA SPECTRUM DISORDERS IN YOUNG WOMAN TREATED WITH RITUXIMAB.

We report a case of a 28-year-old female who had the clinical manifestation of Neuromyelitis optica spectrum disorders with the area postrema syndrome at 24 years old. The patient presented with decreased vision due to acute optic neuritis, gait impairment, tetraplegia, sensory, and bladder disturbances. Magnetic resonance imaging of the spinal cord showed longitudinal high-intensity signals on a T2-weighted image in cervical and thoracic parts. Her serum and cerebrospinal fluid were positive for the anti-AQP4 antibody. The patient received high-dose methylprednisolone, plasmapheresis, but she remained free from relapses only after prescribing Rituximab. Prophylactic treatment of Neuromyelitis optica spectrum disorders recurrence must be immediately performed when it is identified because the progression of disability is related to the severity of attacks.

Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses.

BACKGROUND: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. OBJECTIVE: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. METHODS: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. RESULTS: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. CONCLUSION: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.

Prevalence of disability improvement as a potential outcome for multiple sclerosis trials.

BACKGROUND: The concept of improvement of disability recently emerged as a new target in multiple sclerosis (MS) studies since the approval of new potent drugs and for testing drugs for neuroprotection and repair. OBJECTIVE: To propose a simple estimator for assessing and comparing the prevalence of improvement over time between groups. METHODS: The prevalence of a transient condition takes into account the incidence and the duration of such condition. We propose here the application of a modified Kaplan-Meier estimator to evaluate and compare between groups the prevalence of improvement over time in a cohort of 121 patients treated with autologous hematopoietic stem cell transplantation. RESULTS: The prevalence of improvement after 5 years from transplant was 50.3% (95%CI: [38.0-63.0]) in relapsing-remitting patients and 6.5% (95%CI: [0-17.8]) in secondary-progressive patients (p < 0.001). Such a difference wouldn't be evident considering the traditional cumulative probability of improvement at 5 years (55.5% in relapsing-remitting vs 33.4% in secondary-progressive patients, p = 0.10). CONCLUSION: This study shows the relevance of a new estimator of prevalence of improvement in MS. This estimator gives simple information on whether a drug can induce a durable improvement in disability and can be considered a potential outcome for trials assessing drugs for neuroprotection or repair.

Real-world disability improvement in patients with relapsing-remitting multiple sclerosis treated with natalizumab in the Tysabri Observational Program.

BACKGROUND: Natalizumab has been associated with disability improvement as indicated by a confirmed Expanded Disability Status Scale (EDSS) score decrease. OBJECTIVE: The aim of this study was to characterize disability improvement in patients in the Tysabri Observational Program (TOP), an ongoing observational study of relapsing-remitting multiple sclerosis patients initiating natalizumab in clinical practice. METHODS: TOP data as of November 2018 were included. Confirmed disability improvement (CDI) was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline EDSS score ⩾2.0. Confirmed functional system (FS) improvement was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline score ⩾1.0 in that FS. RESULTS: Of 5384 patients, 1287 (23.9%) had CDI; 51.8% experienced CDI in the first treatment year. Among patients with CDI, 56.6% had CDI ⩾1.5 points; 34.4% had CDI ⩾2.0 points. The cumulative probability of maintaining improvement 8 years after the CDI event was 52.6%. At treatment initiation, 5363 patients (85.2%) had impairment in ⩾1 FS. At 8 years, the cumulative probability of confirmed improvement in any FS was 88.8% and ranged from 38.3% to 58.6% in individual FS. CONCLUSION: These results highlight disability improvement as a potential benefit of natalizumab treatment. Improvements across all FS demonstrate the range of functional improvement.