Expanded Disability Status Score Research Articles

Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity.

MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1β), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS. We specifically focused on the single-nucleotide polymorphism Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene, known for its crucial role in CNS functioning. We assessed the levels of miR-142-3p and IL1β in cerebrospinal fluid (CSF) obtained from a cohort of 114 patients with MS upon diagnosis. By stratifying patients according to their genetic background, statistical correlations with clinical parameters were performed. Notably, in Met-carrier patients, we observed a decoupling of miR-142-3p levels from IL1β levels in the CSF, as well as from of disease severity (Expanded Disability Status Score, EDSS; Multiple Sclerosis Severity Score, MSSS; Age-Related Multiple Sclerosis Severity Score, ARMSS) and progression (Progression Index, PI). Our discovery of the interference between BDNF Val66Met polymorphism and the synaptotoxic IL1β-miR-142-3p axis, therefore hampering miR-142-3p action on MS course, provides valuable insights for further development of personalized medicine in the field.

Gas6/TAM system as potential biomarker for multiple sclerosis prognosis.

The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity. In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay. At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS<3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2= 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Treatment satisfaction with disease-modifying therapy is the only predictor of Adherence among multiple sclerosis patients from Upper Egypt

Despite the proven efficacy of the disease-modifying therapy (DMT) for multiple sclerosis (MS), the rates of non-adherence are frequently high. We aimed to evaluate the rate of non-adherence to the first DMT in Upper Egypt and identify different contributing factors. Out of 310 patients, ninety-seven adult patients with RRMS were recruited from three MS units located in Upper Egypt and were subjected to the following: complete clinical history, expanded disability status score (EDSS), Eight-item Morisky Medication Adherence Scale (MMAS-8), abbreviated Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9), Hamilton depression scale, Fatigue Severity Scale (FSS) and the Pittsburgh Sleep Quality Index (PSQI). According to MMAS-8 scores, 63 (64.9%) of patients were non-adherent to their first DMT. Non-adherent patients are more likely to have longer disease duration (p = 0.002), longer duration on first DMT (p = 0.030), first DMT-start date before 2019 (p = 0.040), and lower treatment satisfaction scores (p = 0.016). However, there was no significant relation with physical disability, depression, fatigue, or sleep quality. On the regression analysis model, a lower treatment satisfaction score was the only predictor of DMT non-adherence (p = 0.012). Despite expanding DMT options, non-adherence among MS patients in Upper Egypt is high. Treatment satisfaction with DMT is the only predictor of adherence among MS patients of Upper Egypt. Adherence and satisfaction with the prescribed DMT should be assessed carefully to maximize DMT benefits.

Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort

Background: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. Methods: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea–hypopnea index ⩾ 15. Results: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. Conclusion: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

Risk Factors for Psychiatric Disorders in Patients with Multiple Sclerosis-A Single-Center Study in the Polish Population.

Aim: The aim of this study was to determine the prevalence of mental disorders in a group of patients with multiple sclerosis (MS) during outpatient treatment. Additionally, an attempt was made to assess the influence of parameters related to patients and their clinical status on the prevalence of mental disorders. Materials and Methods: This study was conducted between 2017 and 2018 in a group of 103 patients with MS who underwent treatment at the Outpatient Clinic of Neurology at the Clinical Hospital No. 1 in Zabrze, Poland. Sociodemographic data were collected, and the course of the underlying disease and comorbidities underwent assessment. The Mini International Neuropsychiatric Interview (MINI) and psychiatric examination were used to assess the occurrence of mental disorders. Results: In this study, female subjects accounted for 67.96% of patients (mean age: 43 years). Of all patients, 67% of subjects were clinically diagnosed with mental disorders during their lifetime. The results of the MINI Questionnaire showed that 33% of MS patients had a history of a major depressive episode, while 8.7% of patients met the criteria for a depressive episode. The same number of patients were treated for recurrent depressive disorders. Generalized anxiety disorder was diagnosed in 10.7% of patients, agoraphobia in 8.7% and panic disorder in 7.8%. Most patients (94.2%) had a low risk of suicide, according to the MINI Questionnaire. This study did not show a significant influence of age, sex, duration of MS symptoms or severity of symptoms as expressed by the Expanded Disability Status Score (EDSS) on the prevalence of mental disorders (p = 0.05). However, a significantly higher median EDSS score was found in patients with a history of mental disorders (p = 0.03). Additionally, a significant negative correlation was found between having a family and a psychiatric diagnosis (p = 0.01). A statistically significant negative correlation was found between the level of education and the suicide risk as assessed by the MINI Questionnaire (p = 0.03). Conclusions: This study showed a high prevalence of mental disorders in patients with MS, of which depressive episodes and anxiety disorders were the most commonly reported. There may exist a relationship between the degree of disability of MS patients and a higher prevalence of mental disorders. Patients with MS who do not have a family may be more susceptible to mental disorders. In turn, patients with a lower level of education may show a higher risk of suicide. This suggests the need for psychological and psychiatric support for patients with MS, with particular consideration given to those who are alone, those with more severe disability and patients with a lower level of education.

A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial.

Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS. The objective of this clinical trial is to evaluate whether metformin, as add-on treatment, is superior to placebo in delaying disease progression in patients with non-active PMS. MACSiMiSE-BRAIN is a multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled clinical trial, conducted at five sites in Belgium. Enrollment of 120 patients with non-active PMS is planned. Each participant will undergo a screening visit with assessment of baseline magnetic resonance imaging (MRI), clinical tests, questionnaires, and a safety laboratory assessment. Following randomization, participants will be assigned to either the treatment (metformin) or placebo group. Subsequently, they will undergo a 96-week follow-up period. The primary outcome is change in walking speed, as measured by the Timed 25-Foot Walk Test, from baseline to 96 weeks. Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) and hand function (9-Hole Peg test). Annual brain MRI will be performed to assess evolution in brain volumetry and diffusion metrics. As patients may not progress in all domains, a composite outcome, the Overall Disability Response Score will be additionally evaluated as an exploratory outcome. Other exploratory outcomes will consist of paramagnetic rim lesions, the 2-minute walking test and health economic analyses as well as both patient- and caregiver-reported outcomes like the EQ-5D-5L, the Multiple Sclerosis Impact Scale and the Caregiver Strain Index. Clinical trial authorization from regulatory agencies [Ethical Committee and Federal Agency for Medicines and Health Products (FAMHP)] was obtained after submission to the centralized European Clinical Trial Information System. The results of this clinical trial will be disseminated at scientific conferences, in peer-reviewed publications, to patient associations and the general public. ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.

Time to Disability Milestones and Annualized Relapse Rates in NMOSD and MOGAD.

To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age. We analyzed data from individuals with NMOSD and MOGAD from the German Neuromyelitis Optica Study Group registry. Applying survival analyses, we estimated risk factors and computed time to disability milestones as defined by the Expanded Disability Status Score (EDSS). We included 483 patients: 298 AQP4-IgG+ NMOSD, 52 AQP4-IgG-/MOG-IgG- NMOSD patients, and 133 patients with MOGAD. Despite comparable annualized attack rates, disability milestones occurred earlier and after less attacks in NMOSD patients than MOGAD patients (median time to EDSS 3: AQP4-IgG+ NMOSD 7.7 (95% CI 6.6-9.6) years, AQP4-IgG-/MOG-IgG- NMOSD 8.7) years, MOGAD 14.1 (95% CI 10.4-27.6) years; EDSS 4: 11.9 (95% CI 9.7-14.7), 11.6 (95% lower CI 7.6) and 20.4 (95% lower CI 14.1) years; EDSS 6: 20.1 (95% CI 16.5-32.1), 20.7 (95% lower CI 11.6), and 37.3 (95% lower CI 29.4) years; and EDSS 7: 34.2 (95% lower CI 31.1) for AQP4-IgG+ NMOSD). Higher age at onset increased the risk for all disability milestones, while risk of disability decreased over time. AQP4-IgG+ NMOSD, AQP4-IgG-/MOG-IgG- NMOSD, and MOGAD patients show distinctive relapse-associated disability progression, with MOGAD having a less severe disease course. Investigator-initiated research has led to increasing awareness and improved treatment strategies appearing to ameliorate disease outcomes for NMOSD and MOGAD. ANN NEUROL 2024;95:720-732.

Individuals With Multiple Sclerosis Exhibit More Regular Center of Mass Accelerations After Physical Therapy

ObjectiveThe purpose of this investigation was to explore if a physical therapy program involving strength, flexibility, balance, and walking can improve the uncharacteristic gait variability and overall mobility of persons living with multiple sclerosis (pwMS). DesignPre-post design to evaluate the mobility improvements after undergoing 6 weeks of a gait and balance physical therapy intervention. SettingThe initial 2 weeks were conducted at a medical center under close supervision of a physical therapist. The remaining 4 weeks were performed by the patient at their home and monitored via teleconferences. ParticipantsFifteen pwMS with relapsing-remitting (N=11) or secondary progressive multiple sclerosis (N=4) were enrolled in this study (7 women; mean age: 54.8±9 years; Kurtzke Expanded Disability Status Score range: 3.0-6.5). A group of healthy age-matched controls (N=15) were used for comparisons. InterventionsThe 6-week physical therapy intervention included exercises that targeted strength, flexibility, balance, and walking. The initial 2 weeks of the intervention were performed on-site with the remaining 4 weeks home-based. The therapy was performed twice-a-day for 5 consecutive days each week. Each session was 45 minutes in length. Main Outcome MeasuresPreferred walking speed, spatiotemporal gait kinematics, and a 6-minute walk test were completed before and after therapy. The standard deviation (SD) and sample entropy were used to evaluate the amount of variability and the regularity of the time-dependent variations in the center of mass (COM) accelerations during the 6-minute walk test. ResultsBefore the intervention, the SD of the COM was reduced, and the time-dependent variations were less regular in the pwMS than the control group. After therapy, the SD was 12% larger, and the time-dependent variations were more 7% regular in the pwMS. The effect size for these changes were large (0.91 and 0.94, respectively), suggesting these changes were meaningful. The changes in the regularity of the COM were related to the mobility improvements in the preferred walking velocity and 6-minute walk test. ConclusionsThe results suggest that pwMS have altered COM variability during gait, which can be improved with a similar physical therapy program. These changes appear to be linked with the extent of the mobility improvements.

The Effectiveness of a Single Dry Needling Session on Gait and Quality of Life in Multiple Sclerosis: A Double-Blind Randomized Sham-Controlled Pilot Trial.

Gait disorders are a major cause of disability and reduced health-related quality of life in people with multiple sclerosis (pwMS). Dry needling (DN) has demonstrated positive results to improve gait parameters in patients with stroke. The main aim of this study was to evaluate the effect of a single session of DN in the gait performance of pwMS. A double-blind parallel randomized sham-controlled pilot trial was conducted. Study participants received a single session of active DN or sham DN in the gastrocnemius medialis muscle. Pre-treatment and immediately post-treatment measurements were taken, as well as at one and four weeks after the intervention. Outcomes related to gait performance (Timed 25-Foot Walk), self-perceived walking capacity (Multiple Sclerosis Walking Scale), risk of falls (Timed Up and Go test), disability level (Expanded Disability Status Score) and quality of life (Multiple Sclerosis Quality of Life-54 questionnaire and Analogic Quality of Life scale) were evaluated. 18 patients who had multiple sclerosis participated in the study. The group who received active DN showed within-group significant statistical differences immediately after treatment for gait performance (p = 0.008) and risk of falls (p = 0.008), as well as for self-perceived walking capacity at one week (p = 0.017) and four weeks (p = 0.011) and quality of life at four weeks (p = 0.014). Regarding the comparison between groups, only significant results were obtained in the physical domain of the quality of life at four weeks (p = 0.014). DN seems to be a promising therapeutic tool for the treatment of gait disorders in pwMS. However, when results were compared with sham DN, no differences were found.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study

BackgroundEndometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. ObjectiveTo characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. MethodsWe retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). ResultsUsing a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. ConclusionWhen controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

Reliability of telemedicine evaluation for EDSS functional systems in multiple sclerosis.

Introduction: There was an increase in telemedicine during the COVID-19 pandemic to follow patients with multiple sclerosis (MS). However, there is scarce data if online evaluations can cover important information assessed during in-clinic appointments, especially the Expanded Disability Status Score (EDSS). This study aims to develop a remote evaluation tool for EDSS functional systems and compare the performance with face-to-face evaluations. Methods: This was a single-center study that included all MS patients followed up at outpatient clinics of Hospital São Lucas Pontifícia Universidade Católica do Rio Grande do Sul, between April and August 2022. Initially, patients were routinely in-clinic evaluated by one trained neurologist for EDSS. After, patients were evaluated remotely without any information about the in-clinic EDSS results. We used a standardized interview with an interactive video platform to evaluate EDSS functional systems by telemedicine. Results: Forty-nine participants completed the two steps. Intra-class coefficient was 0.97 (95% CI: 0.95-0.98), concordance for EDSS below 4.0 was 0.87 (95% CI: 0.77-0.93) and ≥4.0 was 0.97 (95% CI: 0.89-0.99). There was perfect agreement in the final EDSS in 71.4% of the online and in-clinic evaluations. In the multivariate analysis, the visual (beta = 0.453; p = 0.003) and pyramidal (beta = 0.403; p = 0.009) systems contributed significantly to the difference in the final EDSS. Conclusion: The telemedicine tool created in this study can detect changes in functional systems with reliable results compared to in-clinic EDSS assessment. Telemedicine evaluations may reduce the number of in-clinic visits and the disease burden for patients with MS.

Factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorders

ObjectiveTo investigate the factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorder (NMOSD) and provide evidence for disease monitoring and clinical intervention.MethodsEighty-four patients with NMOSD at Xuanwu Hospital Capital Medical University were enrolled in this retrospective study. Before treatment, blood was collected from all patients, and their expanded disability status scores were assessed.ResultsOf the 84 patients assessed, 66 (78.57%) had an expanded disability status scale score < 7, and 18 (21.43%) had scores ≥ 7. The univariate analysis showed that the total bilirubin (TBil), cerebrospinal fluid albumin (CSF ALB), cerebrospinal fluid immunoglobulin G (CSF IgG), QALB, and QIgG levels in the group with scores ≥ 7 were significantly different from those with scores < 7 (P < 0.05). In addition, Spearman’s correlation analysis showed a significant correlation between ALB and expanded disability status scores in patients with NMOSD (P < 0.05), and the multivariate logistic regression analysis showed that TBil was an independent factor influencing the degree of disability in patients with NMOSD (P < 0.05). The receiver operating characteristic curve was constructed using TBil values; the area under the curve of TBil was 0.729 (P < 0.01), and the best cut-off value was 11.015 g/L. Its sensitivity in predicting the severity of disability in NMOSD patients was 51.5% while its specificity was 88.9%.ConclusionTBil is an independent factor that influences the severity of disability in patients with NMOSD. In addition, ALB is closely related to NMOSD severity, and some factors associated with the BBB are significantly increased in severely disabled NMOSD patients.

Evaluation of Inflammation in the Peripheral Multiple Sclerosis Retina Using Ultra-Widefield Optical Coherence Tomography: A Pilot Study.

Reports of fundus fluorescein angiography (FFA) in active multiple sclerosis (MS) have shown peripheral perivenous sheathing. We sought to assess the feasibility of ultra-widefield (UWF) FFA and optical coherence tomography (OCT) in assessing the peripheral retina in MS. Participants with MS and healthy controls underwent bilateral UWF fundus photography and FFA. Swept-source OCTs were captured centrally, peripherally, and to delineate any abnormalities visualized. We recruited five people with relapsing remitting MS, with a mean age of 36.9 (± 9.9), mean disease duration of 11 years (± 6.3), and a median expanded disability status score of 0.75 (0 to 2.5). In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. A pilot study using UWF-FFA and peripheral OCT to examine the retina in MS suggests that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:586-588.].

Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial.

Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population. CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya. A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI. BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS. NCT04377555.

Multiple Sclerosis in Korea: A Hospital-Based, Multicenter, Epidemiological Study

Background: In the present era of rapidly evolving treatment options, there is a need for better understanding of the epidemiology and current management of patients with multiple sclerosis (MS). A survey was conducted to determine the epidemiologic characteristics and the current treatment status of patients with MS in Korea.Methods: In April 2022, we collected data on patients with MS, including number participating in follow up, sex ratio, current disease modifying treatment (DMT), and disability status (Expanded Disability Status Score, EDSS) from 30 major MS centers in Korea.Results: A total of 1,290 patients with MS was identified, with a female to male ratio of 2.4:1. Geographically, 1,047 patients (81%) were being monitored at hospitals in the capital regions (Seoul, Incheon, and Gyeonggi-do), while 243 (19%) were receiving care at hospitals outside the capital regions. There were 1,199 patients on DMTs, with 876 (73%) taking drugs with moderate efficacy and 264 (22%) taking drugs with high efficacy. Patients with current EDSS score greater than 3.0 and 5.5 numbered 242 (20%) and 105 (9%), respectively.Conclusion: The hospital-based prevalence survey revealed the number and geographical distribution of patients with MS in Korea.

Cyclophosphamide for severe acute forms of central nervous system inflammatory disorders

Cyclophosphamide (CYC) may be an effective treatment in patients who fail first line therapy for severe central nervous system (CNS) inflammatory disorders including CNS vasculitis, neuromyelitis optica, autoimmune encephalitis, tumefactive and aggressive multiple sclerosis (MS). We performed a retrospective analysis of 46 patients treated with CYC after failing first line therapy for severe CNS inflammatory conditions. Primary outcomes included modified Rankin Scale (mRS) for patients classified into a non-MS group, Expanded Disability Status Score (EDSS) for MS patients, and Targeted Neurological Deficit score (TND) for all patients. Secondary outcome included neuroimaging studies following CYC treatment. By the second follow up period (average of 7 months) mRS in the non-MS group improved from 3.7 to 2.2 and EDSS in the MS group improved from 5.6 to 3.8. Average TND score at 7 months was 2.8 (mild-marked improvement). At first follow up (average 5.6 months), 76.2% (32/42) patients had either stable or improving imaging, and 83.3% (30/36) patients had stable or improving imaging at second follow up (average 13.6 months). Adverse events were reported by 31.9% of patients with most common being nausea and vomiting, headache, alopecia, and hyponatremia. Treatment with CYC can result in disease stabilization of severe CNS inflammatory diseases and is generally well tolerated.

Functional assessment of the dural lymphatic vessels using dynamic contrast MRI in multiple sclerosis.

The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance. This prospective study included 20 patients with MS (17 women; age=46.4 [27, 65] years; disease duration=13.6 [2.1, 38.0] years, expanded disability status score (EDSS)=2.0 [0, 6.5]). Patients were scanned on a 3.0T MRI system using intravenous contrast-enhanced fluid-attenuated inversion recovery MRI. Signal in the dural lymphatic vessel along the superior sagittal sinus was measured to calculate peak enhancement, time to maximum enhancement, wash-in and washout slopes, and the area under the time-intensity curve (AUC). Correlation analysis was performed to examine the relationship between the lymphatic dynamic parameters and the demographic and clinical characteristics, including the lesion load and the brain parenchymal fraction (BPF). Contrast enhancement was detected in the dural lymphatics in most patients 2-3min after contrast administration. BPF had a significant correlation with AUC (p<.03), peak enhancement (p<.01), and wash-in slope (p=.01). Lymphatic dynamic parameters did not correlate with age, BMI, disease duration, EDSS, or lesion load. Moderate trends were observed for correlation between patient age and AUC (p=.062), BMI and peak enhancement (p=.059), and BMI and AUC (p=.093). Intravenous dynamic contrast MRI of the dural lymphatics is feasible and may be useful in characterizing its hydrodynamics in neurological diseases.

Feasibility of at-home motor assessments using wireless technology in patients with myelopathy: year 1 follow up of CYGNET, an observational study of patients with adrenomyeloneuropathy (P6-6.006)

Feasibility of at-home motor assessments using wireless technology in patients with myelopathy: year 1 follow up of CYGNET, an observational study of patients with adrenomyeloneuropathy (P6-6.006)

Investigating the Relationship Between Verbal Fluency and Some Clinical Characteristics in Patients With Multiple Sclerosis

Background and Objective One of the types of cognitive impairments in patients with multiple sclerosis (MS) is verbal fluency. Clinical characteristics affect verbal fluency. This study investigates the relationship between verbal fluency and some clinical characteristics in patients with MS. Materials &amp; Methods This cross-sectional descriptive study was performed on 71 patients with MS in Rofideh Rehabilitation Hospital. Patients were selected by convenience non-probability sampling method. The study tool included the Pittsburgh sleep quality questionnaire, fatigue severity scale, depression inventory-fast screen, and controlled oral word association test. The collected data were analyzed in SPSS software, version 18. The linear regression model was fitted to evaluate the effect of independent variables on verbal fluency. Results The study included 67.6% of female and 32.4% of male patients. The average age of the patients was 43.9±35.54 years and the average duration of the disease was 13.83±5.62 years. The results showed that some clinical characteristics including fatigue, disease type, first symptom, and sleep status have a significant relationship with the verbal fluency score of patients with MS (P&lt;0.05). No significant relationship was observed between expanded disability status score, depression, and duration of disease with verbal fluency in patients with MS. Conclusion The results showed that patients with the progressive type of the disease and patients whose onset of the disease was reported with visual symptoms had a weaker performance in verbal fluency than other participants. This issue can be considered in the early stages of disease diagnosis.