Expanded Disability Severity Scale Research Articles

International validation of meaningfulness of postural sway and gait to assess myeloneuropathy in adults with adrenoleukodystrophy.

The most common manifestation of X-linked adrenoleukodystrophy (ALD) is a slowly progressive myeloneuropathy, which leads to imbalance and gait disturbances. The variable progression of the disease complicates evaluation of its progression rate. Wearable sensors allow for easy and frequent balance and gait collection. This study reports baseline data from a longitudinal study on the quantitative assessment of balance and gait with wearable sensors and their clinical relevance. Data were collected from adult patients in two institutions. Postural body sway and gait parameters were measured using accelerometers. Disease severity was measured by the Expanded Disability Severity Scale (EDSS). Falling frequency and quality of life (QOL) were collected in men. The relationship between sway and gait variables and EDSS score, participants' use of a walking aid, and falling frequency was evaluated. One hundred twenty individuals with ALD were included. Sway variables significantly differentiate participants' assistive device use. Sway and gait variables were correlated to the EDSS in both sexes. Both gait speed and sway were correlated with falling frequency in men from one institution. Select QOL subscores were correlated with the EDSS in males from one institution. Accelerometry generated comparable results across sites. This study confirms the clinical correlation between spinal cord disease and imbalance and gait in ALD. For the first time, this study shows clinically meaningful relationships for sway and gait with use of an assistive device, falling frequency and QOL. Wearable accelerometers are a valid means to measure sway and gait in ALD. These measures are promising outcomes for clinical trial designs to assess myeloneuropathy in ALD and to monitor disease progression in individuals.

Intensive Aerobic Cycling Is Feasible and Elicits Improvements in Gait Velocity in Individuals With Multiple Sclerosis: A Preliminary Study.

Aerobic exercise (AEx) has many potential benefits; however, it is unknown whether individuals with multiple sclerosis (MS) can attain the optimal intensity and duration to harness its effects. Forced-rate exercise (FE) is a novel paradigm in which the voluntary pedaling rate during cycling is supplemented to achieve a higher exercise intensity. The aim of this pilot trial was to investigate the feasibility and initial efficacy of a 12-week FE or voluntary exercise (VE) cycling intervention for individuals with MS. Twenty-two participants with MS (Expanded Disability Severity Scale [EDSS] 2.0-6.5) were randomly assigned to FE (n = 12) or VE (n = 10), each with twice weekly 45-minute sessions at a prescribed intensity of 60% to 80% of maximum heart rate (HR). Eighteen individuals (FE = 11; VE = 7) completed the intervention, however, adaptations were required in both groups to overcome barriers to cycling. Overall, participants exercised for an average of 42.2 ± 2.3 minutes at an aerobic intensity of 65% ± 7% of maximum HR and a pedaling cadence of 67.3 ± 13.3 RPM. Cycling led to improved treadmill walking speed (0.61 to 0.68 m/sec, P = .010), with somewhat greater improvement with FE compared to VE (increase of 0.09 vs 0.03 m/s, respectively, P = .17) post intervention. Notably, the participant with the highest disability level (EDSS 6.5) tolerated FE but not VE. Aerobic exercise is feasible for individuals with MS, although those with increased disability may require novel paradigms such as FE to achieve targeted intensity. Further trials are warranted to investigate the effects of FE across the MS disability spectrum.

Spatio-Temporal Gait Parameters to Distinguish Multiple Sclerosis Disability during Dual- Task Walk

Background Differences in gait between people with multiple sclerosis (PwMS) and controls are well documented and effective in distinguishing between disability levels based on the Expanded Disability Severity Scale (EDSS) during preferred walking (PrW). However, clinically measured PrW does not consider higher cognitive demand required to perform more complex motor tasks in everyday living (e.g., conversing while walking). A dual-task walk (DTW) mimics this cognitive load, thus offering greater ecological validity when distinguishing between disability levels in PwMS. Purpose To evaluate the utility of spatio-temporal gait parameters during a DTW to distinguish between mild and moderate disability in PwMS. Methods Gait velocity, stride velocity, step width, step length and mean gait variability index were measured in a convenience sample of 44 PwMS (36=mild MS: EDSS 0 to 3.5, 7=moderate MS: EDSS 4.0 to 6.0) during PrW and DTW using a Protokinetic Zeno Walkway. Subjects were dichotomized into mild or moderate disability groups. Variable selection was performed using stepwise linear regression, including all gait metrics and covariates (sex, age, height, type of multiple sclerosis: relapsing or progressive, and disease duration). Logistic regressions were performed separately for PrW and DTW. Results During PrW, greater step length (cm) was associated with mild disability (R^2=0.39, ChiSquare=14.72, p<0.001). During DTW, both stride width (ChiSquare=4.69, p=0.03) and step length (ChiSquare=5.16, p=0.02) were associated with disability (R^2=0.38): people with moderate disability demonstrated increased step width and decreased step length. Discussion Results highlight the need to investigate differences in gait during DTW in addition to PrW in PwMS with different disability levels. However, generalizability is limited due to disproportionate sample sizes of disability groups. Still, DTW protocols may provide supplemental information for monitoring disability among PwMS, which can inform clinicians of the effectiveness of gait interventions or disease progression. Differences in gait between people with multiple sclerosis (PwMS) and controls are well documented and effective in distinguishing between disability levels based on the Expanded Disability Severity Scale (EDSS) during preferred walking (PrW). However, clinically measured PrW does not consider higher cognitive demand required to perform more complex motor tasks in everyday living (e.g., conversing while walking). A dual-task walk (DTW) mimics this cognitive load, thus offering greater ecological validity when distinguishing between disability levels in PwMS. To evaluate the utility of spatio-temporal gait parameters during a DTW to distinguish between mild and moderate disability in PwMS. Gait velocity, stride velocity, step width, step length and mean gait variability index were measured in a convenience sample of 44 PwMS (36=mild MS: EDSS 0 to 3.5, 7=moderate MS: EDSS 4.0 to 6.0) during PrW and DTW using a Protokinetic Zeno Walkway. Subjects were dichotomized into mild or moderate disability groups. Variable selection was performed using stepwise linear regression, including all gait metrics and covariates (sex, age, height, type of multiple sclerosis: relapsing or progressive, and disease duration). Logistic regressions were performed separately for PrW and DTW. During PrW, greater step length (cm) was associated with mild disability (R^2=0.39, ChiSquare=14.72, p<0.001). During DTW, both stride width (ChiSquare=4.69, p=0.03) and step length (ChiSquare=5.16, p=0.02) were associated with disability (R^2=0.38): people with moderate disability demonstrated increased step width and decreased step length. Results highlight the need to investigate differences in gait during DTW in addition to PrW in PwMS with different disability levels. However, generalizability is limited due to disproportionate sample sizes of disability groups. Still, DTW protocols may provide supplemental information for monitoring disability among PwMS, which can inform clinicians of the effectiveness of gait interventions or disease progression.

Cost, efficacy and safety comparison between early intensive and escalating strategies for multiple sclerosis: a Systematic Review and Meta-analysis (P14-3.009)

<h3>Objective:</h3> Our goal was to compare the effectiveness, safety, and cost between Escalating (ESC) and Early intensive (EIT) strategies for the treatment of multiple sclerosis. <h3>Background:</h3> ESC strategy consists in starting low-to-moderate-efficacy disease modifying drugs (DMDs) in the treatment of multiple sclerosis, upscaling to high-efficacy DMDs when facing evidence of active disease. EIT strategy, on the other hand, is based on starting high-efficacy DMDs as first-line therapy. The optimal strategy is unclear in patients with multiple sclerosis. <h3>Design/Methods:</h3> We searched MEDLINE, EMBASE, and SCOPUS until September 4th, 2022 for studies comparing EIT and ESC strategies in adult patients with relapsing-remitting multiple sclerosis and a minimum follow-up of 5 years. Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year time horizon were the main outcomes. Economic analysis followed a Markov model using previously described transition matrix, utility and costs of multiple sclerosis and DMDs. Bias assessment was performed using ROBINS-I. This review was registered with PROSPERO (CRD42022358097). <h3>Results:</h3> Seven studies involving 3,467 participants demonstrated a 30% reduction in the risk of EDSS worsening at 5 years (RR 0.7; [0.59–0.83]; p&lt;0.001) in the EIT group. Safety profile was similar between EIT and ESC strategies (RR 1.92; [0.38–9.72]; p=0.4324). EIT group showed 0.03 increase in QALY and a reduction of £1506 in a 5-year time horizon model. EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and/or cladribine was cost-effective in our models. <h3>Conclusions:</h3> EIT presents a higher efficacy in preventing disability progression, without harnessing safety or cost in a 5-years time horizon. <b>Disclosure:</b> Mr. Pipek has nothing to disclose. Mr. Mahler Ferreira Oliveira has nothing to disclose. Miss Nascimento has nothing to disclose. Samira Luísa Apóstolos-Pereira has nothing to disclose. Dr. SILVA has nothing to disclose. Dr. Callegaro has nothing to disclose.

Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis.

The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies. We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost. Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p<0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p=0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model. EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.

Risk and prognostic factors for SARS-CoV-2 infection in Spanish population with multiple sclerosis during the first five waves.

Data on coronavirus disease 2019 (COVID-19) incidence in patients with multiple sclerosis (MS) during the first wave have been published but are scarce for the remaining waves. Factors associated with COVID-19 infection of any grade are also poorly known. The aim of this study was to analyze the incidence, clinical features, and risk factors for COVID-19 infection of any grade in patients with MS (pwMS) during waves 1-5. This study prospectively analyzes the cumulative incidence of COVID-19 from the first to the fifth waves by periodic case ascertainment in pwMS followed at the University Hospital of Getafe (UHG). Global and stratified cumulative incidence was calculated. Logistic regression models were used to estimate the weight of selected variables as risk and prognostic factors. We included 431 pwMS, of whom 86 (20%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall cumulative incidence of confirmed cases was similar to that of Madrid (13,689 vs. 13,307 per 100,000 habitants) but 3 times higher during the first wave and slightly lower from the second to the fifth waves. The majority (86%) of pwMS developed mild forms of COVID-19. Smoking was the only factor associated with a decreased risk of SARS-CoV2 infection of any grade [odds ratio (OR) 0.491; 95% CI 0.275-0.878; p = 0.017]. Risk factors associated with severe forms were Expanded Disability Severity Scale (EDSS) ≥3.5 (OR 7.569; 95% CI 1.234-46.440) and pulmonary disease (OR 10.763; 95% CI 1.27-91.254). The incidence of COVID-19 was similar in this MS cohort to the general population. Smoking halved the risk of being infected. Higher EDSS and pulmonary comorbidity were associated with an increased risk of severe forms.

Is there a role for off‐label high‐efficacy disease‐modifying drugs in progressive multiple sclerosis? A network meta‐analysis

Ocrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.

TO INVESTIGATE THE ASSOCIATION OF DOSE-DEPENDENT VITAMIN D SUPPLEMENT ON CLINICAL OUTCOMES IN VETERANS WITH MULTIPLE SCLEROSIS

Objective: To investigate the association of daily dose-dependent Vitamin-D supplement on clinical outcomes including mortality in veterans with multiple sclerosis (MS) with low serum Vitamin-D (25[OH]D) levels. This Methods: observational, longitudinal study reports on data collected from 1/1/2000 to 12/31/2020 at the MS Regional Program. We reviewed the electronic records of 163 veterans with MS who were followed every four months in our MS clinic. The study sample was divided into three groups based on the daily Vitamin-D supplement doses: low (1000 IU/day), medium (2000 IU/day) and high (4000 IU/day). The clinical outcomes were changes in physical disability (Expanded Disability Severity Scale (EDSS)), function (Total Function Independence Measures (TFIM)), time-to-event EDSS score of 6 (progressive MS) and mortality. Results: There were 32 patients in the low, 46 in the medium, and 85 in the high-dose daily Vitamin-D supplement groups. The mean age of the entire study sample was 51 12 SD years (range 23 - 79 years). The mean duration of MS was 21.7 13 years. The mean initial EDSS and TFIM scores were 3.4 2.8 and 111 17 SD. At entry, mean serum 25[OH]D and calcium levels were 30 16 nmol/l and 9.3 0.4. The risk of MS-related progressive disability (time-to-event EDSS score 6) was lower and there were fewer deaths in the high- (compared to low- and medium-) dose groups. Conclusion: This study suggests that among veterans with MS and low 25[OH]D levels, those who received high-doses daily of supplemental Vitamin-D supplement were associated with a decreased risk of MS-related progressive disability and death than those who received a lower dose. No adverse clinical or biochemical events were noted.

Word finding, prosody and social cognition in multiple sclerosis.

Impairments in speech and social cognition have been reported in people with multiple sclerosis (pwMS), although their relationships with neuropsychological outcomes and their clinical utility in MS are unclear. To evaluate word finding, prosody and social cognition in pwMS relative to healthy controls (HC). We recruited people with relapsing MS (RMS, n= 21), progressive MS (PMS, n= 24) and HC (n= 25) from an outpatient MS clinic. Participants completed a battery of word-finding, social cognitive, neuropsychological and clinical assessments and performed a speech task for prosodic analysis. Of 45 pwMS, mean (SD) age was 49.4 (9.4) years, and median (range) Expanded Disability Severity Scale score was 3.5 (1.0-6.5). Compared with HC, pwMS were older and had slower information processing speed (measured with the Symbol Digit Modalities Test, SDMT) and higher depression scores. Most speech and social cognitive measures were associated with information processing speed but not with depression. Unlike speech, social cognition consistently correlated with intelligence and memory. Visual naming test mean response time (VNT-MRT) demonstrated worse outcomes in MS versus HC (p= .034, Nagelkerke's R2 =65.0%), and in PMS versus RMS (p= .009, Nagelkerke's R2 =50.2%). Rapid automatised object naming demonstrated worse outcomes in MS versus HC (p= .014, Nagelkerke's R2 =49.1%). These word-finding measures showed larger effect sizes than that of the SDMT (MS vs. HC, p= .010, Nagelkerke's R2 =40.6%; PMS vs. RMS, p= .023, Nagelkerke's R2 =43.5%). Prosody and social cognition did not differ between MS and HC. Word finding, prosody and social cognition in MS are associated with information processing speed and largely independent of mood. Impairment in visual object meaning perception is potentially a unique MS disease-related deficit that could be further explored and cautiously considered as an adjunct disability metric for MS.

042 Determinants of baseline disability in relapsing remitting multiple sclerosis

BackgroundDeterminants of multiple sclerosis aetiology and natural history remain unknown.ObjectivesTo determine factors associated with level of disability measured by Expanded Disability Severity Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS).MethodsWe collected demographic, clinical, smoking and alcohol history in an incidence cohort of patients with RRMS recruited within six months of diagnosis. Ordinal logistic regression was used to examine association of EDSS with clinical and demographic features. Linear regression was used to examine asso- ciation between the same variables and MSFC.ResultsWe recruited 440 patients. Mean age at onset was 33.61 and 75.9% were female. Age at onset was shown to be associated with higher disability as measured by EDSS and MSFC. Sex was not signifi- cantly associated with outcome. After adjustment for age and sex, time to diagnosis, current smoking, having ever smoked and obesity were associated with higher EDSS whereas having ever smoked were associated with worse MSFC scores.ConclusionsDisability in relapsing-remitting multiple sclerosis is partly determined by demographic features and modifiable risk factors even early in disease course. Much of the variation remains to be elucidated and individualised risk prediction is an unmet need.fraser@tonnard.co.uk

Vaccine hesitancy among people with multiple sclerosis

BackgroundThe current severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has raised awareness of vaccine hesitancy. Specific reasons for vaccine hesitancy among people with multiple sclerosis (pwMS) have not been fully described. Notably, pwMS may experience higher morbidity from vaccine-preventable diseases such as influenza, pneumococcal disease, and human papillomavirus (HPV)-associated warts and malignancies. Furthermore, screening for immunity against measles, mumps and rubella (MMR) is not standard practice, despite a resurgence of measles and mumps outbreaks in Europe and worldwide. We aimed to evaluate general vaccination status among pwMS to better inform vaccine practices in this cohort. MethodsThis was a prospective audit of pwMS attending an Irish tertiary referral MS centre. We designed a questionnaire that explored awareness, uptake, and hesitancy for the influenza, pneumococcal, SARS-CoV-2, HPV, and MMR vaccines. The clinician administered the questionnaire during the outpatient MS clinic. ResultsOne-hundred-and-five pwMS participated in the audit, mean (SD) age 47.3 (12.8) years, mean MS disease duration 14.1 (9.5) years, median Expanded Disability Severity Scale (EDSS) score 2.0 (IQR 1.0-6.0), forty-nine (46.7%) were taking either maintenance immunosuppressive or immune reconstitution therapies. SARS-CoV-2 vaccine willingness among pwMS was higher (90.5 vs 60-80%) than that reported in other Western countries, and higher than that for the influenza and pneumococcal vaccines (∼80%) for which perceived unnecessity and unfamiliarity respectively were the main limiting factors. The primary reason for SARS-CoV-2 vaccine hesitancy was safety concern. PwMS who were explicitly advised by a healthcare professional to obtain the influenza vaccine were more likely to do so than those who were not (odds ratio, 8.1, 95% CI 2.8 – 23.4, p<0.001). Of pwMS currently receiving B-cell therapy (ocrelizumab/rituximab, n=12), all but one (n=11, 91.7%) have never received the pneumococcal vaccine, and a quarter (n=3) were uncertain whether to obtain this in the future. Patient-reported uptake of HPV (1.0%) and MMR (51.4%) vaccines were suboptimal. Prevalence of vaccine promotion among healthcare professionals was low (influenza vaccine, 4.8 – 32.4%; pneumococcal vaccine, 0 – 18.1%). ConclusionsVaccine hesitancy is common (10-20%) in pwMS, consequent to insufficient knowledge and misconceptions about vaccination among pwMS and suboptimal vaccine promotion by healthcare professionals who manage pwMS. Conscientious and context-specific vaccination counselling is necessary to tackle vaccine hesitancy among pwMS, including (i) avoiding infection-associated disability accrual during MS relapses, (ii) reducing the potentially higher risk of life-threatening/treatment-refractory complications that may be observed in those who develop vaccine-preventable infections while receiving certain DMTs, and (iii) avoiding attenuated vaccine responses or delayed/interrupted DMT with early pre-treatment vaccine delivery where possible.

Central Vestibular Functions Correlate With Fatigue and Walking Capacity in People With Multiple Sclerosis.

Imbalance and fatigue are among the most common and disabling symptoms of multiple sclerosis (MS). Vestibular rehabilitation studies demonstrate not only improvements in balance but fatigue also, suggesting a relationship between central vestibular integration and fatigue. The objective of this study was to determine whether the relationship between balance and fatigue in people with MS is seen between other measures of central vestibular integration and fatigue and to understand how central vestibular integration measures interrelate. This cross-sectional study consisted of 40 people with MS (age = 27-55years, Expanded Disability Severity Scale score = 1.0-6.5) who completed vestibular ocular reflex testing, subjective visual vertical testing, static posturography, dynamic gait, 2 self-report fatigue surveys, and a 6-Minute Walk Test to assess walking capacity/physical fatigue was completed. Spearman correlations were calculated between variables. Measures of central vestibular integration were significantly correlated with measures of fatigue and walking capacity and with each other. The correlations between physical fatigue and central vestibular functions were larger than self-reported fatigue correlations with central vestibular functions. The relationship between balance and fatigue extends to other measures requiring central vestibular integration, suggesting a deficit in central vestibular processing in people with MS. These measures may compliment balance assessment as outcome measures for vestibular rehabilitation in people with MS. Fatigue measures should be included in vestibular rehabilitation as secondary outcomes. Correlations between central vestibular integration and fatigue in people with MS suggest that future studies of vestibular rehabilitation should include fatigue, as a secondary outcome measure as vestibular function and fatigue may share similar a similar etiology in people with MS.

Do people with multiple sclerosis receive appropriate support from the National Disability Insurance Scheme matching their level of disability? A description of disease 'burden and societal cost in people with multiple sclerosis in Australia' (BAC-MS).

Objective This study is the first to assess if the National Disability Insurance Scheme (NDIS) package allocated to people with multiple sclerosis (pwMS) is correlated with the disability level measured by standardised neurological assessment. Methods We aimed to recruit 10 pwMS per expanded disability status score (EDSS) step, including EDSS 0 (no disability) up to 9 (bedridden), and requested information about their NDIS application. Value of their packages was compared with mobility, cognition and psychological impact. Results Out of 186 pwMS, only 49% of all patients had an NDIS package approved. The mean values of the annual allowance were AU$30 318 for patients with mild disability, AU$38 361 for moderate disability and AU$115 113 for severe disability. There was a striking variability in packages approved, but restricted mobility seems to be the driving factor. Rejection rates were <20% in patients with mild and moderate disability and none in those with severe disability. The package value correlated with EDSS steps, cognitive impairment and physical impact, but not psychological impact. Conclusions This is the first study to assess if NDIS packages correlate with internationally accepted disability scales. The NDIS support was correlated with disability measured by EDSS steps and cognition, but not psychological impact of the disease. What is known about the topic? There are over 25 000 Australians living with multiple sclerosis, which is one of the most common neurological diseases leading to disability in early age. The National Disability Insurance Scheme has been introduced since 2013 to particularly assist young disabled Australians to participate in the community. Whether the approved package correlates with internationally accepted disability scores has not yet been assessed. What does this paper add? This study is the first to correlate disability, as assessed by the Expanded Disability Severity Scale (EDSS), with the approved package value. What are the implications for practitioners? Multiple sclerosis is a very variable disease affecting quality of life not only due to impairment of mobility, but also cognition and mental health. Although the NDIS package value was correlated with an EDSS and cognition, the psychological impact of the disease is often neglected.

A study of prevalence and factors related to cognitive impairment in Thai patients with neuromyelitis optica

AbstractBackgroundNeuromyelitis Optica (NMO) is a demyelinating disease caused by an autoimmune process that attacks the central nervous system resulting in a neurological deficit. Previous studies showed cognitive problems in these patients, especially the decline in processing speed, episodic memory, executive function, and attention. We aimed to study the prevalence and the factors related to cognitive impairment in Thai patients with NMO.MethodWe recruited 83 participants diagnosed with NMO by the 2015 international consensus diagnostic criteria for NMO spectrum disorder who visited the Demyelinating Disease Clinic at Siriraj Hospital. Participants with the last clinical relapse within 3 months or those who could not perform cognitive tests due to disability were excluded. Cognitive functions were assessed by using the Montreal Cognitive Assessment – Thai version (MoCA‐T) and Frontal Assessment Battery (FAB). The subjective reports of any cognitive problem by interviewing participants and their informants were also collected. Demographic data, cognitive performance, and factors related to the MoCA‐T score were analyzed.ResultThe mean MoCA‐T score in patients with NMO was 22.96 ± 3.82, and the mean FAB score was 15.27 ± 2.47. The majority (54%) of them had cognitive impairment according to the cut‐off of the MoCA‐T score of less than 25. Participants with cognitive impairment had significantly less education than those without cognitive impairment (9.9 4.3 and 14.6 3.6 years, p &lt; 0.001), and they used more time to complete the MoCA‐T (p &lt; 0.001). The disease severity evaluated by the Expanded Disability Severity Scale was associated with the MoCA‐T score (r = ‐0.29, p = 0.008). Age, the annual relapse rate in the first five years, duration of disease, and Aquaporin‐4 antibody status were not associated with cognitive impairment (all p &gt; 0.5). Interestingly, the informant‐report of cognitive decline in NMO patients was associated with the less MoCA‐T performance (p = 0.032), but not the self‐report (p = 0.397).ConclusionMost of the Thai patients with NMO had cognitive impairment, which related to education, disease severity, and also the perception of their relatives. Future studies that included more comprehensive neuropsychological evaluations and neuroimaging findings are needed in these patients.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis

Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Can We Improve the Monitoring of People With Multiple Sclerosis Using Simple Tools, Data Sharing, and Patient Engagement?

Technological innovation is transforming traditional clinical practice, enabling people with multiple sclerosis (pwMS) to contribute health care outcome data remotely between clinic visits. In both relapsing and progressive forms of multiple sclerosis (MS), patients may experience variable disability accrual and symptoms throughout their disease course. The potential impact on the quality of life (QoL) in pwMS and their families and carers is profound. The introduction of treatment targets, such as NEDA (no evidence of disease activity) and NEPAD (no evidence of progression or active disease), that guide clinical decision-making, highlight the importance of utilizing sensitive instruments to measure and track disease activity and progression. However, the gold standard neurological disability tool—expanded disability severity scale (EDSS)—has universally recognized limitations. With strides made in our understanding of MS pathophysiology and DMT responsiveness, maintaining the status quo of measuring disability progression is no longer the recommended option. Outside the clinical trial setting, a comprehensive monitoring system has not been robustly established for pwMS. A 21st-century approach is required to integrate clinical, paraclinical, and patient-reported outcome (PRO) data from electronic health records, local databases, and patient registries. Patient and public involvement (PPI) is critical in the design and implementation of this workflow. To take full advantage of the potential of digital technology in the monitoring and care and QoL of pwMS will require iterative feedback between pwMS, health care professionals (HCPs), scientists, and digital experts.

Contribution of cortical lesions to cognitive impairment in Japanese patients with multiple sclerosis

Cortical lesions (CLs) have a low prevalence and are associated with physical disabilities in Japanese patients with multiple sclerosis (MS). However, the contribution of CLs to cognitive impairment remains unclear in Asian MS. Sixty-one prospectively enrolled MS patients underwent three-dimensional double inversion recovery MR imaging, the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Apathy Scale (AS), the Fatigue Questionnaire (FQ), and the Hospital Anxiety and Depression Scale (HADS) within a 1-week period. The cognitive impairment index (CII) score was calculated to measure patients’ overall cognitive impairment. MS patients with CLs had poorer scores than those without CLs in most BRB-N tests, but scored comparably in the FQ, AS, and HADS. The number of CLs correlated negatively with all BRB-N test scores and positively with total CII scores. Leukocortical lesions were more extensively associated with cognitive dysfunction in various domains than intracortical lesions. Stepwise multiple regression analysis revealed that potential confounding factors for the highest quartile of CII score were the number of CLs (odds ratio 2.38, p = 0.0070) and the Expanded Disability Severity Scale score (odds ratio 2.13, p = 0.0003). Our results demonstrate that the presence and number of CLs are robustly associated with cognitive dysfunction in Asian MS patients.

The role of robotic gait training coupled with virtual reality in boosting the rehabilitative outcomes in patients with multiple sclerosis

Motor impairment is the most common symptom in multiple sclerosis (MS). Thus, a variety of new rehabilitative strategies, including robotic gait training, have been implemented, showing their effectiveness. The aim of our study was to investigate whether an intensive robotic gait training, preceding a traditional rehabilitative treatment, could be useful in improving and potentiating motor performance in MS patients. Forty-five patients, who fulfilled the inclusion criteria, were enrolled in this study and randomized into either the control group (CG) or the experimental group (EG). A complete clinical evaluation, including the Expanded Disability Severity Scale, the Functional Independence Measure, the Hamilton Rating Scale for Depression, the time up and go test (TUG), and the Tinetti balance scale, was performed at baseline (T0), after 6 week (T1), at the end of rehabilitative training (T2), and 1 month later (T3). A significant improvement was observed in the EG for all the outcome measures, whereas the CG showed an improvement only in TUG. In contrast, from T1 to T2, only CG significantly improved in all outcomes, whereas the EG had an improvement only regarding TUG. From T2 to T3, no significant differences in Functional Independence Measure scores emerged for both the groups, but a significant worsening in Tinetti balance scale and TUG was observed for the CG and in TUG for the EG. Our study provides evidence that robotic rehabilitationn coupled with two-dimensional virtual reality may be a valuable tool in promoting functional recovery in patients with MS.

Exploring cognitive reserve in multiple sclerosis: New findings from a cross-sectional study

ABSTRACTIntroduction: The cognitive reserve (CR) hypothesis attempts to explain the discrepancy between brain damage and clinical manifestations in neurodegenerative diseases. Recently the concept of CR was applied to the multiple sclerosis (MS) model. Our aim is to investigate the impact of demographic and clinical variables on cognitive outcome in MS patients. Method: A total of 72 MS patients were assessed by Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), and high field magnetic resonance examination. We performed a multivariate linear regression analysis, including each cognitive test scores as dependent variables and CRI together with age, normalized brain volume (NBV), normalized cortical volume (NCV), expanded disability severity scale (EDSS) score, and disease duration as independent variables. Moreover, we assessed whether one of the CRI subscores (CRI–Education, CRI–WorkingActivity, CRI–LeisureTime) predicted cognitive performance more than the other. Finally, to assess the CR hypothesis in our sample, we conducted the same analyses including the interaction term CRI × NCV. Results: From the multiple regression analysis, it emerged that the CRI total score influenced sustained attention, concentration, information processing speed, and verbal learning. Among the three CRI subscores, CRI–Education and CRI–WorkingActivity had the most influence. Age and EDSS score were the other significant predictors. We did not find evidence for a moderation effect of CR on negative influence of atrophy on cognitive status. Conclusions: This study focused on the contribution of CR to predict neuropsychological outcome in MS. We used a new standardized questionnaire to provide a global index including three main source of CR: education, working activity, and leisure time activities. Our preliminary findings suggest that the CR is an important predictor of better performance on cognitive tests in MS patients. However, at this stage of the study, we are unable to confirm the CR hypothesis.

Ocular motor measures of cognitive dysfunction in multiple sclerosis I: inhibitory control.

Our ability to control and inhibit behaviours that are inappropriate, unsafe, or no longer required is crucial for functioning successfully in complex environments. Here, we investigated whether a series of ocular motor (OM) inhibition tasks could dissociate deficits in patients with multiple sclerosis (MS), including patients with only a probable diagnosis (clinically isolated syndrome: CIS), from healthy individuals as well as a function of increasing disease duration. 25 patients with CIS, 25 early clinically definite MS patients (CDMS: ≤7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis), and 25 healthy controls participated. All participants completed a series of classic OM inhibition tasks [antisaccade (AS) task, memory-guided (MG) task, endogenous cue task], and a neuropsychological inhibition task [paced auditory serial addition test (PASAT)]. Clinical disability was characterised in CDMS patients using the Expanded Disability Severity Scale (EDSS). OM (latency and error) and PASAT performance were compared between patient groups and controls, as well as a function of disease duration. For CDMS patients only, results were correlated with EDSS score. All patient groups made more errors than controls on all OM tasks; error rate did not increase with increasing disease duration. In contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with increasing disease duration. PASAT performance did not discriminate patient groups or disease duration. The EDSS did not correlate with any measure. These OM measures appear to dissociate deficit between patients at different disease durations. This suggests their utility as a measure of progression from the earliest inception of the disease.