Lower Expanded Disability Status Scale Scores Research Articles

Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. This prospective observational study was designed in a tertiary center during one year. All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

Health-related quality of life and utilities among Lebanese patients with Multiple Sclerosis: A cross-sectional study

ObjectiveThis study assessed the Health-Related Quality of Life (HRQoL) and utilities of Multiple Sclerosis (MS) patients in Lebanon using generic and MS-specific QoL instruments, categorized by disease severity, and explored factors associated with HRQoL. MethodsThis was a cross-sectional, retrospective HRQoL study collecting data through face-to-face interviews using the EQ-5D-5 L and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaires. We enrolled Lebanese patients aged ≥18 years, diagnosed with MS for >6 months. Patients were categorized by disease severity using the expanded disability status scale (EDSS) scores: 0–3 (mild MS), 4–6.5 (moderate MS), and 7–9 (severe MS). Bivariate and linear regression analyses were performed to study factors associated with HRQoL. ResultsA total of 210 patients (mean age: 43.3 years; 65.7 % females) were included. The mean EQ-5D-5 L utility score was 0.74. This score decreased significantly with disease severity (p < 0.001 for the trend): 0.93, 0.60, and 0.32 for mild, moderate, and severe MS, respectively. The mean MusiQoL global index score was 71.33 and was significantly lower for severe MS (58.68), than for moderate (65.23) and mild (77.80), (p < 0.001 for the trend). Higher educational level, lower EDSS scores, and longer disease duration were associated significantly with a higher EQ-5D-5 L utility (R2 = 0.67), while employment, lower EDSS scores, and decrease in cognitive difficulties were associated with better MusiQoL utility (R2 = 0.46). ConclusionsThis study reveals a significant and gradual deterioration in HRQoL as MS progresses, resulting in low utility scores for patients with severe MS.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran

ObjectiveThe relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. MethodsIn a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. ResultsA total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. ConclusionWe found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Natalizumab treatment of multiple sclerosis - a Danish nationwide study with 13 years of follow-up.

Natalizumab is a widely used high-efficacy treatment in multiple sclerosis (MS). Real-world evidence regarding long-term effectiveness and safety is warranted. We performed a nationwide study evaluating prescription patterns, effectiveness, and adverse events. A nationwide cohort study using the Danish MS Registry. Patients initiating natalizumab between June 2006 and April 2020 were included. Patient characteristics, annualized relapse rates (ARRs), confirmed Expanded Disability Status Scale (EDSS) score worsening, MRI activity (new/enlarging T2- or gadolinium-enhancing lesions), and reported adverse events were evaluated. Further, prescription patterns and outcomes across different time periods ("epochs") were analysed. In total, 2424 patients were enrolled, with a median follow-up time of 2.7 years (interquartile range (IQR) 1.2-5.1). In recent epochs, patients were younger, had lower EDSS scores, had fewer pre-treatment relapses and were more often treatment naïve. At 13 years of follow-up, 36% had a confirmed EDSS worsening. On-treatment ARR was 0.30, corresponding to a 72% reduction from pre-initiation. MRI activity was rare, 6.8% had activity within 2-14 months from treatment start, 3.4% within 14-26 months, and 2.7% within 26-38 months. Approximately 14% of patients reported adverse events, with cephalalgia constituting the majority. During the study, 62.3% discontinued treatment. Of these, the main cause (41%) was due to JCV antibodies, while discontinuations due to disease activity (9%) or adverse events (9%) were less frequent. Natalizumab is increasingly used earlier in the disease course. Most patients treated with natalizumab are clinically stable with few adverse events. JCV antibodies constitute the main cause for discontinuation.

Identification of Neuropsychological Phenotypes in Pediatric Multiple Sclerosis Using Unsupervised Machine Learning (P12-9.001)

<h3>Objective:</h3> To identify cognitive phenotypes in pediatric multiple sclerosis (MS) using an unsupervised machine learning approach. <h3>Background:</h3> Recent studies identified distinct cognitive phenotypes in adult MS patients using unsupervised machine learning approaches. <h3>Design/Methods:</h3> Fifty-three pediatric MS patients underwent clinical examination including Expanded Disability Status Scale (EDSS) to assess global disability. A comprehensive neuropsychological battery (Selective Reminding Test, Spatial Recall Test, Trail Making Test, Symbol Digit Modalities Test, Semantic verbal fluency test and Phonemic verbal fluency test) was administered to all patients. Raw scores of each test were converted to z-scores according to normative data. Cognitive tests z-scores were included in a k-means cluster analysis to identify cognitive phenotypes. Between-group comparisons of demographic, clinical and cognitive variables were computed using linear regression models or nonparametric tests as appropriate. Statistical significance was corrected for multiple comparisons (Bonferroni method). <h3>Results:</h3> In our sample, median age was 15.9 years (interquartile range [IQR] 13.6 – 16.8), 68% (36 patients) were girls and the mean disease duration was 1.8±1.7 years. Cluster analysis identified three cognitive phenotypes: preserved cognition (27 patients [51%]), mild verbal memory/semantic fluency involvement (19 patients [36%]) and severe multidomain involvement (7 patients [13%]). Across groups, there were no significant differences in age, sex and disease duration. Lower EDSS scores were found in patients with preserved cognition (median EDSS 1.0 [IQR 1.0 – 1.0]) than patients with mild verbal memory/semantic fluency involvement (median EDSS 1.5 [IQR 1.0 – 2.0]; p=0.01) and patients with severe multidomain involvement (median EDSS 2.0 [IQR 1.25 – 2.75]; p=0.004). <h3>Conclusions:</h3> Pediatric MS patients present with distinct cognitive phenotypes ranging from preserved cognition to severe multidomain involvement. Cognitive phenotypes are not associated with age, sex and disease duration. Patients with preserved cognition are characterized by low global disability. <b>Disclosure:</b> Damiano Mistri has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Alessandro Meani has nothing to disclose. Carmen Vizzino has nothing to disclose. Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Comparison of 2-year Teriflunomide Outcomes between DMT-naive and switch patients with Relapsing MS: subanalysis of the Real-World TERICARE study (P6-3.003)

<h3>Objective:</h3> To evaluate the effect of teriflunomide on clinical and patient-reported outcomes (PROs) in disease-modifying therapy (DMT)-naive and previously treated (switch) patients with relapsing-remitting multiple sclerosis (RRMS). <h3>Background:</h3> Clinical trials and real-world evidence have shown that patients with RRMS benefit from teriflunomide regardless of prior exposure to DMT. <h3>Design/Methods:</h3> TERICARE was a multicentre, observational and prospective study in Spain. RRMS patients with no relapses within the last 30 days before the inclusion received teriflunomide for 2-years. This analysis compared the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), disability worsening, quality of life (Multiple Sclerosis Impact Scale, MSIS-29), fatigue (Modified Fatigue Impact Scale-5), and depression (Beck Depression Inventory-II) between DMT-naive and switch patients. <h3>Results:</h3> Of 325 patients included, 117 were DMT-naive and 208 switch patients. At baseline, DMT-naive was younger than switch patients (40.9 <i>vs</i> 44.4 years; p=0.003), had shorter disease duration (3.1 <i>vs</i> 9.5 years; p&lt;0.001), lower EDSS score (1.3 <i>vs</i> 2.0; p&lt;0.001), higher number of relapses in the last 2 years (1.3 <i>vs</i> 0.6; p&lt;0.001) and ARR (95% CI) (0.63 [0.53–0.74] <i>vs</i> 0.31 [0.26–0.37]; p&lt;0.001). The ARR was significantly reduced in both groups after 12 months (DMT-naive=0.24; p&lt;0.001; switch=0.21; p=0.032) and 24 months (DMT-naive=0.19; switch=0.16; p&lt;0.001, both groups). A greater reduction of ARR was observed in DMT-naive both at 12 (63% <i>vs</i> 33%) and 24 months (70% <i>vs</i> 49%). Mean change in EDSS score did not vary between groups, nor the percentage of patients with disability worsening at 12 (20% <i>vs</i> 13.2%; p=0.167) and 24 months (24.2% <i>vs</i> 17.6%; p=0.246). DMT-naive experienced a greater and significant reduction (improvement) in psychological MSIS-29 score at month 24 compared to switch group (−7.11 <i>vs</i> −1.48; p=0.019). <h3>Conclusions:</h3> Teriflunomide shows effectiveness in both DMT-naive and switch RRMS patients with a trend towards better relapse and quality of life outcomes in DMT-naive. <b>Disclosure:</b> Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol-Myers-Squibb. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Meca Lallana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Meca Lallana has received research support from Merck. The institution of Dr. Meca Lallana has received research support from Novartis. The institution of Dr. Meca Lallana has received research support from Roche. The institution of Dr. Meca Lallana has received research support from Sanofi. The institution of Dr. Meca Lallana has received research support from Biogen. Dr. Prieto has nothing to disclose. Dr. Caminero Rodriguez has nothing to disclose. Javier Olaskoaga has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi-Genzyme. Rosa Casademont Portell has received personal compensation for serving as an employee of Sanofi. Mrs. Forner has received personal compensation for serving as an employee of Sanofi.

Neuromyelitis Optica Spectrum Disorder With Anti-Aquaporin-4 Antibody: Outcome Prediction Models.

BackgroundRecognizing the predictors of disease relapses in patients with anti-aquaporin-4 antibody (AQP4-ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is essential for individualized treatment strategy. We aimed to identify the factors that predicted relapses among patients with AQP4-ab-positive NMOSD, develop outcome prediction models, and validate them in a multicenter validation cohort.MethodsBetween January 2015 and December 2020, 820 patients with NMOSD were registered at Huashan Hospital. We retrospectively reviewed their medical records, and included 358 AQP4-ab-positive patients with 1135 treatment episodes. Univariate and multivariate analyses were used to explore the predictors of relapse, severe visual or motor disability during follow-up. A model predicting the 1- and 2-year relapse-free probability was developed and validated in an external validation cohort of 92 patients with 213 treatment episodes.ResultsLower serum AQP4-ab titer (< 1:100), higher Expanded Disability Status Scale (EDSS) score at onset (≥ 2.5), and use of intravenous methylprednisolone (IVMP) at the first attack predicted an overall lower annualized relapse rate. Older age (> 48 years), optic neuritis at onset, and higher onset EDSS score (≥ 2.5) significantly increased the risk for blindness, while IVMP at the first attack and maintenance therapy reduced the risk for blindness. Myelitis at onset increased the possibility of motor disability (EDSS ≥ 6.0), severe motor disability or death (EDSS ≥ 8.0), while maintenance therapy reduced these possibilities. Anderson and Gill model identified that the risk factors predicting recurrent relapses under certain treatment status were female gender, high AQP4-ab titer (≥ 1:100), previous attack under same therapy, lower EDSS score at treatment initiation (< 2.5), and no maintenance therapy or oral prednisone lasting less than 6 months. A nomogram using the above factors showed good discrimination and calibration abilities. The concordance indexes in the primary and validation cohort were 0.66 and 0.65, respectively.ConclusionThis study reports the demographic, clinical and therapeutic predictors of relapse, and severe visual or motor disability in NMOSD. Early identification of patients at risk of unfavorable outcomes is of paramount importance to inform treatment decisions.

Performance of Activities of daily living in people with multiple sclerosis

ObjectiveMultiple sclerosis (MS) may result in activity and participation limitations, including the performance of activities of daily living (ADL). This study aims at systematically investigate ADL performance by using Assessment of Motor and Process Skills (AMPS) in people with MS (PwMS) of all disease types and within the Kurtzke Expanded Disability Status Scale (EDSS) range from 1.0 – 8.0. MethodsEight multiple sclerosis (MS) centres participated in data collection of a consecutive sample of PwMS. Participants were referred for assessment to occupational therapy (OT) by treating physician or recruited from neurology department in each hospital and assessed by EDSS and AMPS. The AMPS is an observational, criterion referenced ADL assessment, providing values for a person's ADL performance in terms of motor and process skills. Criterion referenced cut-off scores were established at 2.0 for motor skills and at 1.0 for process skills and both values above the cut-off score indicate competent (independent, safe, efficient and effortless) ADL performance. Process skills refer to the act of carrying out a series of actions and is summarized in terms of efficiency, like initiating without pauses, continuing actions through to completion, performing actions in logical order (sequences), choosing, and completing the task as planned (heeds). ResultsTwo hundred and ten PwMS were recruited (48 +/- 13 years of age, 145 women/65 men, average disease duration was 11.8 +/- 9.6 years, average EDSS was 4.8+/-1.8). Average motor skills score was 1.01+/- 1.12 (indicating need for assistance with evidence of increased clumsiness/physical effort) and average process skills score was 1.02 +/- 0.66 (risk zone, questionable efficiency and more likely to need assistance). Overall, motor skills and process skills decreased with increasing EDSS score. No need for assistance in motor skills was indicated in subjects with lower EDSS scores (1.0 – 2.5). In higher EDSS group (≥4.5), 57% of subjects needed assistance in motor skills and 27% in process skills. The competency in process skills was either questionable or reduced within all EDSS scores. However, 33–38% of subjects with higher EDSS scores (6.0–8.5) showed competent performance in process skills. Overall correlation between motor and process scores was moderate (r = 0.56, p<0.0001), but no significant relationships between motor and process skills were found in the lower EDSS (1–2.5) and high EDSS scores (8–8.5). Further, EDSS and disease type were significant predictors, explaining 52.7% of motor skills and 22.3% of process skills performance. ConclusionProblems in ADL performance were found in EDSS categories 1.0 to 8.0 and in all disease types, therefore it is advisable to screen all PwMS for ADL deficits and provide relevant rehabilitation interventions.

Untreated patients with multiple sclerosis: A study of French expert centers.

Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Of the 21,189 patients with MS (age 47.1±13.1 years; Expanded Disability Status Scale (EDSS) score 3.4±2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n=11,693) were the most likely to receive DMT, 14.8% (95% CI14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR]0.52 [95% CI0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.

Demographic features, behavioral measures, and clinical factors as predictors of cognitive function in patients with multiple sclerosis

Background: One of the most concerning features that involves 40-70% of patients with multiple sclerosis (MS) is cognitive impairment. Moreover, it affects various aspects of patients’ life. In this regard, this study was conducted to find independent predictors of cognitive function.Method: We performed a cross-sectional analysis on 92 patients chosen from MS clinic of Sina hospital, Iran. After completing a general questionnaire of demographic and various clinical features, the included participants (patients with RRMS) underwent neuropsychological assessment using Minimal Assessment of Cognitive function in Multiple Sclerosis (MACFIMS), Expanded disability Status Scale (EDSS), Beck Depression Inventory II (BDI-II), and National American Adult Reading Test (NAART). An un-weighted average of MACFIMS subscales z-scores was reported as cognitive index. In order to find the association between CI and different factors, each variable was entered in a simple regression model first. Then, a univariate multiple regression model was invoked to evaluate the predictors of cognitive index in patients.Results: Simple regression for cognitive index of 92 patients (86% female) with a mean age of 33.4±7.6 years old suffering of RRMS for 6.8±4.8 years revealed patients with history of former smoking (p=0.001), sole visual symptoms as the presentation sign of the study (β=-0.341, p=0.001), lower EDSS score (β=-0.299, p=0.005), higher NAART score (β=0.416, p≤0.0001), and college education (p=0.001), had better cognitive function in our study population. Such factors including age, educational status, BDI-II score, EDSS score, and disease duration were fixed and the other significant factors entered once separately and then simultaneously in the univariate multiple linear regression model. It was revealed that former smoking (β=-0.372, p≤0.0001), NAART (β=0.304, p=0.002), and EDSS (β= -0.185, P=0.045) are associated significantly with the cognitive function of patients with multiple sclerosis.Conclusion: This study demonstrated NAART, as a proxy of premorbid intelligence, history of former smoking, and EDSS score may have effects on cognitive function in MS. Future studies need to be invoked for the evaluation of the causality relation of these factors.

Discriminative ability of fall efficacy scale international in Iranian people with multiple sclerosis

BackgroundThe discriminative validity of fall efficacy scale international (FES-I) in differentiating between fallers and non-fallers, levels of functional mobility, dynamic balance and disability has not been assessed in Persian speaking people with multiple sclerosis (MS). ObjectiveTo assess reliability, factor structure, construct and known group validity, sensitivity and specificity of FES-I for differentiating individuals with and without a history of fall and determining a cutoff point of the Persian version of the FES-I in people with MS. MethodOne hundred thirty people with all subtypes of MS were included. The ability of FES-I in differentiating fall history was assessed using receiver operating characteristic (ROC). Also the FES-I score of groups based on expanded disability status scale (EDSS) 1-3.5 low and 4–6 moderate, time up and go (TUG) ≥14 sec and functional reach test (FRT) ≥25 cm were compared. The correlation between FES-I with EDSS, TUG, FRT and short form health survey (SF-36) was assessed. ResultsThe ROC curve analysis revealed that the FES-I could differentiate people with MS based on fall history at a cutoff score of 35.5. The area under the curve (AUC) was 0.86 (sensitivity 76%; specificity 95%). Significant difference was observed between the FES-I score of groups with moderate and low EDSS scores (d = 2.98), higher than 14 sec TUG (d = 2.18) and lower than 25 cm FRT(d = 2.53). Significant high correlation was observed between FES-I with TUG (r = 0.88), EDSS (r = 0.91), FRT (r = -0.83), SF-36 physical (r = -0.87) and mental (r = -0.70) subscales. ConclusionsThe Persian versions of the FES-I could differentiate people with MS with fall history, higher disability, lower functional mobility and balance deficiency.

Vitamin D and Disease Severity in Multiple Sclerosis-Baseline Data From the Randomized Controlled Trial (EVIDIMS).

Objective: To investigate the associations between hypovitaminosis D and disease activity in a cohort of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) patients.Methods: In 51 RRMS and 2 CIS patients on stable interferon-β-1b (IFN-β-1b) treatment recruited to the EVIDIMS study (Efficacy of Vitamin D Supplementation in Multiple Sclerosis (NCT01440062) baseline serum vitamin D levels were evaluated. Patients were dichotomized based on the definition of vitamin D deficiency which is reflected by a < 30 vs. ≥ 30 ng/ml level of 25-hydroxyvitamin D (25(OH)D). Possible associations between vitamin D deficiency and both clinical and MRI features of the disease were analyzed.Results: Median (25, 75% quartiles, Q) 25(OH)D level was 18 ng/ml (12, 24). Forty eight out of 53 (91%) patients had 25(OH)D levels < 30 ng/ml (p < 0.001). Patients with 25(OH)D ≥ 30 ng/ml had lower median (25, 75% Q) T2-weighted lesion counts [25 (24, 33)] compared to patients with 25(OH)D < 30 ng/ml [60 (36, 84), p = 0.03; adjusted for age, gender and disease duration: p < 0.001]. Expanded disability status scale (EDSS) score was negatively associated with serum 25(OH)D levels in a multiple linear regression, including age, sex, and disease duration (adjusted: p < 0.001).Interpretation: Most patients recruited in the EVIDIMS study were vitamin D deficient. Higher 25(OH)D levels were associated with reduced T2 weighted lesion count and lower EDSS scores.

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients. Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results. Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration &gt; 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0. Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.

How common is truly benign MS in a UK population?

ObjectivesThe prevalence and definition of benign multiple sclerosis (BMS) remain controversial. Most definitions are based on the Expanded Disability Status Scale (EDSS), not encompassing the wider impact of disease. The...

Performed and perceived walking ability in relation to the Expanded Disability Status Scale in persons with multiple sclerosis

BackgroundThe severity of walking impairment in persons with multiple sclerosis (pwMS) at different levels on the expanded disability status scale (EDSS) is unclear. Furthermore, it is unclear if the EDSS is differently related to performed- and perceived walking capacity tests. AimsTo quantify walking impairment and perceived impact of MS on walking according to EDSS scores and to examine the relations between these parameters in pwMS. MethodsEDSS was collected by neurologists and walking was assessed by the timed 25ft walk test (T25FWT), two minute walk test (2MWT), six minute walk test (6MWT) and the 12-item MS walking scale (MSWS-12) in 474 PwMS with mild (EDSS 1–4: n=200) to moderate (EDSS 4.5–6.5: n=274) MS. Magnitude of walking impairment was calculated and related to EDSS. ResultsCompared to predicted values in healthy controls, walking speed was reduced by 41.5±25.8% in the 6MWT for the total MS group and by 21.8±20.2% and 55.8±19.1% in the mild and moderate MS subgroups, respectively. The EDSS score showed the strongest relationship to the 2MWT and the 6MWT in the total MS group (r=−0.76, p<0.0001), to the MSWS-12 score in the mild MS group (r=0.56, p<0.0001), and to the 2MWT in the moderate MS group (r=−0.50, p<0.0001). ConclusionIn pwMS (EDSS scores 1–6.5), walking speed is on average reduced by ~40% when compared to predicted values in healthy controls, and impairments are already present at early disease stages, suggesting early initiation of rehabilitation. The 2MWT and 6MWT show the strongest relationship to EDSS, but the MSWS-12 identify impairments more gradually at low EDSS scores.

Stress Urinary Incontinence in Women With Multiple Sclerosis.

PurposeTo report the prevalence and risk factors of stress urinary incontinence (SUI) and the prevalence of intrinsic sphincter deficiency in women with multiple sclerosis (MS).MethodsWe conducted a retrospective study. Female patients with MS, followed for lower urinary tract symptoms (LUTS) during a 15-year period were included. Demographic data, MS history, expanded disability status scale (EDSS) score at the urodynamic visit, obstetrical past, birth weight, LUTS, and urodynamic findings were collected. SUI was defined as incontinence during cough, or any effort. A maximum urethral closure pressure less than 30 cm H2O defined intrinsic sphincter deficiency.ResultsWe included 363 women with a mean age of 46.7±10.8 years and a mean disease duration of 12.9±8.7 years. The incidence of relapsing remitting MS, a secondary progressive form, and a primary progressive form was 60.6%, 32.8%, and 6.6%, respectively. The prevalence of SUI was 31.4%. The prevalence of intrinsic sphincter deficiency was 1.4% and 0.8% of these patients had a SUI (P=0.300). In a multivariate analysis, women with a SUI had significantly higher birth weight (P=0.030), a pelvic organ prolapse (P=0.021), urgent urinary incontinence (P=0.006), a lower EDSS score (P=0.019), and a weaker containing effort (P<0.001).ConclusionsThe prevalence of SUI in women with MS was 31.4%. This symptom could affect the quality of life of women with MS.

Predictors of long‐term disability accrual in relapse‐onset multiple sclerosis

To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009). We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.

Effectiveness of multi-disciplinary rehabilitation for patients with Neuromyelitis Optica

Introduction: Neuromyelitis optica (NMO), previously considered a subtype of multiple sclerosis (MS), is now known to be a unique disorder associated with autoantibodies against aquaporin-4. The rehabilitation protocols for MS have been applied to NMO, without specific measures of efficacy.Purpose: The evaluation of the effectiveness of an MS type inpatient rehabilitation program for patients with NMO.Patient and Methods: Retrospective chart reviews of 15 inpatients with NMO and 32 inpatients with MS. Clinical severity was assessed by the Expanded Disability Status Scale (EDSS), functional assessments were scored using the Functional Independence Measure (FIM), the Montebello Rehabilitation Factor Score (MRFS), and the Functional Ambulation Category (FAC). There was a higher percentage of women in the NMO group (87% vs 56% P = 0.003). The MS group had significantly more cognitive and communication deficits (P = 0.003 and P = 0.00001). No significant differences were found in admission FIM, EDSS and FAC scores.Results: Both groups benefitted, however at discharge, the NMO group showed greater improvement in FIM scores (NMO admission 79 ± 24, discharge 98 ± 21; MS admission 80 ± 28, discharge 89 ± 28); and lower EDSS score (NMO from 7.2 ± 1.4 to 6.3 ± 1.4; MS from 7.4 ± 1.4 to 7 ± 1.5).Conclusions: Inpatient multidisciplinary rehabilitation programs available for the patients with MS may be successfully implemented for patients with NMO.

Follow-up of pediatric patients treated by IVIG for Langerhans cell histiocytosis (LCH)-related neurodegenerative CNS disease.

The follow-up of eight Japanese children with Langerhans cell histiocytosis (LCH)-related neurodegenerative central nervous system (ND-CNS) disease who were treated with intravenous immunoglobulin (IVIG) for >3 years is described. The patients developed ND-CNS disease at a median age of 5.2 (range 3.5-10.0) years and received IVIG treatment for a median duration of 6.5 + (range 3.7 to 10+) years. After a median follow-up period of 11.6 + (8.3+ to 13.9+) years after ND-CNS disease diagnosis, the median Expanded Disability Status Scale (EDSS) score of the eight patients was 4.0 (range 2.0-9.5). At the last follow-up as of March 2014, three patients have low EDSS scores (<3.0) and can walk without any assistance. Another three patients have EDSS scores of 3.5-4.5 and can walk by themselves, albeit occasionally with supports. However, the remaining two patients are wheelchair bound or bed ridden. The school performance of seven of the eight patients was below average. IVIG appeared to be most beneficial when it was administered soon after ND-CNS disease diagnosis when the EDSS scores were low (1.0-2.5). The patients who began receiving IVIG when their high EDSS scores were higher (4.5-7.0) appeared to obtain less benefit. To prevent progression of ND-CNS disease in patients with LCH, it is recommended to introduce IVIG early and to continue this therapy for >3 years.

P003 - Demographics and clinical characteristics of pediatric onset multiple sclerosis

Background Although several studies indicated that the prevalence of pediatric multiple sclerosis (MS) is approximately 5% of the adult MS cohort, reports on clinical features of pediatric MS is scarce in our region. Objective To study the demographics and clinical characteristics of MS patients whose disease started before the age of 17 years. Methods Utilizing the national MS registry, we conducted a cross-sectional study to identify MS patients who had their disease onset before 17 years of age. Demographics and clinical characteristics (age, age at onset, symptoms presentation at onset, disease duration, disease course, relapses, expanded disability status scale (EDSS), and use of disease modifying therapies (DMTs)) were collected. Results Records of 111 pediatric MS patients were analyzed; of whom 71.2% were females. Mean age at onset and mean disease duration were 14.85 and 9.49 years respectively. Family history was reported in 12.6%. Supratentorial, optic pathway, cerebellar/brainstem, and spinal symptoms were the presenting symptoms in 28.8%, 23.4%, 35.1%, and 27% of patients respectively. 14.4% of patients presented with multifocal symptoms at onset. Most of the patients (82%) had relapsing remitting course, while clinically isolated syndrome group constituted 8.1%. The mean number of relapses was 3.36 and the mean EDSS at last visit was 2.51. Most of the patients (75%) had EDSS less than 4. The mean time to secondary progressive MS in 9.9% of the patients was 14.63 years. Of 79.08% patients who were exposed to DMTs, 13.51% had aggressive course necessitating the use of natalizumab as a first line therapy while 37.36% escalated to second line therapies during their disease course. Conclusions MS patients with pediatric-onset had comparable clinical characteristics to adult onset MS. Most patients had low EDSS scores despite the relatively higher percentage of patients with initial aggressive course and breakthrough disease throughout their disease course. Although several studies indicated that the prevalence of pediatric multiple sclerosis (MS) is approximately 5% of the adult MS cohort, reports on clinical features of pediatric MS is scarce in our region. To study the demographics and clinical characteristics of MS patients whose disease started before the age of 17 years. Utilizing the national MS registry, we conducted a cross-sectional study to identify MS patients who had their disease onset before 17 years of age. Demographics and clinical characteristics (age, age at onset, symptoms presentation at onset, disease duration, disease course, relapses, expanded disability status scale (EDSS), and use of disease modifying therapies (DMTs)) were collected. Records of 111 pediatric MS patients were analyzed; of whom 71.2% were females. Mean age at onset and mean disease duration were 14.85 and 9.49 years respectively. Family history was reported in 12.6%. Supratentorial, optic pathway, cerebellar/brainstem, and spinal symptoms were the presenting symptoms in 28.8%, 23.4%, 35.1%, and 27% of patients respectively. 14.4% of patients presented with multifocal symptoms at onset. Most of the patients (82%) had relapsing remitting course, while clinically isolated syndrome group constituted 8.1%. The mean number of relapses was 3.36 and the mean EDSS at last visit was 2.51. Most of the patients (75%) had EDSS less than 4. The mean time to secondary progressive MS in 9.9% of the patients was 14.63 years. Of 79.08% patients who were exposed to DMTs, 13.51% had aggressive course necessitating the use of natalizumab as a first line therapy while 37.36% escalated to second line therapies during their disease course. MS patients with pediatric-onset had comparable clinical characteristics to adult onset MS. Most patients had low EDSS scores despite the relatively higher percentage of patients with initial aggressive course and breakthrough disease throughout their disease course.