Feasibility of exergaming for upper extremity rehabilitation in people with multiple sclerosis: prospective clinical trial.

BACKGROUND: Exergaming has been suggested as a rehabilitation method since it is more motivational for people with multiple sclerosis (MS, pwMS). However, the major disadvantage of this method is the lack of specific scenarios designed for pwMS. OBJECTIVES: This study aims to assess the feasibility of exergaming, which was developed for pwMS. METHODS: This unblinded prospective clinical trial was performed in the outpatient MS Clinic of Dokuz Eylül University Hospital. Exergaming scenarios were developed in collaboration with medical personnel consisting of physiotherapists and doctors, and computer engineers. A total of 30 participants who had definite MS diagnoses were included. The exergaming scenarios were implemented using the Microsoft Kinect. A physiotherapist applied custom-made exergames for one session. All the participants were assessed immediately after the session. The User Satisfaction Evaluation Questionnaire was used to assess the user's satisfaction with the system and exergaming. RESULTS: The mean age was 41.5, the mean Expanded Disability Status Scale was 4.5 (range between 0 and 7), and the mean disease duration was 10.0 years. Twenty patients were relapsing-remitting, and 10 were secondary-progressive. The mean scores of the User Satisfaction Evaluation Questionnaire were 4.33 (SD = 0.84) for helpfulness for rehabilitation, 1.63 (SD = 1.1) for not disturbing, 4.50 (SD = 1.07) for understandability, 4.0 (SD = 0.91) for easiness to control, and 4.33 (SD = 0.84) for enjoyability. CONCLUSION: These results showed that our custom-made exergaming scenario could be feasible in upper extremity rehabilitation in MS. More research is needed to investigate its effectiveness in the rehabilitation of upper limbs.

Cognition as a parameter in monitoring the effect of multiple sclerosis relapse treatment: A prospective controlled study.

BACKGROUND: Cognitive evaluation was considered to be very important in the relapse period, on the basis of the presence of isolated cognitive attacks and the necessity of monitoring the patient both physically and cognitively. MATERIALS AND METHODS: People with MS (pwMS) who were hospitalized during relapse were included in the study. All MS patients were evaluated by the neurologist with Expanded Disability Status Scale (EDSS), The 9 Hole Peg Test (9HPT) and the Timed 25-Foot Walk Test (T25-FWT). Additionally, all participants were examined cognitively with the Turkish version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Also, schedules were indicated as during relapse before the treatment (pre-treatment) and the first month after relapse (1-month follow-up). RESULTS: A total of 140 MS patients (mean age; 34.98±10.09, mean disease duration; 6.05±5.29 years) and 86 healthy controls (mean age; 36.94±10.83) were included to the present study. The mean EDSS scores in pre-treatment in MS patients was 2.74±1.14 and decreased significantly in the 1-month follow-up (1.74±1.24; p<0.001). The mean SDMT score was lower by 8.76 points in MS patients than in HCs) in pre-treatment and 7.66 points in 1-month follow-up (p<0.001). The mean SDMT scores of all participants increased with measurement time gradually (p<0.001). CONCLUSION: In this study, it was detected which cognitive domains were affected after relapse treatment and cognitive changes in pwMS during relapse and remission periods compared to the healthy controls. All three BICAMS test scores significantly increased in one-month follow-up than the pre-treatment period. The results showed that CVLT-II and BVMT-R scores improved more in pwMS than in HCs, and also SDMT scores of pwMS showed a trend of increase, but was not a significant improvement.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

The outcome of a national MS-Covid-19 study: What the Turkish MS cohort reveals?

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.

Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy.

Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MS-specific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r=0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r=0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r=0.13), and correlation between MSQoL-54 and EDSS was still moderate (r=0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MS-specific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS.

Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes.

The aetiology of multiple sclerosis (MS) is still not fully understood. Infectious agents are believed to play a role in the development of this multifactorial disease. Cases in which this disease occurs after administration of both plasma-derived and recombinant hepatitis B vaccines have been reported. In this study, we compared a group of 11 MS patients who developed first clinical symptoms after hepatitis B vaccination (group I) with 71 MS patients who were never vaccinated against hepatitis B and were negative for hepatitis B serology (group II), and 20 healthy controls (group III). Mean age was 27.75 years (19-39) in group I, 30.16 years (18-50) in group II, and 34.4 years (18-50) in group III. Mean attack rate after 2 years was 1.5 in group I and 1.63 in group II. Mean Expanded Disability Status Scale score after 2 years was 1.31 in group I and 1.89 in group II. Human leucocyte antigen (HLA) typing and serology for hepatitis B surface antigen were performed in all groups. In groups I and II, HLA-DR2 was more frequent than in normal healthy subjects. This reflects the general role of HLA in the pathogenesis of MS but suggests that antigen presentation by different HLA is not involved in the development of MS after hepatitis B vaccination. Since there was no difference in the clinical features between vaccinated and nonvaccinated MS patients, this study supports recent reports that hepatitis B vaccination is safe in MS patients and that hepatitis B vaccination is not involved in the development of MS.

Utilization of the auditory consonant trigram test to screen for cognitive impairment in patients with multiple sclerosis: comparison with the paced auditory serial addition test.

Several screening methods have been evaluated, but most of them are insensitive to MS-related cognitive impairment. The Auditory Consonant Trigram (ACT) test, which contains core features required for a working memory task, has been used to test neuro-cognitive function in different samples of patients to examine the status of working memory. The aim of the present study was to investigate the correlation between ACT and the Paced Auditory Serial Addition Test (PASAT), and the usefulness of ACT for evaluating the cognitive impairment in MS in a brief visit A total of 109 consecutive patients with definite MS were included. The patients were administered ACT, PASAT and EDSS. Mean PASAT score and mean ACT score were 46.19 +/- 8.51 and 45.30 +/- 9.07, respectively. Correlations between EDSS and PASAT, and EDSS and ACT were moderately strong. The correlation between ACT and PASAT was very strong (r = 0.831, P < 0.01). The mean time required to perform ACT was significantly shorter than PASAT (7.25 +/- 4.72 and 14.70 +/- 6.97 minutes, respectively). In conclusion, as a relatively brief measure of working memory, ACT was well accepted by MS patients and has a strong correlation with PASAT. Thus, ACT might be used for rapid evaluation of cognitive impairment in patients with multiple sclerosis.

Nitric oxide as an activity marker in multiple sclerosis.

Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index. Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined. Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 +/- 8.60 micromol/ml in relapse and 6.72 +/- 3.50 micromol/ml in remission, whereas in PS they were 12.89 +/- 7.62 micromol/ml during relapse and 12.35 +/- 6.62 micromol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 +/- 2.81 micromol/ml and 4.37 +/- 1.63 micromol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.