Examining dietary habits in the context of multiple sclerosis: A comprehensive investigative approach.

AIMS: The aim of this study is to evaluate the nutritional status of patients with multiple sclerosis (MS) and to develop suggestions for changing eating habits in a healthy direction. METHODS: The study was conducted on 171 participants (80.1 % female; 19.9 % male) diagnosed with MS between the ages of 18-60 who applied to Ankara Hacettepe University Hospital Neurology Outpatient Clinic between June 2021 and March 2023. Body weight, height, body composition, waist circumference, upper mid-arm circumference and hand grip strength were measured in accordance with the technique of anthropometric measurements. A three-day food consumption record was taken to evaluate the energy, macro, and micronutrient content of the diet. Mediterranean Diet Assessment Tool was used to assess adherence to diet. RESULTS: Mean age of the participants was recorded as 35.2 ± 10.81 years. According to the body mass index (BMI) classification, 59.9 % of females were in normal limits, while 61.8 % of males were classified as overweight and obese. However, when evaluated in terms of body composition, body fat percentage was found to be above of normal limits in both genders. Also, 70.8 % of participants were sedentary. The percentage of patients who met their daily energy requirements in women with light and moderate activity was higher than in men, but it was not statistically significant. In participants with high activity level, the percentage of patients meeting energy requirements was below 50 % for both genders. Dietary fat and saturated fat intake were higher than the recommendations, while monounsaturated fatty acids and dietary fiber intake were less. The percentages of patients meeting their calcium requirement was below 50 % in both genders. Mean intake amounts of vegetables, fruits, legumes, nuts, and dairy products were below the Türkiye Nutrition Guideline recommendations. CONCLUSION: This study shows the nutritional characteristic of patients with MS in detail with different aspects. Although most of the patients were in normal limits in terms of BMI, body fat percentages were found to be above normal limits in both genders. Total fat and saturated fat intakes were found to be high according to scientific recommendations while the intake of food groups required for a fibre-based diet and intake of dairy products were low.

Navigating the discontinuation of multiple sclerosis first line treatments: A paradigm shift in patient care.

BACKGROUND: This retrospective study, conducted between 2005 and 2016, investigated the outcomes of patients with multiple sclerosis (MS) who discontinued injectable first-line disease-modifying therapies (DMTs). The study aimed to identify factors influencing treatment discontinuation and assess the impact of discontinuation on disease progression. METHODS: Data was collected from 2,270 patients who received injectable DMTs for at least two years and subsequently discontinued treatment due to clinical and MRI remission, side effects, or noncompliance. Patients were categorized into two groups: those stable after discontinuation (SAD) and those with relapse after discontinuation (RAD). Survival analysis and logistic regression were employed to assess factors influencing treatment discontinuation. RESULTS: Of the 60 patients who discontinued DMTs, one-third (n = 20) remained stable, while 40 patients experienced clinical and/or MRI activity during follow-up. The SAD group had a significantly later age at treatment discontinuation compared to RAD patients (35.9 ± 11.1 vs. 30.7 ± 6.1, p = 0.025). Patients below 40 years old had a higher likelihood of experiencing worsening (75 %), while those over 50 years old demonstrated an 80 % stability rate. SAD patients used DMTs for a more extended period than RAD patients (69.1 ± 47.3 vs. 46.6 ± 20.3 months, p = 0.012). A notable proportion (42.9 %) of worsened patients discontinued DMTs without consulting a physician, emphasizing potential challenges in treatment adherence. After treatment discontinuation, RAD patients experienced relapses after a median of 21.0 months. Survival analysis suggested a more favorable disease course for patients who discontinued treatment after achieving a stable period (p = 0.237), with evidence of differentiation between groups after four years. Regression analysis indicated that older age at discontinuation had a favorable impact on relapse probability (HR: 0.904; p = 0.031; 95 % CI: 0.825, 0.991). Reasons for discontinuation unrelated to disease stability showed a positive but imprecise effect on relapse probability. CONCLUSION: This study provides insights into the outcomes of MS patients discontinuing injectable DMTs, emphasizing the importance of age at discontinuation and reasons for treatment cessation in predicting disease progression. The findings suggest that discontinuation after achieving stability may lead to more favorable outcomes, highlighting the need for personalized treatment decisions in MS management. Further research is warranted to validate these findings and inform clinical practices.

The acute effect of cervical mobilization on balance in patients with multiple sclerosis: a single-blind, randomized, controlled trial.

The cervical region plays an important role in providing proprioceptive and vestibular input to the postural control system. OBJECTIVE: To investigate the effect of cervical mobilization on balance in multiple sclerosis (MS) patients. METHODS: The study was undertaken at the neurological rehabilitation unit with 36 MS participants who were assigned randomly to the study (n = 18) and control group (n = 18). While the study group received a single session of 15 minutes of cervical and soft tissue mobilization, no intervention was applied to the control group to investigate the learning effect of the assessment. Patients were evaluated using Computerized Dynamic Posturography (CDP) (Sensory Organization Test (SOT), Limits of Stability (LoS), and Adaptation Test (ADT)), which reflects postural stability. RESULTS: In the study group, a treatment effect was found on the vestibular ratio (VEST) score (p < 0.001) and the composite score of SOT (p = 0.002). Improvements were achieved in all parameters of the LoS and ADT in the study group. There was no statistically significant difference in terms of CDP results in the control group. CONCLUSION: Cervical mobilization has beneficial effects on balance in MS patients. Our findings support that cervical mobilization can be included in MS balance rehabilitation programs.

The relationship between bladder functions, pelvic floor muscle strength, fall, and fatigue in multiple sclerosis.

BACKGROUND: The aim of this study was to determine the relationship between the severity of bladder functions, fatigue, quality of life (QoL), fall, and pelvic floor muscle strength in patients with Multiple Sclerosis (PwMS). METHODS: Patients were divided into two groups according to their Expanded Disability Status Scale (EDSS) bladder scores as Group 1 (EDSS bladder score 0-1, mildly affected group, n = 25) and Group 2 (EDSS bladder score 2-3-4, moderate and severely affected group, n = 21). Pelvic floor muscle (PFM) strength (EMG-Biofeedback device), fear of fall (Fall Efficacy Scale (FES-1)), fatigue (Fatigue Severity Scale (FSS)), QoL (Urogenital Distress Inventory-short form (UDI-6), and Incontinence Impact Questionnaire-short form (IIQ-7)) were evaluated. RESULTS: 46 female patients diagnosed with MS were included in this study. No significant differences in baseline characteristics were seen between the groups except age. EDSS bladder score were 1 (0-1) and 3 (2-4), EMG-Biofeedback score were 79,5 ± 8,11 and 41,7 ± 5,48, FSS score were 38,7 ± 2,80 and 54±2,20, FES-I score were 16,9 ± 2,15 and 40,2 ± 7,39, UDI-6 score were 4,24±0,47 and 8,42±0,64, IIQ-7 score were 3,64±0,86 and 18,2 ± 1,42 in Group 1 and Group 2. As a result of statistical analysis, significant differences were found in less fatigue and fall, higher PFM strength and better QoL with mildly affected PwMS (p<0,05). CONCLUSION: There was a significant difference in terms of bladder function level in PFM strength, fall, fatigue and QoL between the mildly affected group and the moderate and severely affected group.

Teriflunomide-Induced Palmoplantar Pustular Psoriasis: Case Report and Review of the Literature.

Teriflunomide is a once-daily oral immunomodulatory disease-modifying treatment for multiple sclerosis (MS). Skin reactions are an infrequent side effect of teriflunomide. Here, we present the case of a 52-year-old female patient with ankylosing spondylitis who was consulted for demyelinating lesions and limb weakness. She was diagnosed with multiple sclerosis and started treatment with teriflunomide. Palmoplantar pustular psoriasis developed after three weeks of treatment initiation. It is a rare side effect related to teriflunomide.

Gait initiation in multiple sclerosis patients with and without functional loss.

BACKGROUND: Gait initiation (GI) is an important functional task related to balance and gait performance. In addition, it has predictive importance for falls and postural instability in patient with multiple sclerosis (MS). However, it is uncertain how GI is affected in patients in the early stage of MS (Expanded Disability Status Scale (EDSS) ≤3). In this study, it was aimed to investigate the anticipatory postural adjustments (APAs), posterior center of pressure (COPap) displacement, and spatiotemporal variability during GI in patients with and without functional loss in the early stage of MS. METHODS: Forty-four participants (31 MS patients and 13 healthy subjects) involved in this prospective cross-sectional study were divided into three groups: Group-I: Patients without functional loss (EDSS 0 to 1.5) (n = 14), Group-II: Patients with functional loss (EDSS 2 to 3) (n = 17) and Group-III: Healthy subjects (n = 13). Electromyographic activity of the bilateral tibialis anterior (TA) and gastrocnemius medialis (GM) and COPap displacement were recorded during the postural phase of GI. Additionally, spatiotemporal parameters were recorded within the first three steps, and the coefficient of variation was calculated with 40 walks for variability. RESULTS: There were significant differences in the Kruskal-Wallis tests of variables (p<0.05). Group-I demonstrated smaller APAs magnitudes in TA [stance (p = 0.01), swing (p = 0.01)], GM of swing limb (p<0.0001), and smaller COPap displacement (p<0.0001) compared to group-III. Group-II demonstrated smaller APAs magnitudes in all muscles (p<0.0001) compared to group-III and the smallest COPap displacement (p<0.0001). Group-I showed a significant increase in stride width variability compared to group-III (p = 0.01). Group-II showed a significant increase in several variabilities [first stride length (p<0.0001), second stride time (p<0.0001), first double support time (p<0.0001), stride width (p<0.0001)] compared to group-III. CONCLUSION: Patients in the early stage of MS had impairment in both the postural and locomotor phases of GI with more obvious in the patients with functional loss. The results indicate that MS patients without functional loss have difficulty initiating gait. Although there is no functional loss, the patients have a risk of falls, postural instability, and gait impairment due to their inability to initiate gait effectively. As a result, rehabilitation is necessary even if there is no functional loss in patients with MS.

Reliability and Validity of The Fullerton Advanced Balance Scale in People with Multiple Sclerosis.

PURPOSE: This study was conducted to evaluate the reliability and validity of the Fullerton Advanced Balance Scale (FAB) in people with Multiple Sclerosis (PwMS). METHODS: A total of 65 people with multiple sclerosis, Expanded Disability Status Scale (EDSS) ranging from 1 to 5.5, were included in the study. Test-retest reliability, intra-rater, inter-rater reliability, and internal consistency (item-total score correlation, Cronbach's alpha coefficient) were investigated to examine the reliability of FAB. In the intra-rater and inter-rater reliability analysis, the FAB application of 34 patients, whose initial evaluation was gathered, was video-recorded and re-watched by two physiotherapists at different times and scored. For the Validity of FAB, concurrent validity with criterion validity; construct validity with hypothesis testing were calculated. Convergent validity was assessed for correlations with EDDS, Dynamic Gait Index (DGI), and Timed Up and Go Test (TUG). RESULTS: Test-retest reliability of FAB Intraclass Correlation Coefficient (ICC) values was excellent (ICC= 0.994, p < 0.001). While the intra-rater reliability (ICC=0.986, p < 0.001) and inter-rater reliability (ICC=0.985, p < 0.001) of the FAB were calculated at an excellent level. Cronbach's alpha value was determined to perfect correlation. (Cronbach's alpha coefficient: 0.929). FAB had an excellent correlation with BBS (0.919 (p < 0.001). For convergent validity of FAB, EDSS (r=-0.885, p < 0.001), TUG (r=-0.833, p < 0.001), and DGI (r = 0.916, p < 0.001), it was determined that the scale had convergent validity. CONCLUSION: The FAB proved to be a reliable and valid in PwMS. The study showed that the FAB could be applied regardless of the physiotherapists' clinical experiences. It has been determined that the scale can be used in PwMS with a wide EDSS score. Considering the inter-rater and intra-rater reliability results, it is thought that the FAB is also suitable for use in the online environment.

Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune, inflammatory disease of the central nervous system affecting the optic nerves and spinal cord. Most NMOSD patients have autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). Eculizumab treatment is used effectively and safely in AQP4-IgG+ NMOSD. Our study evaluated the prognosis and outcomes of all clinical trial (PREVENT) patients from Turkey who received eculizumab treatment for AQP4-IgG+ NMOSD. METHOD: Clinical and demographic data of all patients enrolled in the PREVENT and OLE clinical trial in Turkey were analyzed during the study period and after the study ended. Clinical follow-up results were recorded in detail in patients who had to discontinue eculizumab treatment. RESULTS: The study included 10 patients who participated in PREVENT and OLE. Seven patients completed the studies, three patients did not continue the study and were switched to other treatments. Only one of the seven patients was able to continue treatment after eculizumab was approved in AQP4-IgG+NMOSD. The other six patients could not continue treatment due to reimbursement conditions. Four of the six patients who could not continue eculizumab treatment experienced early relapse (within the first three months after stopping the drug). All of these patients had high disease activity before eculizumab and had never relapsed under eculizumab treatment over the long term. CONCLUSION: Eculizumab was used effectively and safely in Turkish AQP4-IgG+NMOSD patients with high disease activity. Disease reactivation and relapse may occur after discontinuation of eculizumab treatment in patients with a long-term stable course. In these cases, close monitoring for disease reactivation is recommended.

Probable eculizumab-associated hepatotoxicity in a patient with neuromyelitis optica: a case report.

OBJECTIVES: Neuromyelitis optica (NMO) is an inflammatory, autoimmune and demyelinating disease of the central nervous system and is often characterized by attacks of severe optic neuritis and long segment myelitis. Identifying the disease-specific pathogenic anti-AQP4 autoantibody in NMOSD has allowed the development of highly effective disease-modifying drugs in the treatment phase. Eculizumab is a humanized antibody that binds to complement C5 and inhibits the formation of the C5b-induced membrane attack complex. It is approved for treating many diseases in which tissue damage is accompanied by complement (such as neuromyelitis optica, myasthenia gravis, autoimmune hemolytic anemia and paroxysmal hemoglobinuria). METHODS: We present a patient diagnosed with NMO who developed possible drug-induced liver injury three months after the start of eculizumab treatment. RESULT: After discontinuing eculizumab treatment, liver function tests gradually regressed in a month. CONCLUSIONS: Eculizumab-associated hepatotoxicity is a previously unreported adverse event in NMOSD patients. Therefore, patients should be monitored for liver function tests during eculizumab treatment, and care should be taken for hepatotoxicity. If hepatotoxicity is detected while under eculizumab treatment, patients should be investigated for other drug use, complementary food supplementation, or possible autoimmune hepatitis, and other potential causes should be excluded.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.

IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

The evaluation of small fibers in multiple sclerosis.

BACKGROUND: Dysesthetic or ongoing extremity pain is a common symptom in all multiple sclerosis (MS) types. Although the pathology of the disease is the demyelination of central neurons, the patients may also complain of neuropathic pain in distal extremities that is generally related to A-delta and C fiber dysfunction. It is not known whether thinly myelinated and unmyelinated fibers are affected in MS patients. We aim to investigate the small fiber loss and its length dependency. METHODS: We evaluated the skin biopsy taken from proximal and distal leg of MS patients with neuropathic pain. Six patients with primary progressive MS (PPMS), seven with relapsing-remitting MS (RRMS), seven with secondary progressive MS (SPMS) and as a control group ten age and sex-matched healthy controls were included. Neurological examination, electrophysiological evaluation and DN4 questionnaire were performed. Subsequently, skin punch biopsy from 10 cm above the lateral malleolus and proximal thigh were done. The biopsy samples were stained with PGP9.5 antibody and intraepidermal nerve fiber density (IENFD) was determined. RESULTS: The mean proximal IENFD was 8.58±3.58 fibers/mm among MS patients and 14.72±2.89 fiber/mm among healthy controls (p=0.001). However, the mean distal IENFD did not differ between MS patients and healthy controls (9.26±3.24 and 9.75±1.6 fiber/mm respectively. Although proximal and distal IENFD tends to be lower in MS patients with neuropathic pain, there was no statistically significant difference between MS patients with and without neuropathic pain CONCLUSION: Although MS is a demyelinating disease, unmyelinated fibers can also be affected. Our findings suggest non-length dependent small fiber neuropathy in MS patients.

Is there a relationship between respiratory function and trunk control and functional mobility in patients with relapsing-remitting multiple sclerosis?

OBJECTIVE: Multiple sclerosis (MS) causes impairment of respiratory function, trunk control, and functional mobility. The purpose of this study was to investigate the relationship between functional mobility and respiratory function and trunk control in MS patients and to compare the findings with those in healthy individuals. METHODS: Thirty MS patients and 30 healthy subjects were included in this case-control study. All participants were evaluated with a pulmonary function test, maximal inspiratory and expiratory pressure (MIP, MEP), core stability tests, a lumbopelvic stability test (LST), a 2-minute walk test (2MWT), and the Timed Up and Go test (TUG). The disability level of the MS patients was assessed with the Expanded Disability Status Scale (EDSS). RESULTS: Respiratory function, respiratory muscle strength, trunk control, and functional mobility were lower in the MS patients than in the controls (p < 0.05). TUG values had a significant negative correlation and the 2MWT values had a significant positive correlation with MEP, core stability tests, and the LST (p < 0.05). Of the variance in the 2MWT distance, 69% was explained by the LST, EDSS, and MEP; of the variance in TUG time, 40% was explained by the EDSS and MEP (p < 0.05). CONCLUSIONS: To preserve and develop functional mobility in MS patients, approaches to increase respiratory function and trunk control should be included in rehabilitation programs. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT03826095.

The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Fingolimod, natalizumab, and ocrelizumab are commonly used in the second-line treatment of relapsing-remitting multiple sclerosis (RRMS). However, these have only been compared in observational studies, not in controlled trials, with limited and inconclusive results being reported. A comparison of their effect on relapse and disability in a real-world setting is therefore needed. OBJECTIVES: The objective of this study was to compare the efficacy of fingolimod, natalizumab, and ocrelizumab in reducing disease activity in RRMS. METHODS: This multicenter, retrospective observational study was carried out with prospectively collected data from 16 centers. All consecutive RRMS patients treated with fingolimod, natalizumab, and ocrelizumab were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores, and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), time to first relapse, and disability accumulation were compared. RESULTS: Propensity score matching retained 736 patients in the fingolimod versus 370 in the natalizumab groups, 762 in the fingolimod versus 434 in the ocrelizumab groups, and 310 in the natalizumab versus 310 in the ocrelizumab groups for final analyses. Mean ARR decreased markedly from baseline after treatment in all three treatment groups. Mean on-treatment ARR was lower in natalizumab-treated patients (0.09, 95% confidence interval (CI), 0.07-0.12) than in those treated with fingolimod (0.17, 0.15-0.19, p<0.001), ocrelizumab (0.08, 0.06-0.11), and fingolimod (0.14, 0.12-0.16, p=0.001). No significant difference was observed in mean on-treatment ARR between patients treated with natalizumab (0.08, 0.06-0.11) and ocrelizumab (0.09, 0.07-0.12, p=0.54). Compared to fingolimod, the natalizumab and ocrelizumab groups exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients at year 1. No significance differences in disability accumulation were determined between the therapies. CONCLUSION: Natalizumab and ocrelizumab exhibited similar effects on relapse control, and both were associated with better relapse control than fingolimod. The effects of the three therapies on disability outcomes were similar.

Reliability and validity of the incremental shuttle walk test in patients with fully ambulatory multiple sclerosis.

BACKGROUND: Functional exercise capacity evaluation is crucial to monitor treatment effects and disease progression in people with multiple sclerosis (pwMS). Compared to other tests, the incremental shuttle walking test (ISWT), which more accurately reflects cardiovascular responses, may be more useful for assessing exercise capacity. The aim of the study is to investigate the reliability and validity of the ISWT. METHODS: Thirty-six pwMS with an Expanded Disability Status Scale (EDSS) score<4.5 between the ages of 25 and 65 were included in the study. The subjects underwent practice (ISWT-p) before undergoing the test-retest protocol in order to rule out the ISWT learning effect (ISWT-1 - ISWT-2). ISWT-1 and ISWT-2 were administered with a 3-7 day interval for test-retest reliability. Six-minutes walking test (6MWT) were applied for concurrent validity. The EDSS, pulmonary function tests, Fatigue Impact Scale (FIS), respiratory muscle strength [maximum inspiratory and expiratory pressure (MIP-MEP)] measurements were made for convergent validity. RESULTS: ISWT was found to have excellent test-retest reliability with an ICC value of 0.97. The area under the curve value was 0.904 indicating that ISWT has a good performance for predicting disease severity. The moderate correlation between ISWT and 6MWT (rho: 0.68, p<0,001) proved concurrent validity. It was also moderately correlated with EDSS, MEP (rho: -0.58 and 0.47 respectively), weakly correlated with MIP and FIS (rho:0.37 and -0.36, respectively) while not correlated with pulmonary function tests. CONCLUSION: The ISWT had excellent test-retest reliability, acceptable criterion and construct validity in ambulatory MS patients.

Perivascular PDGFRB+ cells accompany lesion formation and clinical evolution differentially in two different EAE models.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that may lead to progressive disability. Here, we explored the behavioral pattern and the role of vasculature especially PDGFRB+ pericytes/ perivascular cells, in MS pathogenesis. METHODS: We have evaluated vascular changes in two different experimental allergic encephalomyelitis (EAE) mice models (MOG and PLP-induced). PDGFRB+ cells demonstrated distinct and different behavioral patterns. In both models, fibrosis formation was detected via collagen, fibronectin, and extracellular matrix accumulation. RESULTS: The PLP-induced animal model revealed that fibrosis predominantly occurs in perivascular locations and that PDGFRB+ cells are accumulated around vessels. Also, the expression of fibrotic genes and genes coding extracellular matrix (ECM) proteins are upregulated. Moreover, the perivascular thick wall structures in affected vessels of this model presented primarily increased PDGFRB+ cells but not NG2+ cells in the transgenic NG2-DsRed transgenic animal model. On the other hand, in MOG induced model, PDGFRB+ perivascular cells were accumulated at the lesion sites. PDGFRB+ cells colocalized with ECM proteins (collagen, fibronectin, and lysyl oxidase L3). Nevertheless, both MOG and PLP-immunized mice showed increasing EAE severity, and disability parallel with enhanced perivascular cell accumulation as the disease progressed from earlier (day 15) to later (day 40). CONCLUSION: As a result, we have concluded that PDGFRB+ perivascular cells may be participating in lesion progression and as well as demonstrating different responses in different EAE models.

Reliability and validity of the glittre activities of daily living test in fully ambulatory multiple sclerosis patients.

BACKGROUND: Evaluation of activities of daily living (ADL) and functional exercise capacity in patients with multiple sclerosis (pwMS) is crucial in demonstrating the effectiveness of interventions. AIMS: To investigate the reliability and validity of the Glittre ADL Test in pwMS. METHODS: Twenty-five pwMS and 26 healthy adults were included in this methodological study. The Glittre ADL Test was applied. Six-Minute Walk Test (6MWT) and Nottingham Extended Activities of Daily Living Index (NEADL) were applied for concurrent validity. Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Mini Balance Evaluation Systems Test (Mini BESTest), Multiple Sclerosis Quality of Life Scale-54 (MSQoL-54), and Five Times Sit-to-Stand Test (5 STST) were applied for construct validity. The Glittre ADL Test was repeated after 3-6 days for test-retest reliability. RESULTS: The test-retest reliability of the Glittre ADL Test was excellent (ICC = 0.941). There was strong correlation of the Glittre ADL Test with 6MWT (rho = - 0.710, p < 0.001), NEADL (rho = - 0.841, p < 0.001), EDSS, (rho = 0.836, p = < 0.001), Mini BESTest (rho = 0.792, p < 0.001), and 5 STST scores (rho = 0.720, p < 0.001). There was a moderate correlation between the Glittre ADL Test and the physical health sub-item score of the MSQoL-54 (rho = - 0.591, p = 0.002). No correlation was found between the Glittre ADL Test and FSS (rho = 0.348, p = 0.096). There was a difference in the Glittre ADL Test results between the pwMS and the healthy adults (p = 0.001). CONCLUSIONS: The Glittre ADL Test has excellent reliability and strong construct and criterion validity for assessing functional exercise capacity and ADL in fully ambulatory pwMS. TRIAL REGISTRATION: TRN: NCT04182269.

Multiple Sclerosis - Like Demyelinating Lesions During Adalimumab Treatment in a Case with Crohn's Disease.

Tumor necrosis factor (TNF) antagonists have made significant progress in treating autoimmune diseases like inflammatory bowel disease. Adalimumab, a human anti-TNF monoclonal antibody, may be a treatment option for patients with moderate to severe Crohn's disease for whom conventional treatments have not been effective. Central nervous system (CNS) and peripheral nervous system (PNS) demyelination may rarely develop during treatment. However, it is unclear whether CNS and PNS demyelination occurs as a coincidence or consequence. This report presents a 45-year-old male patient who developed multiple sclerosis-like demyelinating lesions at the seventh month of TNF alpha-blocker treatment. We discontinued anti-TNF therapy and initiated azathioprine. In the approximately eighteen-month follow-up, he did not show any neurological or radiological deterioration. When the autoimmune disease develops during anti-TNF blocker therapy, it would be a safe approach to choose a different group of biologic agents for disease control. The potential risk of developing neurological side effects requires closely follow-up of patients.

A Rare Central Nervous System Involvement Due to CTLA-4 Gene Defect.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is the defect of one of the checkpoint inhibitory molecules and defined as a primary immunodeficiency characterized by immune dysregulation. A 26-year-old female with a history of autoimmune hemolytic anemia, autoimmune thrombocytopenia, and hypogammaglobulinemia was admitted with an inability to walk, urinary hesitancy, and bowel incontinence. Neurological examination revealed mild weakness, pyramidal, and deep sensorial involvement of the left lower extremity. Brain MRI revealed periventricular, juxtacortical, and cerebellar inflammatory lesions. Thoracic spinal MRI showed a longitudinaly extensive cord lesion. Additionally, thoracal CT showed parenchymal opacities and bilateral hilar lymph nodes. The biopsy from mediastinal lymph nodes and lung parenchyma demonstrated a low-grade lymphoproliferation and grade 1 "Lymphomatoid granulomatosis". Detailed laboratory analyses indicated the diagnosis of ''common variable immunodeficiency''. Next-generation sequencing with primary immunodeficiency panel revealed a heterozygous mutation in CTLA-4 (c.436G>A(p.G146R)(p.Gly146Arg)). After molecular diagnosis, abatacept therapy was started as a targeted therapeutic approach with subcutaneous immunoglobulin therapy.