To evaluate the real-world effectiveness and safety of eculizumab in patients with AQP4-IgG–positive neuromyelitis optica spectrum disorder (NMOSD) and to identify predictors of disability outcomes. This multinational, retrospective cohort study analyzed data from 46 patients across 26 centers. The outcomes included the annualized relapse rate (ARR), relapse-free status, change in expanded disability status scale (EDSS) scores, and adverse events. To identify predictors of EDSS improvement or worsening, patients were stratified into subgroups (improved vs. stable/worsened) at each follow-up time point and compared based on demographic, clinical, and radiological variables. This retrospective cohort study included 46 patients with AQP4-IgG-positive NMOSD from 26 centers, followed for a mean of 27.3 months. The mean ARR significantly decreased from 1.1 in the 2 years pre-treatment to 0.1 during eculizumab therapy. The relapse-free rate increased from 6.5

Background: Both the presence of multiple sclerosis (MS) and the use of immunomodulatory therapy for this disease can change the vaccine response in individuals with MS. In this study, due to the lack of guidelines for vaccination of MS patients in our country, the aim was to create a Delphi consensus on vaccination practices and vaccine types in MS patients. Methods: The Real-time Delphi technique, a more structured and predefined version of the traditional Delphi study was used to ensure a comprehensive research process. The stages of the structured online Delphi application process, which includes repeated rounds, (three rounds) are applied. Fifteen participants are sufficient to achieve homogeneous outcomes according to expertise criteria and in this study, the group comprised 31 experts who met these criteria and participated in all stages. Results: The assessment of the level of consensus among panelists revealed that there was "almost perfect consensus" on 16 items and "significant consensus" on 12 items. When examining the items in which the panelists did not reach a consensus, it was found that there was "minor consensus (slight-1)" on 1 item, and there was "no consensus (indicate poor-0)" on 2 items. Conclusion: We wanted to share a "country" practice and our current recommendations on vaccination strategies, by making use of articles containing country-based recommendations and working-group recommendations, as well as our national experiences.

Amaç: Alzheimer hastalığı nörodejeneratif bir hastalıktır ve yaşlı popülasyonda görülen demansın en sık çeşididir (%50-60). Hastalık beynin belirli bölgelerinde amiloid birikimi ile karakterizedir. Bu birikimler amiloid plak ve nörofibriller yumakları içermektedir. Alzheimer’lı beynin makroskopik özellikleri hafıza ve konuşma ile ilgili olan bölgeleri etkileyen sulkusların genişlemesi, kortikal atrofi ve ventriküler dilatasyondur. Hiperhomosisteineminin vasküler değişiklikleri indükleme vasıtasıyla Alzheimer hastalığı ile bağlantılı olabileceği düşünülmektedir. Homosistein remetilasyon yoluyla metiyonine çevrilmektedir. Bu yolakta metilentetrahidrofolat redüktaz enzimi metilentetrahidrofolatın metiltetrahidrofolata dönüşüm reaksiyonunu katalizlemektedir. Homosisteinin remetilasyonunda folat, B6 ve B12gibi vitaminler de görev almaktadır. Bu çalışmada Alzheimer hastalığı ile homosistein, folat,vitamin B6, B12 düzeyleri ve metilentetrahidrofolat redüktaz genotiplerinin ilişkisini araştırmayı amaçladık. Yöntem: Kan örnekleri 56 Alzheimer hastasından ve 82 sağlıklı bireyden toplandı. Folat ve B12 vitamini düzeyleri Modular E170 (Roche Diagnostics GmbH Mannheim, Germany) biyokimya otoanalizöründe, homosistein ve B6 vitamini düzeyleri ise yüksek basınçlı sıvı kromatografisi yöntemiyle Agilent 1100 Series (Germany) cihazında ölçüldü. Metilentetrahidrofolat redüktaz gen polimorfizmleri real time PCR yöntemiyle LightCycler (Roche Diagnostics GmbH Mannheim, Germany) cihazında tespit edildi. Bulgular: Vitamin B12 düzeyleri hasta grubunda daha yüksek, vitamin B6 ve folat düzeyleri hasta grubunda daha düşük bulunmasına rağmen farklılıklar istatistiksel olarak anlamlı bulunmadı (p>0.05). Homosistein düzeyleri hasta grubunda istatistiksel olarak anlamlı derecede yüksek bulundu (p=0.016).Metilentetrahidrofolat redüktaz C677T polimorfizminin 677CC, 677CT ve 677TT genotipleri ve A1298C polimorfizminin 1298AA, 1298AC ve 1298CC genotipleri bakımından gruplar arasında farklılık olmadığı tespit edildi. Sonuç: Homosisteinin Alzheimer hastalığı için risk faktörü olduğu ve homosistein metabolizmasında görev alan diğer biyomoleküller ve enzimleri de kapsayan çalışmaların Alzheimer hastalığı ve homosistein ilişkisini ortaya çıkarabileceği düşünülmektedir.

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.

Multiple System Atrophy (MSA) is a less common degenerative disorder that impacts the autonomic functions of the body, such as bladder function, blood pressure, breathing and muscle control.Clinically, there are 2 types of MSA: Parkinsonian (MSA-P) and cerebellar (MSA-C).Laryngeal stridor is an important clinical finding that can aid in diagnosis and indicates a poor prognosis.We present here the case of a 53-year-old female patient who had been diagnosed with MSA-C two years earlier, and who presented to the emergency department with dyspnea.

Soluble epoxide hydrolase (sEH) inhibition has currently emerged as a therapeutic target in the treatment of various neuroinflammatory neurodegenerative diseases, including multiple sclerosis. Previously, we reported that treatment of mice with a sEH-selective inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea; TPPU), ameliorated chronic experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein 35-55 peptide immunization followed by injection of pertussis toxin to mice via regulating pro-inflammatory and anti-inflammatory pathways in the central nervous system. This study tested the hypothesis that the pro-inflammatory G protein-coupled receptor (GPR) 75 and anti-apoptotic phospholipase C (PLC) signaling pathways also contribute to the ameliorating effect of TPPU on chronic EAE. Brains and spinal cords of phosphate-buffered saline-, dimethyl sulfoxide-, or TPPU (3 mg/kg)-treated mice were used for the measurement of sEH, GPR75, Gaq/11, activator protein (AP)-1, PLC β4, phosphoinositide 3-kinase (PI3K) p85a, Akt1, mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, cyclic adenosine monophosphate-response element-binding protein (CREB) 1, B-cell lymphoma (Bcl)-2, semaphorin (SEMA) 3A, and myelin proteolipid protein (PLP) expression and/or activity by using the immunoblotting method. Expression of sEH, GPR75, Gaq/11, c-jun, phosphorylated c-Jun, and SEMA3A was lower, while PLCβ4, phosphorylated PI3K p85a, phosphorylated Akt1, phosphorylated MEK1/2, phosphorylated ERK1/2, phosphorylated CREB1, Bcl-2, and myelin PLP expression was higher in the tissues of TPPU (3 mg/kg)-treated mice as compared with the EAE and vehicle control groups. Inhibition of sEH by TPPU ameliorates chronic EAE through suppressing pro-inflammatory GPR75/Gaq/11/AP-1 pathway and reducing expression of the remyelination inhibitor, SEMA3A, as well as increasing anti-apoptotic PLC/PI3K/Akt1/MEK1/2/ERK1/2/CREB1/Bcl-2 pathway activity and myelin PLP expression.

[This corrects the article on p. 23 in vol. 60, PMID: 36911568.].

Background/aim: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. Materials and methods: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. Results: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. Conclusion: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

ABSTRACT Background: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS. Objective: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey. Methods: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D). Results: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables). Conclusions: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.

Background COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. Objective/Methods The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. Results The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. Conclusion In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Introduction:Fingolimod is the first oral immunomodulatory treatment used as secondary care therapy in the treatment of multiple sclerosis for the last 10 years. The objective of our study is to reveal the experiences of the first generic fingolimod active ingredient treatment in different centers across Turkey.Method:The first generic fingolimod efficacy and safety data of patients followed-up in 29 different clinical multiple sclerosis units in Turkey were analyzed retrospectively. Data regarding efficacy and safety of the patients were transferred to the data system both before the treatment and on the 6th, 12th and 24th month following the treatment. The data were analyzed using the IBM SPSS 20.00. P value of <0.05 was considered to be statistically significant.Results:A total of 508 multiple sclerosis patients, 331 of whom were women, were included in the study. Upon comparing the Expanded Disability Status values before and after the treatment, a significant decrease was observed, especially at month 6 and thereafter. Since bradycardia occurred in 11 of the patients (2.3%), the first dose had to be longer than 6 hours. During the observation of the first dose, no issues that could prevent the use of the drug occured. Side effects were seen in 49 (10.3%) patients during the course of fingolimod treatment. Respectively, the most frequent side effects were bradycardia, hypotension, headache, dizziness and tachycardia.Conclusion:The observed results regarding efficacy and safety were similar to clinical trial data in the literature and real life data in terms of the first equivalent with fingolimod active ingredient.

Objective: Depression is the most common psychiatric disorder in Parkinson’s disease (PD). Selective serotonin reuptake inhibitors (SSRIs) are currently used for treating depression in PD. Many cases of extrapyramidal side effects and exacerbation of PD symptoms due to SSRIs have been reported. The aim of the present study was to investigate the effect of sertraline on motor performance and depressive symptoms in a group of depressed PD patients. Method: Twentyfive, nonfluctuating PD patients with depression or dysthymic disorder according to the DSM-IV criteria were enrolled in the study. Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr Scale were used for the assessments of depression and parkinsonism respectively. Cognitive functions were assessed by Kökmen’s Short Test of Mental Status. Patients were given 50mgs/d sertraline for 12 weeks. Results: Twentyone patients (12 men, 9 women) completed the study (mean age±SD: 65.09±10.3 years, mean PD duration±SD: 44.2±27.2 months). Mean baseline MADRS score (24.8±7.36) was significantly reduced (18.04±5.9) (p=0.000) and UPDRS score remained stable. One patient did show an increase of parkinsonian tremor. Three patients excluded from the study due to side effects of sertraline and one patient did not come to the final visit was excluded from the study. Conclusion: The results of the present study suggest that sertraline does not worsen motor performance and may be useful in the treatment of depression in PD.

We aimed to determine the effect of soluble epoxide hydrolase (sEH) inhibition on chronic experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), associated with changes in inflammasome-dependent and -independent inflammatory and anti-inflammatory pathways in the CNS of mice. C57BL/6 mice were used to induce chronic EAE by using an injection of MOG35–55 peptide/PT. Animals were observed daily and scored for EAE signs for 25 days after immunization. Following the induction of EAE, the scores were increased after 9 days and reached peak value as determined by ≥ 2 or ≤ 3 with 8% mortality rate on day 17. On day 17, mice were administered daily PBS, DMSO, or TPPU (a potent sEH inhibitor) (1, 3, or 10 mg/kg) until the end of the study. TPPU only at 3 mg/kg dose decreased the AUC values calculated from EAE scores obtained during the disease compared to EAE and vehicle control groups. On day 25, TPPU also caused an increase in the PPARα/β/γ and NLRC3 proteins and a decrease in the proteins of TLR4, MyD88, NF-κB p65, p-NF-κB p65, iNOS/nNOS, COX-2, NLRC4, ASC, caspase-1 p20, IL-1β, caspase-11 p20, NOX subunits (gp91phox and p47phox), and nitrotyrosine in addition to 14,15-DHET and IL-1β levels compared to EAE and vehicle control groups. Our findings suggest that pharmacological inhibition of sEH attenuates chronic EAE likely because of enhanced levels of anti-inflammatory EETs in addition to PPARα/β/γ and NLRC3 expression associated with suppressed inflammatory TLR4/MyD88/NF-κB signalling pathway, NLRC4/ASC/pro-caspase-1 inflammasome, caspase-11 inflammasome, and NOX activity that are responsible for inflammatory mediator formation in the CNS of mice.

Background Although studies report a high prevalence rate of restless legs syndrome (RLS) among patients with multiple sclerosis (PwMS) ranging from 13.3 to 65.1%, little is known about the causes of this relationship. Methods To ascertain the prevalence, features and impact of RLS among PwMS a nation-wide, multicenter, prospective and a cross-sectional survey, designed to reflect all of the PwMS throughout Turkey, was conducted in 13 centers. Exploring the relationship of the two conditions could possibly contribute to the understanding of the causes of the high and wide-ranging prevalence rates and the pathophysiology of both diseases. Results Of the 1068 participants 173 (16,2%) found to have RLS [RLS(+)] and 895 (83,8%) did not [RLS(-)]. Among the RLS(+) 173, all but 8 patients (4,6%) were underdiagnosed in terms of RLS. More than half of the patients with RLS had 'severe' or 'very severe' RLS. The onset of RLS was before or synchronous with the onset of MS in about a half of our patients. Conclusion We conclude that RLS should be meticulously investigated in PwMS and MS can be a direct cause of RLS at least in part of PwMS. Our data about the timing of the onset of MS and RLS, along with the high prevalence of RLS in PwMS suggest that the pathologic changes in the initial phases of MS can possibly trigger RLS symptoms.

The philosophy of production without waste is the fundamental belief behind lean manufacturing that should be adopted by enterprises. One of the waste elimination methods is assembly line balancing for lean manufacturing, i.e. Yamazumi. The assembly line balancing is to assign tasks to the workstations by minimizing the number of workstations to the required values. There should be no workstation with the excessively high or low workload, and all workstations must ideally work with balanced workloads. Accordingly, in this study, the axiomatic design method is applied for assembly line balancing in order to achieve maximum output with the installed capacity. In order to achieve this aim, all improvement opportunities are defined and utilized as an output of the study. Computational results indicate that the proposed method is effective to reduce operators' idle time by 12%, imbalance workload between workstations by 38%, and the total number of workers by 12%. As a result of these improvements, the production volume is increased by 23%.