Prognostic factors of tumefactive demyelinating lesions and differential features for multiple sclerosis in etiology.

BACKGROUND: Many different pathologies may underlie tumefactive demyelinating lesions. Identifying clinical and radiologic distinguishing features before pathologic examination is essential for diagnosis and treatment. In this study, we aimed to determine the clinical and radiologic features affecting the etiology and disease course of patients with tumefactive lesions (TDL). MATERIALS AND METHODS: We included 35 clinicoradiologically or histologically diagnosed TDL patients in our center over 11 years. Patient records were retrospectively evaluated and recorded. Clinical features, cerebral neuroimaging, and histologic biopsy preparations, if any, were assessed by three independent neurologists, two neuroradiologists, and two pathologists at admission and follow-up, respectively. RESULTS: The mean age of patients with TDL was 40.02±14.40 years. Symptom onset was 15 (1-365) days. The most common complaints at initial presentation were hemiparesis or hemiplegia, sensory complaints, and cognitive impairment (aphasia or apraxia). The lesions were most commonly localized in the frontal lobe (42.9 %). Mass effect was 17.1 %, edema 60 %, diffusion restriction 62.1 %, and contrast enhancement 71.9 % (mostly ring-shaped (68.8 %)) on MR images. Acute onset and OCB type-2 positivity were associated with MS diagnosis. On the other hand, CSF protein levels above 45 mg/dL were found to be related to non-MS etiologies. Only the predominance of aphasia or apraxia at onset was a risk factor for early high disability (EDSS>4; 3rd month). Subacute-chronic onset, being older than 40 years, or having brainstem symptoms at onset were independent risk factors for late high disability (2nd year). CONCLUSION: Acute onset or OCB type 2 positivity is a clue for early diagnosis of MS, while elevated CSF protein is a clue for demyelinating diseases other than MS. Presentation with cognitive dysfunction at onset is an independent risk factor for early disability, while age above 40 years, subacute-chronic presentation and brainstem findings at presentation are independent risk factors for late disability.

Alemtuzumab infusion-associated reactions and laboratory changes in patients with relapsing-remitting multiple sclerosis at baseline and first-year follow-up.

Background: Alemtuzumab (ATZ) is an anti-CD52 humanized monoclonal antibody indicated for treating highly active relapsing-remitting MS (RRMS). It alters the regulation of the immune system by depleting circulating lymphocytes. Changes in blood cell count, infusion-related reactions, and changes in vital parameters can be seen in the early period with ATZ. Aim: Changes in blood tests, serum tests, vital parameters, and characteristics of infusion-associated reactions (IARs) observed during the first course of ATZ treatment and thereafter were evaluated. Materials and methods: The systolic blood pressure (SBP), diastolic blood pressure (DBP), fever, heart rate (HR), changes in blood and serum tests, and IARs developed after the first course of 23 patients with RRMS who received ATZ treatment were evaluated by comparing the results of 26 patients with RRMS who received only intravenous methylprednisolone. Results: Mean age was 36.60 ± 8.98, 73.9% female (n = 17), diagnosis time was 8.52 ± 3.64 years, pre-EDSS: 3.93 ± 1.80. No significant difference was found in vital parameters except for sub-febrile fever that developed on the first day. The number of white blood cells increased significantly after the first day. The hemoglobin level did not change. Lymphocyte (very high) and platelet (mild) counts decreased starting from the first days, and eosinophil (very high) and monocyte (moderate) counts decreased from the third day. There were no significant changes in liver enzymes, thyroid function tests, serum urea, creatinine, and lipid profile during 1-year follow-up. The IAR rate was 95.6% and occurred most frequently on the second and third days. The most common are dermatological findings (52%), headache (20%), pain (10%) and fatigue (8%). Conclusion: Alemtuzumab has no appreciable effect on vital parameters during infusion. However, these changes are not clinically correlated, even if there is. Headache in the first days, dermatological (most common) findings, pain, and fatigue are seen in the following days. Most IARs can be resolved with symptomatic treatment and close follow-up. Lymphocytes, eosinophils, and monocytes are significantly reduced and return to baseline levels towards the end of the first year. The first year does not cause significant pathologies in other serum parameters. However, after the first year, watch out for associated autoimmune pathologies, especially thyroid involvement.

Characteristics of Cerebral Venous Sinus Thrombosis Due to Autoimmune Diseases: A Single-Center Retrospective Observational Study.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) is a cerebrovascular disease characterized by thrombosis of the cerebral venous or dural sinuses. Autoimmune diseases (AD) are important causes of CVST. This study aims to reveal the differences between CVST associated with autoimmune diseases compared with other causes (OCs) and Behcet's syndrome (BS) compared with other ADs. METHODS: This is a single-center retrospective study in which the medical records of 187 patients we followed with a diagnosis of CVST between 2008 and 2023 were collected retrospectively. Four neurologists collected data on initial symptoms, neurological examinations, and laboratory findings. Findings on magnetic resonance imaging and magnetic resonance venography performed on all patients (thrombosis localizations, hemorrhagic or ischemic complications, and collateralization) were re-evaluated by 2 radiologists. The results were compared with AD, other ADs, and OCs groups. RESULTS: There were 28 cases of CVST associated with AD. Of these, 18 were BS, and 10 were other AD. Subacute-chronic onset, headache, and transverse sinus involvement were more common in AD-related patients than in OCs. However, collateralization, venous infarction, hemorrhagic transformation, and bleeding were less common. BS-related patients had earlier age, more frequent transverse sinus, less frequent cortical vein thrombosis, and better collateralization than other ADs. CONCLUSION: CVST is one of the rare complications in autoimmune diseases. It has a more subacute-chronic onset. Since headaches are more common, it is essential to make a differential diagnosis of CVST in autoimmune diseases with chronic headaches. Transverse sinus thrombosis is more common. Collateralization, venous infarction, and hemorrhagic transformation are less.

Efficacy of Accelerated Vaccination against Hbv to Achieve Antibody formation in Multiple Sclerosis Patients Receiving Anti-Cd20 Therapy.

Aim: Ocrelizumab is a monoclonal antibody that has been approved for use in both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Since ocrelizumab acts on B cells, it also affects humoral immunity, thus reducing the vaccine response. In this study, we aimed to elucidate the relationship between the antibody response following rapid vaccination against hepatitis B virus (HBV) in multiple sclerosis (MS) patients receiving ocrelizumab treatment, and the time of vaccination. Materials and Methods: A total of 220 MS patients were included in this retrospective analysis. The patients' baseline HBV serostatuses (HbsAg, Anti-HbsAb, Anti-HbcAb), previous drug history for MS, whether they were vaccinated against HBV in the past, vaccination status before or after ocrelizumab treatment, and protective antibody titers according to vaccination times, occult HBV incidence and initiation of antiviral treatment were evaluated. Results: Forty-nine percent of MS patients using ocrelizumab were not vaccinated against HBV. The patients were divided into three groups according to their vaccination status as: individuals vaccinated in the past (7.3%, n = 16), vaccinated before treatment (4.5%, n = 10), and vaccinated after treatment (22.3%, n = 49). The antibody titers of the patients in the 6th month after ocrelizumab treatment were measured as 78 mIU/ml, 193 mIU/ml, and 0, respectively. The number of patients with occult HBV infection was 38. Conclusion: In patients with a suspected diagnosis of MS, HBV serostatus should be evaluated at the beginning and if necessary, patients should be vaccinated in the early period. Vaccinating patients at least 1 month before initiating multiple sclerosis treatment is more effective in terms of protective antibody formation.

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial.

Importance: Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. Objective: To determine the time to onset of symptoms consistent with MS. Design, Setting, and Participants: From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Interventions: Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Main outcomes: Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Results: Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Conclusion and Relevance: Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. Trial Registration: ClinicalTrials.gov Identifier: NCT03122652.

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.

Use of follow-on fingolimod for multiple sclerosis: Analysis of effectiveness and patient reported outcomes in a real-world clinical setting.

BACKGROUND: Follow-on disease modifying therapies (FO-DMTs) do not always require Phase III studies. There are concerns that cheaper FO-DMTs are only used to reduce healthcare costs. However, the well-being of people with MS (pwMS) should be a priority. We aimed to evaluate the efficacy, safety and treatment satisfaction of one of the FO- Fingolimod (FTY) used in Turkey with the approval of Turkish Ministry of Health. METHODS: PwMS under FTY were recruited from 13 centers and real-world data and answers of satisfaction and adherence statements of pwMS on FTY treatment were analyzed. RESULTS: Data of 239 pwMS were obtained. The duration of FTY treatment was 2.5 ± 0.8 (1-4) years in pwMS who were included in the study and whose treatment continued for at least one year. Significant decreases in annual relapse rate (p < 0.001), Expanded Disability Status Scale (p < 0.001) and neuroimaging findings (p < 0.001) were observed. While 64% of the patients were satisfied and 71.5% were found to adherent with this FO-FTY. CONCLUSION: This multicenter retrospective study found that the efficacy, safety and treatment adherence of a prescribed FO-FTY were consistent with the results of real-world studies. Studies including real-world data may provide guidance to address issues related to FO-FTY use.

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.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: 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. 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. DISCUSSION: 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.

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.

Covid-19 infection as a possible risk factor for longitudinally extensive transverse myelitis!

INTRODUCTION: There is limited data about the neurological effects of Covid-19 in infected patients. In this report, we present 2 LETM cases that are possibly associated with Covid-19 infection. METHODS: Here, we present 2 cases that subsequently developed LETM following Covid-19 infection. The first case presented a finding of tetraparesis prominent in the lower extremities that started ten days after the Covid-19 infection. The second patient was admitted with paraparesis and urinary-stool retention on the 12th day from the onset of symptoms of Covid-19 infection. RESULTS: In these 2 cases, LETM developing following Covid'19 infection was associated with Covid-19 infection. Although Covid-19 PCR was negative in the CSF of both patients, the Covid-19 PCR test was positive in the samples taken from the oropharynx. CONCLUSION: The mechanism of LETM caused by Covid-19 infection is not clearly known. However, both direct infection of the spinal cord and excessive inflammatory response to primary Covid-19 infection may cause spinal cord damage. Therefore, possible Covid-19-associated myelitis should be kept in mind in cases of long segment transverse myelitis grouped under the title of NMOSD and without any etiological factor.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

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.

Effects of quarantine applied during the COVID-19 pandemic on mental health and quality of life in patients with multiple sclerosis and healthy controls.

BACKGROUND: The coronavirus outbreak, which emerged in Wuhan, China, in late 2019 and spread to the world, has changed each of our lives. OBJECTIVE: To investigate the effects of quarantine on depression, anxiety, sleep quality, fatigue, and SF-36 of multiple sclerosis (MS) patients during the COVID-19 outbreak and differences between healthy controls (HC). METHODS: Eighty-six MS patients and 65 HC patients were included in the study. Participants filled out the various scales through face-to-face interviews for mental health assessment from January 15 to February 15, 2021. RESULTS: When both groups were compared in terms of BECK-D inventory (p < 0.001), BECK-A inventory (p = 0.010), and FS (p < 0.001), the patient group had significantly higher results. Physical functioning (p < 0.001), physical role limitation (p = 0.001), energy vitality rates (p = 0.010), and general health perception (p < 0.001) were higher in the HC group. When MS patients were divided according to EDSS scores, BECK-A (p < 0.001), BECK-D (p = 0.001), and PSQI (p = 0.006) scores of the patients with EDSS > 3 were higher, while emotional role restriction rates (p = 0.006), energy and vitality (p = 0.018), and pain (p = 0.005) were significantly lower than those with EDSS ≤ 3. When MS patients were divided into two groups as who had COVID-19 and who did not and compared SF-36 subscale scores, pain, (p = 0.049) and mental status (p = 0.030) were obtained significant differences in the two groups. CONCLUSIONS: Our study revealed that MS patients, who are more susceptible to the new 'normal' that emerged during the pandemic period, are among the priority groups that should be supported in terms of mental health as well as physical health.

The expression and prognostic value of miR-146a and miR-155 in Turkish patients with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases. Therefore, to determine the role of miR-146a and miR-155 in MS and its developmental stages, the expression levels in the serum of MS and clinically isolated syndrome (CIS) patients were compared with those of healthy controls. In the present study, the expression levels of miR-146a and miR-155 were assessed using quantitative Real-Time PCR in blood samples of 15 CIS patients and 61 relapsing-remitting multiple sclerosis (RRMS) patients alongside 32 healthy patients as controls. Furthermore, any associations with the clinicopathologic variables of the patients were also evaluated. Dysregulations were found only in the miR-146a and miR-155 expressions in the RRMS-Control group. When the RRMS patients were evaluated in terms of the characteristics of sex, annual attack rate, age of diagnosis, duration of follow-up, and immunomodulatory treatments used, no significant differences were observed. However, significant dysregulations were identified in miRNA expression in the vitamin D level, EDSS values, and the number of attacks. ROC curve analysis showed that miR-146a and miR-155 were significant in the RRMS-Control group for the area under the curve (AUC). It is possible that miR-146a may be associated with vitamin D deficiency and disease disability, while miR-155 may be associated with the number of attacks.

MS and COVID-19 challenge: asymptomatic COVID-19 infection during treatment with cladribine.

BACKGROUND: The use of disease-modifying therapies (DMTs) in people with multiple sclerosis (pwMS) may affect COVID-19 infection outcomes due to DMTs' immunomodulatory and immunosuppressive effects on immune response. The yet unknown issues are both the early response to the infection, as well as the post-infection development of immunity against the virus under these treatments due to their interaction with the immune system. METHODS: We report two asymptomatic cases of COVID-19 in patients with relapsing-remitting multiple sclerosis (RRMS) shortly after starting cladribine therapy, both developed anti-SARS-CoV-2 antibody response. RESULTS: Patients with MS who are under newly initiated treatment with cladribine tablets may experience an asymptomatic COVID-19 infection and they may develop immunity against SARS-CoV-2. CONCLUSION: These observations raise the probability that DMTs with immunosuppressive effects, such as cladribine, may be considered as a treatment option for selected MS patients with high disease activity during the COVID-19 pandemic.

Comparative analysis of fingolimod versus teriflunomide in relapsing-remitting multiple sclerosis.

BACKGROUND: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. 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 and teriflunomide in reducing disease activity in RRMS. METHODS: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod 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), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared. RESULTS: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001). CONCLUSION: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. The two oral therapies exhibited similar effects on disability outcomes.

A 12-month, Open Label, Multicenter Pilot Study Evaluating Fingolimod Treatment in terms of Patient Satisfaction in Relapsing Remitting Multiple Sclerosis Patients - FINE Trial.

INTRODUCTION: To assess satisfaction and quality of life in patients with relapsing-remitting multiple sclerosis (RRMS) who were receiving fingolimod (0.5 mg/day) for 12 months as a second-line treatment after switching from injectable agents. METHODS: Patients aged 18-65 years with RRMS who fulfilled the eligibility criteria were enrolled from 16 centers throughout Turkey. Treatment Satisfaction Questionnaire for Medication and 36-item Short-Form Health Survey were completed at baseline and four visits to assess patient satisfaction and quality of life. RESULTS: Forty-two patients (62% male; mean age: 35.7±9.4 years) were eligible for inclusion. Patient satisfaction scores at the end of the study (44.7±9.9) were significantly higher than those at baseline [32.0±9.9; (p<0.001)]. The only significant increase in the quality of life survey was in the emotional aspect (p=0.019). There were 124 adverse events and none of the five serious adverse events noted was considered drug-related. CONCLUSION: Large-scale comparative studies performed with disease specific quality of life instruments will allow more information on this issue.

Differences Between General Neurologists and Multiple Sclerosis Specialists in the Management of Multiple Sclerosis Patients: A National Survey.

INTRODUCTION: The management of multiple sclerosis (MS) has become more complicated after the introduction of new diagnostic and treatment options. Despite the abundance of guidelines, the experience of physicians still plays a major role in the management of patients. This study aimed to define differences in behavior patterns between general neurologists (GNs) and MS specialists (MSSs). METHODS: We conducted a survey of 36 questions to 318 neurologists, including 33 MSSs. The survey covered topics including laboratory investigations, pregnancy, and treatment. RESULTS: Our study found many differences between GNs and MSSs in terms of management, the most important being treatment initiation and switching. GNs had a tendency to initiate treatment later than MSSs however, they tended to switch treatment faster. Our study also showed that GNs ordered magnetic resonance imaging (MRI) more frequently than MSSs, even if patients were clinically stable. Moreover, although GNs more frequently relied on MRI, they did not consider brain atrophy as an important measure in the follow-up of their patients. Furthermore, GNs considered replacement therapy less often than MSSs, even in patients with vitamin D deficiency. DISCUSSION: Our study revealed important discrepancies between the management patterns of GNs and MSSs in MS patients. These findings suggest the need for a national education program for GNs on MSSs.

Comparison of Brain Atrophy, Cognition and Optical Coherence Tomography Results Between Multiple Sclerosis Patients and Healthy Controls.

INTRODUCTION: Cognitive impairment is also an important cause of disability in MS in addition to motor, sensory, visual, and cerebellar affections. The aim of this study is to show the relation between the cognitive disability in MS with brain atrophy and retinal nerve fiber layer (RNFL). METHODS: Forty-three multiple sclerosis (MS) patients, and 15 healthy individuals as controls were included in the study. MS patients were divided into three groups as relapsing-remitting MS (RRMS), relapsing-remitting with optic neuritis (RRMS+ON), and secondary-progressive MS (SPMS). An experienced psychologist performed modified Wechsler Memory Scale Revised form (WMS-R), Lines Orientation test, Stroop Color Word Interference test (STROOP), Standard Raven Progressive Matrices (SRPM), Benton Facial Recognition Test, verbal fluency test, and Paced Auditory Serial Addition tests in all cases. Optic coherence tomographies (OCT) were done. Cranial subcortical volumes of all subjects were measured using 3-dimensonal T1A imagines obtained by the cranial subcortical 1.5 tesla MR device (fully automatic Freesurfer program). Brain parenchymal fractions were calculated by proportioning the obtained volume measurements to the total intracranial volume. RESULTS: Fifty-eight subjects (65.5% female, 34.5% male) were enrolled in the study. There were significant differences among the groups in terms of parenchymal thickness, volumes of third ventricle, and white matter. There was a significant correlation between the volumes of the deep gray matter, mesial temporal structures and lateral ventricular volumes, and the test results of the WMS-R. OCT scores of all MS patients, whether or not they experienced optic neuritis, had increased, being worse especially in the SPMS group. Correlation between RNFL and the brain parenchymal fractions of the patients were statistically significant. CONCLUSION: Manual methods instead of automatic segmentation method are being more commonly used in the studies with brain atrophy and MS in our country. A significant correlation between OCT scores and brain atrophy is shown with our present study, and this is followed as a reflection of decrease in cognitive tests that provides valuable and reliable knowledge for the literature.