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.

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.

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.

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.

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.

Acute stroke in familial Mediterranean fever: An analysis of 23 new cases and systematic review of the literature.

OBJECTIVE: The nature of neurovascular involvement in cases of familial Mediterranean fever (FMF) has not been adequately clarified. METHODS AND PATIENTS: Clinical features, infarct topography, vascular status, and stroke etiology were prospectively determined in 35 acute neurovascular events that occurred in 23 FMF patients. Clinicoradiological features were compared with an age- and gender-matched control group of 115 acute stroke patients. Characteristics of additional FMF and acute stroke cases (6 episodes in 6 patients) identified from a systematic literature review (PROSPERO registration no: CRD420212264820) were also analyzed. RESULTS: There were 27 acute ischemic stroke episodes in 19 patients, 7 transient ischemic attack episodes in 3 patients, and 1 patient with a single episode of parietal hematoma in our cohort. Twenty (74%) ischemic stroke episodes in 12 patients were cryptogenic. Ten of these 12 cases had a previous FMF diagnosis and were taking colchicine. There was no significant difference in the FMF group in terms of the presence of vascular risk factors and angiography-documented disease in comparison to controls. Cerebral distal artery involvement was significantly prevalent in FMF (78% vs 45%, P = .002). Especially, midbrain central deep perforating territory involvement was higher (30% vs 1%, P < .001). The long-term prognosis (median 8.5 years) under antiplatelet agents and colchicine is favorable. DISCUSSION: The acute stroke phenotype in FMF cases is herein described for the first time. Several clinicoradiological features such as thrombotic lacunar infarcts located in the central mesencephalon seem so typical that we recommend searching for FMF mutations in geographic regions where FMF is common.

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.

Newer disease modifying treatments in pediatric onset multiple sclerosis: Experience from a single center.

BACKGROUND: Disease modifying treatments (DMTs) for multiple sclerosis include injectable drugs (iDMTs) like interferons (IFNs) or glatiramer acetate (GA), and newer agents (nDMTs) in oral and intravenous forms. nDMTs are usually applied in escalation and less frequently as initial treatment in pediatric-onset (POMS). OBJECTIVE: We intended to evaluate the effect of nDMTs in comparison with iDMTs by retrospective examination of our patients with POMS. METHOD: Clinical records of POMS cases who received nDMTs either as escalation or initial treatment and who had at least 12 months' follow-up in our clinic were examined in two groups: patients who were started on iDMTs and later switched to nDMTs (Group A), and those who received nDMTs from the beginning (Group B). Presenting symptoms, annualized relapsing rate (ARR), recent Expanded Disability Status Scale (EDSS), lesion load and presence of contrast enhancing (CE) lesions on magnetic resonance imaging (MRI) were compared. RESULTS: Total 43 patients were included: 33 in Group A and 10 in Group B. Age at onset, female/male ratio, duration since disease onset and duration under nDMT were similar in both groups. Initial involvement was predominantly brainstem and cerebellar in Group A and sensorial, brainstem/cerebellar, and optic nerve in Group B. The most frequently used nDMT was fingolimod in Group A (n = 17, 51.5%) and teriflunomide (n = 6, 60%) in Group B. Median ARR before any treatment was 2 in Group A and 1.5 in Group B (p > 0.05); it decreased to median 1 under iDMTs in Group A and to 0 under nDMTs. Mean follow-up was 6.7 ± 5 years (1-19, median 6 years) in Group A and 3.9 ± 3.7 years (range 1-12, median 2 years) in Group B. At the latest follow-up median EDSS scores were 1 in Group A and 0 in Group B. ARR had increased and lesion load on MRI went up progressively in both groups during follow-up. However, the rate of patients with CE lesions diminished in Group B. CONCLUSION: This single-center study of POMS shows the ARR decreases under any treatment, more markedly under nDMTs, and nDMTs reduce the rate of patients with CE lesions on MRI without a clear effect on lesion load. The ARR tends to increase after the first 2 years of both iDMT and nDMT, suggesting a re-evaluation at that time. The ARR decreases shorty after treatment is changed from an iDMT to a nDMT.

Post-COVID-19 longitudinally extensive transverse myelitis: is it a new entity?

INTRODUCTION: To the best of our knowledge, here we present two post-COVID19 longitudinally extensive transverse myelitis (LETM) with atypical presentations CASE PRESENTATIONS: A 44-year-old male who did not have any previous medical condition and a 73-year-old male foreigner who did not have any disease other than type 2 diabetes mellitus were admitted to our neurology clinic in the same period with similar clinical presentations of transverse myelitis. Upon admission, paraplegia and urinary-fecal incontinence were observed in their neurological examination. Neurological complaints had started within approximately 3-4 weeks following the resolution of the COVID-19 infection. Thoracic lower segment LETM was observed on spinal magnetic resonance imaging (MRI) in one of the patients, and long segment myelitis extending from the lower thoracic segment to the conus medullaris was observed in the other one. No significant diagnostic positivity was present in their diagnostic evaluation. In both cases, we assume a post-infectious etiology in terms of secondary immunogenic overreaction following COVID-19. CONCLUSION: Our patients improved with multiple treatments such as methylprednisolone, intravenous immunoglobulin, and plasmapheresis. Whether post-infectious myelitis behaves differently from other viral infections after COVID-19 is currently unclear. Long lag times appear to be a post-infectious neurological complication resulting from the host response to the virus.

Factors associated with fingolimod rebound: A single center real-life experience.

Background It is still controversial whether the relapse experienced after discontinuation of fingolimod treatment is a rebound. Increasing cases of rebound have been reported in the literature. The rate of fingolimod rebound in patients after fingolimod cessation is reported between 5% and 52%. The present study aims to determine the rate of rebound after discontinuation of fingolimod treatment and the factors affecting the rebound. Methods This retrospective cohort study consists of adult MS patients who have been admitted to the Hacettepe University Hospital Neurology MS Center outpatient clinic between 2012 and 2020. Results During the study period, 642 patients received fingolimod and 23.1% discontinued the fingolimod treatment. Thirteen of 126 patients had a rebound (10.3%) after fingolimod discontinuation. The patients in the rebound group were significantly younger and washout period were significantly longer than those in the non-rebound group. After discontinuation of fingolimod treatment, the EDSS score of the rebound group was significantly higher than the non-rebound group, while Annualized Relapse Rates were similar. Conclusion Younger age, longer washout time, and previous treatment preferences may increase the occurrence probability of rebound. It is recommended that patients should be closely monitored after fingolimod discontinuation and appropriate disease-modifying therapy should be initiated as soon as possible.

The value of serum immunoglobulin free light chain assessment in patients with monoclonal gammopathies and acute renal failure.

OBJECTIVE: Immunoglobulin free light chain (FLC) abnormalities are common in patients with monoclonal gammopathies and the kidneys are the most affected organs. Immunoassays that provide quantitative measurement of FLC in serum indicate monoclonal FLC production based on the presence of an abnormal FLC kappa:lambda (κ:λ) ratio. The aim of this study was to assess the utility of serum FLC measurement as a diagnostic tool for detecting plasma cell dyscrasias in comparison to standard assays, and to ascertain its sensitivity and specificity in patients with acute renal failure (ARF). MATERIAL AND METHODS: Sera from 82 patients with ARF were assessed using serum protein electrophoresis (SPE), serum immunofixation electrophoresis (SIFE), and FLC measurement. The sensitivity and specificity of the FLC ratio in identifying which ARF patients had multiple myeloma (MM) was compared to those of SPE and SIFE. RESULTS: Among the 82 patients with ARF, 7 were diagnosed as MM using SPE, SIFE, and bone marrow biopsy techniques. In total, 8 patients did not have a FLC κ:λ ratio that was within the published reference range (0:26-1:65); the FLC κ:λ ratio based on FLC measurement had a specificity of 96% and sensitivity of 71%, and positive and negative predictive values of 62.9% and 97.3%, respectively, for the diagnosis of MM. CONCLUSION: The sensitivity and specificity of the FLC κ:λ ratio for diagnosing MM in patients that presented with ARF were lower than those of SPE and SIFE. To further delineate the utility of the FLC κ:λ ratio additional prospective, well-designed large-scale studies are needed. CONFLICT OF INTEREST: None declared.

Non-Hodgkin's lymphoma with bone involvement: a single center experience with 18 patients.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) of bone is a rare entity. The most common histological subtype is diffuse large B cell lymphoma (DLBCL). The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. METHODS: We retrospectively analyzed the 18 patients (11 females, 7 males) with NHL of bone who were diagnosed and treated between 1995-2005. The median age was 56.5 years. The median duration of symptoms was 4.5 months. The bone pain was the first symptom in all patients. Tru-cut biopsy was performed for diagnosis in most of the cases. Diagnosis in five patients (27.8%) required open biopsy. RESULTS: DLBCL (77.8%) was the most common histological type among all patients. Other histological subtypes were anaplastic large cell lymphoma (11.1%), Burkitt-like lymphoma (5.6%) and marginal zone lymphoma (5.6%). According to Ann Arbor staging system, 44.4% of patients were Stage I, 11.1% were Stage II and 44.4% were Stage IV. Bone marrow involvement was determined in four patients (22.2%). All patients except one were treated with anthracycline-containing regimens and eight patients (44.4%) received rituximab combination with chemotherapy. Radiation therapy was performed as the first-line therapy in 9 (50%) patients. The median follow-up was 37 months (range, 2-124 months). Among the 17 patients who achieved complete remission, five (27.8%) relapsed. All patients were still alive. The five-year relapse-free survival was 73.5%. CONCLUSION: The treatment of bone lymphoma can be planned according to the stage and location of the disease. Although we had a relatively low number of patients, it could be concluded that whether or not radiation therapy is performed, rituximab in combination with systemic chemotherapy has been proven beneficial on survival.