Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein.

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayis University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Clinical and demographic characteristics of late-onset multiple sclerosis: LOMS-TR study.

OBJECTIVES: Multiple sclerosis (MS), which is known as a young-adult age disease, is called late-onset MS (LOMS) when it occurs at the age of 50 and older. In our study, we aimed to analyse the clinical and demographic characteristics, comorbidities, diagnostic and treatment challenges and prognosis of LOMS. METHODS: In a retrospective analysis of 136 patients diagnosed with multiple sclerosis (MS) after the age of 50, based on the 2017 McDonald criteria, and who were under observation in eight distinct MS centers across Turkey; demographic information, clinical characteristics of the disease, oligoclonal band (OCB) status, initial and current Expanded Disability Status Scale (EDSS) values, administered treatments, and the existence of spinal lesions on magnetic resonance imaging (MRI) were investigated. RESULTS: The mean age of the 136 patients was 60.96±6.42 years (51-79), the mean age at diagnosis was 54.94±4.30 years, and 89 (65.4 %) of the patients were female. Most of the cases, 61.1 % (83) had at least one comorbidity. In 97 patients who underwent lumbar puncture (LP), OCB positivity was observed in 63.6 %. In 114 patients (83.8 %), spinal lesions were detected on MRI. Eighty-seven patients had relapsing-remitting MS (RRMS) (64 %), 27 patients had secondary progressive MS (SPMS) (19.9 %), and 22 patients had primary progressive MS (PPMS) (16.2 %). The mean EDSS at the time of diagnosis was 2.44±1.46, and the mean current EDSS was 3.15±2.14. CONCLUSIONS: In LOMS patients, the rates of delay in the diagnostic process, treatment disruption and progressive disease are higher than in the general MS population. The high rates of LP applying and OCB positivity of this study may indicate the habit of looking for clear evidences in advanged age in our country. This situation and comorbidities may cause a delay in diagnosis and eliminates the window of opportunity for early diagnosis. Although the high number of spinal lesions is a known marker for progressive disease, it is an issue that needs to be discussed whether the increased frequency of progressive course at older ages is due to the nature of the disease or immune aging itself.

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.

Erratum: Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

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

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.

Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

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.

The Socioeconomic and Psychological Impact of the COVID-19 Pandemic on People with Multiple Sclerosis in Turkey.

Introduction: Various restrictions due to the coronavirus infection have affected working life globally. People with multiple sclerosis (pwMS) have several difficulties in social life, patient follow-up, and receiving treatments. In this study, we aimed to evaluate the experiences of pwMS during the COVID-19 pandemic. Method: We developed a 50-question survey aiming to determine fears, anxieties, and the problems experienced by patients regarding their diseases and social lives during the COVID-19 pandemic. The questionnaire was released online via the Turkish MS Society website, local MS societies websites, and social media accounts. Only the answers of the patients who filled out the questionnaire completely were evaluated. Results: In total, 6008 patients took the survey, and 3255 of them completed the questionnaire. Among all, 378 patients (11.6%) were positive for COVID-19. The most common COVID-19-related symptom was fatigue (48.4%). The routine medical follow-up was interrupted in 61.4% and the medication was discontinued in 14% of the patients. Approximately 25% of the patients reported different symptoms related to relapse activity. The main concern of the patients related to the COVID-19 pandemic was the disruption of the health of the ones they loved. Among all the patients, 4.4% lost their jobs. Conclusion: Our data showed that the COVID-19 pandemic strongly affected the working lives of pwMS. Also, the pandemic changed the attitudes of patients and neurologists. Therefore, the long-term effects of the COVID-19 pandemic on disease approach, patient follow-up, social conditions, and working life should be monitored.

The effect of cognitive performance on self-management behavior of multiple sclerosis patients.

BACKGROUND: Difficulties of self-management in people with MS (pwMS) is considered as one of the most important factors contributing to low rehabilitation efficacy, more severe long-term complications and increase in healthcare costs. Despite the emergence of research in the last decade documenting causes, types, and course of cognitive difficulties in MS disease subtypes, limited evidence is available in the literature for direct comparison of self-management and cognitive deficits. In this study we aimed to investigate the relationship between cognitive performance and self-management in pwMS. METHODS: PwMS who applied to neurology out-patient clinics of seven different centers were included into study. Multiple Sclerosis Self-Management Scale- Revised (MSSM-R) was used for the assessment of self-management behaviors and Multiple Sclerosis inventory cognition scale (MUSIC) was used for the assessment of cognitive performance and fatigue. RESULTS: In this study, 194 (144 female and 50 male) pwMS participated (mean age = 38.9 years). The course of the disease was RRMS in 173 patients and mean EDSS was 2.0. 68.5% of the participants were married, 32.5% were employed, and 57.2% had secondary education. The MSSM-R mean score of the study group was 42.6 ± 10.4 (1-81). There was a positive correlation between MSSM-R and MUSIC-cog scores (r = 0.21, p = 0.003). A hierarchical multiple regression revealed that income level (ß = 0.196, t = 2.692, p = 0.008) and cognitive performance (ß = 0.167, t = 2.063, p = 0.041) together with control variables (gender, age, educational status, employment status, duration of disease, EDSS and fatigue) explained 5.5% of the variance in self-management. CONCLUSION: Cognitive performance is a predictor of self-management in pwMS. Better self-management behavior is also related with employment and income level in pwMS. Studies evaluating patients' cognitive abilities and evaluating the effectiveness of adapted self-management training programs are needed.

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.

Mitochondrial Mutations in Multiple Sclerosis Patients with Atypical Optic Neuropathy.

BACKGROUND: Multiple sclerosis-related optic neuritis is mostly associated with good recovery. The aim of this study was to investigate the causes of progressive visual worsening in multiple sclerosis patients despite treatment. METHODS: We retrospectively reviewed the medical records of multiple sclerosis patients with optic neuritis admitted to the ward of our Neurology Department between 2001 and 2020. The patients with unilateral/bilateral progressive visual loss or non-substantial recovery of visual acuity were screened for genetic testing for Leber's hereditary optic neuropathy. RESULTS: Of 1014 multiple sclerosis patients, 411 (39%) reported having optic neuritis. During follow-up, 11 patients manifested atypical characteristics of multiple sclerosis-related optic neuritis (presence of one of the following clinical findings: bilateral simultaneous or sequential eye involvement, progressive visual loss, or no response to corticosteroids during hospitalization), while others presented with typical multiple sclerosis-related optic neuritis. Those multiple sclerosis patients with atypical characteristics of optic neuritis were screened for other possible etiologies of optic neuropathy. We found pathogenic mitochondrial mutations in 5 patients with multiple sclerosis in our study group. CONCLUSION: In our study group, the prevalence of mitochondrial mutations among all multiple sclerosis patients with optic neuritis was 0.12%. We strongly recommend investigating Leber's hereditary optic neuropathy mutations in MS patients if they suffer from severe or bilateral visual loss without recovery during follow-up. Because Leber's hereditary optic neuropathy mitochondrial mutations indicate relatively poor visual prognosis and have important implications for genetic counseling.

A comprehensive assessment of patient experience and disease-related awareness in multiple sclerosis: A questionnaire-based nation-wide survey in Turkey.

BACKGROUND: Comprehensive assessment of multiple sclerosis (MS) patients in terms of patient profile, clinical and disease-related factors has great epidemiological value. This study aimed to evaluate patient experience and disease-related awareness in MS patients through a nation-wide survey in Turkey Methods: A total of 1379 MS patients participated in this cross-sectional questionnaire survey conducted between November 2018 and December 2018. The online questionnaire form included items on sociodemographic, disease-related, first-admission, treatment and follow up characteristics as well as the disability status. RESULTS: Patients were diagnosed at median 28.0 years of age, while the average time from admission to diagnosis and time from diagnosis to treatment were 1.2 years and 2.5 months, respectively. Neurology (45.4%) and ophthalmology (23.3%) were the most common clinics for the first admission, while numbness-weakness in lower and upper extremities (37.6%) and double vision-visual problems (30.6%) were the most common symptoms on initial admission. Treatment was initiated after the diagnosis in 1213(88.0%) patients, while 166 (12.0%) patients were treatment-naïve. Treatment discontinuation, treatment switch and use of alternative treatment methods were reported by 31.3%, 49.3% and 22.8% of patients, respectively. The ophthalmology admissions (with double vision or visual problems) were associated with the shortest time from presentation to diagnosis as compared with neurosurgery and internal medicine admissions (median 1.0 vs. 3.0 and 4.0 months, p<0.001). The neurology admissions (with numbness-weakness in extremities) were associated with more prompt (median 0.3 vs. 0.5 months, p=0.032) and more frequent onset of treatment after diagnosis (64.5% vs. 2.2% to 15.2%, p<0.001). Time from presentation to diagnosis was longer in patients aged >50 years (median 6.0 months vs. 2.0 months, p<0.001), in patients using alternative medicine (median 3.0 months vs. 1 month, p=0.001) and in patients admitted to a non-MS-center (median 3.0 months vs. 2.0 months, p=0.002). Median (min-max) age at diagnosis was significantly lower in patients with vs. without treatment discontinuation for any reason (26.0(10-56) vs. 29.0(3-60) years, p<0.001) and treatment switching (27.0(5-93) vs. 30.0(3-60) years, p<0.001). CONCLUSIONS: In conclusion, our findings revealed higher likelihood of earlier diagnosis and earlier treatment in patients admitted to an MS-center and in those presenting with ocular problems and sensory-motor deficits, respectively. Our findings also emphasize the association of older patient age with higher likelihood of diagnostic delay, and increased likelihood of treatment discontinuation for any reason and/or treatment switching in case of older patient age, younger age at diagnosis and diagnostic delay. In this regard, our findings highlight the need for improved awareness among patients as well as clinicians on initial manifestations of MS to enable admission or referral to an MS-center and to prevent delay in diagnosis, particularly for onset symptoms other than ocular or sensory-motor characteristics.

Retinal Nerve Fiber Layer Thickness Correlates with Serum and Cerebrospinal Fluid Neurofilament Levels and is Associated with Current Disability in Multiple Sclerosis.

INTRODUCTION: The main purpose of the present study is to confirm Peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness is a biomarker of axonal degeneration in patients with Multiple Sclerosis (MS) and to evaluate its relationship with Neurofilament heavy chain (NfH) and Nitrotyrosine (NT). METHOD: We quantified serum (s) and/or cerebrospinal fluid (CSF) NfH and NT levels in 30 relapsing-remitting MS patients (RRMS), 16 secondary progressive MS (SPMS) patients and in 29 control subjects matched for age and gender. Optical coherence tomography (OCT) measurements of pRNFL were performed in all subjects. Clinical outcomes were tested by Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS). RESULTS: RRMS patients exhibited significantly higher NfH/NT levels (99 pg/mL, 107.52 nM respectively) than controls (74 pg/mL, 48.72 nM) in CSF (p<0.0001), but not in sera. SPMS patients had significantly higher s NfH/NT values (111.25 pg/mL, 1251.77 nM respectively) and lower mean pRNFL thickness (79 µm) than patients with RRMS (98.50 µm) and controls (108 µm) (p<0.0001). pRNFL thickness was significantly correlated with all clinical disability measurements (EDSS, Trail Making test, 9-Hole Peg Test, and PASAT) in both RRMS and SPMS (p<0.001, p=0.02, p=0.03, p=0.02 respectively). A positive correlation was also found between serum and/or CSF NfH levels and EDSS scores in RRMS and SPMS (p<0.001, p=0.02 respectively). The pRNFL thickness was also correlated significantly with serum and/or CSF NfH levels but not with s/CSF NT levels in both clinical forms of MS (p<0.01, p<0.001 respectively). CONCLUSION: The current study demonstrated that both pRNFL and s/CSF NfH are reliable and quantitative biomarkers that correlate with current disease course and cross-sectional measure of disability in patients with MS.

Long-Term Effectiveness of Fingolimod for Multiple Sclerosis in a Real-World Clinical Setting.

INTRODUCTION: The primary aim of the present study was to evaluate the long-term efficacy of fingolimod in patients with multiple sclerosis (MS); secondary aims were to describe the safety of fingolimod with the evaluation of treatment satisfaction and impact on the quality of life in real life. METHODS: We collected clinical, demographical, neuroradiological, and treatment data, including pre- and posttreatment status health-related quality of life from 286 MS patients consecutively treated with fingolimod. Clinical assessment was based on the Expanded Disability Status Scale (EDSS), and quality of life assessment was performed with MS-related quality of life inventory (MSQOLI). The data were recorded at baseline and every 6 months for 2 years. RESULTS: One hundred and fourteen males and 172 females were enrolled. The annualized relapse rate and EDSS showed a statistically significant reduction during the observation period (p < 0.001). The patients also demonstrated substantial improvements in magnetic resonance imaging (MRI) outcomes (p < 0.001). Health-related quality of life scores improved significantly between baseline and 24-month visit (p < 0.001). No serious adverse events occurred. CONCLUSION: In our cohort, fingolimod treatment was associated with reduced relapse, MRI activity, and improved EDSS and MSQOLI scores. Additionally, fingolimod has been able to maintain its effectiveness over a considerable long period of treatment.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Flammer syndrome in multiple sclerosis: diagnostics, prediction, and personalization of treatments.

BACKGROUND: Flammer syndrome (FS) occurs from well-described signs and symptoms. The syndrome itself is not a disease, but it may be a directive marker for advancing therapeutic approaches by predictive and preventive measures as well as for personalization of treatments. The syndrome is related to many diseases, but FS has been rarely studied in multiple sclerosis (MS). The study aimed to determine whether FS signs and symptoms occur more often in people with MS than in healthy controls, and in order to personalize the treatment, we investigated the possible effect of current therapies on FS signs and symptoms. METHODS: Two hundred twenty-two MS patients and 203 healthy controls answered the questionnaire consisting of 15 signs and symptoms of FS. RESULTS: MS patients had significantly more complaints in 9 items of FS signs and symptoms (cold hands or/and feet, the reduced feeling of thirst, dizziness, drug side effects, other headaches (tension-type, medication overuse), weight loss, feeling cold, long sleep-onset time, and skin blotches) compared to healthy controls. Six items (low blood pressure, tinnitus, increased odor sensitivity, low pain threshold, and perfectionism) were similar between the two groups. The treatment agents currently used did not have any effect on the signs and symptoms of FS. CONCLUSION: This study showed that FS might be associated with MS. Injectable or oral agents are not related to the signs and symptoms of FS. Further studies are needed to validate this association. RELEVANCE OF THE ARTICLE FOR PREDICTIVE PREVENTIVE AND PERSONALIZED MEDICINE: FS is common among MS patients. Being aware of this incidence that might impair the life quality of MS patients is useful to predict the comorbidity and develop preventive strategies and applying personalized treatment options and procedures.

Invasive Therapies in Multiple Sclerosis.

Multiple sclerosis is a progressive disease despite so many recent therapy agents. Many symptoms can be seen that can affect the quality of daily life, such as spasticity, urinary incontinence, sensory disturbances, and tremor. These complaints may be refractory to the medical treatments, and the invasive treatment methods may be the only option to improve the quality of life of the patient. Intrathecal baclofen pump therapy can effectively reduce the spasticity in a patient with an inadequate response to oral baclofen. On the other hand, deep brain stimulation significantly reduces tremor and can provide the patient to eat by his/her self. Sacral neuromodulation may be beneficial in a patient with a history of urge incontinence which doesn't respond to oral agents. Adequate pain control can be achieved with spinal cord stimulators when a patient is unresponsive to the neuropathic pain treatment. Common features of all these invasive therapies are that they are used in patients who do not respond to medical treatments, they have a small number of randomized controlled clinical trial, and almost all of them are incompatible with MRI devices. According to the latest researches, more randomized controlled clinical trials and MRI compatible devices have been produced in recent years. We wanted to discuss these treatment methods even they have not yet been used routinely. We think they would be beneficial in clinical practice after their deficiencies have been overcome.

Overactive bladder symptoms in patients with multiple sclerosis: Frequency, severity, diagnosis and treatment.

OBJECTIVE: To determine the frequency and severity as well as the diagnosis and treatment of overactive bladder problems in patients with multiple sclerosis (MS) followed up at five centers in Turkey. DESIGN: Survey study. SETTING: Outpatient tertiary clinics of physical medicine and rehabilitation and neurology. PARTICIPANTS: Consecutive MS patients scheduled for outpatient follow-up (n = 309). INTERVENTION: MS patients were asked to complete a questionnaire regarding the frequency and severity, as well as the diagnosis and treatment of their overactive bladder problems. RESULTS: The mean age ± SD was 39.3 ± 10.6 years. Urinary urgency was the most common urinary symptom (62%), followed by frequency (50.4%), urge incontinence (44.7%) and nocturia (33%). Residual urine volume was measured using a portable ultrasound instrument in 13.3% of the patients and by catheterization in 16.2% of them. Urodynamic investigations and urinary tract ultrasound were performed on 26.5% and 35.3% of the patients, respectively. Anticholinergic medications were prescribed for 27.5% of the patients. Intermittent catheterization and indwelling catheterization were used on 8.1% and 1.9% of the patients, respectively. The overactive bladder symptom score (OABSS) was significantly higher in patients who had had residual urine measurement (P < 0.001), upper urinary tract assessment by ultrasound (P < 0.001), urodynamic assessment (P < 0.001), admitted to a doctor for urinary symptoms (P < 0.001), and current or past catheter use (P = 0.002). CONCLUSION: Urgency was the most common urinary symptom followed by frequency, urge incontinence and nocturia in MS patients. The patients with lower OABSS had detailed urological assessments less frequently than the patients with higher OABSS.

Acute respiratory failure due to unilateral dorsolateral bulbar infarction.

BACKGROUND: Previous clinicopathological studies have reported central hypoventilation alongside unilateral infarcts in the caudal brainstem. As already known, the respiratory centers are located in the medullary and pontine centers. METHODS: We sought patients with acute respiratory failure with brainstem involvement proved by MRI from 4,500 patients with first ischemic stroke consecutively admitted to our stroke unit over a period of 7 years. RESULTS: We report six patients with a unilateral dorsolateral medulla oblongata lesion, completely sparing the corticospinal tract, who presented impairments in automatic and voluntary respiratory movements. Topographical analysis showed involvement of the nucleus and tractus solitarius,nucleus ambiguus and retroambiguus,nucleus reticularis medulla oblongata, and nucleus tractus solitarius. CONCLUSIONS: Our findings provide insight into the central organization of respiratory control in the dorsolateral medulla oblongata in humans, and the importance of critical respiratory management in these patients.