Recai Turkoglu - Academia.edu (original) (raw)

Papers by Recai Turkoglu

Multiple Sclerosis Journal

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assess... more Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse ...

Brain

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whi... more In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments (‘therapeutic lag’) on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represente...

Neurology

ObjectiveTo compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon bet... more ObjectiveTo compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients' profiles associated with efficacy of treatments.MethodsData from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx trial, evaluating GA vs IFNbeta-1a and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.ResultsThe overall ARR ratio of GA vs IFNbeta-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration and EDSS) detected differential response of GA vs IFNbeta-1a: in the trial, patients with the largest benefit from GA vs IFNbeta-1a (lower score quartile) had an ARR ratio of 0.40 (95%confidence interval [CI] = 0.25–0.63), those in the 2...

Immunological Investigations

Multiple Sclerosis Journal

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (M... more Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 39...

Experimed

Objectives: In many studies, blood brain barrier has been shown to be compromised in multiple scl... more Objectives: In many studies, blood brain barrier has been shown to be compromised in multiple sclerosis patients. Pericytes play an active role in ensuring the continuity of the blood brain barrier along with a series of cells. In this study, the effect of pericytic dysfunction on the development of demyelinating plaques in patients with multiple sclerosis was investigated. Material and Method: Concentrations of pericyte dysfunction mediators (PDGFbb, MMP9, TIMP3 and ADAM17) in cerebrospinal fluid of patients with clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS) and healthy control group were measured by ELISA and oligoclonal bands (OCB) were investigated. We aimed to determine whether the concentration of these mediators differed between groups and whether they correlated with lesion load, number of attacks, and EDSS scores. Results: Concentrations of all four mediators were similar in patients with CIS and RRMS. However, both groups were found to be higher than the healthy group. In the CIS and RRMS groups, the levels of the mediators were not correlated with any parameters examined. However, the levels of PDGFbb (p=0.045), MMP9 (p=0.037), and TIMP3 (p=0.033) were higher in OCB positive patients than in those without OCB, whereas ADAM17 levels remained unchanged. Conclusion: This study shows that pericytes may play a role in the pathogenesis of MS from early stages of the disease. The presence of higher levels in patients with OCB suggests that pericyte dysfunction may be associated with OCB formation.

Experimed

Objective: Multiple Sclerosis (MS) is a progresive and an immune mediated inflammatory central ne... more Objective: Multiple Sclerosis (MS) is a progresive and an immune mediated inflammatory central nervous disease. The focus of this study was to determine the possible relationship between B cell immunophenotypes and related gene expressions in the benign MS (BMS) group with disease and cognitive processes. Material and Method: Twenty BMS patients, 16 non-BMS and 28 healthy volunteers were included in the study. Gene expression was performed by real-time PCR (RT-PCR). Immunophenotyping of peripheral B cells was also evaluated by flow cytometry. The relationship between cognitive functions and gene expression levels and B cell subtypes was investigated. Results: It was observed that naïve (CD19 + IgD + CD27-) cells were higher in the BMS group compared to the healthy group (HC), and memory B cells showed opposite changes. Un-switched memory B cells(CD19 + IgD + CD27 +) were found to be higher in the benign group than in the HC. The expression of BANK and BLNK was found to be lower in both MS groups than in the HC. As a result of neuropsychological examinations and cognitive tests; it was observed that motor processes in BMS were better protected than Non-BMS. Conclusion: These findings support that B cell functions may have molecular and cellular effects, and may lead to regression in inflammation and clinical progression. Molecules showing significant changes in our study may play a role as prognostic biomarkers in MS.

Multiple Sclerosis and Related Disorders

Multiple Sclerosis and Related Disorders

Multiple Sclerosis Journal

Background: The risk factors for conversion from relapsing-remitting to secondary progressive mul... more Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. Methods: Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p

Patients with the 'aggressive' form of MS accrue disability at an accelerated rate, typic... more Patients with the 'aggressive' form of MS accrue disability at an accelerated rate, typically reaching EDSS >= 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive MS, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive MS is essential to optimise treatment in this MS subtype. We evaluated whether patients who will develop severe MS can be identified based on early clinical markers, and to replicate this analysis in an independent cohort. Patient data were obtained from MSBase. Inclusion criteria were (a) first recorded disability score (EDSS) within 12 months of symptom onset, (b) at least 2 recorded EDSS scores, and (c) at least 10 years of observation time. Patients were classified as having 'aggressive MS' if they: (a) reached EDSS >= 6 within 10 years of symptom onset, (b) EDSS >=6 was confirmed and...

Journal of Neurology, Neurosurgery & Psychiatry

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sc... more ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fuma...

Multiple sclerosis and related disorders, 2018

Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in ear... more Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life. This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey. The present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI. The analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI. This is the first national cognitive data obtained ...

Multiple sclerosis and related disorders, Jan 24, 2018

Starting from the first attack, activated B cells are found in multiple sclerosis (MS) patients a... more Starting from the first attack, activated B cells are found in multiple sclerosis (MS) patients and are associated with disease activity. Peripheral blood cells of 17 clinically isolated syndrome (CIS) patients were collected during the first attack. CIS patients were divided as those converting to MS (CIS-MS+, n = 8) and not converting to MS (CIS-MS-, n = 9) in three years. Age-gender matched MS patients (n = 19) and healthy individuals (n = 20) were included as controls. Peripheral blood frequencies of total, immature, naive, unswitched and switched memory B cells, plasmablasts and plasma cells were measured by flow cytometry. CIS patients showed reduced unswitched memory B cell and plasma cell frequencies. CIS-MS- patients had significantly increased levels of total B cells and suppressed unswitched memory B cell and plasma cell frequencies. Our results suggest that conversion from CIS to MS occurs due to the inability of the immune system to suppress effector B cell production.

Noro Psikiyatri Arsivi

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS).... more Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS). Its primary characteristics are inflammation and damage to myelin sheaths, oligodendrocytes, axons, and neurons, and it mostly affects young adults. According to global estimates of the Multiple Sclerosis Foundation, more than 2 million people are affected by MS (1,2). Koch-Henriksen and Sørensen performed a large meta-regression analysis from the literature to investigate worldwide changes in demographic patterns of MS incidence and prevalence (2). The prevalence of the disease is higher among Caucasians and the female to male ratio of 2:1 has risen to 4:1 over recent years (3). Its etiology remains obscure; however, MS is believed to be caused through an intricate relationship between infectious agents and genetic and environmental aspects. Multiple sclerosis presents in four forms; the most frequently seen is relapsing-remitting MS (RRMS), which is diagnosed in 85% of patients with MS at onset. RRMS is characterized by more neuroinflammation than neurodegeneration; relapses and the generation of new lesions, which are visible with magnetic resonance imaging (MRI), particularly with contrast-enhancing T1-weighted lesions in particular; and worsening symptoms, followed by periods of stability. Over time, residual disabilities accumulate leading to permanent disability, and approximately 50% of people with untreated RRMS show transition to secondary progressive MS within a decade of the initial diagnosis, which is distinguished by its more extensive neurodegeneration, compared with inflammation (4). The remaining two presentations are primary progressive MS, which has no clear relapses or remissions and is diagnosed in approximately 10% of patients at onset, and progressive-relapsing MS, which affects 5% of patients.

Multiple Sclerosis and Related Disorders

Neurological Sciences, 2017

Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been r... more Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.

American Journal of Case Reports, 2017

Rare co-existance of disease or pathology Background: Autoimmune encephalitis might coexist in pa... more Rare co-existance of disease or pathology Background: Autoimmune encephalitis might coexist in patients with autoimmune demyelinating disorders. Case Report: We report on a case of a 45-year-old female multiple sclerosis (MS) patient presenting with acute onset shortterm memory loss, altered mental status, inflammatory cerebrospinal fluid (CSF) findings and an MRI lesion on the left temporal lobe. An extensive panel for neuronal autoantibodies proved negative. Neuropsychological symptoms gave a prompt response to immunotherapy but nevertheless control MRI showed left hippocampal atrophy. Conclusions: Several recent reports of concurrent emergence of autoimmune encephalitis and MS suggest a common mechanism for these disorders. Since autoimmune encephalitis and MS share certain common CSF and neuroimaging findings, an increased understanding of overlapping autoimmune brain disorders is required to avoid misdiagnosis especially in antibody negative autoimmune encephalitis cases.

Multiple Sclerosis Journal

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assess... more Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse ...

Brain

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whi... more In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments (‘therapeutic lag’) on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represente...

Neurology

ObjectiveTo compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon bet... more ObjectiveTo compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients' profiles associated with efficacy of treatments.MethodsData from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx trial, evaluating GA vs IFNbeta-1a and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.ResultsThe overall ARR ratio of GA vs IFNbeta-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration and EDSS) detected differential response of GA vs IFNbeta-1a: in the trial, patients with the largest benefit from GA vs IFNbeta-1a (lower score quartile) had an ARR ratio of 0.40 (95%confidence interval [CI] = 0.25–0.63), those in the 2...

Immunological Investigations

Multiple Sclerosis Journal

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (M... more Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 39...

Experimed

Objectives: In many studies, blood brain barrier has been shown to be compromised in multiple scl... more Objectives: In many studies, blood brain barrier has been shown to be compromised in multiple sclerosis patients. Pericytes play an active role in ensuring the continuity of the blood brain barrier along with a series of cells. In this study, the effect of pericytic dysfunction on the development of demyelinating plaques in patients with multiple sclerosis was investigated. Material and Method: Concentrations of pericyte dysfunction mediators (PDGFbb, MMP9, TIMP3 and ADAM17) in cerebrospinal fluid of patients with clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS) and healthy control group were measured by ELISA and oligoclonal bands (OCB) were investigated. We aimed to determine whether the concentration of these mediators differed between groups and whether they correlated with lesion load, number of attacks, and EDSS scores. Results: Concentrations of all four mediators were similar in patients with CIS and RRMS. However, both groups were found to be higher than the healthy group. In the CIS and RRMS groups, the levels of the mediators were not correlated with any parameters examined. However, the levels of PDGFbb (p=0.045), MMP9 (p=0.037), and TIMP3 (p=0.033) were higher in OCB positive patients than in those without OCB, whereas ADAM17 levels remained unchanged. Conclusion: This study shows that pericytes may play a role in the pathogenesis of MS from early stages of the disease. The presence of higher levels in patients with OCB suggests that pericyte dysfunction may be associated with OCB formation.

Experimed

Objective: Multiple Sclerosis (MS) is a progresive and an immune mediated inflammatory central ne... more Objective: Multiple Sclerosis (MS) is a progresive and an immune mediated inflammatory central nervous disease. The focus of this study was to determine the possible relationship between B cell immunophenotypes and related gene expressions in the benign MS (BMS) group with disease and cognitive processes. Material and Method: Twenty BMS patients, 16 non-BMS and 28 healthy volunteers were included in the study. Gene expression was performed by real-time PCR (RT-PCR). Immunophenotyping of peripheral B cells was also evaluated by flow cytometry. The relationship between cognitive functions and gene expression levels and B cell subtypes was investigated. Results: It was observed that naïve (CD19 + IgD + CD27-) cells were higher in the BMS group compared to the healthy group (HC), and memory B cells showed opposite changes. Un-switched memory B cells(CD19 + IgD + CD27 +) were found to be higher in the benign group than in the HC. The expression of BANK and BLNK was found to be lower in both MS groups than in the HC. As a result of neuropsychological examinations and cognitive tests; it was observed that motor processes in BMS were better protected than Non-BMS. Conclusion: These findings support that B cell functions may have molecular and cellular effects, and may lead to regression in inflammation and clinical progression. Molecules showing significant changes in our study may play a role as prognostic biomarkers in MS.

Multiple Sclerosis and Related Disorders

Multiple Sclerosis and Related Disorders

Multiple Sclerosis Journal

Background: The risk factors for conversion from relapsing-remitting to secondary progressive mul... more Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. Methods: Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p

Patients with the 'aggressive' form of MS accrue disability at an accelerated rate, typic... more Patients with the 'aggressive' form of MS accrue disability at an accelerated rate, typically reaching EDSS >= 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive MS, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive MS is essential to optimise treatment in this MS subtype. We evaluated whether patients who will develop severe MS can be identified based on early clinical markers, and to replicate this analysis in an independent cohort. Patient data were obtained from MSBase. Inclusion criteria were (a) first recorded disability score (EDSS) within 12 months of symptom onset, (b) at least 2 recorded EDSS scores, and (c) at least 10 years of observation time. Patients were classified as having 'aggressive MS' if they: (a) reached EDSS >= 6 within 10 years of symptom onset, (b) EDSS >=6 was confirmed and...

Journal of Neurology, Neurosurgery & Psychiatry

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sc... more ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fuma...

Multiple sclerosis and related disorders, 2018

Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in ear... more Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life. This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey. The present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI. The analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI. This is the first national cognitive data obtained ...

Multiple sclerosis and related disorders, Jan 24, 2018

Starting from the first attack, activated B cells are found in multiple sclerosis (MS) patients a... more Starting from the first attack, activated B cells are found in multiple sclerosis (MS) patients and are associated with disease activity. Peripheral blood cells of 17 clinically isolated syndrome (CIS) patients were collected during the first attack. CIS patients were divided as those converting to MS (CIS-MS+, n = 8) and not converting to MS (CIS-MS-, n = 9) in three years. Age-gender matched MS patients (n = 19) and healthy individuals (n = 20) were included as controls. Peripheral blood frequencies of total, immature, naive, unswitched and switched memory B cells, plasmablasts and plasma cells were measured by flow cytometry. CIS patients showed reduced unswitched memory B cell and plasma cell frequencies. CIS-MS- patients had significantly increased levels of total B cells and suppressed unswitched memory B cell and plasma cell frequencies. Our results suggest that conversion from CIS to MS occurs due to the inability of the immune system to suppress effector B cell production.

Noro Psikiyatri Arsivi

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS).... more Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS). Its primary characteristics are inflammation and damage to myelin sheaths, oligodendrocytes, axons, and neurons, and it mostly affects young adults. According to global estimates of the Multiple Sclerosis Foundation, more than 2 million people are affected by MS (1,2). Koch-Henriksen and Sørensen performed a large meta-regression analysis from the literature to investigate worldwide changes in demographic patterns of MS incidence and prevalence (2). The prevalence of the disease is higher among Caucasians and the female to male ratio of 2:1 has risen to 4:1 over recent years (3). Its etiology remains obscure; however, MS is believed to be caused through an intricate relationship between infectious agents and genetic and environmental aspects. Multiple sclerosis presents in four forms; the most frequently seen is relapsing-remitting MS (RRMS), which is diagnosed in 85% of patients with MS at onset. RRMS is characterized by more neuroinflammation than neurodegeneration; relapses and the generation of new lesions, which are visible with magnetic resonance imaging (MRI), particularly with contrast-enhancing T1-weighted lesions in particular; and worsening symptoms, followed by periods of stability. Over time, residual disabilities accumulate leading to permanent disability, and approximately 50% of people with untreated RRMS show transition to secondary progressive MS within a decade of the initial diagnosis, which is distinguished by its more extensive neurodegeneration, compared with inflammation (4). The remaining two presentations are primary progressive MS, which has no clear relapses or remissions and is diagnosed in approximately 10% of patients at onset, and progressive-relapsing MS, which affects 5% of patients.

Multiple Sclerosis and Related Disorders

Neurological Sciences, 2017

Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been r... more Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.

American Journal of Case Reports, 2017

Rare co-existance of disease or pathology Background: Autoimmune encephalitis might coexist in pa... more Rare co-existance of disease or pathology Background: Autoimmune encephalitis might coexist in patients with autoimmune demyelinating disorders. Case Report: We report on a case of a 45-year-old female multiple sclerosis (MS) patient presenting with acute onset shortterm memory loss, altered mental status, inflammatory cerebrospinal fluid (CSF) findings and an MRI lesion on the left temporal lobe. An extensive panel for neuronal autoantibodies proved negative. Neuropsychological symptoms gave a prompt response to immunotherapy but nevertheless control MRI showed left hippocampal atrophy. Conclusions: Several recent reports of concurrent emergence of autoimmune encephalitis and MS suggest a common mechanism for these disorders. Since autoimmune encephalitis and MS share certain common CSF and neuroimaging findings, an increased understanding of overlapping autoimmune brain disorders is required to avoid misdiagnosis especially in antibody negative autoimmune encephalitis cases.