Publications by authors named "Recai Turkoglu"

53 Publications

Determinants of therapeutic lag in multiple sclerosis.

Mult Scler 2021 Jan 11:1352458520981300. Epub 2021 Jan 11.

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.

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 rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).

Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
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http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis.

Mult Scler Relat Disord 2021 Feb 17;48:102697. Epub 2020 Dec 17.

Department of Neurology, Istanbul Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.

Introduction: Multiple sclerosis (MS) often initiates with an acute episode of neurological disturbance, known as clinically isolated syndrome (CIS). There is an unmet need for biomarkers that differentiate patients who will convert to MS and who will remain as CIS after the first attack.

Methods: First attack serum and cerebrospinal fluid (CSF) samples of 33 CIS patients were collected and these patients were divided as those who converted to MS (CIS-MS, n=17) and those who continued as CIS (CIS-CIS, n=16) in a 3-year follow-up period. Levels of homeobox protein Hox-B3 (HoxB3) and YKL-40 were measured by ELISA in samples of CIS-CIS, CIS-MS, relapsing remitting MS (RRMS) patients (n=15) and healthy controls (n=20).

Results: CIS-CIS patients showed significantly reduced CSF levels of YKL-40 and increased serum/CSF levels of HoxB3 compared with CIS-MS and RRMS patients. CIS-MS and RRMS patients had comparable YKL-40 and HoxB3 level profiles. Receiver operating characteristic (ROC) curve analysis showed the highest sensitivity for CSF HoxB3 measurements in prediction of CIS-MS conversion. Kaplan-Meier analysis demonstrated that CIS patients with lower CSF HoxB3 (<3.678 ng/ml) and higher CSF YKL-40 (>654.9 ng/ml) displayed a significantly shorter time to clinically definite MS.

Conclusion: CSF levels of HoxB3 and YKL-40 appear to predict CIS to MS conversion, especially when applied in combination. HoxB3, which is a transcription factor involved in immune cell activity, stands out as a potential candidate molecule with biomarker capacity for MS.
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http://dx.doi.org/10.1016/j.msard.2020.102697DOI Listing
February 2021

Expression of Akt1 and p-Akt1 in peripheral T cell subsets of multiple sclerosis patients.

Acta Neurol Belg 2020 Oct 9. Epub 2020 Oct 9.

Department of Immunology, Istanbul University, Aziz Sancar Institute of Experimental Medicine, Vakif Gureba C. Fatih, Istanbul, Turkey.

Multiple sclerosis is an autoimmune disorder induced by the infiltration of autoreactive immune cells into the central nervous system. Akt/PKB signaling pathway is crucially involved in T cell development and survival. We aimed to determine whether Akt1 expression levels of regulatory T (Treg) cells are altered in MS and are associated with disease activity. Relapsing-remitting multiple sclerosis (RR-MS, n = 17) patients and healthy individuals (n = 20) were enrolled. Peripheral blood mononuclear cells were isolated and anti-CD3, -CD4, -CD8, -CD25, -CD127 monoclonal antibodies were used to identify the T cell subsets. After stimulation with phorbol myristate acetate/ionomycin, the Akt1 and phosphorylated-Akt1 (p-Akt1) levels of T cell subsets were detected with intracellular staining using flow cytometry. Total Akt1 and p-Akt1 expression levels were found to be suppressed in CD4T cell and Treg populations of RR-MS patients. Progression indices were positively correlated with Akt1 expression levels of Tregs indicating that the Akt pathway might partake in the progression of multiple sclerosis. Flow cytometry may effectively be used for the evaluation of the Akt pathway activity. Our findings suggest that the magnitude of suppression of the Akt pathway might serve as a biomarker for the prognosis of multiple sclerosis.
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http://dx.doi.org/10.1007/s13760-020-01518-9DOI Listing
October 2020

Treatment Response Score to Glatiramer Acetate or Interferon Beta-1a.

Neurology 2021 01 6;96(2):e214-e227. Epub 2020 Oct 6.

From the Department of Health Sciences (DISSAL) (F.B., M.P.S.), University of Genoa, Italy; CORe (T.K., C.M.), Department of Medicine, University of Melbourne, Australia; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Biostatistics (G.C.), University of Alabama at Birmingham; Department of Neurology and Center for Clinical Neuroscience (D.H., E.K.H.), First Medical Faculty, Charles University, Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Department of Neuroscience (A.P., M.G., P.D.), Faculty of Medicine, Université de Montréal, Quebec, Canada; Department of Neuroscience, Imaging, and Clinical Sciences (M.O.), University G. d'Annunzio, Chieti; IRCCS Istituto delle Scienze Neurologiche di Bologna (A.L.); Dipartimento di Scienze Biomediche e Neuromotorie (A.L.), Università di Bologna, Italy; Hospital Universitario Virgen Macarena (G. Izquierdo. S.E.), Sevilla, Spain; Department of Medical, Surgical Science and Advanced Technology "GF Ingrassia" (F.P.), University of Catania, Italy; Ondokuz Mayis University (M. Terzi), Department of Neurology, Samsun, Turkey; CISSS Chaudi're-Appalache (P.G.), Centre-Hospitalier, Levis, Quebec, Canada; IRCCS Mondino Foundation (R.B.), Pavia; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Department of Neurology (S.O.), Dokuz Eylul University, Izmir, Turkey; Ospedali Riuniti di Salerno (G. Iuliano), Salerno, Italy; Department of Neurology (C.B.), Karadeniz Technical University, Trabzon, Turkey; Department of Neurology (R.H.), Zuyderland Medical Center, Sittard, the Netherlands; Neuro Rive-Sud (F.G.), Hôpital Charles LeMoyne, Greenfield Park, Quebec, Canada; Clinico San Carlos (C.O.-G), Madrid, Spain; Cliniques Universitaires Saint-Luc (V.v.P.); Université Catholique de Louvain (V.v.P.), Brussels, Belgium; UOC Neurologia (E.C.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Kommunehospitalet (T.P.), Arhus C, Denmark; Koc University (A.A.), School of Medicine; Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases (A.S.), Istanbul, Turkey; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; University of Queensland (P.M.), Brisbane, Australia; Haydarpasa Numune Training and Research Hospital (R.T.), Istanbul, Turkey; Central Clinical School (H.B.), Monash University, Melbourne, Australia; The University of Texas Health Science Center at Houston (J.S.W.); Rehabilitation Unit (C.S.), "Mons. L. Novarese" Hospital, Moncrivello; and IRCCS Ospedale Policlinico San Martino (M.P.S.), Genoa, Italy.

Objective: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments.

Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-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.

Results: The overall ARR ratio of GA to IFN-β-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 Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61-1.34), and those in the upper quartile of 1.14 (95% CI 0.59-2.18) (heterogeneity = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46-0.72), 0.92 (95% CI 0.77-1.09,) and 1.29 (95% CI 0.97-1.71); heterogeneity < 0.0001).

Conclusions: We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
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http://dx.doi.org/10.1212/WNL.0000000000010991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905777PMC
January 2021

Delay from treatment start to full effect of immunotherapies for multiple sclerosis.

Brain 2020 09;143(9):2742-2756

CORe, Department of Medicine, University of Melbourne, Melbourne, 3050, Australia.

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 represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag.
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http://dx.doi.org/10.1093/brain/awaa231DOI Listing
September 2020

Effects of Teriflunomide on B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis.

Immunol Invest 2020 Jun 29:1-14. Epub 2020 Jun 29.

Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey.

Antigen-specific immune responses are crucially involved in both multiple sclerosis (MS) and myasthenia gravis (MG). Teriflunomide is an immunomodulatory agent approved for treatment of MS through inhibition of lymphocyte proliferation. MG associated with muscle-specific tyrosine kinase (MuSK) antibodies often manifests with a severe disease course, prompting development of effective treatment methods. To evaluate whether teriflunomide treatment may ameliorate MuSK-autoimmunity, experimental autoimmune MG (EAMG) was induced by immunizing C57BL/6 (B6) mice three times with MuSK in complete Freund's adjuvant (CFA) (n = 17). MuSK-immunized mice were treated daily with teriflunomide (n = 8) or PBS (n = 9) starting from the third immunization (week 8) to termination (week 14). Clinical severity of EAMG was monitored. Immunological alterations were evaluated by measurement of anti-MuSK IgG, neuromuscular junction deposits, and flow cytometric analysis of lymph node cells. In MS patients under teriflunomide treatment, the peripheral blood B cell subset profile was analyzed. B6 mice treated with teriflunomide displayed relatively preserved body weight, lower EAMG prevalence, reduced average clinical grades, higher inverted screen scores, diminished anti-MuSK antibody and NMJ deposit levels. Amelioration of EAMG findings was associated with reduced memory B cell ratios in the lymph nodes. Similarly, MS patients under teriflunomide treatment showed reduced memory B cell, plasma cell, and plasmablast ratios. Teriflunomide treatment has effectively ameliorated MuSK-autoimmunity and thus may putatively be used in long-term management of MuSK-MG as an auxiliary treatment method. Teriflunomide appears to exert beneficial effects through inhibition of effector B cells.
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http://dx.doi.org/10.1080/08820139.2020.1785491DOI Listing
June 2020

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis.

Mult Scler 2020 Jun 15:1352458520926955. Epub 2020 Jun 15.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

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 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37,  < 0.001) and EDSS (β = 0.16,  < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,  = 0.01) and EDSS (β = -0.06,  < 0.001). Neither presentation was associated with changes in relapse risk.

Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
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http://dx.doi.org/10.1177/1352458520926955DOI Listing
June 2020

Early clinical markers of aggressive multiple sclerosis.

Brain 2020 05;143(5):1400-1413

CORe Unit, Department of Medicine, University of Melbourne, Melbourne, Australia.

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, 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 multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis.
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http://dx.doi.org/10.1093/brain/awaa081DOI Listing
May 2020

Nivolumab-induced autoantibody negative limbic encephalitis in a patient with Hodgkin lymphoma.

Leuk Lymphoma 2020 06 12;61(6):1519-1521. Epub 2020 Feb 12.

Department of Neurology, Haydarpasa Numune Training and Research Hospital, Saglik Bilimleri University, Istanbul, Turkey.

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http://dx.doi.org/10.1080/10428194.2020.1725508DOI Listing
June 2020

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Mult Scler Relat Disord 2020 Feb 25;38:101868. Epub 2019 Nov 25.

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address:

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
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http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

Cytokine-chemokine and cognitive profile of multiple sclerosis patients with predominant optic nerve and spinal cord involvement.

J Spinal Cord Med 2019 Sep 26:1-7. Epub 2019 Sep 26.

Department of Neurology, Haydarpasa Numune Education and Research Hospital , Istanbul , Turkey.

: Clinical disease activity in multiple sclerosis (MS) may manifest as predominant involvement of optic nerves and spinal cord, as exemplified by opticospinal multiple sclerosis (OSMS) often encountered in Asian countries. Our aim was to compare the clinical features, neuropsychological profile and cytokine/chemokine levels of patients with conventional MS (CMS) and MS presenting predominantly with spinal cord and optic nerve attacks (MS-SCON). Cross-sectional study. MS Outpatient Clinic. Fourteen MS-SCON patients, 20 CMS patients without myelitis and optic neuritis attacks and 21 healthy individuals. IL-8, IL-10, IFN-γ, IL-17 and TNF-α levels were measured by multiplex assay and CXCL2 and CXCL5 levels were measured by ELISA. A panel of neuropsychological tests, Beck depression inventory, 9-hole peg and timed 25-foot walk tests were employed. CMS and MS-SCON patients showed similar clinical features. Both CMS and MS-SCON patients displayed reduced IL-8 and CXCL2 and increased TNF-α levels, while IL-10 and CXCL5 levels were identical among all groups. Neuropsychological and motor function test performances of CMS and MS-SCON patients were highly comparable. CMS and MS-SCON present with similar clinical, neuropsychological and immunological features. Therefore, optic nerve and spinal cord-dominant form of MS does not necessarily establish a distinct entity in our region. Cognitive networks of the central nervous system may be damaged during the disease course of MS, despite the absence of cerebral or cerebellar clinical attacks.
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http://dx.doi.org/10.1080/10790268.2019.1666238DOI Listing
September 2019

Impact of fingolimod on CD4+ T cell subset and cytokine profile of relapsing remitting multiple sclerosis patients.

J Neuroimmunol 2019 12 11;337:577065. Epub 2019 Sep 11.

Department of Neuroscience, Aziz Sancar Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.

Fingolimod inhibits the egress of lymphocytes from lymphatic tissues and also directly affects their functions by modulation of the sphingosine-1-phosphate receptor 1 (S1P1). Our aim was to evaluate the impact of fingolimod on diverse CD4+ T cell subsets, and cytokines. Sixty-six relapsing remitting multiple sclerosis (RRMS) patients were treated with oral fingolimod (0.5 mg) for 6 months, and blood samples were collected at baseline, 3 months, and 6 months. Serum levels of seven cytokines and five chemokines were measured by multiplex immunoassay, and frequencies of peripheral blood mononuclear cell subsets were assessed by flow cytometry, and compared with those of 60 healthy controls. CCL2 (p = 0.039), and CCL5 (p = 0.001) levels were significantly higher in fingolimod-treated patients than healthy controls, whereas end-of-study serum levels of IL-6, IL-8, IL-17A, IL-22, IL-23, TNF-α, CXCL10, and CXCL13 were comparable to the baseline levels. Six months of fingolimod treatment reduced CD3+ T cell (mean ± standard deviation, 72.9% ± 5.5 vs. 60.1% ± 11.1, p < 0.001), CD4+ T cell (62.2% ± 8.5 vs. 24.6% ± 12.9, p < 0.001), CD4+CD25hi regulatory T cell (Treg) (3.4% ± 1.3 vs. 2.0% ± 1.4, p < 0.01), and CD19+ B cell (13.2% ± 5.8 vs. 5.3% ± 2.7, p < 0.001) frequencies, while CD8+ T cells (31.8% ± 7.8 vs. 57.8% ± 13.2, p < 0.001) were increased, and NK and NKT cells remained unchanged. The proportions of intracytoplasmic IL-4, IL-10, IFN-γ, and TNF-α-producing T cells were increased, whereas IL-17-producing cells remained relatively constant as measured by flow cytometry. Fingolimod appears to primarily diminish lymphocyte subsets involved in antigen presentation (CD19+ B and CD4+ T cells) rather than immune cells (CD8+ T, NK, and NKT cells) in charge of host defense against pathogens. In contrast, a relative increase is observed in pro- and anti-inflammatory cytokine-producing T helper subsets (IFN-γ, TNF-α, IL-4, and IL-10-producing CD4+ T cells), suggesting that effector T cells are suppressed to a lesser degree by S1P1 modulation.
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http://dx.doi.org/10.1016/j.jneuroim.2019.577065DOI Listing
December 2019

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

Mult Scler Relat Disord 2019 Nov 26;36:101376. Epub 2019 Aug 26.

Dokuz Eylul University, Department of Neurology, Izmir, Turkey.

Background: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. Comparison of their effect on relapse and disability in a real-world setting is therefore needed.

Objectives: The objective of this study was to compare the efficacy of fingolimod and teriflunomide in reducing disease activity in RRMS.

Methods: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared.

Results: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001).

Conclusion: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. The two oral therapies exhibited similar effects on disability outcomes.
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http://dx.doi.org/10.1016/j.msard.2019.101376DOI Listing
November 2019

Sleep disturbance and cognitive decline in multiple sclerosis patients with isolated optic neuritis as the first demyelinating event.

Int Ophthalmol 2020 Jan 20;40(1):151-158. Epub 2019 Aug 20.

Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Purpose: Multiple sclerosis (MS) patients whose first demyelinating event is optic neuritis have been claimed to display a milder disease course and reduced physical disability. Our aim was to investigate the impact of the clinical features of the first clinical episode on cognitive disability and sleep dysfunction in MS.

Methods: A total of 26 (10 with optic neuritis as the first clinical event) MS patients were recruited. A comprehensive sleep study was performed, and a panel of tests were administered to examine cognitive and motor performance. Serum levels of sleep-related mediators orexin-A and melatonin were measured by enzyme-linked immunosorbent assay. Subjective sleep quality was evaluated by Pittsburgh sleep quality test, and daytime excessive sleepiness was tested by Epworth sleepiness scale.

Results: MS patients with the first clinical episode of optic neuritis and patients with at least one optic neuritis attack exhibited increased daytime sleepiness, higher sleep efficiency and NREM duration and lower total wake time. Patients with a history of optic neuritis obtained more favorable scores in neuropsychological tests measuring executive functions and complex attention as compared to those who had never experienced optic neuritis. Melatonin and orexin-A levels were lower in patients with optic neuritis onset. The higher no. of optic neuritis attacks was associated with reduced wake time and higher symbol digit modalities test scores.

Conclusions: Having a history of optic neuritis is associated with improved sleep quality and executive functions but increased daytime sleepiness. Reduction of orexin-A and melatonin levels might be one of the underlying mechanisms.
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http://dx.doi.org/10.1007/s10792-019-01157-xDOI Listing
January 2020

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Mult Scler 2020 01 9;26(1):79-90. Epub 2019 Aug 9.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia/L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

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,  < 0.001), longer disease duration (HR = 1.01,  = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30,  < 0.001), more rapid disability trajectory (HR = 2.82,  < 0.001) and greater number of relapses in the previous year (HR = 1.07,  = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62,  = 0.039) and disease-modifying therapy exposure (HR = 0.71,  = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
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http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020

Microbiota stratification identifies disease-specific alterations in neuro-Behçet's disease and multiple sclerosis.

Clin Exp Rheumatol 2019 Nov-Dec;37 Suppl 121(6):58-66. Epub 2019 May 30.

Istanbul University, Department of Neuroscience, Institute for Experimental Medical Research, Istanbul, Turkey.

Objectives: Altered gut microbiota community dynamics are implicated in diverse human diseases including inflammatory disorders such as neuro-Behçet's disease (NBD) and multiple sclerosis (MS). Traditionally, microbiota communities are analysed uniformly across control and disease groups, but recent reports of subsample clustering indicate a potential need for analytical stratification. The objectives of this study are to analyse and compare faecal microbiota community signatures of ethno-geographical, age and gender matched adult healthy controls (HC), MS and NBD individuals.

Methods: Faecal microbiota community compositions in adult HC (n=14), NBD patients (n=13) and MS (n=13) were analysed by 16S rRNA gene sequencing and standard bioinformatics pipelines. Bipartite networks were then used to identify and re-analyse dominant compositional clusters in respective groups.

Results: We identified Prevotella and Bacteroides dominated subsample clusters in HC, MS, and NBD cohorts. Our study confirmed previous reports that Prevotella is a major dysbiotic target in these diseases. We demonstrate that subsample stratification is required to identify significant disease-associated microbiota community shifts with increased Clostridiales evident in Prevotella-stratified NBD and Bacteroides-stratified MS patients.

Conclusions: Patient cohort stratification may be needed to facilitate identification of common microbiota community shifts for causation testing in disease.
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January 2020

Serum orexin-A levels are associated with disease progression and motor impairment in multiple sclerosis.

Neurol Sci 2019 May 15;40(5):1067-1070. Epub 2019 Jan 15.

Department of Neurology, Haydarpasa Numune Education and Research Hospital, Istanbul University, Istanbul, Turkey.

Objective: Diencephalon is frequently affected in multiple sclerosis (MS), and lesions of this region are associated with increased disability. Orexin-A and melatonin, two foremost mediators of diencephalon, modulate cognitive and motor functions through several pathways including the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) signaling pathway. In this pilot study, our aim was to investigate the prognostic value of these factors in progression of cognitive and physical disability.

Methods: Levels of BDNF, melatonin, CREB, and orexin-A were determined by ELISA in sera of 25 relapsing remitting MS (RRMS) patients, 15 secondary progressive MS (SPMS) patients, and 20 healthy controls. Cognitive and motor functions were assessed by a neuropsychological test battery, timed 25-ft walk (T25-FW) and 9-hole peg (9-HP) tests.

Results: MS patients had significantly lower serum levels of orexin-A and BDNF than healthy controls, and SPMS patients had significantly lower levels of melatonin and orexin-A than RRMS patients. Serum orexin-A levels were negatively correlated with 9-HP, T25-FW test scores, and progression index in RRMS patients. BDNF, CREB, and melatonin levels did not show any significant correlation with clinical features including EDSS and cognitive/motor performance of the patients.

Conclusion: Our results suggest that orexin-A levels are decreased in parallel to disease progression and motor system deterioration in the earlier stages of the disease. Thus, orexin-A might be used as a potential biomarker of physical disability.
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http://dx.doi.org/10.1007/s10072-019-3708-zDOI Listing
May 2019

Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis.

J Neurol Neurosurg Psychiatry 2019 04 13;90(4):458-468. Epub 2019 Jan 13.

Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Objective: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.

Methods: We 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).

Results: The 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 fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).

Conclusion: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.
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http://dx.doi.org/10.1136/jnnp-2018-319831DOI Listing
April 2019

Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study.

Mult Scler Relat Disord 2019 Feb 3;28:235-243. Epub 2019 Jan 3.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Australia. Electronic address:

Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing.

Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS.

Methods: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed.

Results: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births.

Conclusions: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month.
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http://dx.doi.org/10.1016/j.msard.2019.01.003DOI Listing
February 2019

Effects of computer-assisted cognitive rehabilitation in benign multiple sclerosis

Turk J Med Sci 2018 Oct 31;48(5):999-1005. Epub 2018 Oct 31.

Background/aim: Benign multiple sclerosis (BMS) patients display preserved somatic neurological functions but nevertheless may develop cognitive dysfunction. Our aim was to explore the impact of computer-assisted cognitive rehabilitation (CCR) on cognitive functions of BMS patients. Materials and methods: Age- and sex-matched BMS patients (n = 21), non-BMS patients (n = 22), and healthy individuals (n = 38) were recruited for evaluation of cognitive functions. CCR was administered to 10 BMS patients and a panel of neuropsychological tests were employed at baseline and 6 months. CCR was based on mental exercise software containing attention, memory, reasoning, visual, and verbal task modules. Results: BMS and non-BMS patients showed impaired selective reminding, spatial recall, symbol digit modalities (SDMTs), controlled oral word association (COWAT), paced auditory serial addition-3 (PASAT-3), and Stroop tests. Timed 25-foot walk and 9-hole peg test results of BMS patients were comparable to those of healthy controls. BMS patients with CCR showed significantly improved SDMTs, COWAT, and Stroop test results compared to those without CCR. Conclusion: Several cognitive domains including memory and executive functions are impaired in BMS patients. CCR has an ameliorating impact particularly on sustained attention, information processing speed, verbal fluency, categorical reasoning, and executive functions of BMS patients.
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http://dx.doi.org/10.3906/sag-1803-53DOI Listing
October 2018

Peripheral blood memory B cell frequency predicts conversion from clinically isolated syndrome to multiple sclerosis.

Mult Scler Relat Disord 2018 Jul 24;23:9-14. Epub 2018 Apr 24.

Department of Neurology, Haydarpasa Numune Education and Research Hospital, Istanbul University, Istanbul, Turkey.

Background: Starting from the first attack, activated B cells are found in multiple sclerosis (MS) patients and are associated with disease activity.

Methods: 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.

Results: 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.

Conclusion: Our results suggest that conversion from CIS to MS occurs due to the inability of the immune system to suppress effector B cell production.
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http://dx.doi.org/10.1016/j.msard.2018.04.015DOI Listing
July 2018

Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: Multi-center, controlled trial.

Mult Scler Relat Disord 2018 May 24;22:70-76. Epub 2018 Mar 24.

Uludag University, Bursa, Turkey.

Background: 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.

Objectives: This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey.

Methods: 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.

Results: 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.

Conclusions: This is the first national cognitive data obtained from MS in Turkey, which is a country between Europe and Asia and thus has characteristics of both continents. The similarity of the results of the present study obtained from Turkey to the Western-based data indicates that CI is universal in MS and the main factors affecting CI have not changed.
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http://dx.doi.org/10.1016/j.msard.2018.03.009DOI Listing
May 2018

A NMOSD case with multifocal nervous system involvement in a single attack.

Mult Scler Relat Disord 2017 11 20;18:82-84. Epub 2017 Sep 20.

Department of Neurology, Haydarpasa Numune Education and Research Hospital, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1016/j.msard.2017.09.019DOI Listing
November 2017

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

Noro Psikiyatr Ars 2019 Dec 22;56(4):253-257. Epub 2017 Jun 22.

Department of Medical, Novartis Pharmaceuticals Turkey, İstanbul, Turkey.

Introduction: To assess satisfaction and quality of life in patients with relapsing-remitting multiple sclerosis (RRMS) who were receiving fingolimod (0.5 mg/day) for 12 months as a second-line treatment after switching from injectable agents.

Methods: Patients aged 18-65 years with RRMS who fulfilled the eligibility criteria were enrolled from 16 centers throughout Turkey. Treatment Satisfaction Questionnaire for Medication and 36-item Short-Form Health Survey were completed at baseline and four visits to assess patient satisfaction and quality of life.

Results: Forty-two patients (62% male; mean age: 35.7±9.4 years) were eligible for inclusion. Patient satisfaction scores at the end of the study (44.7±9.9) were significantly higher than those at baseline [32.0±9.9; (p<0.001)]. The only significant increase in the quality of life survey was in the emotional aspect (p=0.019). There were 124 adverse events and none of the five serious adverse events noted was considered drug-related.

Conclusion: Large-scale comparative studies performed with disease specific quality of life instruments will allow more information on this issue.
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http://dx.doi.org/10.5152/npa.2017.20515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927087PMC
December 2019

Serum Prolactin Levels in Multiple Sclerosis, Neuromyelitis Optica, and Clinically Isolated Syndrome Patients.

Noro Psikiyatr Ars 2016 Dec 1;53(4):353-356. Epub 2016 Dec 1.

Department of Neurology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey.

Introduction: Prolactin has been discussed as a factor likely to play a mediating role in multiple sclerosis (MS). Our aim was to investigate the possible association between prolactin production and clinical features of autoimmune demyelinating central nervous system disorders.

Methods: Serum prolactin levels of 255 MS patients, 19 neuromyelitis optica (NMO) patients, 15 clinically isolated syndrome (CIS) patients, and 240 healthy controls were measured by a heterogeneous sandwich magnetic separation assay.

Results: MS and NMO cohorts had a significantly higher number of patients with hyperprolactinemia than healthy controls. Sera obtained during attacks of both MS and NMO patients displayed higher prolactin levels than those collected during remission. Prolactin level elevations were found to be more prominent in myelitis attacks in MS. No significant correlation was found between prolactin levels and age, disease duration, disability status, number of attacks, and oligoclonal band positivity. CIS patients who converted to MS had higher prolactin levels than those who did not.

Conclusion: Our findings support the possible mediating role of prolactin in the immunopathogenesis of MS, NMO, and conversion from CIS to MS.
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http://dx.doi.org/10.5152/npa.2016.16979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353044PMC
December 2016

Effects of in vivo and in vitro administration of neuro-Behcet's disease IgG.

Neurol Sci 2017 May 21;38(5):833-843. Epub 2017 Feb 21.

Department of Pharmacology and Psychopharmacology Research Unit, Marmara University, Istanbul, Turkey.

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.
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http://dx.doi.org/10.1007/s10072-017-2856-2DOI Listing
May 2017

Recurrent tumefactive demyelinating lesions: a pathological study.

Clin Neuropathol 2017 Jul/Aug;36(4):195-198

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http://dx.doi.org/10.5414/NP301005DOI Listing
August 2018

A Case of Seronegative Limbic Encephalitis with Multiple Sclerosis: A Possible Overlapping Syndrome.

Am J Case Rep 2017 Jan 18;18:64-66. Epub 2017 Jan 18.

Department of Neurology, Haydarpaşa Numune Training and Research Center, Istanbul, Turkey.

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 short-term 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266202PMC
http://dx.doi.org/10.12659/ajcr.901391DOI Listing
January 2017

Reduced fecal GABA levels in multiple sclerosis patients.

Mult Scler Relat Disord 2016 Sep 28;9:60-1. Epub 2016 Jun 28.

Department of Neuroscience, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.msard.2016.06.009DOI Listing
September 2016

Limbic Encephalitis Associated with Sjögren's Syndrome: Report of Three Cases.

Intern Med 2016 15;55(16):2285-9. Epub 2016 Aug 15.

Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Turkey.

Sjögren's syndrome (SS) may be complicated by neurological manifestations. We herein report three women (age range 26-60 years old) who all presented with limbic encephalitis (LE) as the predominant clinical feature 3 months to 15 years after the diagnosis of SS. The 26-year-old patient also developed acute motor axonal neuropathy one week after autoimmune encephalitis. All three patients showed contrast-enhanced MRI lesions and inflammatory cerebrospinal fluid findings, while not displaying any anti-neuronal antibodies and showing a remarkable response to immunotherapy. SS is often overlooked when the symptoms are mild. Therefore, in LE cases with no identifiable cause, serological screening for rheumatologic disorders is recommended.
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http://dx.doi.org/10.2169/internalmedicine.55.6222DOI Listing
March 2017