Publications by authors named "Serkan Ozakbas"

60 Publications

Validity and reliability of "Cognitive Reserve Index Questionnaire" for the Turkish Population.

Authors:
Serkan Ozakbas Pinar Yigit Zeynep Akyuz Ozge Sagici Zuhal Abasiyanik Asiye Tuba Ozdogar Turhan Kahraman Hemdem Rodi Bozan Ilknur Hosgel

Mult Scler Relat Disord 2021 Feb 7;50:102817. Epub 2021 Feb 7.

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

Background: Cognitive reserve (CR) is the ability to counteract brain damage through differential recruitment of brain networks. Besides, it has also been observed that lifetime intellectual enriching skills reduce the effect of disease burden on cognitive status. The Cognitive Reserve Index questionnaire (CRIq), which is a method for the quantitative measurement and comprehensive evaluation of the CR, that individuals have accumulated throughout their lifetimes. The present study aimed to adapt CRIq to the Turkish population.

Methods: CRIq is a 20-item questionnaire consisting of 3 sub-scales (CRI-Education, CRI- Working Activity, CRI-Leisure Time). 271 females and 228 males, a total of 499 healthy volunteers participated in the study (mean age: 39.54±14.05, mean education years 13.14±4.84). Participants were evaluated with the "Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)" and CRIq was applied. BICAMS was used to determine the validity of the CRIq. To determine the reliability, the questionnaire was applied again two weeks after the first application. Internal consistency and test-retest reliability were measured for reliability analysis. Independent sample t-test was conducted to observe the difference between genders.

Results: The Cronbach alpha coefficient of the questionnaire was 0.78, and the reliability of the questionnaire was acceptable. The findings showed that inter-rater reliability was quite high (ICC:0.95, 95% CI=1.000, n=36). The correlation between the first and second application of the questionnaire was found to be acceptable for both the sub-scales and the whole questionnaire. The highest CRIq scores were shown for young adults in CRI-Education and CRI-LeisureTime, for the middle-aged in CRIq-WorkingActivity, no significant differences in total CRIq scores. The males scored significantly higher in CRIq total scores than females, but there was not a significant difference in CRI-LeisureTime between genders.

Conclusion: The Turkish version of CRIq was found to be a valid and reliable method for evaluating cognitive reserve in healthy individuals.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2021.102817DOI Listing
February 2021

Prevalence and determinants of falls in persons with multiple sclerosis without a clinical disability.

Authors:
Zuhal Abasıyanık Turhan Kahraman Özge Ertekin Cavid Baba Serkan Özakbaş

Mult Scler Relat Disord 2021 Jan 18;49:102771. Epub 2021 Jan 18.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Background: Falls are common in persons with Multiple Sclerosis (pwMS) and lead to destructive results, specifically with increasing disability. However, there is only scarce data investigating prevalence and determinants of falls in pwMS without a clinical disability. Therefore, this study aimed to investigate proportion of fallers and related factors in pwMS without a clinical disability.

Methods: One hundred and four pwMS with no clinical disability (EDSS≤1.5) were recruited in this cross-sectional study. The outcome measures comprised of the Timed 25-Foot Walk (T25FW), Six Minute Walk Test (6MWT), Timed Up and Go Test (TUG), Multiple Sclerosis Walking Scale (MSWS-12), Single Leg Stance Test (SLS), Activities-Specific Balance Confidence Scale (ABC), Symbol Digit Modalities Test (SDMT), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory-II (BDI-II). The number of falls during the last three months was recorded.

Results: Twenty-five percent of the pwMS reported at least one fall in the last three months. The TUG and MSWS-12 scores were significantly greater in the fallers compared to non-fallers (p<0.05). Whereas the fallers had significantly less ABC scores (p<0.05). Increasing TUG and MSWS-12 score and decreasing ABC score was related with increased risk of being classified as a faller adjusting for EDSS score.

Conclusion: The present findings highlight that falls are frequent problem for pwMS, even if they do not have a clinical disability. Therefore, falls prevention strategies are also required in the early stages of the disease in clinical practice. The ABC scale, MSWS-12, and TUG test can be used by the clinicians and researchers to predict potential fallers of the pwMS without a clinical disability.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2021.102771DOI Listing
January 2021

Determinants of therapeutic lag in multiple sclerosis.

Authors:
Izanne Roos Emmanuelle Leray Federico Frascoli Romain Casey J William L Brown Dana Horakova Eva Kubala Havrdova Marc Debouverie Maria Trojano Francesco Patti Guillermo Izquierdo Sara Eichau Gilles Edan Alexandre Prat Marc Girard Pierre Duquette Marco Onofrj Alessandra Lugaresi Pierre Grammond Jonathan Ciron Aurélie Ruet Serkan Ozakbas Jérôme De Seze Céline Louapre Hélène Zephir Maria José Sá Patrizia Sola Diana Ferraro Pierre Labauge Gilles Defer Roberto Bergamaschi Christine Lebrun-Frenay Cavit Boz Elisabetta Cartechini Thibault Moreau David Laplaud Jeannette Lechner-Scott Francois Grand'Maison Oliver Gerlach Murat Terzi Franco Granella Raed Alroughani Gerardo Iuliano Vincent Van Pesch Bart Van Wijmeersch Daniele LA Spitaleri Aysun Soysal Eric Berger Julie Prevost Eduardo Aguera-Morales Pamela McCombe Tamara Castillo Triviño Pierre Clavelou Jean Pelletier Recai Turkoglu Bruno Stankoff Olivier Gout Eric Thouvenot Olivier Heinzlef Youssef Sidhom Riadh Gouider Tunde Csepany Bertrand Bourre Abdullatif Al Khedr Olivier Casez Philippe Cabre Alexis Montcuquet Abir Wahab Jean-Philippe Camdessanche Aude Maurousset Ivania Patry Karolina Hankiewicz Corinne Pottier Nicolas Maubeuge Céline Labeyrie Chantal Nifle Alasdair Coles Charles B Malpas Sandra Vukusic Helmut Butzkueven Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

Cross-cultural adaptation and psychometric properties of the Turkish version of the Manual Ability Measure-36 (MAM-36) in people with multiple sclerosis.

Authors:
Ozge Ertekin Turhan Kahraman Mona Aras Cavid Baba Serkan Ozakbas

Neurol Sci 2020 Nov 24. Epub 2020 Nov 24.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Objective: The Manual Ability Measure-36 (MAM-36) has been used to assess subjective upper limb function in people with several neurological and non-neurological diseases. Besides, the MAM-36 is one of the most commonly used patient-reported outcome measures (PROMs) in people with multiple sclerosis (pwMS). The aim was to translate and conduct cross-cultural adaptation of the MAM-36 into Turkish and investigate its psychometric properties in pwMS.

Methods: The MAM-36 was translated and culturally adapted into Turkish. Two hundred pwMS were recruited for the psychometric study. Hand skills, handgrip strength, upper limb spasticity, disability level, and quality of life were evaluated by the validated performance-based tests and questionnaires including the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) which is a validated MS-specific PROM to assess upper limb function.

Results: MAM-36 was significantly correlated with the performance-based tests and questionnaires, EDSS, age, and disease duration (p < 0.05). MAM-36 and AMSQ were strongly correlated (r = - 0.90, p < 0.01). PwMS with spasticity had significantly lower MAM-36 scores compared to those without spasticity (p < 0.01). Internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (ICC = 0.97) was high.

Conclusion: The Turkish version of MAM-36 has been found as a valid and reliable method for measuring upper limb function in pwMS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s10072-020-04927-zDOI Listing
November 2020

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

Authors:
Francesca Bovis Tomas Kalincik Fred Lublin Gary Cutter Charles Malpas Dana Horakova Eva Kubala Havrdova Maria Trojano Alexandre Prat Marc Girard Pierre Duquette Marco Onofrj Alessandra Lugaresi Guillermo Izquierdo Sara Eichau Francesco Patti Murat Terzi Pierre Grammond Roberto Bergamaschi Patrizia Sola Diana Ferraro Serkan Ozakbas Gerardo Iuliano Cavit Boz Raymond Hupperts Francois Grand'Maison Celia Oreja-Guevara Vincent van Pesch Elisabetta Cartechini Thor Petersen Ayse Altintas Aysun Soysal Cristina Ramo-Tello Pamela McCombe Recai Turkoglu Helmut Butzkueven Jerry S Wolinsky Claudio Solaro Maria Pia Sormani

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1212/WNL.0000000000010991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905777PMC
January 2021

The relationship between cognition, depression, fatigue, and disability in patients with multiple sclerosis.

Authors:
Pinar Yigit Ayla Acikgoz Zaur Mehdiyev Ayfer Dayi Serkan Ozakbas

Ir J Med Sci 2020 Oct 1. Epub 2020 Oct 1.

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

Background: Multiple sclerosis (MS) is a chronic, progressive, and neurodegenerative central nervous system disorder. MS usually causes disability, cognitive deficiency, fatigue, and depression symptoms.

Objectives: To assess cognitive functions of people with MS (pwMS) and investigate the impact of depression, fatigue, and disability on cognitive functions.

Methods: We administered the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery to assess 200 pwMS. The Expanded Disability Status Scale (EDSS) was used to evaluate disability levels. Fatigue Severity Scale (FSS) and the Beck Depression Inventory (BDI) were used, respectively, for fatigue and depression levels.

Results: EDSS and FSS scores were significantly higher in those with a disease duration of 5 years or more. Those with the EDSS ≥ 4 were found to have lower BICAMS performances and higher FSS scores. There was a significant difference in Symbol Digit Modalities Test (SDMT) performances between the groups with and without fatigue (FSS ≥ 4 and FSS < 4, respectively). When depression and fatigue symptoms concur or in the existence of just one of them or none of them, significant differences in terms of SDMT performances have been shown.

Conclusion: The level of disability and fatigue adversely affects the cognitive functions of pwMS; depression has no significant effect. BICAMS that is specific for MS can be beneficial to assess the cognitive state of pwMS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s11845-020-02377-2DOI Listing
October 2020

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

Authors:
Izanne Roos Emmanuelle Leray Federico Frascoli Romain Casey J William L Brown Dana Horakova Eva K Havrdova Maria Trojano Francesco Patti Guillermo Izquierdo Sara Eichau Marco Onofrj Alessandra Lugaresi Alexandre Prat Marc Girard Pierre Grammond Patrizia Sola Diana Ferraro Serkan Ozakbas Roberto Bergamaschi Maria José Sá Elisabetta Cartechini Cavit Boz Franco Granella Raymond Hupperts Murat Terzi Jeannette Lechner-Scott Daniele Spitaleri Vincent Van Pesch Aysun Soysal Javier Olascoaga Julie Prevost Eduardo Aguera-Morales Mark Slee Tunde Csepany Recai Turkoglu Youssef Sidhom Riadh Gouider Bart Van Wijmeersch Pamela McCombe Richard Macdonell Alasdair Coles Charles B Malpas Helmut Butzkueven Sandra Vukusic Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1093/brain/awaa231DOI Listing
September 2020

A comparative study of the effects of yoga and clinical Pilates training on walking, cognition, respiratory functions, and quality of life in persons with multiple sclerosis: A quasi-experimental study.

Authors:
Zuhal Abasıyanık Pınar Yiğit Asiye Tuba Özdoğar Turhan Kahraman Özge Ertekin Serkan Özakbaş

Explore (NY) 2020 Aug 24. Epub 2020 Aug 24.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Objective: The purpose was to investigate the effects of yoga and clinical Pilates training on walking, respiratory muscle strength, cognition, and quality of life and compare the effects of two popular exercise methods in persons with multiple sclerosis (pwMS).

Methods: Twenty-eight pwMS (Pilates group = 16, yoga group = 12) received the program once a week for eight weeks in addition to home exercises. At baseline and the end of the training, participants underwent assessments. The outcome measures were walking speed, mobility, balance confidence, respiratory muscle strength, cognition, and quality of life.

Results: Following the program, there was no significant difference in mobility (p = 0.482), perceived walking quality (p = 0.325), respiratory muscle strength (maximum inspiratory pressure: p = 0.263, maximum expiratory pressure: p = 0.866), and cognition (Symbol Digit Modalities Test: p = 0.324, California Verbal Learning Test-II: p = 0.514, Brief Visuospatial Memory Test-Revised: p = 0.279) between the two groups. Improvements were higher in balance confidence (p = 0.006), walking speed (p = 0.004), and quality of life (p = 0.019) in the clinical Pilates group compared to the yoga group.

Conclusion: This study showed positive effects in walking and respiratory aspects in pwMS who received yoga and clinical Pilates training. Pilates training was superior in improving walking speed, quality of life, and balance confidence compared to yoga training.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.explore.2020.07.013DOI Listing
August 2020

Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score.

Authors:
Amy Kunchok Jeannette Lechner-Scott Franco Granella Maria Trojano Raed Alroughani Patrizia Sola Diana Ferraro Alessandra Lugaresi Marco Onofrj Serkan Ozakbas Guillermo Izquierdo Pierre Grammond Jose Luis Sanchez-Menoyo Bart Van Wijmeersch Cavit Boz Eugenio Pucci Pamela McCombe Francois Grand'Maison Daniele Spitaleri Steve Vucic Raymond Hupperts Vilija Jokubaitis Maria Pia Sormani Helmut Butzkueven Tomas Kalincik

Mult Scler 2020 Jul 8:1352458520936823. Epub 2020 Jul 8.

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

Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing-remitting multiple sclerosis (RRMS) treated with interferon-β.

Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions.

Methods: This RRMS MSBase cohort study ( = 2293) used a Cox model to examine the prognostic value of relapses, MRI activity and the MAGNIMS score for disability worsening during treatment with interferon-β and three other DMTs.

Results: Three new T2 lesions (hazard ratio (HR) = 1.60,  = 0.028) or two relapses (HR = 2.24,  = 0.002) on interferon-β (for 12 months) were predictive of disability worsening over 4 years. MAGNIMS score = 2 (1 relapse and ⩾3 T2 lesions or ⩾2 relapses) was associated with a greater risk of disability worsening on interferon-β (HR = 2.0,  = 0.001). In pooled cohort of four DMTs, similar associations were seen (MAGNIMS score = 2: HR = 1.72,  = 0.001). Secondary analyses demonstrated that the addition of Gd+ to the MAGNIMS did not materially improve its prediction of disability worsening.

Conclusion: We have validated the MAGNIMS score in RRMS and extended its application to three other DMTs: 1 relapse and ⩾3 T2 lesions or ⩾2 relapses predicted worsening of disability. Contrast-enhancing lesions did not substantially improve the prognostic score.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1177/1352458520936823DOI Listing
July 2020

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

Authors:
Minh Le Charles Malpas Sifat Sharmin Dana Horáková Eva Havrdova Maria Trojano Guillermo Izquierdo Sara Eichau Serkan Ozakbas Alessandra Lugaresi Alexandre Prat Marc Girard Pierre Duquette Catherine Larochelle Raed Alroughani Roberto Bergamaschi Patrizia Sola Diana Ferraro Pierre Grammond Francois Grand' Maison Murat Terzi Cavit Boz Raymond Hupperts Helmut Butzkueven Eugenio Pucci Franco Granella Vincent Van Pesch Aysun Soysal Bassem I Yamout Jeannette Lechner-Scott Daniele LA Spitaleri Radek Ampapa Recai Turkoglu Gerardo Iuliano Cristina Ramo-Tello Jose Luis Sanchez-Menoyo Youssef Sidhom Riadh Gouider Vahid Shaygannejad Julie Prevost Ayse Altintas Yara Dadalti Fragoso Pamela Ann McCombe Thor Petersen Mark Slee Michael H Barnett Steve Vucic Anneke Van Der Walt Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1177/1352458520926955DOI Listing
June 2020

Explanatory factors of balance confidence in persons with multiple sclerosis: Beyond the physical functions.

Authors:
Zuhal Abasıyanık Asiye Tuba Özdoğar Özge Sağıcı Turhan Kahraman Cavid Baba Özge Ertekin Serkan Özakbaş

Mult Scler Relat Disord 2020 Aug 29;43:102239. Epub 2020 May 29.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Background: Balance confidence is considered a psychological element of falls and balance-demanding activities. The relationship of balance confidence with physical factors has been investigated; however, psychosocial correlates are not well known. The aim was to investigate the relationship between balance confidence and physical and psychosocial factors and to reveal the determinants of balance confidence in persons with MS (pwMS).

Methods: A total of 445 pwMS were enrolled in the study. Balance confidence was assessed with the Activities-Specific Balance Confidence (ABC) Scale. Psychosocial-based measures included the Modified Fatigue Impact Scale (MFIS), Epworth Sleepiness Scale (ESS), Beck Depression Scale (BDI), and Symbol Digit Modalities Test (SDMT). The Godin Leisure-Time Exercise Questionnaire (GLTEQ), Timed 25-Foot Walk (T25FW), Six-Minute Walk Test (6MWT), and Single Leg Stance Test (SLS) were used to assess physical functions.

Results: There was a significant correlation between the ABC score and all physical and psychosocial measures (p<0.05). Hierarchical linear regression analyses indicated that psychosocial factors were significantly associated with ABC accounting for 41% of the variance. The addition of physical variables explained an additional 35% of variance over psychosocial variables. The MFIS, SDMT, BDI, T25FW, 6MWT, and SLS were significantly predictive of the ABC.

Conclusion: This study emphasizes the importance of considering both physical and psychosocial factors for understanding balance confidence in pwMS. Besides, intervention strategies for enhancing balance confidence should aim to improve fatigue, depression, and cognition in addition to physical components.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2020.102239DOI Listing
August 2020

Early clinical markers of aggressive multiple sclerosis.

Authors:
Charles B Malpas Ali Manouchehrinia Sifat Sharmin Izanne Roos Dana Horakova Eva Kubala Havrdova Maria Trojano Guillermo Izquierdo Sara Eichau Roberto Bergamaschi Patrizia Sola Diana Ferraro Alessandra Lugaresi Alexandre Prat Marc Girard Pierre Duquette Pierre Grammond Francois Grand'Maison Serkan Ozakbas Vincent Van Pesch Franco Granella Raymond Hupperts Eugenio Pucci Cavit Boz Youssef Sidhom Riadh Gouider Daniele Spitaleri Aysun Soysal Thor Petersen Freek Verheul Rana Karabudak Recai Turkoglu Cristina Ramo-Tello Murat Terzi Edgardo Cristiano Mark Slee Pamela McCombe Richard Macdonell Yara Fragoso Javier Olascoaga Ayse Altintas Tomas Olsson Helmut Butzkueven Jan Hillert Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1093/brain/awaa081DOI Listing
May 2020

Associations between smoking and walking, fatigue, depression, and health-related quality of life in persons with multiple sclerosis.

Authors:
Turhan Kahraman Asiye Tuba Ozdogar Zuhal Abasiyanik Serkan Ozakbas

Acta Neurol Belg 2020 Mar 28. Epub 2020 Mar 28.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Smoking is associated with increased multiple sclerosis (MS) risk. In addition, some studies have reported that smoking is associated with anxiety and depression. However, the associations between smoking, walking, and fatigue are needed to be investigated. The objective was to investigate the associations between cigarette smoking and walking, fatigue, depression symptom severity, and health-related quality of life in persons with MS. Two hundred seventy-nine persons with MS were evaluated in this cross-sectional study. Study outcomes were neurological disability level, walking speed, walking endurance, perceived walking impact of MS, fatigue, depression symptom severity, and health-related quality of life. There were 95 (34.1%) current smokers who had significantly higher fatigue (p = 0.003, pη = 0.031) and depression (p = 0.044, pη = 0.015), and lower health-related quality of life (p = 0.003, pη = 0.031) after adjusting for age, gender, neurological disability level, and disease duration compared to non-smokers (n = 184). There was no significant difference between smokers and non-smokers in walking measures (p > 0.05). Smoking intensity was significantly correlated with age (r = 0.487), neurological disability level (r = 0.227), disease duration (r = 0.30), walking speed (r = 0.574), walking endurance (r =  - 0.461), perceived walking impact of MS (r = 0.684), fatigue (r = 0.370), health-related quality of life (r =  - 0.259), and depression (r = 0.269) in current smokers. Cigarette smokers with MS had significantly more fatigue and depression symptom severity and less health-related quality of life compared to non-smokers. Increased pack-years of cigarette smoking was associated with worse walking ability and health-related quality of life, and greater depression symptom severity and fatigue.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s13760-020-01341-2DOI Listing
March 2020

Effect of video-based exergaming on arm and cognitive function in persons with multiple sclerosis: A randomized controlled trial.

Authors:
Asiye Tuba Ozdogar Ozge Ertekin Turhan Kahraman Pinar Yigit Serkan Ozakbas

Mult Scler Relat Disord 2020 May 24;40:101966. Epub 2020 Jan 24.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Background: Developments in rehabilitation technology such as video-based exergaming contributes to the treatment process as well as to increase the active participation of persons with multiple sclerosis (pwMS). The aim was to investigate the effect of video-based exergaming training on upper extremity and cognitive function as well as core stability, walking, depression, fatigue, and quality of life in pwMS.

Methods: This randomized controlled trial included 60 pwMS who were randomly divided into three groups; video-based exergaming (n = 21), conventional rehabilitation (n = 19), and control groups (n = 20). The experimental groups received therapy sessions once a week for 8 weeks. All the participants were assessed at baseline and after 8 weeks. The outcome measures included upper extremity and cognitive functions as well as core stability, walking, depression, fatigue, and quality of life measures.

Results: Significant improvements were observed in the primary outcome, measured by Nine-Hole Peg Test in the video-based exergaming [before= 25.8 (11.1) s; after= 22.3 (11.0) s] and conventional rehabilitation [before= 23.3 (8.1) s; after= 19.9 (3.8) s] groups (p < 0.05). Cognitive functions (with the exception of processing speed in the conventional rehabilitation group), most of the lower extremity functions, balance-related measures, fatigue and quality of life levels were significantly improved in the video-based exergaming and conventional rehabilitation groups, however, only the depression level was significantly decreased in the video-based exergaming (p < 0.05). Several significant differences were observed in the changes of the control group compared to the video-based exergaming and conventional rehabilitation groups (p < 0.05).

Conclusion: This study suggests that video-based exergaming is almost as effective as conventional rehabilitation regarding improving walking, upper and lower extremity functions, cognitive functions, fatigue, depression, and health-related quality of life in pwMS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2020.101966DOI Listing
May 2020

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

Authors:
Amy Kunchok Charles Malpas Petra Nytrova Eva Kubala Havrdova Raed Alroughani Murat Terzi Bassem Yamout Jyh Yung Hor Rana Karabudak Cavit Boz Serkan Ozakbas Javier Olascoaga Magdolna Simo Franco Granella Francesco Patti Pamela McCombe Tunde Csepany Bhim Singhal Roberto Bergamaschi Yara Fragoso Talal Al-Harbi Recai Turkoglu Jeannette Lechner-Scott Guy Laureys Celia Oreja-Guevara Eugenio Pucci Patrizia Sola Diana Ferraro Ayse Altintas Aysun Soysal Steve Vucic Francois Grand'Maison Guillermo Izquierdo Sara Eichau Alessandra Lugaresi Marco Onofrj Maria Trojano Mark Marriott Helmut Butzkueven Ilya Kister Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

Effect of hormonal changes on the neurological status in the menstrual cycle of patient with multiple sclerosis.

Authors:
Yuksel Guven Yorgun Serkan Ozakbas

Clin Neurol Neurosurg 2019 Nov 10;186:105499. Epub 2019 Sep 10.

Faculty of Medicine, Department of Neurology, Dokuz Eylul Univesity, Izmir, Turkey. Electronic address:

Objectives: Premenstrual worsening has been often complained by patients with multiple sclerosis (MS). However, there is no quantitative study in the literature regarding premenstrual worsening and there are only a few studies for its reasons. In diseases such as MS, which there are limited evidence about the etiology and the triggers, detection of the variables in menstrual period, which is defined relatively easy, has a great potential to shed light to the disease. In the present study, we aimed to detect whether there was a deterioration in premenstrual period of patients with MS and to measure the observed deterioration and the relationships between demographics, physical and hormonal variables.

Patients And Methods: This study included 44 patients with MS, who were diagnosed according to McDonald criteria, and 14 healthy controls. For two consecutive cycles, cases were evaluated on the basis of neurological functions in the premenstrual and ovulation phases. In each examination, blood samples were obtained for detection of the levels of sex hormones (FSH, LH, E2, Progesterone). In the first and the fourth examinations, we applied Multiple Sclerosis Functional Composite (MSFC).

Results: Patients with MS showed poor performance in all used measurements than the healthy controls. Premenstrual period was worse based on cognitive aspects than the ovulation period in both MS patients and healthy controls. This was more evident in patients with MS. Patients treated with immunomodulatory agents had better cognitive performance than those were not given these agents.

Conclusion: In our study, the patients with MS were found to be worse in cognition, and physical performance when compared with the healthy group. In premenstrual period, cognitive functions, and physical performance deteriorated in patients with MS. Healthy people seemed to be deteriorated on cognition measured with Paced Auditory Serial Addition Test.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.clineuro.2019.105499DOI Listing
November 2019

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

Authors:
Cavit Boz Murat Terzi Bilge Özer Recai Turkoglu Rana Karabudak Hüsnü Efendi Aysun Soysal Serhan Sevim Ayse Altintas Asli Kurne Aylin Akçalı Gülsen Akman Nur Yüceyar Belgin Petek Balcı Özgul Ekmekci Serap Zengin Karahan Meltem Demirkıran Burcu Altunrende Ömer Faruk Turan Gökçen GözübatıkÇelik Nilüfer Kale Mesrure Köseoğlu Serkan Ozakbas

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2019.101376DOI Listing
November 2019

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Authors:
Adam Fambiatos Vilija Jokubaitis Dana Horakova Eva Kubala Havrdova Maria Trojano Alexandre Prat Marc Girard Pierre Duquette Alessandra Lugaresi Guillermo Izquierdo Francois Grand'Maison Pierre Grammond Patrizia Sola Diana Ferraro Raed Alroughani Murat Terzi Raymond Hupperts Cavit Boz Jeannette Lechner-Scott Eugenio Pucci Roberto Bergamaschi Vincent Van Pesch Serkan Ozakbas Franco Granella Recai Turkoglu Gerardo Iuliano Daniele Spitaleri Pamela McCombe Claudio Solaro Mark Slee Radek Ampapa Aysun Soysal Thor Petersen Jose Luis Sanchez-Menoyo Freek Verheul Julie Prevost Youssef Sidhom Bart Van Wijmeersch Steve Vucic Edgardo Cristiano Maria Laura Saladino Norma Deri Michael Barnett Javier Olascoaga Fraser Moore Olga Skibina Orla Gray Yara Fragoso Bassem Yamout Cameron Shaw Bhim Singhal Neil Shuey Suzanne Hodgkinson Ayse Altintas Talal Al-Harbi Tunde Csepany Bruce Taylor Jordana Hughes Jae-Kwan Jun Anneke van der Walt Tim Spelman Helmut Butzkueven Tomas Kalincik

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020

The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.

Authors:
Zuhal Abasıyanık Özge Ertekin Turhan Kahraman Pınar Yigit Serkan Özakbaş

Explore (NY) 2020 Jan - Feb;16(1):12-20. Epub 2019 Jul 17.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Context: Multiple sclerosis (MS) is a chronic progressive and neurodegenerative disease. Exercise programs are needed to maintain and increase functional status in persons with MS (pwMS). Pilates exercises designed by a physiotherapist can enhance participation and functionality in pwMS.

Objective: The aim of this study was to investigate the effects of Clinical Pilates training on balance, walking, fall risk, respiratory, and cognitive functions in pwMS compared with an active comparator (home exercise training).

Design: This study was a randomized controlled study.

Settings: This study was designed by researchers at Dokuz Eylül University, Izmir, Turkey.

Participants: Forty-two pwMS were included in this randomized controlled trial.

Main Outcome Measures: Walking, core stability, balance confidence, respiratory muscle strength, and cognitive functions were assessed before and after the program.

Interventions: The participants were randomly divided into two groups. The Pilates exercises group (n = 21) received therapy weekly for 8 weeks along with a home exercise program. The home exercise group (n = 21) was given standardized exercises reflecting routine clinical practice. The program compliance was monitored by telephone calls once a week.

Results: There were no significant differences in walking speed (p = 0.096), perceived walking ability (p = 0.165), and fear of falling (p = 0.385) between the Pilates and home exercise groups. Clinical Pilates training was superior to the home exercise program in walking endurance (p = 0.001), postural stability (p = 0.028), core stability (p = 0.016), respiratory (maximum inspiratory pressure: p = 0.037, maximum expiratory pressure: p = 0.008), and cognitive functions (p = 0.001-0.007). Clinical Pilates training may be preferred as an alternative method to improve balance, walking, respiratory, and cognitive functions in pwMS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.explore.2019.07.010DOI Listing
July 2019

Monthly Pulse Methylprednisolone Therapy is Effective in Preventing Permanent Disease Progression in Secondary Progressive Multiple Sclerosis.

Authors:
Serkan Özakbaş Bilge Piri Çinar Didem Öz Görkem Kösehasanoğullari Behice Bircan Kurşun Turhan Kahraman

Noro Psikiyatr Ars 2019 Jun 6;56(2):115-118. Epub 2018 Jul 6.

Department of Physiotherapy and Rehabilitation, İzmir Katip Çelebi University Faculty of Health Sciences, İzmir, Turkey.

Introduction: Secondary progressive multiple sclerosis (SPMS) is the phase in which disability continues to worsen with or without accompanying attacks. Monthly methylprednisolone pulse therapy can be used in the secondary progressive phase. The purpose of the present study was to evaluate the effects of methylprednisolone pulse therapy on the basis of clinical and MRI parameters in patients with SPMS.

Methods: This was a multi-center, examiner-blinded, prospective study. Patients with SPMS with EDSS scores of 3 or more, using one or none of azathioprine, interferon or glatiramer acetate, were evaluated. Patients were given IVMP (1 dose of 1 g IV) once a month for 24 months. EDSS scores, MRI findings, quality of life, and adverse events were evaluated.

Results: Ninety-seven SPMS patients were included in the study. Significant decreases in new/enlarging, Gd-enhanced, and spinal lesions were observed from baseline to year 2. EDSS scores remained stable at the end of the second year. Monthly high-dose IVMP resulted in a significant decrease in attacks.

Conclusion: This study is important in terms of emphasizing that this therapeutic option should not be overlooked, since monthly pulse therapy can halt or even reverse progression, regarded as a natural course in SPMS, albeit to a small extent.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.5152/npa.2017.19339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563858PMC
June 2019

Cross-cultural adaptation, validity and reliability of the Turkish version of the patient determined disease steps scale in persons with multiple sclerosis.

Authors:
Turhan Kahraman Asiye Tuba Özdoğar Serkan Özakbaş

Physiother Theory Pract 2019 Jun 20:1-8. Epub 2019 Jun 20.

c Department of Neurology, Faculty of Medicine , Dokuz Eylül University , Balcova , Izmir , Turkey.

: Patient Determined Disease Steps (PDDS) scale is a patient-reported outcome measure to assess disability in persons with multiple sclerosis (pwMS). This scale can be used as an alternative to Expanded Disability Status Scale (EDSS) as it is a costly, more time-consuming, and clinician-based method. This study aimed to conduct Turkish translation and cross-cultural adaptation of PDDS and investigate its psychometric properties. : Turkish translation and cross-cultural adaptation of PDDS was conducted. Its psychometric properties including validity (i.e. content, criterion, and construct) and test-retest reliability (relative and absolute) were investigated in 100 pwMS. : PDDS had a significant strong correlation with EDSS (= 0.61, < .001). Regression model to predict EDSS scores from PDDS scores was significant ( < .001, = 0.67). Both PDDS and EDSS were significantly correlated with age, disease duration, walking speed and endurance, perceived impact of MS on walking, functional mobility, working memory and information processing speed, visual memory, manual dexterity, and health-related quality of life ( < .05). No significant difference was observed in the correlation coefficients of PDDS and EDSS ( > .05). Relative test-retest reliability was found high [ICC = 0.99 (95%CI = 0.99, 0.99)]. Absolute test-retest reliability was high as the Bland-Altman analyses showed no significant systematic bias between the repeated assessments. A narrow range of the limits of agreement indicated that PDDS had high stability and low variation between first and second assessments. : Turkish version of PDDS presented high validity and test-retest reliability in pwMS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1080/09593985.2019.1633715DOI Listing
June 2019

The 20-year history: Change of multiple sclerosis patient profile over 20 years.

Authors:
Serkan Ozakbas Bilge Piri Cinar Turhan Kahraman

Mult Scler Relat Disord 2019 Aug 16;33:1-4. Epub 2019 May 16.

Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Izmir Katip Celebi University, Izmir, Turkey.

Background: Patients attending multiple sclerosis (MS) clinics experience less disability compared to previous years.

Objective: This study was conducted retrospectively examining the patient records of our MS Clinic. The patient records in 1996 were compared to those in 2016.

Methods: Demographic data, duration of disease, time to diagnosis, course of the disease, Expanded Disability Status Scale (EDSS) scores, and whether or not patients used disease modifying therapies were recorded in both 1996 and 2016.

Results: The mean frequency of visits were significantly higher in 1996 compared to 2016 (p = 0.003). There were significantly more number of patients with clinically isolated syndrome (p = 0.004) and secondary progressive MS (p = 0.001) in 1996; however, significantly less number of patients with relapsing-remitting MS (p < 0.001). EDSS scores of ≤3 were significantly higher in 2016 (p < 0.001). On the other hand, the number of patients with the EDSS scores of 6-6.5 and ≥7 were significantly less in 2016 (p < 0.001). Significantly more patients with secondary progressive MS, EDSS scores of 6-6.5 and ≥7 (wheel-chair dependent patients) came to the clinic in 1996 compared to 2016.

Conclusion: The emergence of treatment options in MS and the increasing availability of new treatment options for patients with no/inadequate treatment response have changed the MS patient profile over the 20 years. The number of wheelchair-dependent patients dramatically reduced.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2019.05.002DOI Listing
August 2019

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

Authors:
Tomas Kalincik Eva Kubala Havrdova Dana Horakova Guillermo Izquierdo Alexandre Prat Marc Girard Pierre Duquette Pierre Grammond Marco Onofrj Alessandra Lugaresi Serkan Ozakbas Ludwig Kappos Jens Kuhle Murat Terzi Jeannette Lechner-Scott Cavit Boz Francois Grand'Maison Julie Prevost Patrizia Sola Diana Ferraro Franco Granella Maria Trojano Roberto Bergamaschi Eugenio Pucci Recai Turkoglu Pamela A McCombe Vincent Van Pesch Bart Van Wijmeersch Claudio Solaro Cristina Ramo-Tello Mark Slee Raed Alroughani Bassem Yamout Vahid Shaygannejad Daniele Spitaleri José Luis Sánchez-Menoyo Radek Ampapa Suzanne Hodgkinson Rana Karabudak Ernest Butler Steve Vucic Vilija Jokubaitis Tim Spelman Helmut Butzkueven

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1136/jnnp-2018-319831DOI Listing
April 2019

Frequency, type, distribution of pain and related factors in persons with multiple sclerosis.

Authors:
Turhan Kahraman Asiye Tuba Özdoğar Özge Ertekin Serkan Özakbaş

Mult Scler Relat Disord 2019 Feb 3;28:221-225. Epub 2019 Jan 3.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Background: Although there is accumulating evidence on neuropathic pain in persons with multiple sclerosis (pwMS), little is known about musculoskeletal pain. The aim was to examine the frequency, type, distribution of pain and related factors in pwMS.

Methods: This cross-sectional study included 223 pwMS. The Nordic Musculoskeletal Questionnaire and painDETECT Questionnaire were used to assess pain. Depression, fatigue, sleepiness, and health-related quality of life were assessed.

Results: 23.3% of participants did not have pain, 55.6% had musculoskeletal pain and 21.1% had neuropathic pain. There was no significant difference between the groups in age, gender, disease duration, employment status, marital status and education level (p > .05). The participants without pain had lower Expanded Disability Status Scale (EDSS) scores compared to those with neuropathic pain (p = .024). In addition, the participants with musculoskeletal pain had lower EDSS scores compared to those with neuropathic pain (p = .027). Depression, fatigue, sleepiness and quality of life scores were significantly different between the groups (p < .05). Participants with neuropathic pain had significantly lower quality of life, and higher fatigue, depression and sleepiness compared to participants with musculoskeletal pain and without pain (p < .05). Musculoskeletal pain was most common in low back (52.4%), neck (51.6%), and upper back (45.2%).

Conclusions: This study suggests that pain is a very common symptom among pwMS. Pain frequency is high as 76.7%. In particular, the presence of neuropathic pain is associated with lower health-related quality of life and higher levels of depression, fatigue and sleepiness. Musculoskeletal pain was most common in the spine area including neck, upper back, and low back.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2019.01.002DOI Listing
February 2019

Effects of cigarette smoking on respiratory problems and functional levels in multiple sclerosis patients.

Authors:
Ridvan Aktan Sevgi Ozalevli Serkan Ozakbas

Mult Scler Relat Disord 2018 Oct 17;25:271-275. Epub 2018 Aug 17.

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

Objective: The aim of the study was to investigate the effects of smoking on respiratory symptoms and functional levels by questioning use of cigarette in Multiple Sclerosis (MS) patients.

Methods: A questionnaire was sent via e-mail to the 135 MS patients, who clinically diagnosed with MS and EDSS score was determined.Perceived dyspnea was assessed by the mMRC scale.The severity of dyspnea and fatigue perceived during rest and effort was assessed by the mBORG scale.Functional levels of the patients were assessed by asking the average daily walking distance and the average sitting time daily.

Results: The mean EDSS score of the smoker and the non-smoker group were 2.85 ± 0.75, 2.96 ± 1.03 respectively(p = 0.48).There was no statistically difference found between groups in terms of age,height,weight,BMI,gender,EDSS scores(p > 0.05).The rate of cough, sputum and severity of perceived dyspnea was statistically higher in the smoker group(p < 0.05).The mean walking distance daily of the smokers was statistically lower (p < 0.001).The smoker group had a high level of sedanter lifestyle(p < 0.05).

Conclusion: It has been proven that smoking increases respiratory problems even in MS patients with a good EDSS score.Moreover, these problems lead to a further reduction in the functional levels of the patients, in addition to the disease progression.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2018.08.016DOI Listing
October 2018

Prediction of Conversion from Clinically Isolated Syndrome to Multiple Sclerosis According to Baseline Characteristics: A Prospective Study.

Authors:
Bilge Piri Çinar Serkan Özakbaş

Noro Psikiyatr Ars 2018 Mar 19;55(1):15-21. Epub 2018 Mar 19.

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

Objective: Clinically isolated syndrome (CIS) is a clinical state that proceeds with inflammation and demyelination, suggestive of multiple sclerosis (MS) in the central nervous system in the absence of other alternative diagnoses. The purpose of this study was to determine in a prospective cohort, the predictor factors in conversion from CIS to MS on the basis of clinical, magnetic resonance (MR) imaging and cerebrospinal fluid (CSF) findings.

Methods: Forty-one CIS patients were included in this study and followed up for at least two years.

Results: Clinically, polysymptomatic or sensorial involvement, good prognostic factors and complete response to pulse therapy were found to be of prognostic value in conversion to MS. A greater presence of oligoclonal bands in CSF was identified in the converted group (92.8%). In terms of localization, presence of callosal lesion (71.4%), periventricular lesion (97.1%), Gd-enhanced lesion (48.6%), black hole (54.2%) and brainstem lesion (57.1%) was statistically significant in terms of conversion to MS.

Conclusion: A carefully performed neurological assessment of symptoms and signs, and evaluation of lesions on MR combined with CSF findings are important for identifying the risk of conversion to MS. This information may be useful when considering treatment in CIS patients instead of waiting for conversion to MS.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.29399/npa.12667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045808PMC
March 2018

The multiple sclerosis work difficulties questionnaire: translation and cross-cultural adaptation to Turkish and assessment of validity and reliability.

Authors:
Turhan Kahraman Asiye Tuba Özdoğar Cynthia Alison Honan Özge Ertekin Serkan Özakbaş

Disabil Rehabil 2019 10 9;41(21):2556-2562. Epub 2018 May 9.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University , Izmir , Turkey.

To linguistically and culturally adapt the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) for use in Turkey, and to examine its reliability and validity. Following standard forward-back translation of the MSWDQ-23, it was administered to 124 people with multiple sclerosis (MS). Validity was evaluated using related outcome measures including those related to employment status and expectations, disability level, fatigue, walking, and quality of life. Randomly selected participants were asked to complete the MSWDQ-23 again to assess test-retest reliability. Confirmatory factor analysis on the MSWDQ-23 demonstrated a good fit for the data, and the internal consistency of each subscale was excellent. The test-retest reliability for the total score, psychological/cognitive barriers, physical barriers, and external barriers subscales were high. The MSWDQ-23 and its subscales were positively correlated with the employment, disability level, walking, and fatigue outcome measures. This study suggests that the Turkish version of MSWDQ-23 has high reliability and adequate validity, and it can be used to determine the difficulties faced by people with multiple sclerosis in workplace. Moreover, the study provides evidence about the test-retest reliability of the questionnaire. Implications for rehabilitation Multiple sclerosis affects young people of working age. Understanding work-related problems is crucial to enhance people with multiple sclerosis likelihood of maintaining their job. The Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) is a valid and reliable measure of perceived workplace difficulties in people with multiple sclerosis: we presented its validation to Turkish. Professionals working in the field of vocational rehabilitation may benefit from using the MSWDQ-23 to predict the current work outcomes and future employment expectations.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1080/09638288.2018.1470262DOI Listing
October 2019

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

Authors:
Serkan Ozakbas Recai Turkoglu Yusuf Tamam Murat Terzi Ozlem Taskapilioglu Canan Yucesan Hatice Limoncu Baser Mehmet Gencer Esref Akil Sedat Sen Omer Faruk Turan Mine Hayriye Sorgun Pinar Yigit Nevin Turkes

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.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.msard.2018.03.009DOI Listing
May 2018

The Turkish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery.

Authors:
Serkan Ozakbas Pinar Yigit Bilge Piri Cinar Hatice Limoncu Turhan Kahraman Görkem Kösehasanoğulları

BMC Neurol 2017 Dec 6;17(1):208. Epub 2017 Dec 6.

Department of Neurology, Usak State Hospital, Usak, Turkey.

Background: Cognitive impairment may be seen in as many as 43-70% of patients with multiple sclerosis (MS) and may be observed in all MS subtypes. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) battery may be used to evaluate cognition status. The purpose of the current study is to validate the BICAMS battery in Turkish.

Methods: Patients with MS attending our clinic between September 2014 and April 2015 were invited to participate. Healthy control participants were matched in terms of age, gender and years of education.

Results: One hundred seventy-three MS patients and 153 healthy control participants were enrolled in the study. MS patients performed significantly worse in all trials than the members of the healthy control group. In addition, cognitive dysfunction was identified in 78 of the 173 (45.1%) patients. In the MS with cognitive impairment group, 64 out of 151 (42.4%) subjects were RRMS patients, 12 out of 18 (66.7%) were secondary progressive MS patients, and 2 out of 4 (50%) were primer progressive MS patients.

Conclusions: The BICAMS has been proposed for assessing cognitive impairment in MS patients. This study shows that the battery is suitable for use in Turkey.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1186/s12883-017-0993-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717821PMC
December 2017

Feasibility of a 6-Month Yoga Program to Improve the Physical and Psychosocial Status of Persons with Multiple Sclerosis and their Family Members.

Authors:
Turhan Kahraman Asiye Tuba Ozdogar Pinar Yigit Ilknur Hosgel Zaur Mehdiyev Ozge Ertekin Serkan Ozakbas

Explore (NY) 2018 Jan - Feb;14(1):36-43. Epub 2017 Oct 23.

Department of Neurology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.

Context: To the best of our knowledge, there has been no study on yoga that includes both persons with multiple sclerosis (MS) and their family members. Because yoga has therapeutic effects in both persons with MS and healthy persons, we hypothesized that it would be an effective method to improve not only the physical and psychosocial status but also the time persons with MS and their family members spend together.

Objective: To examine the feasibility of a 6-month (long-term) yoga program to improve the physical and psychosocial status of persons with MS and their family members.

Design: Uncontrolled clinical trial.

Setting: The protocol was developed at the Department of Neurology, Faculty of Medicine, and School of Physical Therapy and Rehabilitation, Dokuz Eylül University, Izmir, Turkey.

Participants: Persons with MS and healthy family members.

Main Outcome Measures: Walking, balance, fatigue, health-related quality of life, depression, pain, and kinesiophobia.

Interventions: Yoga training was given once a week (at least 1h) for 6 months. The same assessors who assessed at baseline also performed the same assessments immediately after the end of the training (i.e., after 6 months).

Results: In total, 44 participants (27 persons with MS and 17 healthy family members) participated in the study. Twelve persons with MS and three healthy family members completed the 6-month yoga intervention. The completion rate for persons with MS and healthy subjects was 44.4% and 17.6%, respectively. In persons with MS, the mental dimension of health-related quality of life, walking speed, fatigue, and depression levels significantly improved after the yoga program (p < .05). However, there was no significant change in the self-reported walking impact, balance, pain, physical dimension of health-related quality of life, and kinesiophobia levels in the persons with MS (p > .05). This study suggests that a 6-month yoga program can improve the mental dimension of health-related quality of life, walking speed, fatigue, and depression in the persons with MS. However, the 6-month yoga program does not appear to be a feasible method to increase the time that persons with MS spend together with their family members.
View Article and Find Full Text PDF

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.explore.2017.07.006DOI Listing
September 2018