Publications by authors named "Christoph Heesen"

169 Publications

Arm Ergometry to Improve Mobility in Progressive Multiple Sclerosis (AMBOS)-Results of a Pilot Randomized Controlled Trial.

Front Neurol 2021 19;12:644533. Epub 2021 Jul 19.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Walking disability is one of the most frequent and burdening symptoms of progressive multiple sclerosis (MS). Most of the exercise intervention studies that showed an improvement in mobility performance were conducted in low to moderately disabled relapsing-remitting MS patients with interventions using the legs. However, MS patients with substantial walking disability hardly can perform these tasks. Earlier work has indicated that aerobic arm training might also improve walking performance and could therefore be a therapeutic option in already moderately disabled progressive MS patients. Patients with progressive MS and EDSS 4-6.5 were randomized using a computer-generated algorithm list to either a waitlist control group (CG) or an intervention group (IG). The IG performed a 12-week home-based, individualized arm ergometry exercise training program. Maximum walking distance as measured by the 6-min walking test (6MWT) was the primary endpoint. Secondary endpoints included aerobic fitness, other mobility tests, cognitive functioning, as well as fatigue and depression. Of = 86 screened patients, 53 with moderate disability (mean EDSS 5.5, SD 0.9) were included and data of 39 patients were analyzed. Patients in the IG showed strong adherence to the program with a mean of 67 (SD 26.4) training sessions. Maximum work load ( ) increased in the training group while other fitness indicators did not. Walking distance in the 6MWT improved in both training and waitlist group but not significantly more in trained patients. Similarly, other mobility measures showed no differential group effect. Cognitive functioning remained unchanged. No serious events attributable to the intervention occurred. Although maximum work load improved, 3 months of high-frequency arm ergometry training of low to moderate intensity could not show improved walking ability or cognitive functioning in progressive MS compared to a waitlist CG. The study was registered at www.clinicaltrials.gov (NCT03147105) and funded by the local MS self-help organization.
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http://dx.doi.org/10.3389/fneur.2021.644533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326796PMC
July 2021

aHSCT is superior to alemtuzumab in maintaining NEDA and improving cognition in multiple sclerosis.

Ann Clin Transl Neurol 2021 06 5;8(6):1269-1278. Epub 2021 May 5.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Centre Hamburg-Eppendorf, Falkenried 94, Hamburg, 20251, Germany.

Objective: Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly recognized as a potential therapy for patients with highly active multiple sclerosis (MS). This study aims to assess outcome differences in disease activity in MS patients treated either with aHSCT or alemtuzumab.

Methods: We conducted a monocentric registry-based cohort study by recording the clinical course (EDSS and relapses), MRI parameters (new T2 lesions), and neuropsychological assessment in all 19 MS patients receiving aHSCT, and all 21 patients receiving alemtuzumab between 2007 and 2018. We used survival analyses of no evidence of disease activity (NEDA) as the primary objective which was defined by no EDSS progression, no relapse, and no new T2 lesion on MRI. Secondary objectives were EDSS improvement and neurocognitive performance.

Results: Both treatment groups were similar in respect of age, gender, disability, and neurocognitive performance except for significantly longer disease duration in the alemtuzumab group. Mean follow-up was 58.8 [range 29-140] months in the aHSCT group compared to 27.6 [range 11-52] months in the alemtuzumab-treated group. We observed significantly more patients maintaining NEDA in the aHSCT group (p = 0.048) compared to the alemtuzumab-treated patients. Furthermore, 37% of the aHSCT patients showed an improvement of EDSS compared to none in the alemtuzumab-treated group (p = 0.033). It is of note that cognitive function was significantly improved in the aHSCT-treated patients.

Interpretation: aHSCT suppresses inflammatory activity more effectively than alemtuzumab and might enable improvement of overall disability and cognition in MS.
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http://dx.doi.org/10.1002/acn3.51366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164852PMC
June 2021

Delayed access to conscious processing in multiple sclerosis: Reduced cortical activation and impaired structural connectivity.

Hum Brain Mapp 2021 Aug 7;42(11):3379-3395. Epub 2021 Apr 7.

Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany.

Although multiple sclerosis (MS) is frequently accompanied by visuo-cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8-150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p < .001). The delay increased with disease duration (p < .001, β = .37) and disability (p < .001, β = .24), but did not correlate with conscious information processing speed (Symbol digit modality test, β = .07, p = .817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS.
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http://dx.doi.org/10.1002/hbm.25440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249884PMC
August 2021

Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis: A Randomized, Placebo-Controlled Trial.

Neurol Neuroimmunol Neuroinflamm 2021 05 24;8(3). Epub 2021 Mar 24.

From the NeuroCure Clinical Research Center (J.B.-S., F.P., J.D., A.B., V.S.), Charité-Universitätsmedizin Berlin; Medical Image Analysis Center (J.W.), University Basel; Institut for Medical Immunology (C.I.-D., E.H.), Charité-Universitätsmedizin Berlin; Department of Neurology and Neuroimaging Center (B.K.), Johannes Gutenberg University, Mainz; Charité-Universitätsmedizin Berlin (C.P.); NeuroCure Clinical Research Center (H.R., R.R.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (O.A.), Medical Faculty, Heinrich Heine University Düsseldorf; Institut für Neuroimmunologie und Multiple Sklerose (C.H.), Universitätsklinikum Hamburg-Eppendorf, Hamburg; Klinik für Neurologie (J.F.), Asklepios Klinik Lübben/Teupitz; Department of Neurology (F.H.), Krankenhaus Martha-Maria Halle-Dölau, Halle/Saale; Medizinische Klinik für Kardiologie und Angiologie (M.L.), Campus Mitte, Charité-Universitätsmedizin Berlin; Institute of Nutritional and Food Sciences (B.Z.), University of Bonn; Department of Neurology and Neuroimaging Center (NIC) (S.G., F.Z.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University, Mainz; and Charité-Universitätsmedizin Berlin and SOSTANA GmbH (K.-D.W.), Berlin.

Objective: To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.

Results: A total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.

Conclusion: In RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.

Classification Of Evidence: This study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.

Trial Registration Information: Clinical trial registration number: NCT00525668.
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http://dx.doi.org/10.1212/NXI.0000000000000981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054966PMC
May 2021

Cognitive performance shows domain specific associations with regional cortical thickness in multiple sclerosis.

Neuroimage Clin 2021 24;30:102606. Epub 2021 Feb 24.

Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Multiple Sclerosis (MS) patients often suffer from significant cognitive impairment. Earlier research has shown relationships between regional cortical atrophy and cognitive deterioration. However, due to a large number of neuropsychological assessments and a heterogenous pattern of cognitive deficits in MS patients, reported associations patterns are also heterogenous. Using an extensive neuropsychological battery of 23 different tasks, we explored domain (attention/information processing, memory, spatial processing, executive functioning) and task-specific associations with regional cortical thickness in a representative sample of MS patients (N = 97). Cortical regions associated with multiple cognitive tasks in the left hemisphere were predominantly located in the inferior insula (attention p < 0.001, memory p = 0.047, spatial processing p = 0.004, executive functioning p = 0.037), the gyrus frontalis superior (attention p = 0.015, memory p = 0.037, spatial processing p = 0.033, executive functioning p = 0.017) and temporal medial (attention p < 0.001, memory two clusters p = 0.016 and p < 0.001, executive functioning p = 0.016). In the right hemisphere, we detected the strongest association in the sulcus interparietalis with five cluster (attention SDMT p = 0.003 and TAP_DA p < 0.001; memory Rey recall p = 0.013 and VLMT verbal learning p = 0.016; spatial processing Rey copy p < 0.001). We replicated parts of our results in an independent sample of 30 mildly disabled MS patients. Moreover, comparisons to 29 healthy controls showed that the regional associations seemed to represent rather pathophysiological dependency than a physiological one. We believe that our results may prove useful in diagnosis and rehabilitation of cognitive impairments and may serve as guidance in future magnetic resonance imaging (MRI) studies.
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http://dx.doi.org/10.1016/j.nicl.2021.102606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985400PMC
July 2021

How to measure fluctuating impairments in people with MS: development of an ambulatory assessment version of the EQ-5D-5L in an exploratory study.

Qual Life Res 2021 Jul 12;30(7):2081-2096. Epub 2021 Mar 12.

School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.

Background: Health fluctuations even within a single day are typical in multiple sclerosis (MS), but are not captured by widely used questionnaires like the EQ-5D-5L. This exploratory study aimed to develop an ambulatory assessment (AA) version of the EQ-5D-5L (EQ-5D-AA) where patients rate their health on mobile phones multiple times per day over several days, and to assess its feasibility and face validity.

Methods: An initial EQ-5D-AA version was based on two patient focus groups. It was then tested and continuously developed in an iterative process: patients completed it over several days, followed by debriefing interviews. Findings were used to refine the EQ-5D-AA, with the resulting version being tested by the subsequent wave of patients until participants declared no need for changes anymore. Before and after the AA period, participants completed the standard paper-based EQ-5D-5L asking about 'today'.

Results: Focus group participants reported that their impairments often fluctuated between and within days. They regarded an AA with three assessments per day over seven days most appropriate; assessment should be retrospective to the previous assessment, but not all items should be assessed at each time point. Four waves of AA testing were conducted. Thirteen out of the 17 participants preferred the AA over standard assessment as they regarded it more informative, but not too burdensome.

Conclusion: The newly developed one-week AA of the EQ-5D-5L captures within-day and day-to-day health fluctuations in people with MS. From the patients' perspective, it is a feasible and face valid way to provide important information beyond what is captured by the standard EQ-5D-5L.
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http://dx.doi.org/10.1007/s11136-021-02802-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233275PMC
July 2021

Study protocol for a randomised controlled trial of a web-based behavioural lifestyle programme for emPOWERment in early Multiple Sclerosis ([email protected]).

BMJ Open 2021 02 16;11(2):e041720. Epub 2021 Feb 16.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that mainly affects young adults. Uncertainty is a major psychological burden of the disease from diagnosis to prognosis, enhanced by the pressure to make early decisions on a diverse set of immunotherapies. Watchful waiting for 1-2 years while adapting goals and lifestyle habits to life with a chronic disease represents another reasonable option for persons with MS (PwMS). A behaviour change programme based on evidence-based patient information (EBPI) is not available in standard care. This randomised controlled trial (RCT) with an embedded process evaluation investigates the efficacy and cost-effectiveness of a web-based behavioural lifestyle programme to change lifestyle behaviour and reduce inflammatory disease activity in PwMS.

Methods And Analysis: A web-based behavioural intervention will be evaluated in an RCT aiming to recruit 328 persons with clinically isolated syndrome, suspected MS or confirmed MS for less than 1 year, who have not yet started immunotherapy. Moreover, a mixed-methods process evaluation and a health economic evaluation will be carried out. Participants will be recruited in at least 16 MS centres across Germany and randomised to an intervention group with 12 months of access to EBPI about lifestyle factors in MS, combined with a complex behaviour change programme or to a control group (optimised standard care). The combined primary endpoint is the incidence of new T2 lesions on MRI or confirmed relapses.

Ethics And Dissemination: The study has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (PV6015). Trial results will be communicated at scientific conferences and meetings and presented on relevant patient websites and in patient education seminars.

Trial Registration Number: ClinicalTrials.gov Registry (NCT03968172); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888332PMC
February 2021

Development and evaluation of an interactive web-based decision-making programme on relapse management for people with multiple sclerosis ([email protected])-study protocol for a randomised controlled trial.

Trials 2021 Feb 14;22(1):139. Epub 2021 Feb 14.

Institute of Nursing Science, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany.

Introduction: Multiple sclerosis is a chronic inflammatory, degenerative disease of the central nervous system manifesting at first with relapses in about 85% of cases. In Germany, intravenous therapy with high-dose corticosteroids is the treatment standard of acute relapses. The treatment leads to a faster reduction of symptoms in about 25 of 100 treated patients but has no proven long-term benefits over placebo treatment. Intravenous treatment is not superior to oral treatment. Therefore, informed decisions on relapse management are required. An earlier randomised controlled trial showed that evidence-based patient information and education on relapse management leads to more informed decisions and more relapses not treated or treated with oral corticosteroids. This study aims to evaluate whether a web-based relapse management programme will positively change relapse management and strengthen autonomy in people with multiple sclerosis.

Methods: The pragmatic double-blind randomised controlled trial is accompanied by a mixed-methods process evaluation and a health economic evaluation and follows the UK Medical Research Council guidance on developing and evaluating complex interventions. A total of 188 people with possible or relapsing-remitting multiple sclerosis with ≥ 1 relapse within the last year and/or ≥ 2 relapses within the last 2 years will be recruited and randomised using blocks. The intervention group receives a web- and dialogue-based decision aid on relapse management, a nurse-led webinar and access to a monitored chat forum. The control group receives standard information, which will be made available via the same online platform as the intervention. The primary endpoint is the proportion of relapses not treated or treated with oral corticosteroids. Key secondary endpoints are the annualised relapse rate, decision-making, empowerment, quality of life and cost-effectiveness. Facilitators and barriers will be assessed by mixed-methods process evaluation measures. The study ends when 81 relapses have been documented or after 24 months of observation per individual patient. Analyses will follow the intention-to-treat principle.

Discussion: We hypothesise that the intervention will enhance patient empowerment and have a positive impact on patients' relapse management.

Trial Registration: ClinicalTrials.gov NCT04233970 . Registered on 18 January 2020.
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http://dx.doi.org/10.1186/s13063-021-05059-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882468PMC
February 2021

Heterogeneity of multiple sclerosis lesions in fast diffusional kurtosis imaging.

PLoS One 2021 4;16(2):e0245844. Epub 2021 Feb 4.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Mean kurtosis (MK), one of the parameters derived from diffusion kurtosis imaging (DKI), has shown increased sensitivity to tissue microstructure damage in several neurological disorders.

Methods: Thirty-seven patients with relapsing-remitting MS and eleven healthy controls (HC) received brain imaging on a 3T MR scanner, including a fast DKI sequence. MK and mean diffusivity (MD) were measured in the white matter of HC, normal-appearing white matter (NAWM) of MS patients, contrast-enhancing lesions (CE-L), FLAIR lesions (FLAIR-L) and black holes (BH).

Results: Overall 1529 lesions were analyzed, including 30 CE-L, 832 FLAIR-L and 667 BH. Highest MK values were obtained in the white matter of HC (0.814 ± 0.129), followed by NAWM (0.724 ± 0.137), CE-L (0.619 ± 0.096), FLAIR-L (0.565 ± 0.123) and BH (0.549 ± 0.12). Lowest MD values were obtained in the white matter of HC (0.747 ± 0.068 10-3mm2/sec), followed by NAWM (0.808 ± 0.163 10-3mm2/sec), CE-L (0.853 ± 0.211 10-3mm2/sec), BH (0.957 ± 0.304 10-3mm2/sec) and FLAIR-L (0.976 ± 0.35 10-3mm2/sec). While MK differed significantly between CE-L and non-enhancing lesions, MD did not.

Conclusion: MK adds predictive value to differentiate between MS lesions and might provide further information about diffuse white matter injury and lesion microstructure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245844PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861404PMC
July 2021

Guest Editorial.

Int J MS Care 2020 Nov-Dec;22(6):xii-xiii. Epub 2020 Dec 28.

RIMS Past President, Department of Rehabilitation Medicine, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

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http://dx.doi.org/10.7224/1537-2073-22.6.xiiDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780703PMC
December 2020

"I Will Respect the Autonomy of My Patient": A Scoping Review of Shared Decision Making in Multiple Sclerosis.

Int J MS Care 2020 Nov-Dec;22(6):285-293. Epub 2020 Dec 28.

Background: Patient autonomy is a bioethical principle that was strengthened in the revised Declaration of Geneva. Shared decision making (SDM) is particularly relevant in the management of multiple sclerosis (MS) because many preference-sensitive decisions have to be made during the disease course. We aimed to summarize the available evidence on SDM in the MS field and to inform future research and practice.

Methods: We performed a scoping review by searching MEDLINE (past 5 years). Studies were included if they reported primary/secondary research and focused on SDM related to people with MS. Data were grouped into topics, with results presented in narrative form.

Results: From 865 references, we included 55 studies conducted mostly in Europe. Half of the studies were observational, followed by qualitative (20%), mixed-methods (17%), randomized controlled trials (RCTs, 5%), quasi-experimental (5%), and reviews (4%). Most studies addressed people with relapsing-remitting MS (85%); the remaining addressed health care professionals, patients' significant others, or a combination. We identified five main topics: decisions on disease-modifying drugs, decisions on chronic cerebrospinal venous insufficiency treatment, information provision and patient education, health literacy, and risk knowledge.

Conclusions: The high proportion of included studies on SDM in MS in Europe suggests an earlier adoption of these concepts in this area. Decisions on disease-modifying drugs was the prevalent topic. Only 5% of studies were RCTs, indicating that more research is needed to study the effectiveness of SDM interventions. Studies addressing people with primary and secondary progressive MS are also needed.
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http://dx.doi.org/10.7224/1537-2073.2020-027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780705PMC
December 2020

Psychobehavioral Treatment Options for Sexual Dysfunction in Multiple Sclerosis: A Systematic Review.

Int J MS Care 2020 Nov-Dec;22(6):276-284. Epub 2020 Dec 28.

Background: Sexual dysfunction in multiple sclerosis (MS) is a significant but overlooked impairment, and treatment options are rare. The aims of this systematic review were to identify psychological interventions used to treat sexual dysfunction in MS, to estimate their benefit, and to note appropriate treatment approaches for research projects and clinical use.

Methods: A systematic review update was conducted to find psychological interventions aiming to improve sexual dysfunction in MS. A comprehensive search and review of MEDLINE, PsycINFO, CINAHL, and PubMed were completed, and the effects and quality of selected studies were reported.

Results: Six publications with 295 participants were identified. All selected studies assessed the effectiveness of psychological interventions on sexual dysfunction or sexual satisfaction in people with MS; four studies directly targeted sexual dysfunction in MS, one was a mindfulness yoga program to improve fatigue and quality of life, and one other presented a secondary analysis of a study targeting depression in MS. All six studies reported significant improvements in sexual dysfunction or sexual satisfaction and somewhat in psychological variables.

Conclusions: A pressing need for development and adequate evaluation of psychological interventions for sexual dysfunction in MS remains. In addition, assessment of sexual dysfunction in MS and its treatment should be more focused in clinical care.
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http://dx.doi.org/10.7224/1537-2073.2020-012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780698PMC
December 2020

Current and Long-Term Physical Activity Among Adults with Multiple Sclerosis in the United States: COM-B Variables as Explanatory Factors.

Int J Behav Med 2021 Oct 8;28(5):561-574. Epub 2021 Jan 8.

Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, 35294, United States.

Background: Physical activity is an evidence-based, safe second-line approach for improved multiple sclerosis (MS) symptoms and disease progression. This study examined the contributions of Capability-Opportunity-Motivation-Behavior (COM-B) factors for understanding engagement in current and long-term physical activity among persons with MS in the United States (U.S.).

Method: Adults with MS in the U.S. (N = 854) completed an online survey that included questions regarding demographic and clinical characteristics, COM-B constructs, Godin Leisure Time Exercise Questionnaire (GLTEQ), and Physical Activity Staging Questionnaire (PASQ). Participants were classified into groups based on the GLTEQ regarding current physical activity behavior and PASQ for long-term physical activity behavior. MANOVA and discriminant function analysis (DFA) identified COM-B constructs that differentiated physical activity groups.

Results: MANOVA analyses indicated that all COM-B constructs were significantly different for both GLTEQ current physical activity groups (Wilks's λ = .5, F(44, 1432) = 14.8) and PASQ long-term physical activity groups (Wilks's λ = .4, F(44, 1464) = 16.9) status except Information Provision. DFA analysis regarding GLTEQ identified a function including exclusively Capability and Motivation sources of behavior that differentiated current physical activity groups such as intention and self-efficacy. DFA for PASQ identified a different function of the Capability and Motivation sources of behavior that differentiated long-term physical activity groups; the primary differentiating variables were action control and intention.

Conclusion: Our results identify internal factors as the primary COM-B predictors of current and long-term physical activity among adults with MS in the U.S., and health promotion interventions may focus on assessing individual competencies and behavioral regulation for changing physical activity in MS.
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http://dx.doi.org/10.1007/s12529-020-09946-wDOI Listing
October 2021

Impact of a multimedia website with patient experiences of multiple sclerosis (PExMS) on immunotherapy decision-making: study protocol for a pilot randomised controlled trial in a mixed-methods design.

Pilot Feasibility Stud 2021 Jan 7;7(1):16. Epub 2021 Jan 7.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.

Background: A variety of management options (e.g. immunotherapies, lifestyle interventions, and rehabilitation) are available for people with relapsing-remitting multiple sclerosis (RRMS). Besides coping with the diagnosis, people with MS (pwMS) have to make complex decisions such as deciding about immunotherapies. In addition to factual information, reports of patient experiences (PEx) may support patients in decision-making. The added value of PEx in decision-making is not clear, and controlled studies are rare. Therefore, systematic methods are necessary to develop and analyse PEx. As there are no evaluated PEx for MS in Germany, we are currently creating a website presenting PEx structured according to topics and illustrated by video, audio, and text files. We aim to determine the feasibility of an intervention using PEx and evaluate whether PEx may help pwMS in their immunotherapy decision-making processes as a supplement to evidence-based information.

Methods: This project will follow the Medical Research Council framework for development and evaluation of complex interventions. After the development of a website with PEx, a randomised controlled pilot trial (pilot RCT) will be conducted in 2-3 MS centres, clinics, or rehabilitation centres including 55 pwMS and accompanied by a process evaluation. Patients with a RRMS diagnosis considering immunotherapy are eligible. The primary outcome is decision self-efficacy. Secondary outcomes include preparation for decision-making, decisional conflict, risk knowledge, confidence in active participation, affective forecasting, social support, and self-reported impact of eHealth on its users. Participants will be randomly assigned either to (i) an intervention group with 4 weeks access to an evidence-based patient information resource and the PExMS-website as an adjunct or to (ii) the control group with access to evidence-based information alone. A 6-member advisory panel involving representatives of pwMS, researchers, and neurologists, who accompany the whole project, will mentor this pilot RCT.

Discussion: The intervention was developed with systematic methods, created with active patient involvement and in critical appraisal by an expert advisory panel. The study is innovative as it contributes to the controversial evidence on the use of PEx in the context of evidence-based patient information.

Trial Registration: ClinicalTrials.gov, NCT04236544.
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http://dx.doi.org/10.1186/s40814-020-00749-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788927PMC
January 2021

Frequent neurocognitive deficits after recovery from mild COVID-19.

Brain Commun 2020 23;2(2):fcaa205. Epub 2020 Nov 23.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.

Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20-105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.
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http://dx.doi.org/10.1093/braincomms/fcaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717144PMC
November 2020

Quality of Stroke Patient Information Applied in Randomized Controlled Trials-Literature Review.

Front Neurol 2020 7;11:526515. Epub 2020 Dec 7.

Institute of Nursing Science, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Strokes have a huge impact on patients' quality of life. Although there are potentially effective secondary preventions and treatment options for stroke patients, adherence is mostly low. Low disease and treatment-related knowledge and, consequently, a lack of informed decision-making in stroke patients may contribute to this problem. However, stroke patient information did not seem to have relevant effects on patients' knowledge in randomized controlled trials. contributing factor may be the lack of thoroughly developed patient information materials. We aimed to evaluate the quality of patient information materials for stroke patients by using randomized controlled trials, applying quality criteria for evidence-based patient information (EBPI). We conducted a literature search (MEDLINE, Embase, CINAHL, PsycINFO, and CENTRAL). To be included in the review, research had to be randomized controlled trials that provided stroke patient information, were published in English, and had knowledge assessed as the primary endpoint. Authors of primary studies were contacted and asked for information materials applied. We screened 15,507 hits and identified 30 eligible studies. Information materials were available for only eight studies. Analyses revealed that all available materials had important shortcomings concerning EBPI quality criteria [concerning, for example, structural information (e.g., reporting conflicts of interest), content information (e.g., reporting sources of information), or comprehensive descriptions of treatment effects and side effects]. Frequently, treatment effects were reported only narratively without providing absolute numbers, values, or frequencies. Quality of materials differed, but none sufficiently fulfilled EBPI quality criteria. Unsatisfactory trial results concerning patient knowledge and patient involvement in decision-making may at least partially be explained by limitations of the provided materials. Future patient information should consider EBPI quality criteria.
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http://dx.doi.org/10.3389/fneur.2020.526515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750452PMC
December 2020

Blunted neural and psychological stress processing predicts future grey matter atrophy in multiple sclerosis.

Neurobiol Stress 2020 Nov 27;13:100244. Epub 2020 Jul 27.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany.

Background: Multiple sclerosis (MS) is characterized by two neuropathological key aspects: inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability.

Methods: We tested whether neural network activity triggered in a psychological fMRI stress paradigm (a mental arithmetic task including social evaluation) conducted at a baseline time point predicts future GM atrophy in 25 persons with MS (14 females). Atrophy was determined between the baseline and a follow-up time point with a median delay of 1012 (Rg: 717-1439) days. Additionally, atrophy was assessed in 22 healthy subjects (13 females; median delay 771 [Rg: 740-908] days between baseline and follow-up) for comparison.

Results: An analysis of longitudinal atrophy in patients revealed GM loss in frontal, parietal, and cerebellar areas. Cerebellar atrophy was more pronounced in patients than controls. Future parietal and cerebellar atrophy could be predicted based on activity of two networks. Perceived psychological stress was negatively related to future parietal atrophy in patients and activity of the network predictive of parietal atrophy was positively linked to perceived stress.

Conclusions: We have shown that blunted neural and psychological stress processing have a detrimental effect on the course of MS and are interrelated. Together with research showing that psychological and neural stress processing can be altered through interventions, our findings suggest that stress processing might constitute an important modifiable disease factor.
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http://dx.doi.org/10.1016/j.ynstr.2020.100244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739031PMC
November 2020

Assessing the effect of an evidence-based patient online educational tool for people with multiple sclerosis called UMIMS-understanding magnetic resonance imaging in multiple sclerosis: study protocol for a double-blind, randomized controlled trial.

Trials 2020 Dec 9;21(1):1008. Epub 2020 Dec 9.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.

Background: While magnetic resonance imaging (MRI) plays a major role in the lives of people with multiple sclerosis (pwMS), studies have shown that MRI-specific knowledge in pwMS is limited. Moreover, poor knowledge was associated with negative feelings towards MRI (e.g. anxiety concerning MRI scan). Because information sources about MRI in MS for pwMS are not available, we designed and evaluated an evidence-based online educational platform about MRI in MS called "Understanding MRI in MS" (UMIMS). Based on a pilot study in n= 79 subjects, an educational intervention was found to be feasible and effective. We hypothesize that MRI-specific knowledge can be increased by using UMIMS and that, subsequently, negative feelings towards MRI will be reduced and shared decision-making competences increased.

Methods: This randomized, controlled, double-blinded trial (RCT) will recruit n = 120 pwMS. The intervention group will receive access to UMIMS. The control group will get access to a specifically developed control website, which visually imitates UMIMS and contains the standard information available by several MS self-help organizations. The change in MRI-specific knowledge assessed via the MRI-risk knowledge questionnaire (MRI-RIKNO) after the intervention is the primary endpoint at 2 weeks. Several secondary endpoints will be assessed at different timepoints throughout the study, e.g. emotions towards MRI, autonomy preferences, threat by MS and shared decision-making competences. The study includes a process evaluation.

Discussion: The aim of this RCT is to prove that access to an education tool on MRI in MS will increase pwMS' MRI-specific knowledge and enhance shared decision-making when discussing decisions involving MRI results during patient-physician encounters.

Trial Registration: Clinicaltrials.gov NCT03872583 . Registered on 13 March 2019.
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http://dx.doi.org/10.1186/s13063-020-04855-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724874PMC
December 2020

Patient autonomy in dentistry: demonstrating the role for shared decision making.

BMC Med Inform Decis Mak 2020 12 2;20(1):318. Epub 2020 Dec 2.

Department of Prosthetic Dentistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Evidence-based practice, decision aids, patient preferences and autonomy preferences (AP) play an important role in making decisions with the patient. They are crucial in the process of a shared decision making (SDM) and can be incorporated into quality criteria for patient involvement in health care. However, there are few studies on SDM and AP in the field of dentistry. This study explored patients' autonomy preferences in dentistry in comparison to other medical domains, comparing them with patient preferences in two other cohorts of patients with different conditions and in different health care settings.

Methods: A sample of 100 dental patients attending 16 dentists was consecutively recruited in a university-based prosthodontic clinic. Patients' and dentists' preferences regarding their roles in dental decision making for commonly performed diagnostic and treatment decisions were compared using the Control Preference Scale (CPS). This was followed by cross sectional surveys to study autonomy preferences in three additional cohorts recruited from general practices (n = 100), a multiple sclerosis clinic (n = 109), and a university-based prosthodontic clinic (n = 100). A questionnaire with combined items from the Autonomy Preference Index (API) to assess general and the CPS to assess specific preferences was used in the additional cohorts.

Results: Dentists were less willing to give patients control than patients were willing to enact autonomy. However, decisions about management of tooth loss were considered relevant for a shared decision making by both parties. When comparing cohorts from different samples, the highest AP was expressed by people with multiple sclerosis and the lowest by patients in dentistry (means: dentistry 2.5, multiple sclerosis 2.1, general practice 2.4, p = .035). There were considerable intra-individual differences in autonomy preferences referring to different decision types (p < .001). In general, more autonomy was desired for treatment decisions in comparison to diagnostic decisions, for trivial compared to severe conditions, and for dental care compared to general practice (all: p < .001).

Conclusion: There is an important role of patient participation in decision making in dentistry. Furthermore, PA should be considered with respect to specific medical decisions instead of assessing autonomy preferences in general implying a need for communication skills training of health care professionals.
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http://dx.doi.org/10.1186/s12911-020-01317-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709219PMC
December 2020

Exploring Adherence to First-Line and Second-Line Immunotherapies in Multiple Sclerosis: An Interview Study.

Int J MS Care 2020 Sep-Oct;22(5):219-225. Epub 2020 Jan 22.

Background: Treatment adherence is fundamental in multiple sclerosis (MS) management. Adherence rates vary significantly between studies, ranging from 30% to almost 90%, depending on assessment method and medication type. This study aimed to identify patient-related categories associated with treatment modification or discontinuation in people with MS receiving either first- or second-line treatment.

Methods: Semistructured interviews were performed with 23 people with MS: 11 receiving first-line treatment and 12 receiving second-line treatment. Medication history, experiences with previous medications, decision-making processes regarding immunotherapy, adherence behavior, and reasons for adherence/nonadherence were explored using open-ended questions. Qualitative content analysis was performed using a combined deductive-inductive approach in building a coding frame. Differences in coding frequencies were compared between the two groups and analyzed quantitatively. Cohen's kappas of 0.76 for people with MS receiving first-line treatment and 0.64 for the second-line sample were achieved between the two coders.

Results: One key reason for nonadherence reported by first-line-treated people with MS was and for adherence was . In people with MS receiving second-line treatment, was a key category related to changes in or discontinuation of immunotherapy. Reasons for adherence were and . Intentional nonadherence was a major issue for first-line treatment and less relevant for second-line treatment.

Conclusions: These results indicate specific differences in factors mitigating adherence in people with MS receiving first- and second-line treatment.
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http://dx.doi.org/10.7224/1537-2073.2018-068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643847PMC
January 2020

Long-term prognostic counselling in people with multiple sclerosis using an online analytical processing tool.

Mult Scler 2021 Aug 26;27(9):1442-1450. Epub 2020 Oct 26.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany/Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Prognostic counselling is a sensitive issue in medicine and especially so in MS due to the highly heterogeneous disease course. However, people with MS (pwMS) seek prognostic information. The web-based 'Evidence-Based Decision Support Tool in Multiple Sclerosis' (EBDiMS) uses data of 717 patients from the London/Ontario cohort to calculate personalized long-term prognostic information.

Objective: The aim of this study was to investigate the feasibility and effect of long-term prognostic counselling in pwMS using EBDiMS.

Methods: Ninety consecutive pwMS were provided with personalized estimations of expected time to reach Expanded Disability Status Scale (EDSS) scores of 6 and 8 and time to conversion to secondary-progressive MS. Participants gave estimates on their own putative prognosis and rated the tool's acceptability on six-step Likert-type scales.

Results: Participants rated EBDiMS as highly understandable, interesting and relevant for patient-physician encounters, coping and therapy decisions. Although it provoked a certain degree of worry in some participants, 95% would recommend using the tool. Participants' own prognosis estimates did not change significantly following EBDiMS.

Conclusion: Long-term prognostic counselling using an online tool has been shown to be feasible in a clinical setting. EBDiMS provides pwMS with relevant, easy-to-understand, long-term prognostic information without causing relevant anxiety.
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http://dx.doi.org/10.1177/1352458520964774DOI Listing
August 2021

Comprehension of confidence intervals in audio-visual patient information materials for people with multiple sclerosis (COCO-MS): A web-based randomised controlled, parallel group trial.

Patient Educ Couns 2021 05 29;104(5):1132-1139. Epub 2020 Sep 29.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objectives: To evaluate patient information materials on confidence intervals (CIs) in multiple sclerosis to be used with patient decision aids.

Methods: Web-based randomised controlled parallel group trial with four study arms. Participants were equally allocated to one of three versions of audio-visual patient information or to a standard written information (arm IV). In the short version (arm III), CIs were explained without using an example, in the other two versions examples were used (arm I and arm II). The examples are based on an apple farmer who wants to estimate the average weight of his apples (arm I) and to test a treatment against worms (arm II). Primary endpoint was comprehension of CIs, assessed with a six-item multiple-choice questionnaire.

Results: 855 of 1068 (80 %) randomised participants completed the survey (71 % arm I, 73 % arm II, 87 % arm III, 90 % arm IV). The median of correctly answered questions on CIs was 4 out of 6 questions in arms I and II and 5 out of 6 questions in arm III. Compared to the standard information (arm IV), all the other arms scored better on the comprehension questionnaire (ANOVA, p ≤ 0.003).

Conclusions: Information about CIs can be presented comprehensibly. High scores and a high rate of completers indicate that the short version is the favourable one.

Practice Implications: Information materials on CIs should be used alongside absolute risk reductions in patient decision aids to enhance the interpretation of study results.
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http://dx.doi.org/10.1016/j.pec.2020.09.035DOI Listing
May 2021

Construction of a User-Led Resource for People Transitioning to Secondary Progressive Multiple Sclerosis: Results of an International Nominal Group Study.

Front Neurol 2020 18;11:798. Epub 2020 Aug 18.

Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

ManTra is a mixed-methods, co-production research project for developing an intervention (resource) for people with newly diagnosed secondary progressive multiple sclerosis (pwSPMS) in Italy and Germany. In previous project actions, six resources were outlined, meeting the needs prioritized by pwSPMS. This study aims to achieve multiple-stakeholder consensus on the most suitable resource and to refine the consensus resource. Two nominal group technique (NGT) meetings were held, one in Milan and one in Hamburg. Participants were pwSPMS (five in Italy/six in Germany), pwSPMS significant others (SOs, four/five), healthcare professionals (HPs, seven/four), and health service researchers/patient and citizen organizations representatives (HPCORs, five/five). Two of the four resources discussed in each meeting were the same in Italy and Germany: "Promoting the engagement of pwSPMS: a program for the patients and the HPs" and "Enriched physiotherapy program for pwSPMS." The other two were "A personalized care plan for pwSPMS" and "Roadmap for social and economic benefits" in Italy and "Metacognitive and everyday life training for pwSPMS" and "Psychological support for pwSPMS" in Germany. Each meeting consisted of two plenary sessions and a parallel group session (four stakeholder groups: pwSPMS, SOs, HPs, and HPCORs) in between. Meetings' narratives were analyzed thematically. The two meetings were rich in participation and discussion. In Italy, the consensus resource was "A personalized care plan for pwSPMS." Refinements included enrichment with pwSPMS engagement, inclusion of additional HPs, improved definition of the MS nurse's role within the interdisciplinary panel, and community care integration. In Germany, the consensus resource was "Psychological support for pwSPMS." Refinements included reshaping this resource into a more comprehensive and adaptive rehabilitation intervention and training the psychologist in recognizing client's rehabilitative needs and enhancing his/her autonomy. The NGT eased multiple-stakeholder deliberation and resource fine-tuning in both countries.
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http://dx.doi.org/10.3389/fneur.2020.00798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461961PMC
August 2020

Fatigue in Multiple Sclerosis Is Associated With Childhood Adversities.

Front Psychiatry 2020 28;11:811. Epub 2020 Aug 28.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Fatigue is a common and disabling symptom in patients with Multiple Sclerosis (PwMS). Its pathogenesis, however, is still not fully understood. Potential psychological roots, in particular, have received little attention to date. The present study examined the association of childhood adversities, specific trait characteristics, and MS disease characteristics with fatigue symptoms utilizing path analysis. Five hundred and seventy-one PwMS participated in an online survey. Standardized psychometric tools were applied. The Childhood Trauma Questionnaire (CTQ) served to assess childhood adversities. Trait variables were alexithymia (Toronto Alexithymia Scale; TAS-26) and early maladaptive schemas (Young Schema Questionnaire; YSQ). Current pathology comprised depression (Beck's Depression Inventory FastScreen; BDI-FS) and anxiety symptoms (State-Trait Anxiety Inventory; STAI-state), as well as physical disability (Patient determined Disease Steps; PDDS). The Fatigue Scale for Motor and Cognitive Functions (FSMC) was the primary outcome variable measuring fatigue. PwMS displayed high levels of fatigue and depression (mean FSMC score: 72; mean BDI-II score: 18). The final path model revealed that CTQ emotional neglect and emotional abuse remained as the only significant childhood adversity variables associated with fatigue. There were differential associations for the trait variables and current pathology: TAS-26, the YSQ domain impaired autonomy and performance, as well as all current pathology measures had direct effects on fatigue symptoms, accounting for 28.2% of the FSMC variance. Bayesian estimation also revealed indirect effects from the two CTQ subscales on FSMC. The final model fitted the data well, also after a cross-validation check and after replacing the FSMC with the Chalder Fatigue Questionnaire (CFQ). This study suggests an association psychological factors on fatigue in Multiple Sclerosis. Childhood adversities, as well as specific trait characteristics, seem to be associated with current pathology and fatigue symptoms. The article discusses potential implications and limitations.
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http://dx.doi.org/10.3389/fpsyt.2020.00811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485280PMC
August 2020

Smartphone Accelerometry: A Smart and Reliable Measurement of Real-Life Physical Activity in Multiple Sclerosis and Healthy Individuals.

Front Neurol 2020 14;11:688. Epub 2020 Aug 14.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Mobility impairment is common in persons with multiple sclerosis (pwMS) and can be assessed with clinical tests and surveys that have restricted ecological validity. Commercial research-based accelerometers are considered to be more valuable as they measure real-life mobility. Smartphone accelerometry might be an easily accessible alternative. To explore smartphone accelerometry in comparison to clinical tests, surveys, and a wrist-worn ActiGraph in pwMS and controls. Sixty-seven pwMS and 70 matched controls underwent mobility tests and surveys. Real-life data were collected with a smartphone and an ActiGraph over 7 days. We explored different smartphone metrics in a technical validation course and computed afterward correlation between ActiGraph (steps per minute), smartphone accelerometry (variance of vector magnitude), clinical tests, and surveys. We also determined the ability to separate between patients and controls as well as between different disability groups. Based on the technical validation, we found the variance of the vector magnitude as a reliable estimate to discriminate wear time and no wear-time of the smartphone. Due to a further association with different activity levels, it was selected for real-life analyses. In the cross-sectional study, ActiGraph correlated moderately ( = 0.43, < 0.05) with the smartphone but less with clinical tests (rho between |0.211| and |0.337|). Smartphone data showed stronger correlations with age (rho = -0.487) and clinical tests (rho between |0.565| and |0.605|). ActiGraph only differed between pwMS and controls ( < 0.001) but not between disability groups. At the same time, the smartphone showed differences between pwMS and controls, between RRMS and PP-/SPMS, and between participants with/without ambulatory impairment (all < 0.001). Smartphone accelerometry provides better estimates of mobility and disability than a wrist-worn standard accelerometer in a free-living context for both controls and pwMS. Given the fact that no additional device is needed, smartphone accelerometry might be a convenient outcome of real-life ambulation in healthy individuals and chronic diseases such as MS.
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http://dx.doi.org/10.3389/fneur.2020.00688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456810PMC
August 2020

Aerobic Exercise Induces Functional and Structural Reorganization of CNS Networks in Multiple Sclerosis: A Randomized Controlled Trial.

Front Hum Neurosci 2020 30;14:255. Epub 2020 Jun 30.

Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

: Evidence from animal studies suggests that aerobic exercise may promote neuroplasticity and could, therefore, provide therapeutic benefits for neurological diseases such as multiple sclerosis (MS). However, the effects of exercise in human CNS disorders on the topology of brain networks, which might serve as an outcome at the interface between biology and clinical performance, remain poorly understood. : We investigated functional and structural networks in patients with relapsing-remitting MS in a clinical trial of standardized aerobic exercise. Fifty-seven patients were randomly assigned to moderate-intensity exercise for 3 months or a non-exercise control group. We reconstructed functional networks based on resting-state functional magnetic resonance imaging (MRI) and used probabilistic tractography on diffusion-weighted imaging data for structural networks. : At baseline, compared to 30 healthy controls, patients exhibited decreased structural connectivity that was most pronounced in hub regions of the brain. Vice versa, functional connectivity was increased in hubs. After 3 months, we observed hub independent increased functional connectivity in the exercise group while the control group presented a loss of functional hub connectivity. On a structural level, the control group remained unchanged, while the exercise group had also increased connectivity. Increased clustering of hubs indicates a better structural integration and internal connectivity at the top of the network hierarchy. : Increased functional connectivity of hubs contrasts a loss of structural connectivity in relapsing-remitting MS. Under an exercise condition, a further hub independent increase of functional connectivity seems to translate in higher structural connectivity of the whole brain.
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http://dx.doi.org/10.3389/fnhum.2020.00255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340166PMC
June 2020

Distinct Functional Connectivity Signatures of Impaired Social Cognition in Multiple Sclerosis.

Front Neurol 2020 25;11:507. Epub 2020 Jun 25.

Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Berlin, Germany.

Multiple sclerosis (MS) is characterized by impairments in basic cognitive functions such as information processing speed as well as in more complex, higher-order domains such as social cognition. However, as these deficits often co-occur, it has remained challenging to determine whether they have a specific pathological basis or are driven by shared biology. To identify neural signatures of social cognition deficits in MS, data were analyzed from = 29 patients with relapsing-remitting MS and = 29 healthy controls matched for age, sex, and education. We used neuropsychological assessments of information processing speed, attention, learning, working memory, and relevant aspects of social cognition (theory of mind, emotion recognition (ER), empathy) and employed neuroimaging of CNS networks using resting-state functional connectivity. MS patients showed significant deficits in verbal learning and memory, as well as implicit ER. Performance in these domains was uncorrelated. Functional connectivity analysis identified a distinct network characterized by significant associations between poorer ER and lower connectivity of the fusiform gyrus (FFG) with the right lateral occipital cortex, which also showed lower connectivity in patients compared to controls. Moreover, while ER was correlated with MS symptoms such as fatigue and motor/sensory functioning on a behavioral level, FFG connectivity signatures of social cognition deficits showed no overlap with these symptoms. Our analyses identify distinct functional connectivity signatures of social cognition deficits in MS, indicating that these alterations may occur independently from those in other neuropsychological functions.
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http://dx.doi.org/10.3389/fneur.2020.00507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330009PMC
June 2020

Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients.

J Neurol 2021 Jan 11;268(1):5-7. Epub 2020 Jul 11.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

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http://dx.doi.org/10.1007/s00415-020-10046-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353821PMC
January 2021

Feasibility of a smartphone app to enhance physical activity in progressive MS: a pilot randomized controlled pilot trial over three months.

PeerJ 2020 23;8:e9303. Epub 2020 Jun 23.

Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: People with chronic progressive multiple sclerosis (CPMS) have limited options in medical treatment. Enhancing physical activity (PA) might promote neuroregeneration in multiple sclerosis (MS) and positively influence disability, thus providing an alternative to medical treatment. Previous studies indicate that evidence-based patient information (EBPI) is essential for inducing behavioral change, e.g. enhancing PA.

Objective: To investigate feasibility of a smartphone app providing EBPI about the benefit of PA and a simple activity feedback to enhance PA in people with CPMS in a pilot randomized controlled trial over 3 months.

Methods: Thirty-eight people with CPMS (mean age 51 years, median Expanded Disability Status Scale 4.0) were 1:1 randomized into either a control group ( = 20) or an intervention group ( = 18). The intervention group received access to a multimedia EBPI app including activity feedback, texts, figures and videos. In the control group, participants received a leaflet with unspecific information about exercising in general. The EPBI itself was designed based on a systematic review. At baseline and after 3 months, all participants underwent clinical performance tests, filled in questionnaires and received an activity monitor (Actigraph) for 7 days. The primary endpoint was the rate of responders defined as participants with a 20% increase of physical acitivity (time of moderate or vigiorous PA-MVPA) or 20% increase of the number of steps, both assessed with the activity monitor. As secondary endpoints, we compared accelerometry, performance and questionnaires adjusted for baseline measurments between the groups (ANCOVA). Moreover, we used questionnaires to compare knowledge about exercise (activity requiring physical effort, carried out to improve or improve health and fitness) in MS, usability of the app in general and motivation towards a more active lifestyle after 3 months in both groups.

Results: The groups showed significant differences in disease duration and PA according to the Godin-Leisure Time Exercise Questionnaire at baseline. After 3 months, we detected no difference in the rate of responders, which was an overall 22%. However, MVPA significantly increased in both groups ( < 0.001) and the intervention group tended to have a higher motivation towards a more active lifestyle (Cohens = 0.7, = 0.09) as measured by the questionnaire. Reponses also showed, that participants appreciated the app but claimed a lack of interactivity as a short-coming.

Conclusion: Just providing information in a multimedia smartphone app did not enhance physical activitiy more than a simple leaflet in this small pilot trial in CPMS. However, the group of app users tended to have a higher motivation towards a more active lifestyle. Overall, the concept of a smartphone app to support an active lifestyle in MS is highly appreciated by participants.
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http://dx.doi.org/10.7717/peerj.9303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319035PMC
June 2020
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