Jana Pöttgen

Impaired social cognition in multiple sclerosis

Background Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the CNS that is frequently associated with neuropsychiatric symptoms and decreased quality of life. Social support, which has been found to buffer the psychosocial burden of MS, critically depends on intact social cognition. Here we assess social cognition in patients with MS using a naturalistic video based test and explore if potential deficits in theory of mind (ToM) occur independently of known MS associated neuropsychiatric symptoms, such as depression and cognitive impairment. Methods 45 outpatients with clinically definite MS and 45 age, sex and education matched healthy control subjects (HCs) underwent standardised testing using the Movie for the Assessment of Social Cognition. MS patients also completed a neuropsychological battery. Results MS patients showed significantly impaired ToM compared with HCs. Impairments were more pronounced in identification of emotions than in identification of thoughts or intentions. Significantly lower ToM compared with HCs was detected in MS patients during the early disease stages, with limited disability and without substantial neuropsychological deficits. Conclusions These results suggest impaired social cognition in MS. Importantly, ToM impairments in this group may not simply be a consequence of the well known neuropsychological deficits. Difficulties with correctly identifying emotions, thoughts and intentions in social situations may result in interpersonal problems and could contribute to the psychosocial burden of MS.

An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial

BACKGROUND With a lifetime risk for major depressive disorder of up to 50%, depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated. We investigated the potential of a fully automated, internet-based, cognitive behavioural therapy programme, Deprexis, to reduce depressive symptoms in patients with multiple sclerosis. METHODS For this randomised controlled trial, we recruited patients from an outpatient clinic in Hamburg, Germany. Patients aged 18-65 years were eligible for inclusion if they had multiple sclerosis and self-reported depressive symptoms. By use of a computer-generated randomisation sequence, we allocated 90 patients (1:1; no blocking or stratification) to either the intervention group or a waitlist control group for 9 weeks. The primary endpoint was the Beck Depression Inventory (BDI), as assessed by an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT01663649. FINDINGS 71 patients completed the trial: 35 patients in the intervention group and 36 patients in the control group. During the intervention, BDI scores decreased in the Deprexis group and increased in the control group, yielding a positive effect of Deprexis relative to the waitlist group (mean group difference -4·02 points [95% CI -7·26 to -0·79], p=0·015, effect size d=0·53). Worsening of depressive symptoms from below to above the clinical cutoff (BDI >13) occurred in three (7%) of 45 patients in the control group and no patients in the Deprexis group. We noted no adverse events with respect to new occurrence of suicidal ideation during the trial. INTERPRETATION Psychological online-intervention programmes could be suitable for patients with multiple sclerosis who are unable to regularly attend therapeutic sessions because of mobility impairments. FUNDING European Union and the Deutsche Forschungsgemeinschaft.

Evidence-based patient information programme in early multiple sclerosis: a randomised controlled trial

Objective To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). Background Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice in MS patients. Methods A 12-month, six-centre, double-blind randomised controlled clinical trial with 192 patients with a diagnosis of confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h interactive evidence-based educational programme was compared with a 4-h MS-specific stress management programme. The primary endpoint was informed choice after 6 months comprising risk knowledge and congruency between attitude towards immunotherapy and actual immunotherapy uptake. Secondary endpoints included autonomy preference, decision autonomy, decisional conflict and satisfaction, anxiety and depression, and number of immunotherapies. Results For the primary endpoint, a significant difference was shown with 50 of 85 (59%) participants in the intervention group achieving informed choice after 6 months compared with 18 of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p<0.001). Four weeks after the intervention, more participants in the intervention group showed good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p<0.001). There were no significant differences between groups for attitude towards immunotherapy and for immunotherapy uptake. There were trends towards increased autonomy preference after the intervention and increased adherence to immunotherapies in the intervention group. Conclusions The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.

Managing Neuropsychological Impairment in Multiple Sclerosis: Pilot Study on a Standardized Metacognitive Intervention.

BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system of potential autoimmune origin that is frequently associated with psychological disorders and cognitive deficits, as well as with fatigue, stress, and psychosocial burden. These factors often cause decreased quality of life, social withdrawal, and unemployment. We describe the development of a cognitive-behavioral group intervention based on the concept of metacognition and evaluation of the feasibility and acceptance of the program as a rehabilitation tool. METHODS Metacognitive Training in MS (MaTiMS) consists of six modules, each 90 minutes in duration. We tested acceptance and design of the program in six focus groups (entire sample, n = 27). Framework analysis of transcripts was used to identify key topics and categories. Program modules were revised in accordance with appropriate recommendations of focus group members. We subsequently evaluated MaTiMS in two groups (n = 5, n = 6) in a rehabilitation center. Neuropsychological functioning as well as coping self-efficacy, depression, stress, perceived cognitive deficit, fatigue, and quality of life were assessed. Acceptance of MaTiMS from the patient perspective was also studied. RESULTS The modules were highly accepted by patients. Pre-post assessments showed significant improvements in the Coping Self Efficacy Scale (P = .007), the Würzburger Fatigue Inventory for MS Score (P = .028), and the Hamburg Quality of Life Questionnaire in Multiple Sclerosis Mood subscale (P = .046). CONCLUSIONS These preliminary results suggest that MaTiMS represents a feasible psychological group training program that may foster improvements in self-efficacy, fatigue, and mood. The next step will be an evaluation of the program in a randomized controlled trial.

Patient education for people with multiple sclerosis-associated fatigue: A systematic review

Background Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease often causing decreased quality of life, social withdrawal and unemployment. Studies examining the effect of pharmacological interventions demonstrated only minor effects, whereas non-pharmacological interventions as e.g. patient education programs have shown promising results. Objective We aim to systematically review the literature to determine the effect of patient education programs on fatigue in MS. Methods We conducted a comprehensive search in PubMed for randomized controlled trials (RCTs) that evaluated patient education programs for MS-related fatigue. Interventions evaluating physical exercise and/or pharmacological treatments were not included. Meta-analyses were performed using the generic inverse variance method. Results The search identified 856 citations. After full-text screening we identified ten trials that met the inclusion criteria. Data of 1021 participants were analyzed. Meta-analyses showed significant positive effects on fatigue severity (weighted mean difference -0.43; 95% CI -0.74 to -0.11) and fatigue impact (-0.48; -0.82 to -0.15), but not for depression (-0.35 (95% CI -0.75 to 0.05; p = 0.08). Essentially, we categorized patient education programs into two types: firstly, interventions with a focus on cognitive-behavioral therapy (CBT) and secondly, interventions that teach patients ways of managing daily fatigue. CBT-based approaches seem to generate better results in reducing patient-reported fatigue severity. Analysing CBT studies only, the pooled weighted mean difference for fatigue severity was -0.60 (95% CI; -1.08 to -0.11) compared to non-CBT approaches (-0.20; 95% CI; -0.60 to -0.19). Furthermore, interventions employing an individual approach seem to reduce fatigue more effectively than group-based approaches (pooled weighted mean difference for fatigue severity in face-to-face studies was -0.80 (95% CI; -1.13 to -0.47) compared to group-based studies with -0,17 (95% CI; -0,39 to 0,05). Longest follow-up data were available for 12 months post-intervention. Conclusion Overall, included studies demonstrated that educational programs and especially CBT-based approaches have a positive effect on reducing fatigue. Since fatigue is thought to be a multidimensional symptom, it should be treated with a multidimensional approach targeting patients’ behavior as well as their emotional and mental attitude towards fatigue. However, the clinical relevance of the treatment effects i.e. the relevance for patients’ daily functioning remains unclear and long-term effects, i.e. sustainability of effects beyond 6 months, warrants further work. This review has been registered in the PROSPERO international prospective register of systematic reviews data base (Registration number: CRD42014014224).

A new graphical format to communicate treatment effects to patients—A web‐based randomized controlled trial

Patients making treatment decisions require understandable evidence‐based information. However, evidence on graphical presentation of benefits and side‐effects of medical treatments is not conclusive. The study evaluated a new space‐saving format, CLARIFIG (clarifying risk figures), aiming to facilitate accuracy of comprehension.

Patient education programme on immunotherapy in multiple sclerosis (PEPIMS): a controlled rater-blinded study:

Objective: To investigate the effectiveness of a multi-component evidence-based education programme on disease modifying therapies in multiple sclerosis. Design: Controlled trial with two consecutive patient cohorts and a gap of two months between cohorts. Setting: Three neurological rehabilitation centres. Subjects: Patients with multiple sclerosis within rehabilitation. Interventions: Control group (CG) participants were recruited and received standard information. Two months later, intervention group (IG) participants were recruited and received a six-hour nurse-led interactive group education programme consisting of two parts and a comprehensive information brochure. Main measures: Primary endpoint was “informed choice”, comprising of adequate risk knowledge in combination with congruency between attitude towards immunotherapy and actual immunotherapy uptake. Further outcomes comprised risk knowledge, decision autonomy, anxiety and depression, self-efficacy, and fatigue. Results: A total of 156 patients were included (IG=75, CG=81). The intervention led to significantly more participants with informed choice (IG: 47% vs. CG: 23%, P=0.004). The rate of persons with adequate risk knowledge was significantly higher in the IG two weeks after the intervention (IG: 54% vs. CG: 31%, P=0.007), but not after six months (IG: 48% vs. CG: 31%, P=0.058). No significant differences were shown for positive attitude towards disease modifying therapy (IG: 62% vs. CG: 71%,P=0.29) and for disease modifying therapy status after six months (IG: 61.5% vs CG: 68.6%, P=0.39). Also no differences were found for autonomy preferences and decisional conflict after six months. Conclusion: Delivering evidence-based information on multiple sclerosis disease modifying therapies within a rehabilitation setting led to a marked increase of informed choices.

Introducing a new method to assess vision: Computer-adaptive contrast-sensitivity testing predicts visual functioning better than charts in multiple sclerosis patients:

Background Impaired low-contrast visual acuity (LCVA) is common in multiple sclerosis (MS) and other neurological diseases. Its assessment is often limited to selected contrasts, for example, 2.5% or 1.25%. Computerized adaptive testing with the quick contrast-sensitivity function (qCSF) method allows assessment across expanded contrast and spatial frequency ranges. Objective The objective of this article is to compare qCSF with high- and low-contrast charts and patient-reported visual function. Methods We enrolled 131 consecutive MS patients (mean age 39.6 years) to assess high-contrast visual acuity (HCVA) at 30 cm and 5 m, low-contrast vision with Sloan charts at 2.5% and 1.25%, qCSF and the National Eye Institute Visual Functioning Questionnaire (NEIVFQ). Associations between the different measures were estimated with linear regression models corrected for age, gender and multiple testing. Results The association between qCSF and Sloan charts (R2 = 0.68) was higher than with HCVA (5 m: R2 = 0.5; 30 cm: R2 = 0.41). The highest association with NEIVFQ subscales was observed for qCSF (R2 0.20–0.57), while Sloan charts were not associated with any NEIVFQ subscale after correction for multiple testing. Conclusion The qCSF is a promising new outcome for low-contrast vision in MS and other neurological diseases. Here we show a closer link to patient-reported visual function than standard low- and high-contrast charts.

Sexual dysfunctions in MS in relation to neuropsychiatric aspects and its psychological treatment: A scoping review

Objective Sexual dysfunction in multiple sclerosis (MS) is a significant, but often underestimated and overlooked suffering. Interventions to treat sexual dysfunction in MS are rare. The relation between sexual dysfunction in MS and psychological as well as neuropsychological aspects is evident. However, this field of research remains markedly underdeveloped in this severe chronic illness. The aim of this scoping review is to describe the relevant knowledge in this area and to identify psychological interventions to treat sexual dysfunctions in MS. Methods A scoping review was conducted to answer the following questions: (1) Which psychological and neuropsychological factors impact on sexual dysfunction in MS and vice versa? (2) What kind of psychological interventions aiming to improve sexual dysfunctions in MS are available? A comprehensive search and review of MEDLINE, PsycINFO, and CINAHL was completed by using a recent methodological framework for scoping reviews. Results 23 publications covering a total of 13,259 people with MS and 532 healthy controls were identified. Sexual dysfunction was found to be very common in MS and there is an obvious relation to psychological disorders as e.g. depression and anxiety and also to psychological aspects as partner relationship and quality of life. The relation between sexual dysfunction in MS and neuropsychological impairment has only rarely been studied and no clear results were found. Only two studies were identified, assessing the effectiveness of psychological intervention studies on sexual dysfunction in people with MS, and a third study presenting a secondary analysis of a study targeting depression. All three studies reported significant improvements in sexual dysfunction as well as partly in psychological variables. Conclusions There is a pressing need for the development and adequate evaluation of psychological interventions for sexual dysfunctions in MS. In addition, sexual dysfunction and its impact on psychological wellbeing should be more focussed in clinical care. Registration This review is registered with PROSPERO; Registration number: CRD42016033066.

Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis

Objective Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. Methods Patients with MS and self-reported fatigue were recruited via the website of the German MS Society and assigned via an automated randomisation generator (1:1, no blocking or stratification) to a 12-week online intervention (ELEVIDA, n=139, 82% female, mean age 40.8, median patient determined disease steps (PDDS) 3.0) or a waitlist control group (n=136, 79% female, mean age 41.9, median PDDS 3.0). The primary outcome was the Chalder Fatigue Scale. Outcomes were assessed at baseline, at week 12 (postintervention) and at follow-up (week 24). Results Compared with the control group, significantly greater reductions in Chalder Fatigue Scale scores were seen in the ELEVIDA group at week 12 (primary endpoint, intention-to-treat analysis: between-group mean difference 2.74 points; 95% CI 1.16 to 4.32; p=0.0007; effect size d=0.53), with effects sustained at week 24 (intention-to-treat analysis: between-group mean difference 2.19 points; 95% CI 0.57 to 3.82; p=0.0080). Conclusions Our trial provides evidence for the effectiveness of a self-guided , internet-based intervention to reduce fatigue in MS. Interventions such as ELEVIDA may be a suitable low barrier, cost-effective treatment option for MS fatigue. Trial registration number ISRCTN registry (number ISRCTN25692173).