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

ObjectiveFatigue 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.MethodsPatients 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).ResultsCompared 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).ConclusionsOur 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 numberISRCTN registry (number ISRCTN25692173).</jats:sec

Spinal cord gray and white matter atrophy in patients with motor neuron diseases

Motor neuron disorders (MND) are a heterogeneous group of disease of the upper (UMN) and lower motor neurons (LMN) with a wide spectrum of etiologies. Among them, Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative MND leading to the decline of the UMN and LMN and thus, to progressive muscular spasticity and weakness. Death usually occurs from respiratory failure. Despite ever-increasing efforts in last years, there are no curative therapeutic options and disease-prolonging therapies are sparse. In order to identify potentially effective new treatment options, valid and reliable biomarkers are needed to assess disease progression and to evaluate the effect of new therapeutic approaches. Imaging markers may serve this purpose, but so far, reliable and easily implementable imaging biomarkers for ALS are lacking. The radially acquired Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA) is a novel Magnetic Resonance Imaging (MRI) technique that enables high-resolution imaging of the spinal cord (SC) gray (GM) and white matter (WM) in clinically feasible acquisitions times. Using rAMIRA imaging, GM and WM metrics may have the potential to become new imaging markers in patients with MND. This PhD thesis comprises three studies evaluating SC metrics in patients with MND, evaluating their potential as new imaging markers. As a first step, we investigate the SC GM atrophy as a surrogate for LMN damage in a presumably pure LMN disorder, the Post-Polio Syndrome (PPS). This work was the first implementation of the rAMIRA sequence in an MND. By essentially using PPS as a model disease, this first work built a basis for the implementation of rAMIRA in other MND. As a second step, both SC GM and WM were evaluated in a combined UMN and LMN disorder, i.e. ALS. As a third step, a new MRI sign for ALS was evaluated in patients with ALS and other non-ALS MND. In the first study, we evaluated the SC GM in patients with PPS. We compared the cervical and thoracic SC GM of patients with PPS to healthy, age- and sex-matched controls (HC) and assessed the relationship between the SC GM at different intervertebral disc levels and the segmental muscle strength at the respective corresponding myotomes. We were able to demonstrate significant cervical and thoracic SC GM atrophy in patients with PPS and found significant correlations between SC GM areas and muscle strength at corresponding myotomes. This study provided an encouraging first step for the implementation of the rAMIRA sequence in further MND. In the second study, we evaluated both the SC GM and WM in patients with ALS, which is a combined disorder of the UMN and LMN. Similar to the first study, we compared the cervical and thoracic SC GM and WM of patients with ALS to age- and sex-matched HC and assessed the relationship of SC GM and WM at cervical and thoracic levels with segmental muscle strength. Moreover, we analyzed the relationship between the SC GM and WM and established markers of disease progression. We were able to demonstrate significant atrophy of cervical and thoracic SC GM and WM compared to controls, and found significant correlations between GM atrophy and muscle strength at corresponding myotomes as well as significant correlations with markers of respiratory strength and overall disability. The third study describes and evaluates an observation we made during the analyses of the data from the second study: We observed a hyperintensity of the SC corticospinal lateral tracts on rAMIRA imaging in a patient with ALS who clinically presented a predominant UMN disease type. We then observed that these hyperintensities were visible in patients with, but also in some patients without a predominant UMN ALS. Building on these observations, we identified, defined, and analyzed the presence of the sign in a group of patients with ALS, a group of HC and a control group comprised of patients with non-ALS LMN disorders. The sign showed a good sensitivity and an excellent specificity for the diagnosis of ALS. Furthermore, we performed post-mortem imaging and consecutive histopathological analysis of one patient with ALS and an UMN predominant disease type. The histopathological analysis showed a rarefaction of myelinated axons in the region of the hyperintensities observed on rAMIRA imaging. Taken together, the results from these three projects suggest that SC metrics acquired using rAMIRA imaging show promise as potential future imaging markers in patients with MND

Acute Polyradiculomyelitis With Spinal Cord Gray Matter Lesions: A Report of Two Cases

Objective: Inflammatory polyradiculomyelitis belongs to a rare group of immune-mediated diseases affecting both the central and peripheral nervous system. We aimed to describe an unusual presentation of acute polyradiculomyelitis with marked spinal cord lesions restricted to the gray matter. Methods: Thorough examination of two case reports including clinical, MRI, serologic, electrophysiologic and CSF examinations as well as short-term follow-up. Results: We present two adult patients with acute polyradiculomyelitis and unusual spinal cord lesions restricted to the gray matter on MRI. The clinical presentation, serologic, electrophysiologic and CSF features of the two patients varied, whereas both patients demonstrated severe, asymmetrical, predominantly distal, motor deficits of the lower extremities as well as bladder and bowel dysfunction. Both patients only partially responded to anti-inflammatory treatment. Severe motor impairment and bladder dysfunction persisted even months after symptom onset. Conclusions: To our best of knowledge, these are the first reports of acute polyradiculomyelitis with distinct involvement of the lower thoracic spinal cord gray matter. Currently, it remains unclear whether gray matter lesions reflect a separate pathophysiologic mechanism or an exceedingly rare presentation of spinal cord involvement in acute polyradiculomyelitis

Effect of cocoa on the brain and gut in healthy subjects: a randomised controlled trial

Dark chocolate is claimed to have effects on gastrointestinal function and to improve well-being. This randomised controlled study tested the hypothesis that cocoa slows gastric emptying and intestinal transit. Functional brain imaging identified central effects of cocoa on cortical activity. Healthy volunteers (HV) ingested 100 g dark (72 % cocoa) or white (0 % cocoa) chocolate for 5 d, in randomised order. Participants recorded abdominal symptoms and stool consistency by the Bristol Stool Score (BSS). Gastric emptying (GE) and intestinal and colonic transit time were assessed by scintigraphy and marker studies, respectively. Combined positron emission tomography-computed tomography (PET-CT) imaging assessed regional brain activity. A total of sixteen HV (seven females and nine males) completed the studies (mean age 34 (21-58) years, BMI 22·8 (18·5-26·0) kg/m2). Dark chocolate had no effect on upper gastrointestinal function (GE half-time 82 (75-120) v. 83 (60-120) min; P=0·937); however, stool consistency was increased (BSS 3 (3-5) v. 4 (4-6); P=0·011) and there was a trend to slower colonic transit (17 (13-26) v. 21 (15-47) h; P=0·075). PET-CT imaging showed increased [18F]fluorodeoxyglucose (FDG) in the visual cortex, with increased FDG uptake also in somatosensory, motor and pre-frontal cortices (P&lt;0·001). In conclusion, dark chocolate with a high cocoa content has effects on colonic and cerebral function in HV. Future research will assess its effects in patients with functional gastrointestinal diseases with disturbed bowel function and psychological complaints

Development and feasibility of an evidence-based patient education program for managing fatigue in multiple sclerosis:The "Fatigue Management in MS" program (fatima)

Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. Fatigue is a common and disabling symptom, often causing decreased quality of life, social withdrawal, and unemployment. We developed and studied the feasibility of a cognitive-behavioral group intervention to manage fatigue in MS. We aimed to integrate the concepts of cognitive-behavioral therapy and evidence-based patient information. Methods: We conducted patient interviews and a focus group to assess patients' interest in and need for fatigue self-management training and developed the program accordingly. The program consists of six 90-minute modules, which were structured with the use of moderation cards, helping to guarantee treatment fidelity. The program was tested on three pilot groups (N = 16) in a rehabilitation center. Fatigue, depression, and coping self-efficacy were assessed at baseline and after the intervention. Acceptance and general satisfaction with the program were also evaluated. Results: Patient interviews elicited different characteristics of fatigue, suggesting that patients had different requirements. The program was very acceptable to patients. Pre-post assessments of the pilot study showed significantly improved scores on the Coping Self-Efficacy Scale (P = .013) but not on the Fatigue Scale for Motor and Cognitive Functions and the 30-item Inventory of Depressive Symptomatology. Conclusions: These preliminary results suggest that this program is a feasible cognitive-behavioral group training program that may improve coping self-efficacy and has the potential to subsequently reduce fatigue. The next step is evaluation of the program in a randomized controlled trial

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

<div><p>Background</p><p>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.</p><p>Objective</p><p>We aim to systematically review the literature to determine the effect of patient education programs on fatigue in MS.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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).</p></div

Fatigue impact.

<p>Fatigue impact.</p

Study selection process.

<p>Study selection process.</p

Depression (CBT vs. non-CBT approaches).

<p>Depression (CBT vs. non-CBT approaches).</p

Risk of bias in individual studies.

<p>(+) low risk of bias; (?) unclear risk of bias; (-) high risk of bias.</p