A protocol for a randomised double-blind placebo-controlled feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing and remitting multiple sclerosis (RRMS).

BACKGROUND: Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis. METHODS: Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (< 10 years) of relapsing and remitting MS (RRMS) and who are over 18 years of age will be recruited from neurology clinics and throughout the Thames Valley community. During a 6-week nutrition intervention period, participants will consume the cocoa beverage, high flavonoid or low flavonoid content, at breakfast daily. At baseline, demographic factors and disease-related factors will be assessed. Fatigue, activity and quality of life, in addition to other measures, will be taken at three visits (baseline, week 3 and week 6) in a university setting by a researcher blinded to group membership. Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial.We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. DISCUSSION: We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. TRIAL REGISTRATION: Registered with ISRCTN Registry. Trial registration No: ISRCTN69897291; Date April 2016.

Nurse led telephone assessment of expanded disability status scale assessment in MS patients at high levels of disability.

BACKGROUND: In clinical trials drop out bias reduces the validity of results. This is a particular problem in long-term multiple sclerosis (MS) studies, particularly when patients become progressively disabled and have increasing difficulty attending assessment clinics. OBJECTIVE: To assess the validity of nurse led telephone assessment of Expanded Disability Status Scale (TEDSS) in MS patients with EDSS scores >6.0. METHODS: We performed a multi-centre, single blind trial to assess nurse derived TEDSS against physician face-to-face EDSS scores derived from neurological examination (FEDSS) in patients with clinically definite MS and EDSS >6.0. RESULTS: Ninety patients (n=15 primary progressive MS, n=74 secondary progressive MS, n=1 relapsing remitting MS) had a mean baseline FEDSS of 7.5. TEDSS correlated with FEDSS (r=0.76, p<0.0001) and kappa scores for perfect agreement, within 0.5 of an EDSS points, and within 1 EDSS point were 0.25, 0.86, and 1.0 respectively. Intra-class correlation between the scoring systems was 0.88, representing a high level of agreement. CONCLUSION: Nurse-led telephone assessment of EDSS gives good agreement with physician derived face-to-face EDSS in MS patients with higher disability scores. This may be a valuable tool to improve clinical follow-up in routine clinical practice and improve patient retention in long-term outcome studies.

Multiple sclerosis in Japan appears to be a milder disease compared to the UK.

Multiple sclerosis (MS) is relatively common in the West, but rare in Japan. In the literature, there are few comparative data regarding disease severity throughout the world. The objective of this study was to compare disability in patients from a UK and a Japanese MS cohort. We retrospectively analysed the clinical features of patients with MS from a UK and Japanese MS centre. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Expanded Disability Status Scale score according to disease duration, was used as a marker of disease severity. One thousand one hundred forty-eight UK patients and 104 Japanese patient were identified representing the relative national prevalence. Demographics and disease duration did not differ between the groups. Median MSSS was significantly different between the two groups (Japan 3.34 vs. UK 5.87, p < 0.001). Primary progressive MS was more common in the UK (12.9%) than in the Japanese cohort (3%, p = 0.044). The majority of Japanese patients (83.7% vs. UK 17%) had been exposed to disease modifying treatments (DMTs). Exposure to DMTs did not show a significant effect on disability. In conclusion, this study suggests that MS in Japan may be associated with less disability than in UK. More Japanese patients were treated with DMTs. Differences in treatments do not seem to explain the disparity in disability severity. This suggests either genetic or environmental influences on disease severity.

Serum antibodies in epilepsy and seizure-associated disorders.

OBJECTIVE: To investigate whether autoantibodies to ion channels and other neural antigens are present in the sera of patients with epilepsy and seizure-related diseases. METHODS: Sera were obtained from 139 patients, including 26 with preexisting autoimmune disease, 46 in whom an autoimmune basis was suspected, and 67 with drug-resistant epilepsy. The sera were assayed for antibodies to voltage-gated potassium (VGKC) and calcium (VGCC) channels, glutamic acid decarboxylase (GAD), gangliosides, glutamate receptor type 3, cardiolipins, DNA, and nuclear antigens; the results were compared with results from a large cohort of healthy and disease controls. RESULTS: Increased titers of VGKC antibodies (>100 pM) were detected in 16 of 139 (11%) patients with seizures but only 1 control (0.5%). Eight VGKC-positive patients presented with an acute/subacute illness, and 5 of these had the highest VGKC antibodies; 3 patients improved spontaneously, another 5 patients responded well to immunomodulatory therapy. The other VGKC-positive patients had longer disease duration (>6 years) and intermediate levels of antibodies; immunotherapies have not been tested in this group. Very high levels of GAD antibodies (>1,000 U) were found in an additional 3 patients (2.1%) with long-standing drug-resistant epilepsy. CONCLUSIONS: The presence of autoantibodies to voltage-gated potassium channels and glutamic acid decarboxylase suggests that the immune system may contribute to certain forms of epilepsy or seizure-associated disorders. Further studies are needed to determine whether the antibodies are pathogenic.