Regional variation in the incidence rate and sex ratio of multiple sclerosis in Scotland 2010-2017: findings from the Scottish Multiple Sclerosis Register.

BACKGROUND: Fifteen regional studies published over the last six decades surveying prevalence, mortality and hospital admissions have suggested that Scotland is amongst the highest risk nations for multiple sclerosis (MS) in the world. However, substantial intranational variation in rates (between regions) has been described in numerous countries, including in the only previous Scottish national survey, which used hospital admission data, to address this issue. Against this backdrop, the Scottish Multiple Sclerosis Register (SMSR) was established in 2010 to prospectively collect nationally comprehensive incidence data and to allow for regional comparisons. METHODS: Here, we present the SMSR and analyse the variation in crude and age-sex standardized incidence rates, lifetime risk (cumulative incidence), and the sex distribution of cases and rates, between the 14 administrative Health Boards or regions of Scotland: 01 January 2010 to 31 December 2017. RESULTS: The overall incidence rate for Scotland was 8.76/100,000 person-years (standardized: 8.54). Regional incidence rates varied significantly-up to threefold-between Health Boards (p < 1 × 10-13). The national female-to-male sex ratio was 2.3:1, but this too varied regionally (outlier regions result in a range from 1.0 to 4.2:1). Lifetime risk ranged from 19.9/1000 for females in Orkney (58.98°N) to 1.6/1000 for males in the Borders (55.60°N). Comparison with a previous national survey suggests that these differences are longstanding. In 6 of 14 regions the lifetime risk for women exceeds 1%. CONCLUSIONS: This study introduces a national incidence register: a valuable research tool and the result of substantial public investment. The wide variation in incidence rates and sex ratios between regions, in a relatively homogenous population, raises questions for future study.

Latitudinal variation in MS incidence in Scotland.

AIMS: To explore the effect of latitude on incidence of multiple sclerosis (MS) in Scotland. METHODS: MS case data (2010-2015) was ascertained from the Scottish Multiple Sclerosis Register. Patient's postcode at diagnosis was linked to the Scottish Index of Multiple Deprivation (SIMD). Geographical data from SIMD was converted into latitude and longitude and patients were grouped by latitude band. A linear regression analysis was then performed. MS Cumulative Incidence was compared to population density calculated from SIMD. RESULTS: Latitude was associated with MS Incidence rate. Using a linear regression analysis (r2 = 0.22, p = 0.03), the data predicted an increase in the average MS Incidence of 1.31 cases/100,000 person years per increase in degree latitude. MS Cumulative Incidence rates rise with increasing northern latitude up until 59° north. CONCLUSIONS: We found an increasing incidence of MS with latitude without any relationship to population in Scotland. The reasons for this are likely to be multifactorial.

Web-based physiotherapy for people affected by multiple sclerosis: a single blind, randomized controlled feasibility study.

OBJECTIVE:: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. DESIGN:: Multi-centre, randomized controlled, feasibility study. SETTING:: Three multiple sclerosis out-patient centres. PARTICIPANTS:: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4-6.5). INTERVENTIONS:: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy ( n = 45; intervention) or a sheet of exercises ( n = 45; active comparator). OUTCOME MEASURES:: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists. RESULTS:: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%-63% and 53%-71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial. CONCLUSION:: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants.

Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature.

Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/ß receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation.

Habitual functional electrical stimulation therapy improves gait kinematics and walking performance, but not patient-reported functional outcomes, of people with multiple sclerosis who present with foot-drop.

BACKGROUND: People with Multiple Sclerosis (pwMS) often experience a disturbed gait function such as foot-drop. The objective of this pilot study was to investigate the medium term effects of using Functional Electrical Stimulation (FES) to treat foot-drop over a period 12 weeks on gait and patient reported outcomes of pwMS. METHODS AND FINDINGS: Nine pwMS aged 35 to 64 (2 males, 7 females) were assessed on four occasions; four weeks before baseline, at baseline and after six weeks and twelve weeks of FES use. Joint kinematics and performance on the 10 meter and 2 minute walk tests (10WT, 2 minWT) were assessed with and without FES. Participants also completed the MS walking Scale (MSWS), MS impact scale (MSIS29), Fatigue Severity Score (FSS) and wore an activity monitor for seven days after each assessment. Compared to unassisted walking, FES resulted in statistically significant improvements in peak dorsiflexion in swing (p = 0.006), 10MWT (p = 0.006) and 2 minWT (p = 0.002). Effect sizes for the training effect, defined as the change from unassisted walking at baseline to that at 12 weeks, indicated improved ankle angle at initial contact (2.6°, 95% CI -1° to 4°, d = 0.78), and a decrease in perceived exertion over the 2 min walking tests (-1.2 points, 95% CI -5.7 to 3.4, d = -0.86). Five participants exceeded the Minimally Detectable Change (MDC) for a training effect on the 10mWT, but only two did so for the 2 minWT. No effects of the use of FES for 12 weeks were found for MSWS, MSIS29, FSS or step count. CONCLUSION: Although FES to treat foot-drop appears to offer the potential for a medium term training effect on ankle kinematics and walking speed, this was not reflected in the patient reported outcomes. This observed lack of relationship between objective walking performance and patient reported outcomes warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01977287.

Case report: Eastern equine encephalitis virus imported to the UK.

Eastern equine encephalitis (EEE) is rare, but the most severe of the mosquito-borne encephalitides in the United States with a high case fatality rate of 30%. Here, we present a patient with EEE. EEE virus causes sporadic human disease in the Eastern parts of the United States, but the case we describe was a Scottish tourist who acquired the disease from mosquito bites while in holiday in the United States. This is a first report of an imported case to Europe.