Literature DB >> 24052635

Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.

I S Mackenzie1, S V Morant, G A Bloomfield, T M MacDonald, J O'Riordan.   

Abstract

OBJECTIVES: To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK.
DESIGN: A descriptive study.
SETTING: The study was carried out in the General Practice Research Database (GPRD), a primary care database representative of the UK population. MAIN OUTCOME MEASURES: Incidence and prevalence of MS per 100 000 population. Secular and geographical trends in incidence and prevalence of MS.
RESULTS: The prevalence of MS recorded in GPRD increased by about 2.4% per year (95% CI 2.3% to 2.6%) reaching 285.8 per 100 000 in women (95% CI 278.7 to 293.1) and 113.1 per 100 000 in men (95% CI 108.6 to 117.7) by 2010. There was a consistent downward trend in incidence of MS reaching 11.52 per 100 000/year (95% CI 10.96 to 12.11) in women and 4.84 per 100 000/year (95% CI 4.54 to 5.16) in men by 2010. Peak incidence occurred between ages 40 and 50 years and maximum prevalence between ages 55 and 60 years. Women accounted for 72% of prevalent and 71% of incident cases. Scotland had the highest incidence and prevalence rates in the UK.
CONCLUSIONS: We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

Entities:  

Keywords:  Epidemiology; Multiple Sclerosis

Mesh:

Year:  2013        PMID: 24052635      PMCID: PMC3888639          DOI: 10.1136/jnnp-2013-305450

Source DB:  PubMed          Journal:  J Neurol Neurosurg Psychiatry        ISSN: 0022-3050            Impact factor:   10.154


Background

Individuals with multiple sclerosis (MS) can experience high levels of disability and impaired quality of life for prolonged periods. The costs of the disease in the UK, including health and social care and productivity losses, are high and correlate with disease severity.1 2 It is important to have accurate and up to date information on the prevalence of MS in the UK in order to understand the impact of this disease and to ensure that adequate resources are provided nationally and regionally for people affected by MS. National studies have been carried out in the past, but recent data are lacking.3–6 To address this need, work on compiling an online national MS register began in 2011 (http://www.ukmsregister.org). A dedicated Scottish National MS Register for incident MS cases was established in 2010.7 The General Practice Research Database (GPRD) is a longitudinal database containing details of patients’ demographics, medical diagnoses, referrals to consultants and hospitals, and primary care prescriptions from a representative sample of general practices in the UK.8 Two previous studies have used the GPRD to study the epidemiology of MS in the UK, the first reporting for the period 1993–2000.6 A more recent study investigated the prevalence of MS between 2000 and 2008 stratified by age, sex, geographical region and calendar year.7

Methods

Study design

This was a population-based study using the GPRD. The study protocol was reviewed and approved by the Independent Scientific Advisory Committee (ISAC) of GPRD. No further ethical approval is required for studies using GPRD that do not involve patient contact.

Hypothesis

This was a descriptive study. Its aim was to estimate the incidence and prevalence of MS by age in men and women and to describe secular trends and geographic variations within the UK between 1990 and 2010.

Study population

The study population included all patients with acceptable data who contributed follow-up time to the database after 1990. GPRD defines a patient's data as unacceptable if there is evidence of poor data recording, non-contiguous follow-up or if their registration with the practice is temporary. Eligible follow-up time for each patient started with their practice's ‘up-to-standard’ (UTS) date or the patient's date of registration with the practice if this was later. GPRD applies standard criteria to define the date at which any individual practice's data become ‘UTS’ to ensure quality of data. The first 2 years of follow-up time for each patient were treated as a screening period, and incidence and prevalence rates were calculated for follow-up time after the screening period. We chose this screening period because preliminary analyses showed that incidence rates were high in the first 2 years of follow-up and prevalence rates were low, particularly in the first year. This is probably due to inclusion of patients with prevalent disease whose initial diagnosis pre-dated the computerisation of their practice's records. The follow-up period ended with the earlier of either their transfer-out date or their practice's last data collection date.

Outcomes

For GPRD, Read codes for confirmed diagnoses of MS (ie, codes beginning F20) were used. For Hospital Episode Statistics (HES) the International Classification of Diseases (ICD10) code for MS (G35) was used. Incident cases were defined as the first occurrence of a code for MS if it occurred after the 2-year screening period.

Statistical analysis

The analysis plan is shown in figure 1.
Figure 1

Analysis plan. GPRD, General Practice Research Database; HES, Hospital Episode Statistics; ONS, Office of National Statistics; MS, multiple sclerosis.

Analysis plan. GPRD, General Practice Research Database; HES, Hospital Episode Statistics; ONS, Office of National Statistics; MS, multiple sclerosis.

GPRD

For every patient, the number of days of follow-up available on the GPRD was calculated for each year from 1990 to 2010. We determined whether patients had any prior diagnosis of MS in the GPRD on the 1st January each year and, if not, whether any incident diagnosis occurred during the year. Incidence rates were estimated from Poisson regression models with log(time at risk) as an offset variable. Prevalence rates were estimated from logistic regression models. The explanatory variables in the models were age, year and region. Geographical regions were defined as Scotland, Wales, Northern Ireland and the 10 Strategic Health Authorities of England. Data for men and women were analysed separately. Mortality rates were analysed using logistic regression models.

Hospital episode statistics

HES data were available for about 44% of patients in the GPRD from 1997 to 2010. We estimated the prevalence and incidence of MS in these patients over this period of time using GPRD data only, as described above. We compared these rates with those calculated for the same patients using the additional diagnoses obtained from HES. Age-specific rates of under-recording of MS in the GPRD were estimated from inverse polynomials fitted to the ratios of cases identified from HES and the GPRD together versus the GPRD alone. These rates were used to adjust estimates of incidence and prevalence rates for the whole GPRD population.

Office for National Statistics

We applied these adjusted age-specific and gender-specific incidence and prevalence rates to population statistics obtained from the Office for National Statistics (ONS) for the UK population to estimate the absolute numbers of new and prevalent cases of MS in the UK population in 2010.9 We obtained sex-specific and age-specific mortality rates for England and Wales in 2000 and 2010 from the ONS10 and used them to calculate period life expectancy at birth in those years. To estimate the numbers of incident and prevalent cases of MS in the UK population in 2010 for men and women in each decade of life, we calculated incidence and prevalence rates in the entire GPRD population and applied age-specific correction factors to account for under-reporting in GP records alone. We applied the corrected rates in 2010 to the total national UK population based on ONS figures.9

Results

The numbers of patients with UTS follow-up time on the GPRD increased from 1.1 million in 1990 to at least 4.0 million between 2006 and 2010. The GPRD population included about 8% of the UK population in 2010, and their age and sex distributions were similar to those of the whole population (table 1).
Table 1

Age and sex distributions of the UK population (ONS) and the GPRD population in 2010

 MaleFemale
ONSGPRDONSGPRD
NPer centNPer centNPer centNPer cent
Under 207 576 80024.7583 20123.77 206 50022.8560 77822.3
20–242 213 1007.2152 4176.22 096 8006.6157 8706.3
25–292 168 6007.1164 3756.72 081 1006.6173 4446.9
30–341 959 8006.4167 3216.81 931 7006.1167 4726.7
35–392 084 6006.8178 1307.22 117 1006.7171 0336.8
40–442 293 5007.5191 9927.82 338 6007.4182 9457.3
45–492 250 1007.3190 1897.72 316 1007.3181 9197.2
50–541 964 7006.4165 7616.72 016 5006.4159 8856.4
55–591 758 7005.7144 4105.91 819 8005.8142 4605.7
60–641 840 1006.0149 9286.11 923 5006.1151 6616.0
65–691 412 1004.6115 6264.71 519 6004.8119 8594.8
70–741 160 3003.890 9763.71 307 5004.199 8594.0
75–79893 9002.971 2872.91 107 8003.586 2663.4
80 plus1 067 0003.591 9633.71 836 4005.8159 3096.3
All30 643 300100.02 457 576100.031 619 000100.02 514 760100.0

GPRD, General Practice Research Database; ONS, Office for National Statistics.

Age and sex distributions of the UK population (ONS) and the GPRD population in 2010 GPRD, General Practice Research Database; ONS, Office for National Statistics.

Secular trends

The prevalence of MS increased by about 2.4% per year (95% CI 2.3% to 2.6%) in men and women over the study period (figure 2A) and reached 285.8 per 100 000 in women (95% CI 278.7 to 293.1) and 113.1 per 100 000 in men (95% CI 108.6 to 117.7) in 2010. The prevalence rates that are below the trend line in the early 1990s may be an artefact due to patients being first diagnosed before their entry to the database, despite the 2-year screening period. There was no change in MS prevalence in patients below the age of 50, but annual rates of increase were over 4% in patients aged ≥60 years (figure 2B).
Figure 2

Secular trends in the prevalence of multiple sclerosis (General Practice Research Database 1990–2010). (A) Prevalence (per 105 (per 100 000) patients) in women and men (all age groups). (B) Variation in prevalence by age group (% change per year, both sexes).

Secular trends in the prevalence of multiple sclerosis (General Practice Research Database 1990–2010). (A) Prevalence (per 105 (per 100 000) patients) in women and men (all age groups). (B) Variation in prevalence by age group (% change per year, both sexes). There was a consistent downward trend in the incidence of MS in the whole study population over the 20-year study period (figure 3A). In 2010, MS incidence in women fell to 11.52 per 100 000/year (95% CI 10.96 to 12.11) and in men to 4.84 per 100 000/year (95% CI 4.54 to 5.16). The rate of decline between 1990 and 2010 was 1.51% per year (95% CI 0.99% to 2.07%) and did not differ between men and women (p=0.682) or with age (p=0.494) (figure 3B). This implies that the female-to-male ratio among incident cases, approximately 2.4, did not change significantly over the study period.
Figure 3

Secular trends in the incidence of multiple sclerosis (General Practice Research Database 1990–2010). (A) Incidence (per 105 patient years) in women and men (all age groups). (B) Variation in incidence by age group (% change per year, both sexes).

Secular trends in the incidence of multiple sclerosis (General Practice Research Database 1990–2010). (A) Incidence (per 105 patient years) in women and men (all age groups). (B) Variation in incidence by age group (% change per year, both sexes). Mortality rates fell in the GPRD population over the study period. In the 70–79-year age group, for example, they fell from 5.41% per year (95% CI 5.25% to 5.58%) in 1990 to 2.82% per year (95% CI 2.76% to 2.87%) in 2010 in men and from 3.15% per year (95% CI 3.04% to 3.26%) to 1.88% per year (95% CI 1.84% to 1.92%) in women over the same time period. Among other age groups, the proportional decline was similar. The mortality rate among patients with MS was more than twice that of other patients in all age groups and in both sexes, but also declined at a similar proportional rate. Life expectancy rose from 75.6 to 78.3 years in men and from 79.9 to 81.8 years in women. We applied the age-specific mortality ratios for people with and without MS observed in the present study to estimate changes in life expectancies in people with MS over the same decade. They increased from 61.4 to 65.4 years in men and from 68.7 to 71.6 years in women.

Age trends

The peak incidence of MS occurred at the age of 40 years in women and 45 years in men (figure 4A), while peak prevalence rates occurred at the ages of 56 years and 59 years, respectively, (figure 4B).
Figure 4

Incidence and prevalence of multiple sclerosis in women and men by age (General Practice Research Database 1990–2010). (A) Incidence (per 105 patient years). (B) Prevalence (per 105 patients).

Incidence and prevalence of multiple sclerosis in women and men by age (General Practice Research Database 1990–2010). (A) Incidence (per 105 patient years). (B) Prevalence (per 105 patients).

Regional variation

There was significant variation in the incidence and the prevalence of MS between regions of the UK (p<0.001) (see online supplementary Figures 5a and 5b). The highest prevalence and incidence rates were observed in Scotland. Among the other 12 regions of the UK, latitude accounted for 13.8% (men) and 4.0% (women) of the variation in incidence rates, and 2.0% (men) and 0.2% (women) of the variation in prevalence rates, none of which was statistically significant. Between 1997 and 2010 GPRD and HES data were available for a subset of patients (approximately 44%, table 2). Tables 3 and 4 show the age-specific and sex-specific prevalence and incidence rates of MS in this subgroup of patients based on the GPRD alone, and the rates when the additional diagnoses recorded in HES are included. HES identified an additional 744 prevalent cases and 121 incident cases in men and 1521 prevalent cases and 227 incident cases in women. GPRD alone underestimated the prevalence of MS by 7.0% in men and 5.5% in women and incidence by 21.3% in men and 17.2% in women over the period 1997–2010. Age-specific correction factors were estimated.
Table 2

GPRD study population by year and the subset with HES data available

YearGPRDGPRD with HES
19901 088 206
19911 318 334
19921 508 239
19931 630 354
19941 750 630
19951 862 669
19962 224 963
19972 551 3631 149 379
19982 978 9051 345 591
19993 561 9681 592 080
20003 951 4521 760 716
20014 256 1651 892 812
20024 508 7211 949 061
20034 629 8961 968 050
20044 778 8542 018 928
20054 858 5412 059 654
20064 961 5062 116 992
20075 017 3962 184 142
20084 989 8682 223 688
20094 955 1792 240 931
20104 972 3361 981 005
20114 665 090

GPRD, General Practice Research Database; HES, Hospital Episode Statistics.

Table 3

Age-specific and gender-specific prevalence of MS using GPRD alone and GPRD with HES (1997–2010)

Patients (thousands)GPRD data where HES availableGPRD plus HES
CasesPrevalence (/105)CasesPrevalence (/105)
Male
 Under 10894.650.550.5
 10–191209.3332.7403.3
 20–291055.623021.723722.4
 30–391389.2113881.9116683.9
 40–491514.52255148.82341154.5
 50–591368.82959216.13146229.8
 60–691073.62182203.22337217.6
 70–79719.5882122.51054146.4
80–89327.115045.824474.5
90 Plus48.1816.61633.2
 Total9600.29842102.510 586110.2
Female
 Under 10855.200.080.9
 10–191096.6222.0343.1
 20–29960.149851.854957.1
 30–391340.03392253.13488260.2
 40–491464.26541446.76724459.2
 50–591341.17845584.98153607.9
 60–691092.55040461.35415495.6
 70–79856.72014235.02292267.5
 80–89544.6563103.3755138.6
 90 Plus139.54230.16043.0
 Total9690.625 957267.827 478283.5

GPRD, General Practice Research Database; HES, Hospital Episode Statistics; MS, multiple sclerosis.

Table 4

Age-specific and gender-specific incidence of MS using GPRD alone and GPRD with HES (1997–2010)

 Patient years (thousands)GPRD only where HES availableGPRD plus HES
New casesIncidence (/105/year)New casesIncidence (/105/year)
Male
Under 10841.000.0010.11
10–191146.260.5270.61
20–29974.8404.10424.30
30–391294.11007.721078.26
40–491429.61299.0214310.00
50–591301.4977.451239.45
60–691013.5535.22757.39
70–79675.6162.36507.40
80–89296.241.35144.72
90 Plus40.10049.98
Total9012.64454.935666.28
Female
Under 10804.10.0000.00
10–191035.07.67100.96
20–29870.311112.7512113.90
30–391250.028222.5530023.99
40–491387.433324.0035825.80
50–591277.122317.4627021.14
60–691035.510410.0414213.71
70–79810.7253.08789.62
80–89499.271.40357.01
90 Plus117.910.8465.08
Total9087.3109312.02132014.52

GPRD, General Practice Research Database; HES, Hospital Episode Statistics; MS, multiple sclerosis.

GPRD study population by year and the subset with HES data available GPRD, General Practice Research Database; HES, Hospital Episode Statistics. Age-specific and gender-specific prevalence of MS using GPRD alone and GPRD with HES (1997–2010) GPRD, General Practice Research Database; HES, Hospital Episode Statistics; MS, multiple sclerosis. Age-specific and gender-specific incidence of MS using GPRD alone and GPRD with HES (1997–2010) GPRD, General Practice Research Database; HES, Hospital Episode Statistics; MS, multiple sclerosis.

Overall estimates of the UK MS population in 2010

Table 5 shows overall estimates of the numbers of incident and prevalent cases of MS in the UK population in 2010 for men and women in each decade of life. We estimate that 126 669 people were living with MS in the UK at the beginning of 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed during that year (9.64 per 100 000/year). Women accounted for 72% of prevalent and 71% of incident cases. We also estimated the numbers of incident and prevalent cases of MS in the four countries which comprise the UK (table 5).
Table 5

Estimated numbers of incident and prevalent cases of MS in the UK population in 2010

Population (thousands)Incidence (/105/year)Incident casesPrevalence (/105)Prevalent cases
Male
 Under 103738.80.0420.312
 10–193838.00.41162.492
 20–294381.73.8516919.6860
 30–394044.47.2529388.83593
 40–494543.69.34425166.57568
 50–593723.410.12377248.69259
 60–693252.28.21267287.09336
 70–792054.27.20148183.93779
 80–89933.26.115772.7679
 90 Plus133.80.00035.648
 Total30 643.35.721754114.935 225
Female
 Under 103566.00.0930.210
 10–193640.51.43523.0110
 20–294177.911.6248658.42440
 30–394048.820.41827274.011 095
 40–494654.724.401136470.221 887
 50–593836.322.12849638.724 502
 60–693443.114.70506597.020 555
 70–792415.310.10244340.88232
 80–891494.18.06121156.62341
 90 Plus342.37.622679.1271
 Total31 619.013.444250289.291 444
Both sexes, all ages
UK62 262.39.646003203.4126 669
England52 233.99.084745199.9104 451
Wales3006.37.92238168.05052
Scotland5222.315.29798255.213 328
Northern Ireland1799.812.25221213.23838

MS, multiple sclerosis.

Estimated numbers of incident and prevalent cases of MS in the UK population in 2010 MS, multiple sclerosis.

Discussion

Principal findings of the study

We estimate that the prevalence of MS in the UK in 2010, including diagnoses obtained from HES, was 289.0 per 100 000 in women and 115.0 per 100 000 in men. The overall prevalence of MS increased by approximately 2.4% per year between 1990 and 2010 in women and men. This increase in prevalence was due to a convergence of absolute mortality rates in patients with and without MS, the result of mortality rates falling by about 3% per year in both groups. There was no change in MS prevalence in patients below the age of 50, but annual rates of increase were over 4% in patients aged ≥60 years. We observed a decline in the rate at which new cases of MS were diagnosed, and the rising prevalence rate can likely be accounted for by trends in mortality rates. There was a consistent downward trend in overall incidence of MS in the whole study population over the 20-year study period, and the rate of decline did not differ between men and women or with age. It is possible that this is due to new diagnostic techniques which reduced the risk of false positive diagnoses over the study period. The maximum incidence of MS occurred at age 40 years (women) to 45 years (men). We were not able to analyse the effects of prior pregnancy on the age of onset of MS in women in this study, although it has previously been reported that pregnancy reduces the risk of onset of MS.11 We found significant regional variation in incidence and prevalence rates in the UK. We found the highest incidence and prevalence rates among the 13 regions of the UK in Scotland, but no trend with latitude among the other 12 regions. This suggests that the difference between Scotland and other regions of the UK is probably not the result of a consistent trend with latitude, but may involve factors not associated with latitude. We were not able to analyse the different regions of Scotland separately using the GPRD.

Strengths and weaknesses of the study

A major strength of this study is that it covers a representative sample of GPs spread geographically throughout the UK, and a patient population with age and sex distributions similar to those of the general UK population. The study population of some 4 million patients provides greater statistical precision than earlier regional surveys. Our analyses depend upon the accuracy of diagnosis and recording of MS by GPs: there may have been miscoding of tentative MS diagnoses as definite MS cases, leading to an overestimate in the number of MS cases, or under-recording may have led to an underestimate in the number of cases. In a systematic review of 212 publications using the GPRD, Herrett et al reported that the median proportion of cases with a confirmed diagnosis based on additional internal or external validation was 89% across all disease groups and 81% for nervous system diseases12 but there has not yet been a validation of MS diagnoses specifically within GPRD. We addressed some of the limitations of the GPRD records by also using HES, which allowed us to estimate the extent of under-recording of MS in the GPRD.

Relation to other studies

The prevalence rates we found are slightly higher than the rates reported by Thomas et al in 2007, also using the GPRD: 281.0 per 100 000 (95% CI 273.0 to 289.0) among women and 108.0 per 100 000 (95% CI 103.0 to 113.0) among men, with the highest prevalence in those aged 55–64 years.13 This study and our study found maximum prevalence for MS in patients around the age of 60. Alonso and colleagues reported incidence rates of 7.2 (95% CI 6.5 to 7.7) per 100 000 person-years in women and 3.1 (95% CI 2.6 to 3.5) in men in the UK between 1993 and 2000 in their GPRD study, which are somewhat lower than our findings.6 The UK has a relatively high incidence of MS compared to other countries. An overall incidence rate of MS of 3.6 per 100 000 person-years in women and 2.0 in men was reported in a review of studies of the incidence of MS published between 1966 and 2007.14 The downward trend in incidence that we found is in contrast to studies in Denmark, where the female incidence of MS has almost doubled since the 1970s while male incidence has remained constant.15 These authors found a general, but not ubiquitous, increase in MS incidence in Western Europe and North America.15 However, they point out that many of the studies included only small numbers of cases and random variations may have contributed to the irregular patterns observed. Moreover, separate surveys carried out and analysed at different times may be subject to methodological differences. It is not clear why our study has detected a decreasing incidence while others have suggested increasing incidence. Changes in awareness of MS and the challenges of diagnosing MS may account for changes incidence over time. However, we could identify no specific reason why the methodology or data source we used should have had an impact on our finding of decreasing incidence of MS over the period of the study.

Sex ratio in MS

In the current study, the mean female-to-male ratio for MS was 2.4 and there was no trend with time over the 20-year study period. In their 2008 review of published studies on the incidence of MS, Alonso and Hernán reported that the female-to-male ratio increased from 1.4 in 1955 to 2.3 in 2000.14 This increase in the sex ratio for MS is not ubiquitous, however, and there are striking geographic variations. For example, a recent analysis of trends in the sex ratio in MS for individuals born between 1930 and 1989 found a marked increase in Northern Europe (not including the UK) (from 2.09 to 3.77), but only a moderate increase in Southern Europe (from 1.46 to 2.31).16 In contrast, a study in Sweden found a mean female-to-male ratio for MS of 2.62, with no clear trend with year of birth for individuals born between 1931 and 1985.17 A recent review reported a significant increase in the MS prevalence female-to-male sex ratio in the UK between 1949 and 2009—a much longer time period than our study.18 It is possible that this historical trend in female-to-male sex ratio for MS has now stabilised. This may be partly accounted for by changing health-related behaviours of men in recent years, perhaps having more contact with medical services than was the case historically. We are not able to identify any particular reason why the study methodology or data source could have confounded our findings regarding sex-ratio.

Regional variations in MS

A recent study using HES data for the period 1999–2005 showed regional variations in hospital admission rates for MS in England.19 This study found significantly higher MS admissions in more northern regions of England even after adjusting for social deprivation and UK birthplace. Early studies on MS suggested a trend with latitude with increasing prevalence in more temperate climates in Northern and Southern hemispheres.3 20–26 However, the idea that there is a relationship between latitude and MS incidence or prevalence in Western Europe has been dismissed recently by some authors.15 In contrast, Simpson and colleagues reported that there was a statistically significant positive association between MS prevalence and latitude globally, although there were some exceptions to the latitudinal gradient in some parts of Europe.18 Regional variation in MS epidemiology may be due to genetic or environmental factors and interactions between them. A study in Ireland found that the HLA DRB1*15 allele associated with MS susceptibility is more common in areas of higher prevalence.25 The exact role of such factors in the epidemiology of MS remains to be ascertained. One recent study found that the distribution of HLA DRB1 accounted for 52% of the variation in MS prevalence by latitude in Europe,27 whereas another study suggested that non-HLA DRB1 factors play an important role in regional MS variations in Europe.18 For example, it has been suggested that lack of vitamin D may increase susceptibility to MS. This is supported by studies on the effect of month of birth on subsequent risk of MS in Northern and Southern hemispheres.28–29 Vitamin D also reversibly blocks the progression of experimental autoimmune encephalomyelitis, a mouse model of MS.30 Further evidence comes from a recent genetic study which demonstrated a causative role for the CYP27B1 gene, which encodes the vitamin D-activating 1-α hydroxylase enzyme.31 Such factors may have a role in increasing the incidence of MS in Scotland relative to other parts of the UK. Further studies are needed to investigate the causative factors of MS, particularly the role of Vitamin D, genetic susceptibility factors and infective agents.

Conclusions

This study provides a comprehensive picture of the prevalence and incidence of MS throughout the UK over two decades. It shows that more than 6000 people in the UK were newly diagnosed with MS in 2010 and that patients with MS are living longer, leading to a rising population living with the disease. This has important implications for resource provision in the UK.
  27 in total

1.  The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist?

Authors:  R B Forbes; S V Wilson; R J Swingler
Journal:  J Neurol       Date:  1999-11       Impact factor: 4.849

2.  Studies in the epidemiology of multiple sclerosis in the Orkney and Shetland Islands.

Authors:  D C Poskanzer; A M Walker; J Yonkondy; J L Sheridan
Journal:  Neurology       Date:  1976-06       Impact factor: 9.910

3.  The distribution of multiple sclerosis in the United Kingdom.

Authors:  R J Swingler; D Compston
Journal:  J Neurol Neurosurg Psychiatry       Date:  1986-10       Impact factor: 10.154

4.  On the risk of multiple sclerosis according to age at immigration to South Africa.

Authors:  G Dean; J F Kurtzke
Journal:  Br Med J       Date:  1971-09-25

5.  Rare variants in the CYP27B1 gene are associated with multiple sclerosis.

Authors:  Sreeram V Ramagopalan; David A Dyment; M Zameel Cader; Katie M Morrison; Giulio Disanto; Julia M Morahan; Antonio J Berlanga-Taylor; Adam Handel; Gabriele C De Luca; A Dessa Sadovnick; Pierre Lepage; Alexandre Montpetit; George C Ebers
Journal:  Ann Neurol       Date:  2011-12       Impact factor: 10.422

6.  Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg).

Authors:  Inger Boström; Leszek Stawiarz; Anne-Marie Landtblom
Journal:  Mult Scler       Date:  2012-06-18       Impact factor: 6.312

7.  Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.

Authors:  I A F van der Mei; A-L Ponsonby; T Dwyer; L Blizzard; R Simmons; B V Taylor; H Butzkueven; T Kilpatrick
Journal:  BMJ       Date:  2003-08-09

Review 8.  The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude.

Authors:  Ruth Dobson; Gavin Giovannoni; Sreeram Ramagopalan
Journal:  J Neurol Neurosurg Psychiatry       Date:  2012-11-14       Impact factor: 10.154

9.  Geography of hospital admissions for multiple sclerosis in England and comparison with the geography of hospital admissions for infectious mononucleosis: a descriptive study.

Authors:  Sreeram V Ramagopalan; Uy Hoang; Valerie Seagroatt; Adam Handel; George C Ebers; Gavin Giovannoni; Michael J Goldacre
Journal:  J Neurol Neurosurg Psychiatry       Date:  2011-01-06       Impact factor: 10.154

10.  Geographical variations in sex ratio trends over time in multiple sclerosis.

Authors:  Maria Trojano; Guglielmo Lucchese; Giusi Graziano; Bruce V Taylor; Steve Simpson; Vito Lepore; Francois Grand'maison; Pierre Duquette; Guillermo Izquierdo; Pierre Grammond; Maria Pia Amato; Roberto Bergamaschi; Giorgio Giuliani; Cavit Boz; Raymond Hupperts; Vincent Van Pesch; Jeannette Lechner-Scott; Edgardo Cristiano; Marcela Fiol; Celia Oreja-Guevara; Maria Laura Saladino; Freek Verheul; Mark Slee; Damiano Paolicelli; Carla Tortorella; Mariangela D'Onghia; Pietro Iaffaldano; Vita Direnzo; Helmut Butzkueven
Journal:  PLoS One       Date:  2012-10-25       Impact factor: 3.240

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  71 in total

1.  Delayed diagnosis of multiple sclerosis in males: may account for and dispel common understandings of different MS 'types'.

Authors:  Abi Eccles
Journal:  Br J Gen Pract       Date:  2019-03       Impact factor: 5.386

2.  Hormonal contraception and the development of autoimmunity: A review of the literature.

Authors:  William V Williams
Journal:  Linacre Q       Date:  2017-08-18

Review 3.  Inflammation in CNS neurodegenerative diseases.

Authors:  Jodie Stephenson; Erik Nutma; Paul van der Valk; Sandra Amor
Journal:  Immunology       Date:  2018-04-17       Impact factor: 7.397

4.  Use of optokinetics based OKCSIB protocol in restoring mobility in primary progressive MS.

Authors:  Benjamin Chitambira; Ciara McConaghy
Journal:  BMJ Case Rep       Date:  2017-10-04

5.  A Systematic Review of Cognition in Chiari I Malformation.

Authors:  Jeffrey M Rogers; Greg Savage; Marcus A Stoodley
Journal:  Neuropsychol Rev       Date:  2018-02-21       Impact factor: 7.444

6.  Group cognitive rehabilitation to reduce the psychological impact of multiple sclerosis on quality of life: the CRAMMS RCT.

Authors:  Nadina B Lincoln; Lucy E Bradshaw; Cris S Constantinescu; Florence Day; Avril Er Drummond; Deborah Fitzsimmons; Shaun Harris; Alan A Montgomery; Roshan das Nair
Journal:  Health Technol Assess       Date:  2020-01       Impact factor: 4.014

7.  Preferences for Multiple Sclerosis Treatments: Using a Discrete-Choice Experiment to Examine Differences Across Subgroups of US Patients.

Authors:  Carol Mansfield; Nina Thomas; David Gebben; Maria Lucas; A Brett Hauber
Journal:  Int J MS Care       Date:  2017 Jul-Aug

Review 8.  The hygiene hypothesis in autoimmunity: the role of pathogens and commensals.

Authors:  Jean-François Bach
Journal:  Nat Rev Immunol       Date:  2017-10-16       Impact factor: 53.106

9.  Kallmann syndrome patient with gender dysphoria, multiple sclerosis, and thrombophilia.

Authors:  Aniruthan Renukanthan; Richard Quinton; Benjamin Turner; Peter MacCallum; Leighton Seal; Andrew Davies; Richard Green; Jane Evanson; Márta Korbonits
Journal:  Endocrine       Date:  2015-03-05       Impact factor: 3.633

10.  Impact of Proactive Case Management by Multiple Sclerosis Specialist Nurses on Use of Unscheduled Care and Emergency Presentation in Multiple Sclerosis: A Case Study.

Authors:  Alison Leary; Debbie Quinn; Amy Bowen
Journal:  Int J MS Care       Date:  2015 Jul-Aug
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