1. Multiple Sclerosis Podcast: Epidemiology
Kevin Yen
Neurology R1
University of Alberta

2. Introduction
Multiple Sclerosis (MS) is the most common immune-mediated inflammatory demyelinating disease affecting the central nervous system (CNS)
The exact cause and pathophysiology of MS is currently under research
The working theory is that a combination of genetic and environmental factors activate immune cells to attack the CNS causing neuro-degeneration

3. Goals for this Lecture
To go over the basic pattern and statistics of MS population
Identify a few potential risk factors for developing MS
And clarify common misconceptions about MS risk factors and statistics.

4. Prevalence and Incidence
Prevalence and incidence of MS varies geographically
In North America, it is estimated 400,000 people are affected with MS
Worldwide, estimated to be 2.5 million people
The rate of MS in US is approximated 100/100,000
The rates of MS are higher in the northern states compared to the southern states, 120 vs. 60
In Canada, the rate of MS is estimated to be greater than 200/100,000

5. Age of Onset MS can present 10-80 years of age
Majority of the patient usually present years of age
Mean age of onset: years in various studies
Rare to have cases present at age <10 and >70
Overall, female present few years earlier than male
Different types of MS have different age of onset
Relapsing-remitting MS 25 – 29
Primary progressive MS
Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin 2011; 29:207.

6. Gender Mean age of onset is earlier in females
MS affects female more often than male
Estimated 2:1
In fact, studies have shown increasing incidence in female
It is unknown why females are affected more frequently
Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008; 71:129.

7. Genetics- Part 1 MS is not consider a hereditary condition
However, a number of genes have been shown to increase risk of MS
Genetic variation in Major Histocompatibility complex (MHC) are suspected to be related to MS presentation
In particular, the HLA-DRB1 locus
Some alleles are shown to be protective of MS while others are shown to increase the risk of MS
Other genes in other loci are currently under research
International Multiple Sclerosis Genetics Consortium, Hafler DA, Compston A, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357:851.
International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476:214.

8. Genetics- Part 2
Overall, chance of developing MS is higher in relatives of MS patients
Data for familial MS differ between studies
Estimated to be at least 2% absolute risk increase from sporadic
Up to 4% of asymptomatic relatives will have MS-like lesions on MRI
Up to 10% of asymptomatic relatives with multiple family members with MS
Dizygotic twins and sibling both show 5% risk of developing MS
However, monozygotic twins show 20-30% risk of developing MS
Sadovnick AD, Armstrong H, Rice GP, et al. A population-based study of multiple sclerosis in twins: update. Ann Neurol 1993; 33:281.
Nielsen NM, Westergaard T, Rostgaard K, et al. Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol 2005; 162:774.

9. Autoimmune Disorder
Currently there is conflicting evidence regarding the link between MS and other autoimmune disorder
Some studies have shown that MS patients are more likely to develop autoimmune disorders
Common disorder are psoriasis, thyroid disease, inflammatory bowel disease, and uveitis
Other studies have also shown that patient with autoimmune disorders are more likely to develop MS
Some of these disorders are type 1 diabetes mellitus and inflammatory bowel disease
Heinzlef O, Alamowitch S, Sazdovitch V, et al. Autoimmune diseases in families of French patients with multiple sclerosis. Acta Neurol Scand 2000; 101:36.
Ramagopalan SV, Dyment DA, Valdar W, et al. Autoimmune disease in families with multiple sclerosis: a population-based study. Lancet Neurol 2007; 6:604.

10. Geographic
Many study show that MS prevalence and incidence vary geographically
There is an observation showing increase prevalence and incidence of MS with increasing latitude from south to north
Following areas with prevalence >60/100,000
Northern US
Southern Canada
Europe
Russia
New Zealand
Southeast Australia
Currently unknown as to why there is a geographic variability
genetic difference/ethnicity vs. variable surveillance?
Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol 2008; 7:268.
Simpson S Jr, Blizzard L, Otahal P, et al. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011; 82:1132.

11. multiplesclerosis.net/wp-content/uploads/2013/01/global_2x.png

12. Sunlight Exposure
Many studies have found an inverse relationship between sun exposure (ultraviolet radiation) or serum vitamin D level and the prevalence of MS
Many studies have also found an inverse relationship between sun exposure (ultraviolet radiation) or serum vitamin D level and MS disease activity/progression
Overall the hypothesis is that sun exposure (ultraviolet radiation) or serum vitamin D level may be protective of MS
These finding support the observation that MS prevalence varies with latitude
Currently still under research
Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007; 61:504.

13. Viral Infection
Some studies hypothesize that viral infections could be the stimulus leading to activation of MS
Some of virus in question include Epstein-Barr virus and varicella zoster virus
No specific study has been able to prove direct causation of these virus to MS activation
Hernán MA, Zhang SM, Lipworth L, et al. Multiple sclerosis and age at infection with common viruses. Epidemiology 2001; 12:301.

14. Vaccinations
The idea that vaccines cause MS came from the hypothesis that vaccines might stimulate the immune system which leads to the activation of MS
Overall there has been no substantial evidence supporting the association between vaccines and MS
No associations with HBV, HPV, Tetanus, and several other vaccines with MS
Also, no association between several different vaccines and MS relapse in patients with MS
Also, there is no association between hepatitis B infection and MS
Confavreux C, Suissa S, Saddier P, et al. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med 2001; 344:319.

15. Other Associations with MS
Some research have looked at the association between smoking and MS
Overall no formal conclusion has been reached
Difference in microbiome have been proposed to be linked with MS
Some studies hypothesize that certain birth months maybe associated with risk of developing MS
April and May
Overall, more research needed to conclude the association between these factors and MS

16. Summary MS affects females more than males, 2:1
Mean age of onset is between 20-30
There are both genetic and environmental factors that contribute to the development of MS
Incidence and prevalence vary geographically likely due to an inverse relationship between UV radiation exposure and vitamin D level
The relationship between viral infections and MS are still under research
No proven risk of MS with vaccinations

17. Thank you for your time
Kevin Yen R1