Wednesday, 12 October 2011

MS north-south gradient disappearing

Epub ahead of printKoch-Henriksen and Sorensen. Why does the north-south gradient of incidence of multiple sclerosis seem to have disappeared on the Northern hemisphere? J Neurol Sci. 2011 Oct 6. 


The traditional view is that MS is particularly prevalent in temperate zones both on the northern and southern hemisphere. This uneven distribution of MS is attributed to differences in genes and environment and their interactions. 

Diagnostic accuracy (making sure the daignosis of MS is correct) and case ascertainment (finding cases of MS) are sources of error and have their shares in the geographical and temporal variations, and improvements in diagnostic accuracy and case ascertainment influence incidence- and prevalence rates of MS. 

MS prevalence also depends on survival; improving survival increases prevalence. 

In this meta-analysis the authors have focused on the trend in the incidence and sex ratio of MS through the last five decades, and they analysed the latitudinal distribution of MS incidence, based on a recent literature search. 

Their findings indicate that the prevalence and incidence rates had increased in almost all areas, but the previously reported latitudinal gradient of incidence of MS in Europe and North America could not be confirmed even when restricting the search to surveys published before 1980 or 1970. Conversely, the latitudinal gradient of prevalence rates seemed to be preserved. This apparent discrepancy can be explained by the circumstance that incidence estimates only depend on complete ascertainment for a relative short recent period of time, whereas reliable prevalence rates presuppose complete ascertainment decades back in time. 

A contributory explanation for the missing latitudinal gradient for incidence may be changes in environmental factors, levelling out differences in habits of life across Europe and North America, and, not least, that the interpretation of a latitudinal gradient in Europe was based primarily on prevalence studies and reviews. 

They observed in most regions studied a profound increase in female incidence of MS. The authors' suggest that last observation should prompt epidemiological studies focusing on change in female life style.

"I bet part of it is linked to smoking and vitamin D."


"Since the second world war there has been a gradual increase in the number of woman smoking. The latter is due to clever marketing on the part of the tobacco industry; particularly the manipulation of teenage girls through celebrity role models."


"Woman are now getting less good quality sun exposure due to several factors: (1) less outdoor activity (The Facebook generation), (2) the ubiquitous use of sun block and its addition to make-up products, (3) covering-up (a big problem in the Middle East and Asia), (4) a change in diet (less fish or a switch to farmed fish that has less vitamin D compared to wild fish)."

"Some experts, including me, think another factor is the greater chance of acquiring EBV infection during a early adolescence. Infectious mononucleosis is commoner in adolescent girls compared to adolescent boys."

"All this is very fascinating and if you want to propose that factor X causes MS it has to explain all these observations. Hence my cynicism about certain recent claims about causation."

"I am sure there are other factors; if you have any ideas please let me know."

18 comments:

  1. Do you think a lack of Vit D in the mothers of MSer's prior to conception or during pregnancy, or smoking, or having been infected with EBV, may lead to a greater risk of their children getting MS? For years mums to be were told to be careful about supplements, but maybe there is a case for extra Vit D in pregnancy?

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  2. Do you think that my MS is more my mum's fault for not getting enough vit D during gestation rather than me not getting enough vit D in my childhood? Also, as a baby of the late-70s, my mum was encouraged to bottle feed as opposed to breastfeed me. My big sisters were breastfed and don't have MS yet I do.

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  4. Re: "Do you think a lack of Vit D in the mothers of MSer's prior to conception or during pregnancy, or smoking, or having been infected with EBV, may lead to a greater risk of their children getting MS?"

    Vitamin D deficiency in pregnancy is very likely to be an important risk factor and may explain the month of birth effect; i.e. if you mother was pregnant during winter (last 6 months) and you were born in April you are at increased risk of developing MS. In contrast if you mother was pregnant during summer and you were born in November you are reduced risk of MS. The opposite happens in the Southern hemisphere. Interesting?

    In France all pregnant mothers are put in high-dose vitamin D supplements.

    I am not sure about EBV and smoking; the data is poor for this.

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  5. Re "Hence my cynicism about certain recent claims about causation."

    The alleged EBV infection prevalence in MS could very well be the RESULT of a congenital, therefore, chronic state of some kind of venous insufficiency. Bacteria like to hang around in ulcers: http://www.ncbi.nlm.nih.gov/pubmed/9192256

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  6. Re: "Do you think that my MS is more my mum's fault for not getting enough vit D during gestation rather than me not getting enough vit D in my childhood? Also, as a baby of the late-70s, my mum was encouraged to bottle feed as opposed to breastfeed me. My big sisters were breastfed and don't have MS yet I do."

    I don't think you can blame anyone for you getting MS, in particular your mother. The information about vitamin D is only emerging now and the public health officials are still sitting on the fence regarding advice to pregnant woman. In my opinion all pregnant woman should be on 5,000 to 10,000U per day of vitamin D3 supplements.

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  7. Re: "The alleged EBV infection prevalence in MS could very well be the RESULT of a congenital, therefore, chronic state of some kind of venous insufficiency. Bacteria like to hang around in ulcers: http://www.ncbi.nlm.nih.gov/pubmed/9192256"

    The link with EBV is not related to congenital infection, but rather late symptomatic infection; i.e. infectious mononucleosis or glandular fever that typically occurs in adolescence.

    EBV is not a bacteria, but a virus. EBV lies dormant in B cells (lymph nodes, spleen, bone marrow, tonsils and blood) and the salivary glands. The latter results in it being transmitted via saliva; that is why infectious mononucleosis is also called the kissing disease. I am not aware of any evidence of it being in ulcers.

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  8. Re "The link with EBV is not related to congenital infection, but rather late symptomatic infection; i.e. infectious mononucleosis or glandular fever that typically occurs in adolescence."

    That does not disprove the possibility of EBV infection being caused by something pre-existent, as a venous malformation for example. Instead it supports it. Adolescence is the right time for congenital venous malformations, like hypoplasia of jugular, lumbar, azygos vein, to manifest their insufficiency.

    Re "EBV is not a bacteria, but a virus"

    Of course it is. I posted a link to a research that identified persistent bacteria in leg ulcers caused by venous insufficiency. How sure can one be that something similar can not implicate viruses? Is there any research that proves it impossible?

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  9. Re: "Adolescence is the right time for congenital venous malformations, like hypoplasia of jugular, lumbar, azygos vein, to manifest their insufficiency."

    For others reading this blog I want to stress that the evidence that MS is associated with venous malformations, either acquired or congenital (present from birth) is very weak. The early claims that there are venous abnormalties in the majority of MS'ers have not been substantiated in several independent studies.

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  10. Re 'Since the second world war there has been a gradual increase in the number of woman smoking': That may be true for some groups in some countries, but on the whole smoking by women has been going down.
    http://www.who.int/tobacco/en/atlas6.pdf
    http://info.cancerresearchuk.org/cancerstats/types/lung/smoking/#percent

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  11. Re: "Smoking"

    Thanks for this. Alberto Ascherio has calculated that ~50% of the increase in incidence of MS in woman is driven by smoking. You have to remember that smoking has a long lag phase; probably in the order of 20 years.

    Smoking is clearly not the only factor driving the increasing incidence of MS amongst woman.

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  12. Re "The early claims that there are venous abnormalties in the majority of MS'ers have not been substantiated in several independent studies.
    "

    The truth is that these "several independent studies" did not search for venous abnormalities per se, but rather investigated the visibility via ultrasound of a subset of them. MS is related to abormalities in internal jugular veins, vertebral veins - visible through ultrasound - but also azygos vein, hemiazygos vein, lumbar veins and left kidney vein, that are NOT visible through ultrasound. Eventually, vein abnormalities are all about flow, not anatomy.

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  13. As for smoking, it's devastating influence on vascular diseases is well established.

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  14. Prof G,

    Smoking was way more popular in the 1930s - my grandmother operated the projector in a cinema and always mentioned this. Was very popular among women - who wore heavy clothes / hats and didn't have holidays to the costas etc. Stick with the EBV in adolescence angle. This is the real decider. If you are never infected with EBV, the chances of getting MS are virtually zero. So a person never infected by EBV can smoke as much as they like and stay indoors and won't get MS. The contribution that smoking and Vit D makes are probably in the way they affect the body's ability to keep EBV under control. If you appeared on Egghead and the question was - which of the following is the main risk factor for getting MS (I) EBV infection in adolescence, (ii) smoking, or (iii) Vit D deciciency, what would your answer be? An EBV vaccine is the solution.

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  15. Professor G,

    Could you comment on the relationship between vitamin d and male gender. I have read information stating that vitamin d has no impact on male multiple sclerosis or that it is has lower efficacy in men. Which do you believe is true.

    Thank you.

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  16. Prof G said
    "Since the second world war there has been a gradual increase in the number of woman smoking. The latter is due to clever marketing on the part of the tobacco industry; particularly the manipulation of teenage girls through celebrity role models."

    I think a much stronger argument is that smoking suppresses the appetite making it much easier to lose weight and stay thin. So the fashion industry is the real culprit.

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  17. Re: "Could you comment on the relationship between vitamin d and male gender. I have read information stating that vitamin d has no impact on male multiple sclerosis or that it is has lower efficacy in men. Which do you believe is true."

    I am not aware of any differences in relation to sex and vD and MS. I will ask Dr Vitamin D. Ram, any comments?

    However, there is a tendency in some countries for men to have higher levels due to cultural reasons; for example covering-up, not wearing make-up with sun blocker and more outdoor activity.

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  18. Hi Devin, the evidence is consistent in showing that the risk of developing MS is increased in both males and females deficient for vitamin D (http://www.ncbi.nlm.nih.gov/pubmed/17179460) and that the risk of relapse is increased in both male and female MSers deficient for vitamin D (http://www.ncbi.nlm.nih.gov/pubmed/20695012). There is some suggestion that vitamin D may be more protective in females via a combined action of estrogen and vitamin D on the immune system http://www.ncbi.nlm.nih.gov/pubmed/20855882), but this was just an in vitro (lab based study) and remains to be formally proven in a randomised controlled trial in MSers. We cannot stress the importance to all MSers and their family members of being vitamin D replete!

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