Possible explanation for the higher incidence of MS in Doctors

  • 33 Replies
  • 20782 Views

0 Members and 1 Guest are viewing this topic.

*

ROBERT

  • Guest
There is a higher incidence of Multiple Sclerosis (MS) in certain professions, most notably doctors of medicine (MDs). It has been suggested that there is something about practicing medicine which causes doctors to develop MS, e.g. exposure to anaesthetic gases, (http://www.thenakedscientists.com/forum/index.php?topic=62.0).

I have an alternative hypothesis. I suggest that being a MD does not predispose a person to develop MS, but that the converse is true: having MS predisposes an individual to become a doctor of medicine.

This converse theory is not as absurd as it first appears. People have symptoms of MS many years, sometimes decades, before they are diagnosed with it. So true onset of MS can be in childhood/adolescence, (although diagnosis will be many years later). The demyelination of MS can cause hyperreflexia which can include emotional incontinence. Whilst full emotional incontinence is associated with the latter stages of MS, I suggest that a milder version of this emotional hyperreflexia could exist at the earliest stages of the disease, during childhood/adolescence.

This hypersensitivity would cause people with this condition to overreact to emotional stimuli, e.g. emotions, (including empathy), would be more readily evoked. Children/adolescents affected would be more sensitive to the emotional pressure from parents & peers to achieve academically, and consequently would be exceptionally diligent students.

So amongst people who have MS when children/adolescents, (although not diagnosed until many years later), this emotional hypersensitivity will create a disproportionately high number of academic high-achievers who are abnormally sensitive to the suffering of others, (hyper-empathic). Such individuals are predisposed to become doctors of medicine.

My MS =>MD theory is supported by the fact that there is a higher than normal incidence of MS in other empathic professions such as nurses & police, in academics generally and amongst high-achievers in the arts and industry (entrepreneurs).

The idea that certain neurological disorders can predispose individuals to enter certain professions is not original, e.g. aspergic mathematicians & bipolar artists.  However I have never heard it suggested as a possible explanation for the high incidence of MS in MDs.
« Last Edit: 06/11/2006 15:42:40 by ROBERT »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Hi Robert,
I couldn't find confirmed evidence (transl.= more data) about MS in docs.
Surely these days only few of them are exposed to anesthetic gases.
They often work too much and tan too little...not to mention cod liver oil abstinence (I'm joking).
Find recent epidemiol. abstract you may have missed.
Ciao,

ikod

quote:

Epidemiology and natural history of multiple sclerosis: new insights.
Kantarci O, Wingerchuk D.
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.

PURPOSE OF REVIEW: The cause of multiple sclerosis remains elusive. We review recent epidemiological studies of genetic and environmental factors that influence susceptibility to the disease and its clinical course. RECENT FINDINGS: Genetic advances strengthen the association of multiple sclerosis with the human leukocyte antigen (HLA)-DRB1 allele and interferon-gamma polymorphisms and suggest that apolipoprotein E alleles play an important role. In the environmental realm, nested case-control studies show that prior Epstein-Barr virus exposure is overrepresented in multiple sclerosis. Smoking has been associated with both risk of multiple sclerosis and progressive disease. Vitamin D deficiency might tie together environmental clues with higher multiple sclerosis prevalence rates; dietary vitamin supplementation is also associated with reduced multiple sclerosis risk. Natural history studies demonstrated dissociation between relapses and disease progression, facilitated the ability to distinguish neuromyelitis optica and related syndromes from typical multiple sclerosis, and spawned the exploration of large datasets to model long-term disease activity. SUMMARY: Our understanding of the contributions of specific genetic and environmental factors that contribute to multiple sclerosis has improved. Further refinements will eventually allow powerful longitudinal studies to assess genetic and environmental interactions with implications for prediction of individual disease susceptibility, clinical course, and response to therapy.

Curr Opin Neurol. 2006 Jun;19(3):248-54.


*

ROBERT

  • Guest
Thanks Iko,
I suspected you would crowbar in a reference to the panacea of cod liver oil  [:)] .
More stats on the occupational associations of MS would be of interest.

I forgot to specifically mention school teachers as another group disproportionally affected by MS:
(they are academic and empathic):-

" Excess autoimmune disease mortality among school teachers "
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11469459&dopt=Citation
« Last Edit: 02/11/2006 16:35:19 by ROBERT »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
...and other recents bits may help...epidemiological studies.
There are many studies about vitamin D3 and prevention of immunoallergic encephalitis in mice, a widely accepted experimental model for MS.


Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis.
van der Mei IA, Blizzard L, Ponsonby AL, Dwyer T.

BACKGROUND: Measurement of past sun exposure through recall by adults has the potential for measurement error. We aimed to investigate aspects of validity and reliability of self-reported past sun exposure. METHODS: A population-based case-control study was conducted in Tasmania on 136 cases with multiple sclerosis and 272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52 controls were done on average 11 weeks after the initial interview. Sun exposure was assessed by questionnaire and lifetime calendar. Other measurements included serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. RESULTS: There was an association between recent sun exposure and serum vitamin D (time in the sun: r = 0.22, P < 0.01; activities outside: r = 0.31, P < 0.01 for controls) and between lifetime sun exposure and actinic damage [correlation between 0.34 (P < 0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted kappa statistic of self-reported sun exposure ranged from 0.43 to 0.74. Recall of childhood/adolescent sun exposure by standardized questioning was no less reproducible than recall of recent adult sun exposure and no less reliable when made with the calendar method. Comparing the questionnaire and calendar method, the measures of childhood/adolescent sun exposure had a similar predictive validity for multiple sclerosis. CONCLUSIONS: The results of this study provide further evidence that adults are able to recall past sun exposure with shown validity and reliability and present information about the possible reasons for the good reliability of recalled sun exposure measures.

Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1538-44.



*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Thanks Iko,
I suspected you would crowbar in a reference to the panacea of cod liver oil  [:)] .
More stats on the occupational associations of MS would be of interest.

There are epidemiological studies about increased incidence of childhood leukemia in families where one of the parents works in hospitals (doctors, nurses), but I'm much more interested in the effects of 1year of clo on the immune system: it's more practical and direct.  Time is money!
Cheers,

ikod

P.S. : Epidemiology helps a lot, but sometime makes you go around in circles (I don't know how you say that).
I remember when AIDS cause was still unknown, in the beginning of the '80s.
It was a very well known viral disease in monkeys and had exactly the same distribution observed in patients with HBV hepatitis (i.v. drug addicts, transfused pts, hemophiliacs). No need to epidemiologize around...just go and spot the nasty bug!
Unfortunately no virus had been found, so a viral etiology had been discarded.
Today I would say: infectious theories were a bit neglected...
Prestigious journals published 'evidences' suggesting different causes for such an immunological devastation: drug addicts were sniffing glues and blocking monocyte function, hemophiliacs had a block due to foreign proteins infused with Factor VIII and IX, transfused patients were confused by donors' leukocytes and so on.
It was not so difficult...we should have searched more in the same direction!
But for many it would have been a total waste of time and efforts.
Robert Gallo and Luc Montagnier had the guts, the authority and character to perseverate in AIDS viral research.
They had enough brains and experience to know that it had to be a viral disease.
« Last Edit: 04/11/2006 17:08:17 by iko »

*

ROBERT

  • Guest
" [PDF] anaesthetists: a register based study The risk for multiple ...File Format: PDF/Adobe Acrobat
3 Detels R. Case control studies of multiple sclerosis. Neuroepidemiology. 1982;1:117. 4 Riise T, Wolfson C. The epidemiologic study of exogenous factors in ...
oem.bmjjournals.com/cgi/reprint/63/6/387.pdf - Similar pages "

Radiologists:-
" Some studies also associate multiple sclerosis with radiological work "
http://www.ilo.org/encyclopaedia/?print&nd=857400162
« Last Edit: 02/11/2006 18:38:51 by ROBERT »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Thank you Robert,
I read the abstract about nurses anaesthetists (and teachers!) and I see your point.
So I have one question ready for you: why should a volatile solvent be the cause?
If I support an overidden immune reaction to a persistent infectious pathogen, I know for sure that anaesthetists work for long hours (sometime most of the day) really close to their patients' breaths and all the air circulating in and out through mechanical ventilators.  Even more than surgeons they have a very close 'contact' with their patients...and their viruses and 'opportunistic' bacteria.
Few other healthcare professionals are so close to patients in crucial situations when the available self-protection devices are never enough safe.
Many critical patients carry hyperselected and antibiotic resistant germs that normal people will never encounter in all their lives!
Sorry Robert, but cod liver oil intoxication leads me to think 'out of the box' most of the time.

ikod
« Last Edit: 03/11/2006 23:40:43 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
New idea from ikod, who has never been an MS expert in his life, just an affectionate reader:

...Prior to the AIDS epidemic, Robert Gallo was the first to identify a human retrovirus and the only known human leukemia virus - HTLV - one of few known viruses shown to cause a human cancer. In 1976, he and his colleagues discovered Interleukin-2, which is a growth regulating substance now used as therapy in some cancers and sometimes AIDS. And in 1986, he and his group discovered the first new human herpes virus in more than 25 years (HHV-6), which was later shown to cause an infantile disease known as Roseola and currently is hypothesized as a strong suspect in the origin of multiple sclerosis.

from a short biography, type 1 page 1 life: http://www.ihv.org/bios/gallo.html


20yrs have past...   
« Last Edit: 02/11/2006 22:15:09 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
quote:

...The idea that certain neurological disorders can predispose individuals to enter certain professions is not original, e.g. aspergic mathematicians & bipolar artists.  However I have never heard it suggested as a possible explanation for the high incidence of MS in MDs.


...so poor starving people are depressed and develop silicosis from that...
(not to mention they spent most of their life in a coal mine...)
We surely must find the REAL cause of something.
Even if we are able to cure it 100percent!
Ciao Roberto! (my BIGboy is named like you)

ikod
 
« Last Edit: 02/11/2006 22:27:50 by iko »

*

another_someone

  • Guest
I would suggest that one thing that doctors and teachers have in common is that both groups are exposed to a large number of members of the public, and are thus more likely to become infected with a wide range of infectious illnesses.

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile

I have an alternative hypothesis. I suggest that being a MD does not predispose a person to develop MS, but that the converse is true: having MS predisposes an individual to become a doctor of medicine.
...
So amongst people who have MS when children/adolescents, (although not diagnosed until many years later), this emotional hypersensitivity will create a disproportionately high number of academic high-achievers who are abnormally sensitive to the suffering of others, (hyper-empathic). Such individuals are predisposed to become doctors of medicine.
When I was a student, statistics showed that prestige and money moved more than 60% of the University students to choose the Medical School.  Things might have changed.
Hyper-empathic attitudes do not help much in the clinical practice. 

Dr. Gregory House
« Last Edit: 19/01/2007 23:19:47 by iko »

*

Offline daveshorts

  • Moderator
  • Neilep Level Member
  • *****
  • 2582
  • Physics, Experiments
    • View Profile
    • http://www.chaosscience.org.uk
I have noticed that a lot of the medical students I know either have an interesting medical condition or are closely related to someone who has/had one. If MS is at all inherited this could be causing it...

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
I have noticed that a lot of the medical students I know either have an interesting medical condition or are closely related to someone who has/had one. If MS is at all inherited this could be causing it...
daveshorts

Medical students are more interested and involved in studying various diseases and might pay much more attention to specific ailments affecting their relatives (at the 3rd, 4th degree...) or even their friends.  They might maximize their medical problems too, instead of keeping them private like most people do. It would be really tricky to search for something statistically sound.

from Childhood Leukemia topic:

...Studying homozygous twins lives from the cradle to the end of life we get lots of data about gene & environment interactions: if a certain disease is due to an inherited genetic defect, the incidence in twins will be much higher than in the general population. If the cause is mostly environmental, the incidence in twins will be similar to the control population.

As far as I could read, the incidence of MS in identical twins has not been reported much higher than the rest of the poeple, suggesting that multiple environmental factors are probably responsible for this chronic neurological disease.
MS could be quite similar to an autoimmune disease, as widely reported in the literature.

...one out of many (and more recent) papers:
Multiple sclerosis and Hashimoto's thyroiditis
...The association of multiple sclerosis with other autoimmune diseases is infrequent but supports the immune hypothesis of the pathogenesis of multiple sclerosis.
from: Roquer J. et al.  J. Neurol. 234(1):23-24;1987.

ikod
http://www.abc.net.au/science/news/stories/s1024783.htm
Hooops!...sorry,ok, ok, I won't do it again...
« Last Edit: 05/11/2006 11:45:46 by iko »

*

another_someone

  • Guest
I have noticed that a lot of the medical students I know either have an interesting medical condition or are closely related to someone who has/had one. If MS is at all inherited this could be causing it...

I have certainly noticed this tendency in psychiatrists.


Then again, could we not argue that most people probably are related to someone who has an interesting medical condition - but medical students may simply talk about it more.  I think it goes without saying that we are all related to someone who died.

*

ROBERT

  • Guest
I would suggest that one thing that doctors and teachers have in common is that both groups are exposed to a large number of members of the public, and are thus more likely to become infected with a wide range of infectious illnesses.

The excess human contact theory would not explain those whose whose MS was diagnosed whilst they were in training to become doctors/nurses/police/teacher, (my hyper-empathic theory would explain it):-

Kim Bowerman was in the middle of a series of exams for the Indiana Law Enforcement Academy in March, 1990. She was twenty-five years old and planned to join the South Bend, Indiana police force.
"Suddenly, I was incredibly dizzy every time I stood up," Ms. Bowerman remembers. "I lost about twenty pounds because I couldn't keep any food down. The right side of my body seemed to be numb. I was sent to a neurologist. He said I either had a brain tumor or multiple sclerosis. I prayed for MS
http://www.findarticles.com/p/articles/mi_m0850/is_n2_v11/ai_14276055

Aren't shopworkers (e.g. the people in Mc Donalds), exposed to a greater number of humans than teachers/doctors/nurses ?
« Last Edit: 06/11/2006 14:12:38 by ROBERT »

*

ROBERT

  • Guest
Thank you Robert,
I read the abstract about nurses anaesthetists (and teachers!) and I see your point.
So I have one question ready for you: why should a volatile solvent be the cause?
If I support an overidden immune reaction to a persistent infectious pathogen, I know for sure that anaesthetists work for long hours (sometime most of the day) really close to their patients' breaths and all the air circulating in and out through mechanical ventilators.  Even more than surgeons they have a very close 'contact' with their patients...and their viruses and 'opportunistic' bacteria.
Few other healthcare professionals are so close to patients in crucial situations when the available self-protection devices are never enough safe.
Many critical patients carry hyperselected and antibiotic resistant germs that normal people will never encounter in all their lives!
Sorry Robert, but cod liver oil intoxication leads me to think 'out of the box' most of the time.

ikod

Iko, I am not suggesting that anesthetics cause MS, nor any other medical practice, such as exposure to infected patients. My theory is that MS predisposes people to become doctors, nurses, teachers & police officers, by causing them to become hyper-empathic as children-adolescents.
« Last Edit: 06/11/2006 14:10:45 by ROBERT »

*

ROBERT

  • Guest
"Further information about disabilities experienced by medical students and
doctors comes from a survey of deans of medical schools, postgraduate deans,
associate postgraduate deans and regional advisors in general practice carried out by
a working party convened by the BritishMedical Association (BMA) (British Medical
Association, 1997). A long list of physical diseases was collated. The conditions
reported most frequently were
paraplegia, hearing impairment, multiple sclerosis,
visual impairment, hemiplegia and epilepsy. More than half of the respondents had
their condition prior to, or developed the condition during, training at medical
school....
Multiple sclerosis is relatively common, usually beginning in the early years of
working life. In any deanery or NHS region it is likely that there will be several
junior doctors and two or three career grade doctors, either in hospital practice or
in general practice, with the condition. Its nature is variable. Relapses may occur
intermittently, causing periods of temporary unfitness followed by long periods of
fitness to practise. Other cases progress more steadily.."

www.radcliffe-oxford.com/books/samplechapter/7661/01_maintext_Cox.pdf


Note: Paraplegia, hemiplegia, seizures, deafness and visual impairment, are all symptoms of MS.
« Last Edit: 06/11/2006 17:17:40 by ROBERT »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Hi Robert,
I stay with the infectious hypothesis and an overidden immune response to a common pathogen.  This is the same hypothesis to explain autoimmune diseases.
There is no congenital predisposition (omozygous twins).
Of course we may find predisposing factors like hormones, sex, enzyme defects; but the main role is probably played by environmental factors like infections, stress, diet, toxics and...sunshine.
MS doesn't strike in a restricted area of the central nervous system, but here and there in the myelin-rich white matter.
Hypothesizing a predisposed brain with peculiar differences in very specific areas of the brain (and not spinal cord) that would condition such a particular behaviour (amygdala, frontal cortex?) BEFORE the onset of a disease like MS is...quite difficult in this setting.
As in the leukemia issue the point could be: why don't we reccomend vitamin D for these patients?
Even if the disease is already present, wouldn't a protective effect (demonstrated in normal people) give positive results over the years in these patients? We should go for this, the lot of us!
Don't you think?

ikod

I'm quite sure that shop keepers do not meet the bulk of nasty bugs that nurses and doctors deal with every day.
« Last Edit: 06/11/2006 19:19:28 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
There is not much in PubMed about MS and VitD3.
It might be another neglected area of investigation.
Have got nothing to loose? Let's go for it then!

Vitamin D and multiple sclerosis.
Hayes CE, Cantorna MT, DeLuca HF.
Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
Proc Soc Exp Biol Med. 1997 Oct;216(1):21-7.

Recently, it has been clearly demonstrated that exogenous 1,25-dihydroxyvitamin D3, the hormonal form of vitamin D3, can completely prevent experimental autoimmune encephalomyelitis (EAE), a widely accepted mouse model of human multiple sclerosis (MS). This finding has focused attention on the possible relationship of this disease to vitamin D. Although genetic traits certainly contribute to MS susceptibility, an environmental factor is also clearly involved. It is our hypothesis that one crucial environmental factor is the degree of sunlight exposure catalyzing the production of vitamin D3 in skin, and, further, that the hormonal form of vitamin D3 is a selective immune system regulator inhibiting this autoimmune disease. Thus, under low-sunlight conditions, insufficient vitamin D3 is produced, limiting production of 1,25-dihydroxyvitamin D3, providing a risk for MS. Although the evidence that vitamin D3 is a protective environmental factor against MS is circumstantial, it is compelling. This theory can explain the striking geographic distribution of MS, which is nearly zero in equatorial regions and increases dramatically with latitude in both hemispheres. It can also explain two peculiar geographic anomalies, one in Switzerland with high MS rates at low altitudes and low MS rates at high altitudes, and one in Norway with a high MS prevalence inland and a lower MS prevalence along the coast. Ultraviolet (UV) light intensity is higher at high altitudes, resulting in a greater vitamin D3 synthetic rate, thereby accounting for low MS rates at higher altitudes. On the Norwegian coast, fish is consumed at high rates and fish oils are rich in vitamin D3. Further, experimental work on EAE provides strong support for the importance of vitamin D3 in reducing the risk and susceptibility for MS. If this hypothesis is correct, then 1,25-dihydroxyvitamin D3 or its analogs may have great therapeutic potential in patients with MS. More importantly, current research together with data from migration studies opens the possibility that MS may be preventable in genetically susceptible individuals with early intervention strategies that provide adequate levels of hormonally active 1,25-dihydroxyvitamin D3 or its analogs.

...and so almost 10yrs have past (why medical progress is so slow?...it could be a new topic!)
« Last Edit: 06/11/2006 19:58:16 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
I forgot to insist on this point:

Iko, I am not suggesting that anesthetics cause MS, nor any other medical practice, such as exposure to infected patients. My theory is that MS predisposes people to become doctors, nurses, teachers & police officers, by causing them to become hyper-empathic as children-adolescents

...I ignore how many nurses, doctors or medical students you have met so far.
I spent my last 33yrs in this battlefield and didn't find all this hyper-empathism you mentioned.
You actually tend to protect your soul and become really tough over the years.

iko     
« Last Edit: 06/11/2006 22:41:08 by iko »

*

ROBERT

  • Guest
Hi Robert,
Hypothesizing a predisposed brain with peculiar differences in very specific areas of the brain (and not spinal cord) that would condition such a particular behaviour
(amygdala, frontal cortex?) BEFORE the onset of a disease like MS is...quite difficult in this setting.

ikod

Emotional Incontinence, a.k.a. Emotional Lability is common in MS.
" Emotional symptoms are common and can be the normal response to having a debilitating disease or the result of damage to the nerves that generate and control emotions."
http://en.wikipedia.org/wiki/Multiple_sclerosis
http://en.wikipedia.org/wiki/Labile_affect

My suggestion was that the true onset of MS was many years, even decades, before diagnosis, and a lesser form of this emotional lability could exist at this early stage, (in childhood / adolescence).

I forgot to insist on this point:
...I ignore how many nurses, doctors or medical students you have met so far.
I spent my last 33yrs in this battlefield and didn't find all this hyper-empathism you mentioned.
You actually tend to protect your soul and become really tough over the years.

iko     

I am not suggesting all doctors hyper-empathic, IIRC the incidence of MS in MDs is quadruple the normal incidence, so we are discussing something which affects approx 0.5% of MDs.
« Last Edit: 07/11/2006 15:32:25 by ROBERT »

*

another_someone

  • Guest
Ofcourse, if sunlight is a factor mitigating against MS, then the population wide average, which includes sub-populations that do outdoor work, would be different from selecting sub-populations of people who work long hours away from sunlight.  Those with a propensity for careers that require extensive university training may already be spanning long hours indoors reading books long before they get to graduating as doctors.

*

another_someone

  • Guest
Medical students are more interested and involved in studying various diseases and might pay much more attention to specific ailments affecting their relatives (at the 3rd, 4th degree...) or even their friends.  They might maximize their medical problems too, instead of keeping them private like most people do. It would be really tricky to search for something statistically sound.

This would inevitably be true is early stage desease, but would probably have less of an impact on late state desease.  The question has to be whether there are any statistics about the probability of debilitating MS (ignoring the early stage desease) that would be likely to be diagnosed no matter who the patient was.

As far as I could read, the incidence of MS in identical twins has not been reported much higher than the rest of the poeple, suggesting that multiple environmental factors are probably responsible for this chronic neurological disease.

http://en.wikipedia.org/wiki/Multiple_sclerosis
Quote
In the population at large, the chance of developing MS is less than a tenth of one percent. However, if one person in a family has MS, that person's first-degree relatives—parents, children, and siblings—have a one to three percent chance of getting the disease.

For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30%; for fraternal twins (who do not inherit identical gene pools), the likelihood is closer to that for non-twin siblings, or about 4%. The fact that the rate for identical twins both developing MS is significantly less than 100% suggests that the disease is not entirely genetically controlled. Some (but definitely not all) of this effect may be due to shared exposure to something in the environment, or to the fact that some people with MS lesions remain essentially asymptomatic throughout their lives.

Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS. Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system.

The HLA patterns of MS patients tend to be different from those of people without the disease. Investigations in northern Europe and America have detected three HLAs that are more prevalent in people with MS than in the general population. Studies of American MS patients have shown that people with MS also tend to exhibit these HLAs in combination-that is, they have more than one of the three HLAs-more frequently than the rest of the population. Furthermore, there is evidence that different combinations of the HLAs may correspond to variations in disease severity and progression.

Studies of families with multiple cases of MS and research comparing genetic regions of humans to those of mice with EAE suggest that another area related to MS susceptibility may be located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11, 17, 19, and X have also been identified as possibly containing genes involved in the development of MS.

These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene's interactions with other genes and with the environment make an individual susceptible to MS.

*

ROBERT

  • Guest
I have noticed that a lot of the medical students I know either have an interesting medical condition or are closely related to someone who has/had one. If MS is at all inherited this could be causing it...

I have certainly noticed this tendency in psychiatrists.


MS sufferers include psychiatrists:-

" Alexander (Sandy) Burnfield
Date of Birth: 5th December 1944
Year of Diagnosis: 1969
Occupation: Consultant in Child and Family Psychiatry
Country of Residence: UK
Type of MS: Secondary Progressive (currently stable)
Sex: Male

I first realised I might have MS when I was a 20 year old medical student in 1965. Although there wasn’t a definite diagnosis at the time, the first symptom - blurred vision in my left eye - was indicative of MS. Then there was little information available and MS wasn’t talked about. I therefore discovered the implications of my condition by studying textbooks in the medical school library. It was a big shock. "
http://www.msif.org/en/people_with_ms/people_profiles/profile_of_the.html
« Last Edit: 07/11/2006 16:32:33 by ROBERT »

*

another_someone

  • Guest
I have noticed that a lot of the medical students I know either have an interesting medical condition or are closely related to someone who has/had one. If MS is at all inherited this could be causing it...

I have certainly noticed this tendency in psychiatrists.


MS sufferers include psychiatrists:-

Sorry, I think you misunderstood me (my fault, I was too ambiguous) - what I meant is that I find many psychiatrists have psychiatric problems, and this may well have been a factor that lead them into psychiatry (although whether this is in the patenits best interest is another matter).

*

another_someone

  • Guest
http://www.mult-sclerosis.org/HumanHerpesVirus6.html
Quote
Human Herpes Virus 6 (HHV-6) is a very common virus which infects most children by the time they are 2 years of age. HHV-6 causes roseola with associated fever and skin rash in about 30% of babies. It rarely causes significant immediate problems and is almost never fatal. It is a very infectious agent, which is probably transmitted through saliva.

HHV-6 was discovered in 1986. It is a member of the herpes family of viruses, a group which also includes Herpes Simplex Virus-1 and -2, which cause cold sores, Epstein-Barr virus, which causes infectious mononucleosis, and Varicella-Zoster Virus, which causes chicken pox.

Human Herpes Virus 6 is of interest to multiple sclerosis (MS) because several studies have found indicators of the virus to be significantly higher in people with MS (PwMS) than in control subjects. This link is controversial - some commentators allege that HHV-6 is the cause of the disease, others that it is merely an opportunist invader, while still others discount its role altogether.

People with multiple sclerosis have been found to have higher levels of anti-HHV-6 antibodies than control subjects [Caselli et al, 2002 and Soldan et al, 1997], more HHV-6 DNA in blood serum [Álvarez-Lafuente et al, 2002, Tejada-Simon et al, 2002 and Tomsone et al, 2001] and evidence of active HHV-6 infection more often [Chapenko et al, 2003 and Álvarez-Lafuente et al, 2002]. None of these studies found these HHV-6 markers in all the subjects with MS and all the markers were found in some of the control subjects.

Another study found higher levels of HHV-6 DNA from PwMS during relapses than those who were in remission [Berti et al, 2002], although another study was unable to detect a difference [Alvarez-Lafuente et al, 2002].

A study of people with multiple sclerosis in Kuwait failed to find evidence of HHV-6 DNA in the blood of a small sample of people with MS [Al-Shammari et al, 2003].

Attempts to find active HHV-6 in cerebrospinal fluid (CSF) or other CNS tissue have been mixed. Some studies have been successful [Goodman et al, 2003, Cermelli et al, 2003, Tejada-Simon et al, 2002 and Knox et al, 2000] but others have failed to replicate these findings [Rodriguez Carnero et al, 2002 and Gutiérrez et al, 2002].

One way that HHV-6 might be involved is through a mechanism called molecular mimicry. It is proposed that a small section of one of the HHV-6 proteins resembles a small section of one of the proteins in myelin - the insulating substance around brain cells that is damaged in multiple sclerosis. This resemblance means that our immune systems are unable to differentiate between the two and mistakenly attack the myelin as well as the virus. One study has identified a candidate section in one myelin protein, called Myelin Basic Protein (MBP), and showed it to be activated by an HHV-6 protein in people with MS [Tejada-Simon et al, 2003]. However, another laboratory failed to show any increased ability of HHV-6 to activate MBP-reactive T cells in PwMS [Cirone et al, 2002].

It has also been suggested that protein produced by HHV-6 attracts certain immune system cells (macrophages and monocytes) [Luttichau et al, 2003]. Perhaps it does this so that it can infect them but these researchers suggest that this function is also involved in the multiple sclerosis disease process.

Another way HHV-6 might be involved in MS is via a cell surface protein, called membrane cofactor protein (CD46). CD46 is responsible for regulating a branch of the immune system, called complement, and preventing complement activation on the bodies own cells. However, CD46 has also been identified as the cellular receptor for HHV-6 [Santoro et al, 1999]. Elevated levels of soluble CD46 have been found in both the blood and the cerebrospinal fluid of people with MS [Soldan et al, 2001].

http://www.ninds.nih.gov/news_and_events/press_releases/pressrelease_herpes_virus_strain_112497.htm
Quote
A strain of reactivated herpes virus may be associated with multiple sclerosis (MS), an autoimmune disorder in which the body attacks its own tissues. Results of a study conducted by scientists at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland, add to mounting evidence of the role of viral triggers in MS and may serve as the cornerstone for clinical trials using antiherpetic agents as a treatment. This is the first published large-scale study suggesting an association of a human herpes virus in the disease process of MS.

In the study, more than 70 percent of patients with the relapsing-remitting form of MS showed an increased immune response to human herpes virus-6 (HHV-6) and approximately 35 percent of all MS patients studied had detectable levels of active HHV-6 in their serum. Scientists believe that there may be a point in time during the progression of MS when the virus, which lies dormant in the body for years, reactivates, accounting for its presence in a subset of MS patients. The study appears in the December 1997 issue of Nature Medicine.

"We expect that currently available antiviral treatments - for example, acyclovir - might one day be applied successfully to MS," said Steven Jacobson, Ph.D., Chief of the NINDS Viral Immunology Section and the study's principal investigator. "We've suspected a possible role for a virus in MS for quite some time, and these results certainly point to this particular virus. But we need to know more before we move to the clinical trial stage."

As many as 350,000 Americans are affected by MS, which is most often diagnosed in patients between the ages of 20 and 40 and is characterized by muscle weakness, visual disturbances, and a variety of other neurological impairments. The array and severity of symptoms varies widely from patient to patient and women are more likely to be affected than men. The most common form of MS is the relapsing-remitting type. In this type of MS, new symptoms appear or existing ones become more severe, followed by periods of partial or total recovery. These flare-ups of new or intensified symptoms last for variable amounts of time. A second form of MS is a chronic and progressive one in which symptoms steadily worsen. Either form can lead to disability and paralysis.

"We've thought for a long time that genetics, an autoimmune factor, or something in the environment - like a virus - might cause MS," says Dr. Jacobson. "One can certainly make the case for a combination of these factors, namely that a small group of individuals may be genetically susceptible to a virus. If the HHV-6 virus is really behind MS, then we also need to know why infection with such a common virus causes disease in so few people."

HHV-6 is relatively new to scientists and is known to cause a common childhood illness, roseola. HHV-6 is known to be present in 90 percent of the adult American population as a result of infection during the first few years of life.

Scientists believe that the reactivation of HHV-6 virus may be associated with the breakdown of the protective covering of nerves, called myelin. Reactivation is characteristic of herpes viruses.

In the study, investigators screened the serum of 102 individuals, 36 of whom had MS. Of the 22 individuals with the relapsing-remitting form of MS, 73 percent had an increase in immune response to an early antigen of HHV-6, compared to only 18 percent of those participants who served as normal volunteers. In addition, the scientists detected HHV-6 DNA in the serum (a marker of active virus infection) of 15 of 50 individuals with MS. All 47 individuals without MS tested negative for the presence of active HHV-6 viral infection.

Additional testing for the presence of HHV-6 virus in larger numbers of MS patients - and in patients with other autoimmune disorders - is under way.

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
...Someone liked another different hypothesis cited by iko!
Welcome HHV-6: they are used to mess humans up, they enjoy it.
I got wrong data from a goophy PubMed search about twins...sorry.
Wikipedia seems to do better.
Regards,   
ikod
« Last Edit: 22/07/2007 08:45:31 by iko »

*

ROBERT

  • Guest
I'm not disputing that a viral trigger may be the cause of MS in genetically susceptible people.
If it is the Herpes (cold sore) virus that triggers MS, then that would be consistent with my theory as most people have been infected with this virus as children/adolescents, so the true onset of MS would be in childhood/adolescence as I have suggested.

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
A quick note about MS trying to resuscitate the hypotonic topic...

Are multiple sclerosis patients risk-takers?


Hawkes CH.
Essex Neuroscience Centre, Oldchurch Hospital, Romford, UK. chrishawkes@msn.com

Several factors appear to be associated with multiple sclerosis (MS), and each has a postulated immune or environmental explanation, but a common theme is lacking. This article suggests that a unifying premise could be risk-associated behaviour. Evidence is reviewed for associations with smoking, alcohol, recreational drug use, oral contraception, cholesterol intake, risk attitude and behaviour, ultraviolet light and vitamin D exposure, frequency of MS in healthy societies, and viral infection. The evidence associated with smoking, not taking vitamin D supplements and Epstein-Barr viral infection appears good. There may be a pattern of risk-associated behaviour that characterizes patients with MS and brings them into contact with one or more causative agents. Of the possible agents, viral infection seems the most likely.

QJM. 2005 Dec;98(12):895-911.



« Last Edit: 17/12/2006 17:20:56 by iko »

*

ROBERT

  • Guest
Hi Iko,
The risky behaviour you quote from Chris Hawkes could be an effect of having MS , rather than contributing to its causation.   (Do remember that people have MS many years before they are diagnosed with it, this can lead to effects being mistaken for causes).

My Hyper-emotional theory could cause individuals to behave in “risky” ways, e.g. hypersexuality.
I recall in the case of cellist Jacqueline du Pre, (another high-achiever who had MS), that she had an affair with her sister’s husband  [:0].

Here is another case where MS caused hypersexual behaviour and other "risky" impulsive behaviour :-
http://www.nature.com/ijir/journal/v16/n4/full/3901201a.html

(This MS sufferer was a primary school teacher).
« Last Edit: 18/12/2006 17:41:08 by ROBERT »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Possible explanation for the higher incidence of MS in Doctors
« Reply #30 on: 25/06/2007 11:14:16 »
Medical students studied too much
hiding from the sunlight for years,
rejecting cod liver oil use as a
foolish relic from the past, just
quackery.

Maybe  [;D]


http://www.andrewswihart.net/pictures/evildocfullbody300.png

Crossing MS and vitamin D on PubMed Database
you find plenty of studies and experimental
data suggesting a positive effect in such a
chronic, long-lasting and highly debilitating
disease like multiple sclerosis.
Strangely enough, I could not find any clinical
study with vitamin D3 GIVEN to the patients...
I might have missed some report or trial, maybe.
It would not cost much, compared with all the
various expensive new drugs being tested on MS!
We seem to be quite late, approximately 2-3
decades behind with this.


A longitudinal study of serum 25-hydroxyvitamin D and intact PTH levels
indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis.

Soilu-Hanninen M, Laaksonen M, Laitinen I, Eralinna JP, Lilius EM, Mononen I.
University of Turku, Finland.

BACKGROUND: Past sun exposure and vitamin D3 supplementation have been associated with a reduced risk of multiple sclerosis (MS). There are no previous longitudinal studies of vitamin D in MS.
OBJECTIVES: To compare regulation of vitamin D and calcium homeostasis between MS patients and healthy controls. To study correlation of parameters of vitamin D metabolism with MS activity.
METHODS: We measured 25-hydroxyvitamin D, intact PTH, calcium, phosphate, magnesium, chloride, alkaline phosphatase, albumin and TSH in serum every three months and at the time of relapses during one year in 23 MS patients and in 23 healthy controls. MRI BOD and T2 activity was assessed every 6 months.
RESULTS: Vitamin D deficiency [S-25(OH)D </= 37 nmol/L] was common affecting half of the patients and controls at some time of the year. Seasonal variation of 25(OH)D was similar in the patients and in the controls, but the 25(OH)D serum levels were lower and the iPTH serum levels were higher during MS relapses than in remission.
All 21 relapses during the study occurred at serum iPTH > 20 ng/L (2.2 pmol/L)
, whereas 38% of patients in remission had iPTH </= 20 ng/L. MS patients had a relative hypocalcaemia and a blunted PTH response in the winter. There was no correlation between serum 25(OH)D and MRI parameters.
CONCLUSIONS: The endocrine circuitry regulating serum calcium may be altered in MS. There is an inverse relationship between serum vitamin D level and MS clinical activity. The role of vitamin D in MS must be explored further.

J Neurol Neurosurg Psychiatry. 2007 Jun 19; [Epub ahead of print]



Maybe something is actually 'moving' !

http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=96

« Last Edit: 21/07/2007 14:11:07 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Possible explanation for the higher incidence of MS in Doctors
« Reply #31 on: 21/07/2007 14:02:06 »
The "Vitamin D Tsunami" is definitely coming,
spinning out of the restricted scientific circuit.
Finally prof. Michael Holick is in the New England
Journal of Medicine...
and -as usual- lay press will follow pretty soon!



"...rickets can be considered the tip of the vitamin D-deficiency iceberg.  In fact, vitamin D deficiency remains common in children and adults."

Michael F. Holick "Vitamin D Deficiency" N Eng J Med 2007;357:266-81.

July 19, 2007 splendid review article in 'Medical Progress'
Unfortunately this one is not available in free full-text...you may go to last year paper published in J Clin Invest for similar refreshing good news:





As far as this topic is concerned, multiple sclerosis is obviously mentioned, and four references cited:

"...Among white men and women, the risk of multiple sclerosis decreased by 41% for every increase of 20 ng per milliliter in 25-hydroxyvitamin D above approximately 24 ng per milliliter (60 nmol per liter) (odds ratio, 0.59; 95%CI, o.36 to 0.97; P=0.04).   Women who ingested more than 400 IU of vitamin D per day had a reduced risk of developing multiple sclerosis."







Ultraviolet radiation and autoimmune disease: insights from epidemiological research.

Ponsonby AL, McMichael A, van der Mei I.

National Centre for Epidemiology and Population Health, The Australian National University, Canberra ACT 0200, Australia. anne-louise.ponsonby@anu.edu.au

This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the individual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed.

Toxicology. 2002 Dec 27;181-182:71-8.



Multiple sclerosis and vitamin D: an update.

VanAmerongen BM, Dijkstra CD, Lips P, Polman CH.
Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands. b.m.van.amerongen@inter.nl.net

MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood.
The prevalence of MS is highest where environmental supplies of vitamin D are lowest.
It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)(2)D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1 alpha-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH)(2)D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH)(2)D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH)(2)D is thought to be operating on CNS constituent cells as well. Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D(3) intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.

Eur J Clin Nutr. 2004 Aug;58(8):1095-109.



Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A.
Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA.

CONTEXT: Epidemiological and experimental evidence suggests that high levels of vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis. There are no prospective studies addressing this hypothesis. OBJECTIVE: To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-control study among more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial multiple sclerosis symptoms. MAIN OUTCOME MEASURES: Odds ratios of multiple sclerosis associated with continuous or categorical levels (quantiles or a priori-defined categories) of serum 25-hydroxyvitamin D within each racial/ethnic group. RESULTS: Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found.

CONCLUSION: The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.

JAMA. 2006 Dec 20;296(23):2832-8.



Vitamin D intake and incidence of multiple sclerosis.

Munger KL, Zhang SM, O'Reilly E, Hernán MA, Olek MJ, Willett WC, Ascherio A.
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA. kgorham@hsph.harvard.edu

BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis.
METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed.
RESULTS: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of >or=400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend = 0.006). No association was found between vitamin D from food and MS incidence.
CONCLUSION: These results support a protective effect of vitamin D intake on risk of developing MS.

Neurology. 2004 Jan 13;62(1):60-5.




« Last Edit: 21/07/2007 14:17:55 by iko »

*

Offline iko

  • Neilep Level Member
  • ******
  • 1625
    • View Profile
Possible explanation for the higher incidence of MS in Doctors
« Reply #32 on: 30/07/2007 21:58:05 »


Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins.


Islam T, Gauderman WJ, Cozen W, Mack TM.Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

OBJECTIVE: To address the role of childhood sun exposure on the risk of multiple sclerosis (MS) after controlling for genetic susceptibility, we investigated the association between sun exposure and MS comparing disease-discordant monozygotic (MZ) twins.
METHOD: Twins with MS were sought by yearly newspaper advertisements throughout North America from 1980 to 1992. Diagnosis was verified by updated medical documentation through 2005. This analysis was restricted to 79 disease- and exposure-discordant monozygotic twin pairs who had ranked themselves before 1993 in relation to each of nine childhood sun exposure activities. A sun exposure index (SI) was defined as the sum of those exposures for which one twin ranked higher than his or her co-twin. The SI difference within each twin pair was calculated by subtracting the SI value of the affected twin from the SI value of the unaffected twin (range -9 to +9). The results were then analyzed using conditional logistic models.
Result: Each of the nine sun exposure-related activities during childhood seemed to convey a strong protection against MS within MZ twin pairs. Depending on the activity, the odds ratio (OR) ranged from 0.25 to 0.57. For example, the risk of subsequent MS was substantially lower (OR 0.40, 95% CI 0.19 to 0.83) for the twin who spent more time suntanning in comparison with the co-twin. For each unit increase in SI, the relative risk of MS decreased by 25%.

CONCLUSION: Early sun avoidance seems to precede the diagnosis of multiple sclerosis (MS). This protective effect is independent of genetic susceptibility to MS.

Neurology. 2007 Jul 24;69(4):381-8.