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Author Topic: Possible explanation for the higher incidence of MS in Doctors  (Read 20231 times)


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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].
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

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...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.
« Last Edit: 22/07/2007 08:45:31 by iko »


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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.

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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.

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 »


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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 :-

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

Offline iko

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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

Maybe  ;D

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' !

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

Offline iko

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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 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.

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.

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.

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

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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. 


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Possible explanation for the higher incidence of MS in Doctors
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