A paper by David Perlmutter, M.D.

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A paper by David Perlmutter, M.D.

Postby lyndacarol » Tue Oct 01, 2013 5:37 pm

I have just started reading this paper by Dr. David Perlmutter. I find it interesting so far and thought I would share it with you:

http://drperlmutter.com/wp-content/uplo ... /09/ms.pdf

The historical attempts to identify the cause of multiple sclerosis have been filled with
bleak commentary. As Godfried Sonderdank, Court Physician of Schiedam, Holland,
reported in the 14th century when describing a disease now thought to represent MS:
“Believe me, there is no cure for this illness. It comes directly from God. Even
Hippocrates and Gallenus would not be of any help here.” 5

...

By 1998, at least 16 infectious agents had been identified as possibly causing multiple
sclerosis. Under strict scientific scrutiny, none has been found to specifically induce the
disease.

But recently, the most convincing data ever presented relating infection with a specific
organism to multiple sclerosis has been reported from the Department of Neurology and
Pathology, Vanderbilt School of Medicine, Nashville, Tennessee. Dr. Subramaniam
Sriram and co-workers, publishing their results in the July 1999 issue of Annals of
Neurology, have demonstrated the presence of a specific type of bacteria in 100% of the
37 multiple sclerosis patients they studied.

...

The idea that multiple sclerosis may be caused by some form of infectious agent is
supported by several interesting observations. On the Faroe Islands prior to 1920, MS was
essentially unknown. Subsequent to the invasion of British troops, the incidence of MS
increased dramatically.9 This would support the contention that MS, at least on the Faroe
Islands, was caused by some infectious agent to which the native population had not been
previously exposed.

...

Dysbiosis, an imbalance of gut bacteria, is commonly recognized in patients suffering
from inflammatory diseases of the bowel. How this specifically relates to multiple
sclerosis was elegantly described in a report appearing in the highly respected medical
journal, The Lancet. This study, also published in 1995, evaluated the frequency of brain
MRI changes like those seen in multiple sclerosis (white matter plaques) in patients with
inflammatory bowel disease compared to normal non-afflicted individuals. The results of
this study were profound. Hyper-intense, focal, white-matter lesions ranging from 2 – 8
mm in diameter were seen in 20 of 48 patients (42%) with Crohn’s disease (an
inflammatory condition of the bowel), and in 11 of 24 patients (46%) with ulcerative
colitis (another inflammatory bowel condition). These were patients who didn’t have MS
or any other nervous system disease, just bowel inflammation. And yet, their MRI scans
were identical to those of patients with documented MS!

...

Dr. David Perlmutter is a leader in the field of nutritional influences in neurological disorders and the author of the book, Grain Brain.
My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"
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Re: A paper by David Perlmutter, M.D.

Postby mrbarlow » Tue Oct 01, 2013 8:31 pm

The arrival of British troops also brought other vices - tobacco, tinned foods (especially fruits with a high methanol content).

My view for what its worth is that MS is a cumulative effect of different factors - dietary, metabolic, infection trigger, genetics all contributing towards an expression of immune disfunction.
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Re: A paper by David Perlmutter, M.D.

Postby Annesse » Tue Oct 01, 2013 10:00 pm

I think Crohn's and MS (and all autoimmune diseases) share a common underlying disease pathway that originates with a lack of protease and DNase 1 (pancreatic enzymes that digest dietary proteins and DNA).

In the following study the researchers found that DNase 1 activity was significantly lower in patients with inflammatory bowel diseases (and lupus) than in healthy individuals.

Autoimmune Dis. 2011; 2011: 945861.
Impaired Deoxyribonuclease I Activity in Patients with Inflammatory Bowel Diseases

"Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin breakdown and promotes susceptibility to autoimmune disorders. The aim of current study was to investigate serum DNase I activity in patients with inflammatory bowel diseases (IBD). Patients and Methods. A cohort of 110 IBD patients was evaluated, aged 35 ± 12 years, 77 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). 50SLE patients and 50 healthy blood donors were examined as control groups. Results. DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients (P < .0001)... DNase I activity has shown a strong negative correlation with the serum concentration of anti-nucleosomal antibodies in the autoimmune (SLE + IBD) cohort, as well as in the separate IBD cohort. Conclusions. Reduced serum DNase I activity probably has pathogenetic consequences in IBD. Induction of autoantibodies towards nucleosomes could be a reflection of impaired DNase I activity."




A lack of these enzymes would initiate the same disease cascade found in MS.
For instance, the white matter lesions in Crohn's would be caused by the same things that cause white matter lesions in MS-an inability to properly metabolize vitamin B12, elevated homocysteine and excess tumor necrosis factor.

Under the thread "Some Interesting Connections" I have posted numerous studies on the inability of MS patients to properly metabolize vitamin B12 due to a lack of protease (protease bind and transport vitamin B12). Studies show that a lack of vitamin B12 is associated with white matter lesions and elevated homocysteine. Homocysteine disrupts the blood brain barrier, damages the endothelial cells, attracts leukocytes etc.


In the following study the researchers found that patients with Crohn's disease also have elevated homocysteine and concluded this may be due to altered vitamin B12 metabolism.


Dig Dis Sci. 1996 Jul;41(7):1417-22.
Crohn's disease and vitamin B12 metabolism.
Lambert D, Benhayoun S, Adjalla C, Gelot MA, Renkes P, Felden F, Gerard P, Belleville F, Gaucher P, Guéant JL, Nicolas JP.

"The serum concentrations of the markers of vitamin B12 status, homocysteine and methylmalonic acid, showed an increase (P < 0.01) in homocysteine in the Crohn's disease patients, but no change in methylmalonic acid. As the hyperhomocysteinemia was associated with normal folate concentrations, there may have been a defect in the activation of the enzyme due to altered intracellular vitamin B12 status."




A lack of vitamin B12 would also lead to autonomic nervous system dysfunction, just as in MS. In the following study the researchers found that almost half of the Crohn's disease patients showed signs of automonic neuropathy.

Scand J Gastroenterol. 1991 Apr;26(4):361-6.
Disturbed autonomic nerve function in patients with Crohn's disease.


"...almost half of the patients, 48% (16/33), showed signs of autonomic neuropathy (AN). The occurrence of AN was not related to duration or severity of Crohn's disease or to biochemical evidence of inflammation or malabsorption of vitamins and trace elements..."



The inability to break down proteins and release essential amino acids would lead to missing neurotransmitters, such as dopamine. A lack of dopamine would result in brain gray matter (GM) damage and also elevated levels of prolactin. Prolactin would promote B cell autoreactivity. The following studies confirm brain gray matter damage and elevated prolactin in Crohn's disease.


Neurogastroenterol Motil. 2013 Feb;25(2):147-e82. doi: 10.1111/nmo.12017. Epub 2012 Sep 23.
New insights into the brain involvement in patients with Crohn's disease: a voxel-based morphometry study.
Agostini A, Benuzzi F, Filippini N, Bertani A, Scarcelli A, Farinelli V, Marchetta C, Calabrese C, Rizzello F, Gionchetti P, Ercolani M, Campieri M, Nichelli P.


With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.


Arch Dis Child. 1997 Aug;77(2):155-7.
Serum prolactin in coeliac disease: a marker for disease activity.
Reifen R, Buskila D, Maislos M, Press J, Lerner A.
SourceSchool of Nutritional Sciences, Hebrew University of Jerusalem, Rehovot.


"Prolactin, a polypeptide hormone of anterior pituitary origin, has pronounced physiological effects on growth, reproduction, and osmoregulation. Increasing evidence indicates that prolactin also has an immunomodulatory influence on the immune system. The status of prolactin in patients with coeliac disease was investigated by obtaining serum samples from 48 patients with active and non-active coeliac disease...Serum prolactin in patients with active coeliac disease was significantly higher than in the other groups studied and reference values. Serum prolactin correlated well with the degree of mucosal atrophy and with the serum concentration of antiendomysial antibodies. Prolactin may play a part in immune modulation in the intestinal damage of coeliac disease and serve as a potential marker for disease activity.



As the first study I posted stated, "DNase I activity has shown a strong negative correlation with the serum concentration of anti-nucleosomal antibodies in the autoimmune (SLE + IBD) cohort, as well as in the separate IBD cohort." Specialized immune cells called "dendritic cells" are activated in autoimmune disease in response to anti-nucleosomal antibodies, as the following study confirms. Dendritic cells release proinflammatory cytokines such as tumor necrosis factor and interferon gamma.

Semin Nephrol. 2011 Jul;31(4):376-89. doi: 10.1016/j.semnephrol.2011.06.009.
Lupus nephritis: role of antinucleosome autoantibodies.

"The discovery of autoantigen clustering in blebs at the surface of apoptotic cells boosted research on the role of apoptosis in systemic lupus erythematosus (SLE) and led to the discovery of autoantigen modification during apoptosis. Normally, apoptotic cells are cleared efficiently and swiftly. However, it became clear that in SLE insufficient removal of apoptotic material leads to the release of these modified autoantigens. This creates the danger that these modified autoantigens are recognized by the immune system. Indeed, dendritic cells, the professional antigen-presenting cells, phagocytose these modified autoantigens, which leads to maturation and induction of a proinflammatory state of these dendritic cells.




In the following study the researchers stated that dendritic cells may play a role in the initiation and/or maintenance of chronic inflammation in Crohn's disease.

Inflamm Bowel Dis. 2004 Sep;10(5):504-12.
Characterization and distribution of colonic dendritic cells in Crohn's disease.
Silva MA, López CB, Riverin F, Oligny L, Menezes J, Seidman EG.


"Dendritic cells (DCs) are thought to play an important role in the pathogenesis of autoimmune inflammation, including Crohn's disease (CD)...Our data suggest that an imbalance in intestinal DC subpopulations may play a role in the initiation and/or the maintenance of chronic inflammation in CD."



In the next study the researchers stated that emerging evidence indicates that dendritic cells also play a “critical role” in the initiation and progression of MS.

Targeting dendritic cells to treat multiple sclerosis.
Comabella, M., X. Montalban, C. Münz, J.D. Lünemann. 2010. Nat Rev Neurol. 6(9):499-507. doi: 10.1038/nrneurol.2010.112. Epub 2010 Aug 17.

“Multiple sclerosis (MS) is considered to be a predominantly T-cell-mediated disease, and emerging evidence indicates that dendritic cells have a critical role in the initiation and progression of this debilitating condition…”


In the following study the researchers confirm that dendritic cells (DCs) play a “pivotal role” in the initiation and progression of systemic lupus erythematosus (SLE).

The role of dendritic cells in the pathogenesis of systemic lupus erythematosus
Fransen J, Van der Vlag J, Ruben J, Adema GJ, Berden JH, Hilbrands LB. 2010. Arthritis Research & Therapy 12:207 doi: 10.1186/ar2966

“…DCs play a pivotal role in the initiation and progression of SLE…”


Here is some additional information on dendritic cells.

Dendritic cells in autoimmune diseases.
Maddur, M.S., J. Vani, J.D. Dimitrovi, K.N. Balaji, S.Lacroix-Desmazes, S.V. Kaveri, J. Bayry. 2010. The Open Arthritis Journal, 3, 1-7 1 1876-5394/10 Bentham Open.

“Dendritic cells are the prime initiators and mediators of autoimmune diseases…Dendritic cells (DCs) are professional antigen presenting cells, which play a crucial role both in maintaining immune tolerance and in inducing adaptive immune responses…Therefore, DCs are the most sought after cells in inciting autoimmunity and its sustenance to autoimmune diseases…DCs act in concert with adaptive and other innate immune cells in moulding the autoimmune response...Individuals with autoimmune disease show a high number of aberrantly activated DCs either in circulation or in the autoimmune lesions secreting large amounts of proinflammatory cytokines that mediate inflammation…”
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Re: A paper by David Perlmutter, M.D.

Postby HarryZ » Wed Oct 02, 2013 7:24 am

I've been following MS research for some 45 years now and it seems the number of questions and possible causes of the disease are growing! At least now other areas are being explored unlike the past when all the focus was placed on the immune system at the insistence of the drug companies who provide us with the current and very expensive DMDs.

Hopefully we'll get some answers in the not too distant future.

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Re: A paper by David Perlmutter, M.D.

Postby Loriyas » Wed Oct 02, 2013 4:50 pm

I was a patient of Dr. Perlmutter's several years ago. It was he who started me on minocycline as he believed there was some bacterial component to MS. Although he did not follow the antibiotic protocol as we know it, I credit him for starting me on that path. I saw improvement on the minocycline and because of that I went to Vanderbilt to pursue the entire antibiotic protocol. Dr. Perlmutter is willing to look at MS in a broader sense than most neurologists. And he is also willing to work with alternative medicine.
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