Sjogrens World Forums

Does anyone know, do the white brain lesions found in Sjogren's/MS patients show up on CT scans or does it only show up on MRI's?

I don't know if they show up on CT's. My last brain CT radiology report (dec 2012) only stated nothing acute. It may depend on how the doctor writes the order. The doctor who ordered it was specifically looking for anything acute.

Typically, when my doctors want to check for brain lesions and subsequently check status on my white matter lesions, the choice has been consistently MRI, W & WO contrast.

Thanks.  I was reading earlier on the threads concerning enzymes/itching and all the scientific info and the referral was made to research showing these lesions are associated with Sjogren's.  I had only heard of them being associated with MS.  My sister has them and the drs. thought she might have MS.  Now I am wondering if I might have them also.  I have had a CT scan of my head 5 years ago for a major headache.  I never had a headache like that one!  I hope I never do again!  It was around that time I got the dx for Sjogren's although I did not see that as anything primarily associated with my dx (the headache, that is).  I always believed that if there was anything wrong the dr. would follow up.  Now I am wondering if I should try to find out if he could see anything like that, but if MRI is the only way to see them, then I would be wasting everyone's time.  Sometimes I believe my sis does have MS or some type of AI thing going on.  She had an episode of falling and not being able to walk and some episodes of shakiness that was quite severe.  She started to follow up, but then gave up due to no insurance and family problems.  I try to encourage her to go to the dr. although she has not had any more episodes like the ones I described.

I also have essential tremor which slowly seems to be worsening.  I have not had to do anything about it (yet), but one day I will if I am going to be able to get anything done or write down anything.  It's very annoying!

Thanks for answering my post.  Have a great evening! :)

Hi nannysbaby~White matter lesions are also associated with numerous other autoimmune diseases, such as celiac disease and rheumatoid arthritis. Research has found that patients with CFS and Alzheimers also have white matter lesions.

For instance, in the study entitled ?Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients? seventy-five patients with biopsy proven CD were tested for neurologic complications. Ten patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development. White matter lesions were detected in 15 patients (20%). The study concluded, ?Focal white matter lesions in the brain may represent an extraintestinal manifestation of celiac disease? (Kieslich, 2001).

So, you would have to look at what all of these diseases have in common that would lead to white matter lesions. The common denominator between all of these diseases is an inability to properly metabolize vitamin B12, due to a lack of the enzymes responsible for the "binding and transport" of vitamin B12-protease. Vitamin B12 helps maintain the myelin sheath by playing a crucial role in the metabolism of fatty acids essential for the maintenance of the myelin.

I have recently posted studies to show that patients with MS and Sjogrens lack vitamin B12. Patients with celiac disease are also deficient in vitamin B12. The study entitled ?Low serum vitamin B12 is common in celiac disease and is not due to autoimmune gastritis? concluded, ?Low B12 is common in celiac disease without concurrent pernicious anemia, and may be a presenting manifestation? (Dickey, 2002).

Here is one of the studies I have in my book on the association between vitamin B12 and white matter lesions.


"In our next study published in Journal of the Neurological Sciences the study authors discussed the neurological manifestations of a vitamin B12 deficiency, which are all consistent with pathological findings and symptoms of MS. These manifestations include demyelination, axonal degeneration and death, spinal cord degeneration, and such common MS symptoms as Lhermitte?s sign, optic neuropathy, paresthesias (abnormal sensations), and white matter lesions.

Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.
Miller A, Korem M, Almog R, Galboiz Y. 2005. J Neurol Sci. 233(1-2):93-7.


"low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders?Vitamin B12 deficiency leads to defective formation of the myelin sheath, due to incorporation into neuronal lipids of non-physiologic fatty acids as well as to defective methylation of myelin basic protein, a major component of CNS myelin?The neurologic manifestations [of vitamin B12 deficiency] begin pathologically with demyelination, followed by axonal degeneration and eventual irreversible damage due to axonal death. The spinal cord, brain, optic nerves, and peripheral nerves may all be affected by cobalamin deficiency. The spinal cord is usually affected first?The patient first notices general weakness and paresthesias. As the illness progresses the gait becomes unsteady and stiffness and weakness of the limbs develop, as well as ataxic paraplegia. The Lhermitte phenomenon is not an uncommon finding. Mental signs are frequent and range from irritability, apathy, somnolence and emotional instability to marked confusional or depressive states. Visual impairment due to optic neuropathy may occasionally be the earliest or sole manifestation?In a study evaluating the neuro-physiological and magnetic resonance imaging (MRI) changes in patients presenting with vitamin B12 deficiency and neurological syndromes, the evoked potentials and MRI changes were found to be consistent with focal demyelination of white matter in the spinal cord and optic nerve. MRI imaging of the brain and spinal cord demonstrates, in some cases of vitamin B12 deficiency, a typical pattern of white matter degeneration commonly seen in MS, such as extensive areas of T2 high-intensity signal in the periventricular white matter?"

Also, here is a link to a study that demonstrates the association between Alzheimer's disease and white matter lesions.

http://jnnp.bmj.com/content/76/9/1286

I think Alzheimer's disease is just a later stage development of missing protease. For instance, in the following study the researchers stated that there is increasing evidence for an association between Alzheimer's disease and "nutritionally independent" cobalamin (vitamin B12) deficiency. The researchers believe this may be due to a "protease" inhibition, a common factor in Alzheimer?s disease. The lack of protease results in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
McCaddon, A., B. Regland, C.F. Fear. 1995. Med Hypotheses. 45(2):200-4.

"There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology?This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism."

Nat, Thanks for responding to my question.  My father had AD.  I wonder, can supplements help or did I read in another one of your posts that the situation would exist even if you took supplements of the B-12 or enzymes? In other words it's something that cannot be fixed, right?  I know much smarter people than me would have already jumped on that answer by now.  Are we all grasping at straws with supplementation?  I don't recall my dad taking anything except a multi-vitamin, but he took around 17 other meds before he died.  He had other serious complicated diseases also (he did live a long life though-91).  But after the dimentia took over all he did for two years was sit in a wheel chair.  It was very sad.  My mom on the other hand is 94 and her mind is better than my brain-fogged gray matter.  I tell her that all the time, but she refuses just because she is 94 and I am 66.  There is not much she does not remember--it amazes me.  She only goes to the dr. once/year because he insists. LOL  But I know the inevitable has to come.  I am happy she can enjoy her life and stay up to date with the family, etc., and that I get to be with her at this time.

The lack of vitamin B12 in autoimmune disease is due to an inability to properly metabolize the vitamin because of the missing enzymes protease and DNase 1.  Let me show you another example of how these missing enzymes would lead to a "cellular" deficiency of vitamin B12.

Here is a study that shows patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis)have significantly lower DNase 1. 

Autoimmune Dis. 2011;2011:945861. doi: 10.4061/2011/945861. Epub 2011 May 29.
Impaired deoxyribonuclease I activity in patients with inflammatory bowel diseases.

Mal?čkov? K, Duricov? D, Bortl?k M, Hru?kov? Z, Svobodov? B, Machkov? N, Kom?rek V, Fuč?kov? T, Janatkov? I, Zima T, Luk?? M.

"Results. DNase I activity in IBD patients was significantly lower than in healthy individuals..."



Since protease and DNase 1 are needed  for the proper metabolism of vitamin B12, we would expect to find white matter lesions in patients with IBS.

Here is a study that confirms this.

http://www.ncbi.nlm.nih.gov/pubmed/21091817


Here is a study entitled "Crohn's disease and vitamin B12 metabolism" that concluded Crohn's disease patients may have altered "intracellular" vitamin B12 status.

http://www.ncbi.nlm.nih.gov/pubmed/8689919

So, the reason autoimmune patients lack vitamin B12 is due to an inability to properly metabolize the vitamin into normal healthy cells, due to missing enzymes.   Taking supplements will not restore your body's ability to metabolize vitamin B12.


The situation is far from hopeless though. Quite the contrary. If DNase 1 and protease were restored, your body would then be able to properly metabolize vitamin B12. These enzymes also digest proteins and release essential amino acids, among other vital functions, so it is imperative they be restored.

They can easily be replaced through diet. You would need to also heal your GI tract and avoid anything that might do further harm to these enzymes or your GI tract.  I completely recovered from lupus, CFS, and fibro by healing my GI tract and replacing these enzymes through diet alone.

Mine never showed on CT just MRI.

Quote from: Nat on November 23, 2013, 08:06:14 PM
Also, here is a link to a study that demonstrates the association between Alzheimer's disease and white matter lesions.

http://jnnp.bmj.com/content/76/9/1286

I think Alzheimer's disease is just a later stage development of missing protease. For instance, in the following study the researchers stated that there is increasing evidence for an association between Alzheimer's disease and "nutritionally independent" cobalamin (vitamin B12) deficiency. The researchers believe this may be due to a "protease" inhibition, a common factor in Alzheimer?s disease. The lack of protease results in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
McCaddon, A., B. Regland, C.F. Fear. 1995. Med Hypotheses. 45(2):200-4.

"There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology?This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism."

Nat,

Have you found any Sjogren's patients with Alpha 1 Antitripsyin Deficiency?  If so, what % roughly?

Do BCAAs help Alpha 1 Anti-Trypsin Deficiency?

My memory problems could hypothetically  come from my body being unable to assimilate B vitamins.....despite my supplementation of them.

Does Protease deficiency then go hand in hand with MTHFR deficiency?

(methylhydrofolate reductase)


Thank you Nat!

Hi SjoAmy~

Sorry, I haven't done any research on Alpha 1 Antitripsyin Deficiency.

For a person with autoimmune disease, taking supplemental BCAA's could be harmful.

If you lack the ability to properly metabolize proteins, not only would you be deprived of the amino acids and vitamin B12 found in those proteins, but the components of which those proteins are comprised (amino acids) would enter the bloodstream and trigger an immune response.

Here is a picture of these unbroken down protein particles in a lupus patients bloodstream. (Notice the last paragraph where it states lupus patients lack the enzyme DNase 1)

http://www.sciencedaily.com/releases/2010/05/100503161423.htm

Taking additional amino acids in supplement form would lead to an increased risk of disease. This is evident in the findings from a study entitled ?Intermediary metabolism of phenylalanine and tyrosine in diffuse collagen diseases? (Nishimura, 1959). When lupus patients were given supplements of tyrosine and phenylalanine, the supplements ?unfailingly aggravated both clinical signs and laboratory data of collagen disease.?

I think this is one of the strongest lesions that can be learned about autoimmune disease--you shouldn't take supplemental nutrients into your body that you have lost the ability to properly metabolize-even if you lack them. They will just do as the researchers stated in the lupus study-unfailingly aggravate both clinical signs and laboratory data of the disease. The nutrients that are lacking in patients with autoimmune disease--amino acids, vitamin B12, zinc, iron, calcium, magnesium, and vitamin D are all lacking because the body has lost the ability to properly metabolize them.

I can address your question about the MTHFR deficiency in the next post.

This is so interesting and yet intricate and complicated.  Bottom line that may be why the drs don't rx more supplementation then because it could exacerbate the original problems.  Better to educate on the right foods to eat and get better nutrition and approach the problem from that direction.  So by plugging the holes in your diet you were able to completely get over your illnesses or their symptoms?  That is so wonderful! 

When I first got my dx for pSS I felt like it was just dry mouth and dry eyes and wasn't all that.  Two years later a nurse recommended I read a book about AI diseases (I guess she sensed that I was not taking it seriously enough).  I did, and the longer I search and try to learn more, the more it brings me to my knees.  It is so serious!  Not long ago I saw a video of a dr. on You Tube who had MS and cured herself of her symptoms of MS.  At the time I did not feel that particularly applied to me in any way, but with what I am learning here now concerning the white brain lesions and the inabilities of our bodies to metabolize correctly, it makes me think we are all connected and perhaps one has MS and another has Lupus and another has Sjogren's, but we are all different branches connected to the same trunk of the tree (if that makes sense).  We all have one disease (AI) and demonstrate differing symptoms based on our unique individual makeup.  If I am misunderstanding, please correct me Nat and thank you for including these research locations.  I believe I will relook at that video.

Hi SjoAmy~

I wanted to address your comment about memory problems next. Autoimmune disease patients all share the same exact underlying disease pathway that originates with missing enzymes called protease and DNase 1. These enzymes digest dietary proteins and release essential amino acids. A lack of these enzymes would lead to a lack of essential amino acids.  I have been posting studies that show autoimmune patients lack essential amino acids--one of which is phenylalanine.


The essential amino acid phenylalanine is needed to produce dopamine (Phenylalanine>Tyrosine>Dopamine) A lack of dopamine would lead to brain gray matter loss.

In the following study published in The Journal of Pain researchers found a strong correlation between dopamine metabolism and gray matter density.


Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism.
Wood, P.B., M.F. Glabus, R. Simpson, J.C. Patterson 2nd. 2009. J Pain 10(6):609-18. Epub 2009 Apr 23.

"Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes."


The gray matter involves regions of the brain concerned with muscle control, emotions, learning and MEMORY, speech, and sensory perception such as seeing and hearing. In the following study published in Neurology the researchers stated that gray matter atrophy is detected even in the earliest stages of MS.


Gray matter involvement in multiple sclerosis.
Pirko I, Lucchinetti CF, Sriram S, Bakshi R. 2007. Neurology. 68(9):634-42.


"Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression?"



In the following study the researchers concluded that patients with Sjogren's syndrome had decreased brain gray matter.

CNS involvement in primary Sjogren?s syndrome: assessment of gray and white
matter changes with MRI and voxel-based morphometry.
Tzarouchi, L.C., N. Tsifetaki, S. Konitsiotis, A. Zikou, L. Astrakas, A. Drosos, M.I. Argyropoulou. 2011. AJR Am J Roentgenol.197(5):1207-12. doi: 10.2214/AJR.10.5984.

"?In comparison with the controls, patients with primary Sj?gren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum?"


Researchers in the following study discovered that the gray matter (GM) was "particularly affected" in patients with neuropsychiatric lupus (NPSLE).

Selective gray matter damage in neuropsychiatric lupus.
Steens, S.C., F. Admiraal-Behloul, G.P. Bosma, G.M. Steup-Beekman, H. Olofsen, S. Le Cessie, T.W. Huizinga, M.A. Van Buchem. 2004. Arthritis Rheum. 50(9):2877-81.

"?This is the first study to demonstrate? that in SLE patients with a history of NP symptoms ?the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE."

How bad is it to have brain gray matter loss due to a lack of dopamine? In the following study published in the Journal of Neuroscience researchers found that the longer the individuals had fibromyalgia, the greater the brain gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging.

Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?
Kuchinad, A. P. Schweinhardt, D.A. Seminowicz, P.B. Wood, B.A. Chizh, M.C. Bushnell. 2007. J Neurosci 11;27(15):4004-7.

"We found that fibromyalgia patients had significantly less total gray matter volume and showed a 3.3 times greater age-associated decrease in gray matter than healthy controls. The longer the individuals had had fibromyalgia, the greater the gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging."

A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT

http://stroke.ahajournals.org/content/32/6/1318.long

Imaging in Progressive Multifocal Leukodystrophy

Progressive multifocal leukoencephalopathy (PML) is a fatal subacute progressive demyelinating disease seen in persons with impaired cell-mediated immune response. PML predominantly occurs in patients with acquired immunodeficiency syndrome (AIDS). Before the AIDS epidemic, PML was rare and associated with other immunocompromised conditions, such as leukemia, lymphoma, systemic lupus erythematosus (SLE), organ transplantation, Wiskott-Aldrich syndrome, and severe combined immunodeficiency (SCID).

MRI is the preferred diagnostic imaging modality. It is sensitive to white matter lesions and shows hyperintense lesions on T2-weighted (T2W) images in affected regions. Because of its superior contrast resolution, it can be used to detect subtle white matter abnormalities, whereas CT depicts the lesions at an advanced stage.

http://emedicine.medscape.com/article/343475-overview

I have brain lesions and was told it is due (probably - not a definitive answer by the neuro I saw) from sjogrens but could also be caused continued migraine headaches or other headaches.  I must say I was quite concerned when the neurologist called me a year ago to tell me this...so many things ran through my mind.   

I hope you are able to find some answers.

Sending positive thought your way.

Thank you Lighthouse 33.  I thought the information you cited was very interesting and for sure it answers the question without any doubt.

Thank you Finallyadx for taking the time to respond.  Sorry to hear you have lesions.  Do you have cognitive problems associated with Sjogren's.  I do.  Lately it worries me a lot and I intend to bring it up with my rheum on the next visit.  (He probably already knows.  I say that because sometimes when he asks how I've been doing I feel like I don't know where to start and I hesitate a couple of times I really went blank.)  He never said anything and neither did I, but I think I am including it on my list this time just so he is aware. 

Nat, I don't see any mention of MTHFR Deficiency.....

Hi SjoAmy~MTHFR deficiency can lead to elevated homocysteine, but I am sure you already knew that. Homocysteine is elevated in autoimmune disease patients and it plays a very large role in the autoimmune disease process, but in the vast majority of cases it is not due to MTHFR.

Homocysteine is elevated in autoimmune disease due to a lack of vitamin B12. Vitamin B12 is required for the proper metabolism of homocysteine. For instance, in the following study published in the Journal of Clinical Neuroscience the researchers found high homocysteine and low vitamin B12 in patients with MS and concluded there is a "significant relationship" between MS and vitamin B12 deficiency.


Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple sclerosis.
Kocer B, Engur S, Ak F, Yilmaz M. 2009. J Clin Neurosci. 16(3):399-403. doi: 10.1016/j.jocn.2008.05.015. Epub 2009 Jan 18.

"?Levels were high in?patients with MS but were within normal limits in the control group?Thus, we found a significant relationship between MS and vitamin B12 deficiency?"


I noticed you have COPD in your profile.This would be associated with elevated homocysteine.
Here is a section from my book on this.


"Researchers in our next study discovered there was a more than two-fold increased risk of MS in patients with chronic obstructive pulmonary disease (COPD), a progressive lung disease that makes it hard to breathe. In COPD, the small capillaries that run through the walls of the air sacs in the lungs are damaged or completely destroyed.  Symptoms of COPD include coughing that produces large amounts of mucus, wheezing, shortness of breath, and chest tightness.  The researchers concluded their results indicate that COPD and MS have an "inflammatory vulnerability" in common.

Increased prevalence of multiple sclerosis among COPD patients and their first-degree relatives: a population-based study.
Egesten A, Brandt L, Olsson T, Granath F, Inghammar M, L?fdahl CG, Ekbom A. 2008. Lung 186(3):173-8. doi: 10.1007/s00408-008-9081-y. Epub 2008 Mar 20.


"?In the COPD cohort, there was a more than twofold increased risk of MS compared with controls? This study indicates that COPD and MS have an inflammatory vulnerability in common...These diseases may share inflammatory pathways?"

Homocysteine would be the "inflammatory vulnerability" that both COPD and MS patients share. In the following study the researchers found that homocysteine was significantly elevated in COPD patients and was related to serum C-reactive protein (CRP), a common inflammatory marker, and COPD severity.


Plasma homocysteine is elevated in COPD patients and is related to COPD severity.
Seemungal TA, Lun JC, et al. 2007. Int J Chron Obstruct Pulmon Dis 2(3):313-21.

"?Plasma homocysteine is significantly elevated in COPD patients?and is related to serum CRP and COPD severity."


Homocysteine destroys the cells that line the blood vessels. These cells are called "endothelial cells".


In the following study the researchers concluded that homocysteine induced programmed cell death (apoptosis) in endothelial cells.

Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response.
Zhang C, Cai Y, Adachi MT, Oshiro S, Aso T, Kaufman RJ, Kitajima S. 2001. J Biol Chem. 276(38):35867-74.

"?In this study, homocysteine induced programmed cell death in endothelial cells..."




The researchers from the following study concluded that "endothelium" dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud?s phenomenon??

Endothelial dysfunction in patients with primary Sj?gren?s syndrome.
Pirildar, T., C. Tikiz, S. Ozkaya, S. Tarhan, O. Ut?k, H. Tikiz, U.K. Tezcan. 2005. Rheumatol Int . 25(7):536-9.

"The aim of this study was to determine the endothelial function in patients with primary Sj?gren?s syndrome (SS)? We concluded that endothelium-dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud?s phenomenon, when compared with the healthy controls?"

True....and from what I know by book and personal experience, folic acid and B12 can both lower high homocystiene levels.

There's an inability to metabolize the methylation part of MTHFR and DHFR.  So a true break down doesn't occur.

I agree the COPD can be related to homocystiene......but now I have another pulmonary culprit.....To consider at least....Alpha 1 Anti Trypsin Deficiency.  This deficiency relates back to protease inhibition.  Correct me, if I am wrong......but A 1 A T Deficiency could likely then cause low albumin, an inflammation state, COPD/Bronchitis /Asthma /Emphysema, liver damage, and an inability to assimilate any protein because most proteins are bigger than albumin....and high homocystiene. ;)

It is sad that so many with A1AT Deficiency go unscreened and just left with the COPD label until they get worse. Methotrexate with this combo can end up in end stage liver disease.  I'll post the study.....gotta find it first.  Lol

http://www.ncbi.nlm.nih.gov/m/pubmed/7612033/ (http://www.ncbi.nlm.nih.gov/m/pubmed/7612033/)

A1AT deficency, Methotrexate & end stage liver disease

I think if a disease does originate at a certain point, which I believe the evidence shows with autoimmue disease is with missing digestive enzymes, it will follow a very straightforward pathway. For instance, as the research I posted above shows, due to a lack of vitamin B12, patients with MS have elevated levels of homocysteine. As the research shows, homocysteine is linked to COPD. This would be why patients with MS have a more than two-fold increased risk of developing COPD.

So, you can take this a step further and look at another autoimmune disease, such as RA, to see if a lack of digestive enzymes would follow the same pathway. I have already posted research that shows patients with RA lack these digestive enzymes.

This means we should find low B12, high homocysteine, and an increased risk of developing COPD.


Here is a study that shows patients with RA have elevated homocysteine.

Abnormal homocysteine metabolism in rheumatoid arthritis.
Roubenoff, R., P. Dellaripa, M.R. Nadeau, L.W. Abad, B.A. Muldoon, J. Selhub, I.H. Rosenberg IH. 1997. Arthritis Rheum. 40(4):718-22.

"?Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted."


This leads to the same increased risk of developing COPD in RA as it does in MS.  More book info:

"A new study presented at the EULAR (European League Against Rheumatism) 2011 Annual Congress has confirmed a link between rheumatoid arthritis and COPD. An article discussing this study published in News-Medical stated, "Patients with rheumatoid arthritis are two times more likely to have COPD than healthy controls. The study, of 15,766 patients with RA and 15,340 controls, found that the prevalence of COPD was significantly higher in RA patients than healthy controls. Interestingly, the link was still significant after risk factors common in both RA and COPD patients, such as smoking, obesity and socioeconomic status, were controlled for" (News- Medical, 2011).


Taking this one step further...

In the following study from Rome researchers discovered that patients with COPD had low levels of vitamin B12 and, as a consequence, increased homocysteine. The researchers concluded this may contribute to the COPD-related atherothrombotic risk.

Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease
Fimognari, F.L., L. Loffredo, S. Di Simone, F. Sampietro, R. Pastorelli, M. Monaldo, F. Violi, A. D?Angelo. 2009. Nutr Metab Cardiovasc Dis. 19(9):654-9.

"Patients with chronic obstructive pulmonary disease (COPD) are at increased atherothrombotic risk. Preliminary findings have suggested that COPD patients may have increased plasma total homocysteine (tHcy), a cardiovascular risk factor often caused by a poor B vitamin status?COPD patients have a poor B vitamin status and, as a consequence,increased tHcy. These abnormalities may contribute to the COPD-related atherothrombotic risk."

I have also posted research that shows the white matter lesions in autoimmune disease are caused by the inability to properly metabolize vitamin B12.

The low levels of vitamin B12 found in COPD would also lead to an increased risk of white matter lesions. The following study confirms that COPD is associated with white matter lesions.

Arterial oxygen saturation, COPD, and cerebral small vessel disease.
Van Dijk, E.J., S. Vermeer, J.C. de Groot, J. van de Minkelis, N. Prins, M. Oudkerk, A. Hofman, P. Koudstaal, and M. Breteler. 2004. J Neurol Neurosurg Psychiatry 75(5):
733?736.

"?Participants with COPD had more severe periventricular white matter lesions than those without?Lower SaO2 and COPD are associated with more severe periventricular white matter lesions."

You have to look at the "entire" disease pathway in order to determine where it originates.
I think the evidence is clear that in autoimmune disease, this pathway originates with missing enzymes.

And yes, it is true you may be able to lower the serum (blood) levels of homocysteine through B12 supplementation, but research has confirmed you will not stop the damage being caused by homocysteine on the "cellular" level.

So, high homocysteine is one of the elephants in the room - how many of us have had our levels of homocysteine checked - not me.

And what is the connection with women predominantly having sjogren's syndrome.  Could this be it?



Free Radic Biol Med. 2013 Aug 6. pii: S0891-5849(13)00394-8. doi: 10.1016/j.freeradbiomed.2013.07.041. [Epub ahead of print]

"Mass spectrometry evidence for formation of estrogen-homocysteine conjugates: Estrogens can regulate homocysteine levels."

Gaikwad NW.

And just for fun, we can do it again. (mistyrain, I will address your question in the next post).


In the following study the researchers link the peripheral neuropathy found in patients with diabetes with impaired exocrine pancreatic function. The exocrine pancreas is where DNase I and protease originate. The researchers stated that compared to normal controls, ALL diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli.

Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy.

El Newihi, H., C.P. Dooley, C. Saad, J. Staples, A. Zeidler, J.E. Valenzuela. 1998. Dig Dis Sci. 33(6):705-10.

"?Compared to normals, all diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli. This reduction was not corrected by administering bethanechol?We conclude that diabetics with diarrhea and peripheral neuropathy exhibit impairment of their exocrine pancreatic secretion?"

So, why would peripheral neuropathy be linked to impairment of the exocrine pancrease? Because the exocrine pancreatic enzymes protease are responsible for the proper metabolism of vitamin B12 and a "clear link" has been established between a lack of vitamin B12 and peripheral neuropathy.

Low B12 would lead to elevated homocysteine in patients with diabetes, as the following study confirms.


Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus.
Soinio, M., J. Marniemi, M. Laakso, S. Lehto, T. R?nnemaa. 2004. Ann Intern Med. 140(2):94-100.

"?In this large cohort of patients with type 2 diabetes, plasma homocysteine level was a strong and independent risk factor for CHD events."



Elevated homocysteine would then lead to the same risk found in all autoimmune disease pateints of developing COPD.

In the following study, researchers found that those with COPD were nearly twice as likely to develop type 2 diabetes as those without COPD. The researchers believe that inflammation may explain this association.

Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women.
Rana, J.S., M.A. Mittleman, J. Sheikh, F.B. Hu, J.E. Manson, G.A. Colditz, F.E. Speizer, R.G. Barr, C.A. Carnargo, Jr. 2004. Diabetes Care vol. 27 no. 10 2478-2484.

"?Inflammation plays a key role in chronic obstructive pulmonary disease (COPD)? Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes?Our findings suggest that COPD may be a risk factor for developing type 2 diabetes?"


And then of course, we would expect to find that patients with diabetes have white matter lesions, just like all patients with autoimmune disease. Also, just like all patients with autoimmune disease, patients with diabetes have a loss of brain grey matter, due to the inability to properly metabolize dopamine.

In the following study published in Diabetologia the researchers concluded that type 2 diabetes was associated with a smaller volume of brain grey matter and with larger white matter lesion (WML) volume.

Automated measurement of brain and white matter lesion volume in type 2 diabetes
mellitus.
Jongen, C., J. van der Grond, L.J. Kappelle, G.J. Biessels, M.A. Viergever, J.P. Pluim. Utrecht Diabetic Encephalopathy Study Group. 2007. Diabetologia. 50(7):1509-16. Epub 2007 May 11.

"Type 2 diabetes mellitus has been associated with brain atrophy and cognitive decline, but the association with ischaemic white matter lesions is unclear?Type 2 diabetes was associated with a smaller volume of grey matter? and with larger white matter lesion volume?The combination of atrophy with larger WML volume indicates that type 2 diabetes is associated with mixed pathology in the brain."

Bearing in mind that almost all studies in this line contain at some point the words "commonly found", "frequently found" or "in some cases"; as much as this sounds like a valid pathway to an eventual control or cure, it only pertains to some of the people with SjS.

Yes, following homocysteine levels can be of value, considering the possibility of predicting or preventing heart and lung disease, but it doesn't always show a complete picture. For example, my levels consistently run between 1 and 3 micromoles/l (>10 micromoles/liter as a normal), so quite low, but I have a history of both heart disease and COPD (restrictive in nature, not classic). I also have consistently normal, mid to high range, B12 levels, and have documented peripheral and autonomic neuropathy.

I might add that my immune mediated diagnosis (sarcoidosis, Sjogrens, dermatomyositis, vasculitis, inflammatory polyarthritis and aseptic tendonitis), have all been diagnosed with positive autoantibodies and/or tissue biopsy, so there is little question that I do have autoimmune diseases.

I think the problem lies at the "cellular" levels, due to a functional deficiency, so serum (blood) levels would not be a reliable indicator. For instance, one of the known associations with Sjogrens  and other autoimmune disease patients is "subacute combined degeneration of the spinal cord" which is caused, according to the National Institutes of Health, by a lack of vitamin B12.




The following study demonstrates that subacute combined degeneration of the spinal cord can occur even with so-called ?normal? levels of vitamin B12 in the blood.

Subacute combined degeneration with high serum vitamin B12 level and abnormal vitamin B12 binding protein New cause of an old syndrome.
Reynolds E.H., T. Bottiglieri, M. Laundy, J. Stern, J. Payan, J. Linnell, J. Faludy 1993. Arch Neurol. Jul;50(7):739-42.

"Subacute combined degeneration of the spinal cord due to vitamin B12 deficiency invariably has been associated with a low serum vitamin B12 level? To our knowledge, this is the first example of neurologic disease associated with high serum vitamin B12 level and provides further evidence that sometimes a serum vitamin B12 level may not be a reliable guide to vitamin B12 deficiency??

The same is true of elevated homocysteine.

For instance, in the following study on CFS and fibromyalgia the researchers found low B12 and high homocysteine in the "cerebrospinal fluid" of patients with CFS and fibro and  stated they believe that the low vitamin B12 levels found in the cerebrospinal fluid may reflect disruption of the "mechanism of transport" across the blood brain barrier. The researchers also stated they believe additional evidence from other studies further support the idea that deficiencies of "enzymatic" pathways involving vitamin B12 and homocysteine underlie a range of neurological disorders. Here is the conclusion of the study I have in my book.


"This study provides convincing preliminary evidence that a high homocysteine level in cerebrospinal fluid is an underlying factor in patients suffering from fibromyalgia and chronic fatigue syndrome. Low vitamin B12 levels in cerebrospinal fluid and possibly low SAMe levels are implicated as contributing factors. Additional evidence from other studies further support the idea that deficiencies in enzymatic pathways in the brain involving vitamin B12, homocysteine, and folic acid underlie a range of neurological disorders. Deficiencies in these essential biochemical pathways in the brain should be considered by health practitioners in the evaluation of successful interventions for reversing symptoms of fibromyalgia, chronic fatigue syndrome, and other neurological conditions (Regland,1997)."

Here are a few more studies that demonstate the inability of autoimmune patients to properly metabolize vitamin B12.

For instance, as the following study states, "Neuropathic features, such as trigeminal neuralgia, peripheral neuropathy, and subacute combined degeneration of the spinal cord as a consequence of vitamin B12 MALABSORPTION  are well recognised in systemic sclerosis." Systemic sclerosis is scleroderma. 

Autonomic neuropathy in systemic sclerosis.
Klimiuk, P.S., L. Taylor, R.D. Baker, and M.I. Jayson. 1988. Ann Rheum Dis. 47(7): 542?545.

??Neuropathic features such as trigeminal neuralgia, peripheral neuropathy, and subacute combined degeneration of the cord as a consequence of vitamin B12 malabsorption are well recognised in systemic sclerosis??


Here is one in MS.

In the following study the researchers stated they suspected the vitamin B12 deficiency in MS may be due to problems with binding and/or transport. In addition, the researchers concluded that further studies of vitamin B12 metabolism, binding, and transport in MS are indicated, as they feel this may offer clues to the understanding of MS.

Multiple sclerosis associated with vitamin B12 deficiency.
Reynolds EH, Linnell JC, Faludy JE. 1991. Arch Neurol. 48(8):808-11.

"?A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder."


Also here is one on vitamin B12 "metabolism" and Crohn's disease  that found elevated homocysteine and concluded it might be due to altered "intracellular" vitamin B12 status.

http://www.ncbi.nlm.nih.gov/pubmed/8689919

Finallyadx, I agree with you and have many 'abnormal white foci' located together in the lower center of my brain MRI.  I've had a brain MRI each year for the last three years.  NO MORE for me though.  Unless I have something catostrophic happen I'm done with doctors not being able to fix my cognitive slowing down.  I just adapt to my 'new normal' life.

Neuro says that my brain fog is a symptom of fibro and SJS and says that the white brain matter spots that seem to increase annually are caused from getting older, high blood pressure, headaches, etc.

I had neuropsch. testing that showed 'marked difficulty' with facial recognition, (only with seeing a new face on a flash card and trying to remember if I'd seen it earlier in the test)  cognitive problem solving, etc.

I've completely given up on anyone being able to help me overcome my cognitive challenges.
I sing for a living everyday and sing the same songs for over seven years.   I can't learn any new songs.  Anything new that's complex involving memory is too hard but I do challenge myself daily with other easier things.

Doctors seem to be looking for the big things on MRIs....tumors, brain bleeds, bruising, and large MS type lesions.   I wish you all luck in your search for relief.    Gina   

I was told my MRI showed white spots called UBO's which are unidentified bright objects-not MS lesions. Saw a neuro and he said 4 or more might be concerning and I have 5, but he said I don't have MS symptoms so not to worry about them. I wonder why I have them though and wonder if any of you have them?

Perhaps calcifications?

Quote from: Nat on November 24, 2013, 08:59:43 AM
Hi SjoAmy~

Sorry, I haven't done any research on Alpha 1 Antitripsyin Deficiency.

For a person with autoimmune disease, taking supplemental BCAA's could be harmful.

If you lack the ability to properly metabolize proteins, not only would you be deprived of the amino acids and vitamin B12 found in those proteins, but the components of which those proteins are comprised (amino acids) would enter the bloodstream and trigger an immune response.

Here is a picture of these unbroken down protein particles in a lupus patients bloodstream. (Notice the last paragraph where it states lupus patients lack the enzyme DNase 1)

http://www.sciencedaily.com/releases/2010/05/100503161423.htm

Taking additional amino acids in supplement form would lead to an increased risk of disease. This is evident in the findings from a study entitled ?Intermediary metabolism of phenylalanine and tyrosine in diffuse collagen diseases? (Nishimura, 1959). When lupus patients were given supplements of tyrosine and phenylalanine, the supplements ?unfailingly aggravated both clinical signs and laboratory data of collagen disease.?

I think this is one of the strongest lesions that can be learned about autoimmune disease--you shouldn't take supplemental nutrients into your body that you have lost the ability to properly metabolize-even if you lack them. They will just do as the researchers stated in the lupus study-unfailingly aggravate both clinical signs and laboratory data of the disease. The nutrients that are lacking in patients with autoimmune disease--amino acids, vitamin B12, zinc, iron, calcium, magnesium, and vitamin D are all lacking because the body has lost the ability to properly metabolize them.

I can address your question about the MTHFR deficiency in the next post.

hi the original subject in this thread was brain lesions but I did a search on branched chain amino acids (BCAA) and this thread came up and Nat's info is incredibly helpful to me! I was recommended to take them because am on a limited soft diet right now, dental problems coupled with food reactivity that is getting worse. Unfortunately pretty quickly I realized I feel worse on them, increases pain and fatigue etc and just awful feeling....which has happened to me with other aminos and supplements....Nat has best explanation I have seen backed up with studies he cites to why so many things bother me that I "need" like vitamin D

curious if there are others that have tried BCAA with same bad effect? trying to figure out the anti-dote now....best can come up with is activated charcoal, more water, quercetin, bit of molybdenum and tinch of this one digestive enzyme I can sometimes tolerate.

I was glad to find this thread although I don't understand most of it.  I had an MRI with & without contrast in 2016.  My doctor just said it was "normal".

I recently found the report online and read it.  To my dismay it said I had "one focus of T2/FLAIR hyperintensities ... within the subcritical white matter of the right frontal lobe..." ..."In this age group, minimal chronic small vessel ischemic gliosis is a leading consideration."

Is this the same as white brain lesions?  It also sounds like I'm a candidate for a stroke.  ☹️

I would have to go thru reams of medical notes to find what the MTHFR factor is.  I do have a seizure disorder and associated with it is positive for the MTH,etc.  (can't recall all the letters in order).  anyway, I was given a strange B vitamin # ??  I believe it was 12.  It cost a lot.  This was to "stop progression" of the condition...and the way the progression was tracked was by blood work.  It is a genetic condition.  I took this supplemental B  12 (?) for over a year.  My numbers decreased where they were supposed to increase.  The neurologist actually panicked.  After spending an inordinate amount for something which apparently was not doing it's prescribed job, I refused to take it any longer.  One of the reasons is my age. This was over a year ago when I stopped taking it.  The neurologist agreed with me. 

I am 75 now.  I told him I figured whatever happened (I forget) with the progression, couldn't be damaging my body more rapidly than advancing age.

btw: I was told this is discovered thru ordinary battery of tests done with people with seizure disorders.  NOT associated with Sjogren's.  The MTHFR (if that is correct) is rather common was my take.

Hate to be vague about all this, yet thinking back, no one could adequately explain the numbers on the tests, the actual harm this does, nor what the B 12 did. btw: you can buy b12 from Amazon...and I was told the amount is infinitesimal.  The supplement I took ( I WAS TOLD) was 100s of times more powerful.  I ordered this from a source given to my by my neurologist as discounts were given at that particular location. 

Good luck,
c3

I haven't read all the posts, but vitamin b12 can be bought at any pharmacy or grocery store or Walmart, etc. It is a common vitamin and is not expensive. It is the vitamin that is used to treat pernicious anemia. I don't know quite what you are referring to. Maybe I misunderstood. Irish

I just re-read your post and it may be that your dosage was so large that this is what caused the price to be so high.

Way2dry, Thanks for posting.  I'm wondering the same thing.  I'm told I'm having TIAs which do run in my family, and they are leaving 'marks' or something on my brain.

way2dry, you got me thinking, I had an MRI in 2012 and my doc just said it was normal as well, I think I will try to get the original report after reading what you said.....I hope you are ok, let us know if you find out more

Tomorrow I am having an EEG to look for possible partial seizure activity. We may follow up with an MRI if there is a high degree of suspicion. Does anyone else have seizures related to these lesions?

This is a very old thread..but has been renewed and I am attempting to discuss lesions in the brain and seizure disorders. 

Nymph: I do have partial onset seizures controlled by medication.  It was identified bu EEG over two years ago. When I explained to a neurologist my experiences, he nailed it immediately.  I was stunned.  I did have a subsequent MRI w'out any brain damage detected. Your major concern is the seizure itself where mine was to explain my "lost" time.  The seizures themselves last for seconds (according to the doctor).  The confusion which follows depends where you are.  I identified those which occurred when I was in a car.  The longest confusion period I had was less than 10 minutes.  Usually they will last less than five minutes.  In your home, I have been told many instances I "forget" why I walked into a room, etc , can actually be one of these seizures and your recovery response time is shorter due to so much being familiar surroundings.

Returning to an earlier discussion of a supplement prescribed which  are identified as a medicine "food".  It is called Deplin and used to treat depression and a blood factor of MTHR.  I was on a high dose.  I forget.  It was 15mg...and dr. wanted to up it to 30 when I refused to take it any longer (I took it for a year with no change in my bloodwork).   When I took it I found it excessively expensive for what I considered a "supplement" with a fancy name.  The MTHR factor is a genetic condition.  Again, it was prescribed for the factor yet commonly used to treat depression.  I tried to recall this, and finally remembered the name of the drug.  It has now been decreased in price.  I would believe the price resulted in a lot of people rejecting it.  You can now get it online @ less than 200.00 for a 3 month supply. 

A cursory cross reference on Amazon to compared amounts of mg. of B12 available in vitamins follows:
Gummy bear B 12 vitamins - 500 mcg (Amazon or drug stores)
Deplin- 1 mg, 7.5mg, 15mg, and 30mg (online)

There are 1000 micrograms in one milligram.

If you wish to know more about Deplin or treatment for MTFR, please google Deplin

Thx,
ccc

I had that show up on an MRI years ago.
The neurologist simply said it wasn't in the area of the brain associated with MS and didn't seem to discuss it anymore.
I have issues with migraines and some of those patients have told me they have had white brain lesions show up on their xrays in a similar fashion.

The MTHFR gene has to do with the body's inability to detox. There are different variations of this gene. I came to awareness of it via a support group for breast implant illness, ad it also applies to other implantable devices such as the birth control devices that over time release toxins. Those with the MTHFR gene have a much more difficult time detoxing the residual toxins once these devices are removed. you might find additional info on this via healing breast implant illness dot com. Some women with this defect have found the gerson detox protocol helpful. But of course always check with your medical team.

Quote from: cccourt1942 on April 09, 2017, 10:28:04 AM
I would have to go thru reams of medical notes to find what the MTHFR factor is.  I do have a seizure disorder and associated with it is positive for the MTH,etc.  (can't recall all the letters in order).  anyway, I was given a strange B vitamin # ??  I believe it was 12.  It cost a lot.  This was to "stop progression" of the condition...and the way the progression was tracked was by blood work.  It is a genetic condition.  I took this supplemental B  12 (?) for over a year.  My numbers decreased where they were supposed to increase.  The neurologist actually panicked.  After spending an inordinate amount for something which apparently was not doing it's prescribed job, I refused to take it any longer.  One of the reasons is my age. This was over a year ago when I stopped taking it.  The neurologist agreed with me. 

I am 75 now.  I told him I figured whatever happened (I forget) with the progression, couldn't be damaging my body more rapidly than advancing age.

btw: I was told this is discovered thru ordinary battery of tests done with people with seizure disorders.  NOT associated with Sjogren's.  The MTHFR (if that is correct) is rather common was my take.

Hate to be vague about all this, yet thinking back, no one could adequately explain the numbers on the tests, the actual harm this does, nor what the B 12 did. btw: you can buy b12 from Amazon...and I was told the amount is infinitesimal.  The supplement I took ( I WAS TOLD) was 100s of times more powerful.  I ordered this from a source given to my by my neurologist as discounts were given at that particular location. 

Good luck,
c3