This Is MS Multiple Sclerosis Knowledge & Support Community

In trying to explore various issues relating to supplements, I realized that I needed a more detailed understanding of just how exactly MS works and demyelination comes to be. So this is a thread that is strictly for trying to understand what is known and unknown about how the disease process happens. I realize that a lot of you understand all this, but for me (and I figure there are a few more others like me) starting simple and building up to the more complex is the only way to grasp this stuff. I’ve made hyperlinks in blue in hopes that this narrative may be more like a beginning than an end. As in my prior posts, I’m not a medical professional, I’m an MS Fiancé and these are my thoughts, and you should see your doctor about medical decisions, yada, yada, yada………………

Starting Point: A Definition of MS

I’m choosing Medicinenet.com as my starting point. Here’s the Definition of Multiple Sclerosis from that website:

“Multiple sclerosis: Abbreviated MS. A disease of the central nervous system (CNS) marked by numbness, weakness, loss of muscle coordination, and problems with vision, speech, and bladder control. MS is an autoimmune disease in which the body's immune system attacks myelin, a key substance that serves as a nerve insulator and helps in the transmission of nerve signals. The progress, severity and specific symptoms in MS are unpredictable. One never knows when attacks will occur, how long they will last, or how severe they will be. Most people with MS are between the ages of 20 and 40 at the time of diagnosis. The term "multiple" refers to the multiple places in the CNS that are affected and to the multiple relapses and remissions characteristic of MS.
MS causes demyelinization of the white matter of the brain, with this process sometimes extending into the gray matter. Demyelinization is loss of myelin, which is composed of lipids (fats) and protein. The white matter is the part of the brain which contains myelinated nerve fibers and appears white, whereas the gray matter is the cortex of the brain which contains nerve cell bodies and appears gray. When myelin is damaged in MS, nerve fiber conduction is faulty or absent. Impaired bodily functions or altered sensations associated with those demyelinated nerve fibers give rise to the symptoms of MS.

The understanding of the basic causes of the disease is notably incomplete. It is known that nerve cell death is part of the nervous system injury in MS. It is known, too, that in MS some types of blood cells, namely lymphocytes and monocytes, gain access to the central nervous system by breaking through the blood-brain barrier at sites of inflammation. The migration of these cells across the endothelium (lining of the blood vessels) and the activation of these immune cells depends on the cell surface molecule called integrin.”

Second Point: Separating “is” from “likely”

If you go to the Medicinenet website, you’ll find that a number of the words in the definition are further defined with hyperlinks. I have not included all the hyperlinks because it’s a lot more work to write a post with lots of links in it. What I liked about this definition is that it deals with what is known and doesn’t speculate about what “maybe”, “might be” or “is believed”. I’ve learned that “may” is one of the most important words is multiple sclerosis medical literature.

Here are a few examples, look for the words “believed” and “may”:

While the etiology of MS is unknown, a Th1-mediated autoimmune component driven by myelin protein-specific, proinflammatory cytokine-secreting T lymphocytes is believed to be involved in the pathogenesis.

In general, Th1 lymphocytes secrete proinflammatory cytokines (e.g., IL-2, IL-12, IFN- , and TNF- ) that promote cellular immunity, while Th2 lymphocytes produce anti-inflammatory cytokines (e.g., IL-4, IL-5, IL-6, and IL-10) that promote humoral immunity. Th2 cytokines are associated with the down-regulation of Th1 cytokines and may confer protection from Th1-mediated autoimmune diseases.

Multiple sclerosis (MS) is an autoimmune disease thought to be caused by a concerted attack of T cells, B cells, and macrophages against myelin components of the CNS

Third Point: Learning Doctor Speak

The examples above are parts of opening descriptions of MS from medical journal articles written by MS researchers. Clearly in order to understand what they say one needs to understand some of the more technical language of MS and medical research. I bought a copy of the Dictionary of Multiple Sclerosis (from Amazon) to try and help understand all these terms better. Here are some of the definitions from the dictionary:

Autoimmune disease: Pathological form of autoimmunity that results from the failure of the immune system to distinguish foreign proteins from normal tissue components (self vs non-self) resulting in damage to normal tissues. There is increasing evidence that MS has autoimmune pathological mechanisms. This includes female dominance (as seen in most autoimmune diseases), similarities to EAE, association with certain HLA antigens, association with other autoimmune diseases for patients or relatives, response to immunosuppressive or immunomodulatory drugs.

Integrin: Important mediator of immune cell migration into the CNS in inflammatory diseases. The binding of integrin and its receptor VCAM-1 on the vascular endothelium facilitates leukocyte trafficking to the site of inflammation. Antibodies against a-4 integrin are effective in EAE models and MS.

T-helper 1 cells (Th1): Subset of CD4+ cells that synthesize IL-2, IFN- and TNF-a, or especially TNF-b (lymphotoxin-a) that are involved in cell-mediated immunity. Th1 and Th2 responses are usually reciprocally inhibitory. The major inducer of Th1 responses is interleukin-12 (IL-12). EAE is mediated by Th1 cells so that blocking Th1 development (e.g. by IL-12 suppression) prevents EAE. Likewise, MS is believed to be dependent on an activation of Th1 cells that is not sufficiently counterbalanced by Th2 cells. Enhanced Th1 responses have been shown in MS, although there are still some discrepancies within the Th1/Th2 model.

Cytokines: Soluble glycoproteins secreted by immune system cells that modulate immune and inflammatory responses. They are divided into two broad categories: pro- and anti-inflammatory cytokines. Pro-inflammatory cytokines, including tumour necrosis factor (TNF), interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-g), are associated with the T-helper type 1 (Th1) cell subclass, and upregulate cell mediated inflammatory responses. Anti-inflammatory cytokines include transforming growth factor beta (TGFb), interferons alpha (IFNa) and beta (IFNb) and interleukin-10 (IL-10). Interleukin 4 (IL-4), associated with the T-helper type 2 (Th2) subclass is involved in allergic inflammation, but downregulates cell-mediated immune responses. Cytokines play an important role in MS, based on studies of both the EAE animal model and human disease. The pro-inflammatory cytokines are considered to induce or worsen disease features in MS. In contrast, anti-inflammatory cytokines are thought to be protective and to ameliorate disease features in MS.

T lymphocytes (T cells): Thymus-derived lymphocytes that confer cell-mediated immunity. They co-operate with B lymphocytes, enabling them to synthesize antibodies. T cells are subdivided according to their expression of CD4 or CD8 surface molecules. CD4 cells recognize antigen in association with class II MHC molecules and largely function as T-helper (Th) cells. CD8 cells recognize antigen in association with class I MHC molecules and largely function as T-cytotoxic (Tc) cells. After a Th cell recognizes and interacts with an antigen-MHC II molecule complex on the membrane of the antigen-presenting cell, the cell is activated and secretes various cytokines, which, in turn, activate B cells, Tc cells, macrophages and various other cells that participate in the immune response.

Antigen: Material (normally foreign) that is specifically bound by lymphocytes or antibodies. An antigen capable of eliciting an immune response is an immunogen.

Humoral immune response: Major component of the immune system characterized by the production of antibodies specific for antigenic determinants on foreign pathogens or self-antigens in autoimmune conditions. Although MS is associated with a T-cell-mediated inflammatory response, antibodies may play a role in pathogenesis. Autoantibodies to several myelin proteins including MBP, PLP, MAG and MOG may be present in MS, but their role in disease pathogenesis is unclear. Antibodies may even play a protective role (rationale for the use of normal human immunoglobulins in MS).

Of course a lot of this was hard to read too. Here are a few more words that I did not know the definitions of and I wanted to be certain about what they meant in a medical context so I looked them up on the internet

Gene expression is the first stage of a process that decodes what the DNA holds in a cell. It is the expression of a gene that gives rise to a protein.
How does gene expression occur? It starts of with transcription that gives rise to the middlemen namely the RNA. The RNA relay information from the chromosomal DNA to the cytoplasm where the machinary for protein synthesis resides. Translation occurs following transcription wherein the protein synthesis machinary gets into action and uses its tools to read out the message that the RNA holds.

Macrophage: A type of white blood that ingests (takes in) foreign material. Macrophages are key players in the immune response to foreign invaders such as infectious microorganisms. Blood monocytes migrate into the tissues of the body and there differentiate (evolve) into macrophages. Macrophages help destroy bacteria, protozoa, and tumor cells. They also release substances that stimulate other cells of the immune system. And they are involved in antigen presentation. To do this, they carry the antigen on their surface and present it to a T cells.

Pathogenesis: The development of a disease. The origin of a disease and the chain of events leading to that disease.

Mediate: transitive verb PHYSIOLOGY transfer something: to act as a medium that transfers something from one place to another in the body.

Fourth Point: Understand the Players, Understand the Opponent

This might be a bad analogy, but here goes. If your goal is to stop a football team, you need to understand what their players do and how they work together to move the ball. As I read through all the aforementioned material it seems to me that there is a widely accepted hypothesis (as opposed to proven fact, see second point again if needed) that the MS activity of demyelination is brought about by a coordination of various cellular activities. So this point of interest is to try and identify the key players and what they do.

T lymphocytes
I know I included the medical definition above. This is my effort to explain them in plain English. I’ve found that it helps to think about these cells chronologically, meaning that these cells do things over time and they can grow and change over time. T lymphocyte cells are a broad category of cells that have different names as they mature/change over time. There are 5 kinds if white blood cells (also called Leukocytes) and T lymphocytes are one of them. These cells are called “T” because they originate in the Thymus. While they are maturing in the Thymus they receive an identity through a process called expression and they either become “CD4+ T Cells” or “CD8+ T Cells”. There are a variety of names that these cells are given in medical writing and the key is to know that they are all the same thing. I’m sure there are more names, but here’s what I’ve found so far:

CD4+ T Cells = CD4+ T-Helper Cells = CD4 Positive T Cells = CD4+ T Lymphocytes
CD8+ T Cells = CD8+ T-Cytotoxic Cells = CD8 Positive T cells = CD8+ T Lymphocytes

Now if you set aside the CD8+ T Cells for a bit, the CD4+ T Cells further mature into either Th0, Th1 or Th2 Cells. There are also cells called Th3, but I’ve not found anything that explains exactly where they come from yet and I refuse to assume anything. Medical literature further confuses things by referring to these cells as T-Helper 0 Cells, T-Helper 1 Cells and T-Helper 2 Cells. If you want to read more about this “player” here’s a link to an article titled T cell Classification.

Macrophages
I’ve come to think of these are the garbage collectors. They are another type of white blood cell. There isn’t much more to say. Here’s a link that has a picture of a Macrophage (it’s in the middle of the page under the heading for Monocyte). Here's a website that had some more description of Macrophages.

B lymphocytes
These are another type of white blood cell. They are called “B” because they originate from bone marrow. It is the B lymphocytes that produce antibodies. Here’s a cool web page from CellsAlive that shows how the three would normally work together to get rid of foreign material. The official medical term for foreign material is “antigens”. Antigen is a generic sort of medical term for “stuff that doesn’t belong” like bacteria.

Myelin
Most everyone understands the electrical wire explanation. The key thing about myelin is that it’s a key part of the body that is ultimately damaged by MS. Here’s a good web page about Myelin. Myelin is composed of lipids (about 80%) and proteins (about 20%). The proteins are Myelin Basic Protein (MBP), Myelin Oligodendrocyte Glycoprotein (MOG) and Myelin Proteolipid Protein (PLP).

Oligodendrocyte
This is a member of the Myelin team. An Oligodenrocyte is the cell that makes Myelin in the brain. Here's a weblink to a page that has a picture of one of these cells. Here’s a link to the Multiple Sclerosis Information Trust site that I thought was very helpful. Oligodendrocytes are a member of a larger group of brain support cells that is collectively referred to as Glial cells.

Fifth Point: Equipment, the Tools of the Trade

So those are the key players. I’ll continue with the sports analogy in suggesting that we would want to know about the gear that the opposing players are using to help them carry out their roles. I’m going to also say that while my explanation of things might sound very casual and non-medical, I’m hoping to achieve understanding by organizing this material in a not-so-medical simplified way.

MHC Class 1
These are the football jersey’s that every cell in your body wears. One cell looks at another cell and sees the team jersey and knows that it’s part of you. The medical books refer to this as self/not self discrimination or recognition. Like a jersey the MHC Class 1 (By the way, MHC means Major Histocompatibility Complex) is on the surface of the cell. The MHC Class 1 checks out what’s inside the cell and displays the contents for the immune system to see. When reading about MHC you’ll also see the terms “expression” and “presenting”. Using the football jersey example, you would be right to say that the MHC Class 1 is presenting or expressing that it is a Pittsburgh Steeler.

MHC Class 2
Similar name, but totally different gear. They are similar because they are displayed on the outside of the cell. Only certain kinds of cells can express MHC Class 2. Two of the cells that can are Macrophages and B Lymphocytes. So there you go, additional gear to think about. In this case we’re not talking about jerseys though. Suppose you kept a list of the opponent’s you had beaten with names, info about your successful strategy and little torn samples of jersey from them so that when you run into them again, BAM! You would know what to do, meaning you are keeping a catalog of sorts of prior victories. To make this even easier, you write all this information on your jersey so the other folks on your team can read it too. They are not reading it to know if you are part of the team, that’s what the jersey is for. They are reading it to know that this is a previously defeated opponent and we already have a playbook ready for taking the bad guys down. In this analogy, the players are “presenting” or “expressing” information about the opponent which in medical language is called an “antigen. So, the MHC Class 2 is created by and displayed on Macrophages and B Lymphocytes. Since these cells are presenting the antigens this way, Macrophages and B Lymphocytes are also called Antigen Presenting Cells or APC.

Peptides
You might have wondered about the little torn bits of jersey in the last analogy. These are Peptides. When a Macrophage or B Lymphocyte consumes and kills an Antigen, the Macrophage or B Lymphocyte cells don’t waste the win. They break the Antigen down into tiny fragments and use those fragments to make the MHC Class 2 molecules. The part of the MHC Class 2 molecule that is the fragment of the defeated opponent’s jersey is called the Peptide. You might want to review all this together. I recommend clicking the link to CellsAlive above for the most readable explanation of how these work together. I also liked the explanation titled “What the Heck is an MHC Molecule”. Here’s another more advanced webpage I looked at and here’s one more. I think you might like checking some of these out to understand better and I also like that they have lots of links to more information.

Cytokines
If you have ever seen Peyton Manning play football, you know that he spends a lot of time yelling instructions (audibles) to his teammates before he takes the snap. I'm not a Manning Fan, but this process of shouting out a new set of instructions to his teammates based on what he sees in front of him is impressive. Now let's suppose (I'm building up the analogy here) he's not allowed to yell out the instructions, he's only allowed to send little notes to everyone telling them what to do, maybe to run faster, or run slower. These little notes are Cytokines. A bunch of different "players" can write these notes and pass them out, including Macrophages and all the different kinds of Lymphocytes (explained above). Cytokines is a general term, you'll see other terms for the specific kinds of "little notes" like, lymphokine, monokine, chemokine, interleukin and interferons. The shorthand for some of these Cytokines are; IL=Interleukin and IFN=Interferon. There are a bunch of these and the list of them is quite technical looking/not so user friendly. Don't panic! The key thing to know right now is that these are a communication tool for cells. Here's a link to a page that is somewhat understandable and has a table that lists out some types of cytokines. Here's a link to a chart that you might need to click on to blow up and print - a visual version of the table. (I found that I got a better printout of the chart by right clicking on the picture and saving it first)

Sixth Point: Being in the Right Place at the Right time

I’ve talked about players and equipment. Now it’s time to add some perspective by associating places. I’m not meaning positions on the field, rather I’m thinking of players belonging on the field and sidelines and spectators belonging in the stands. In a football stadium these groups are kept segregated by a fence or a wall. In the body, the blood is supposed to be segregated from the brain by the …

Blood Brain Barrier
Oddly enough, if you read through a lot of medical journals there is a lot of medical interest in trying to figure out how to get stuff through the Blood Brain Barrier, namely medicine. The barrier keeps the fluid in the brain (cerebro-spinal fluid) separate from the blood that rushing through the veins in your head. This barrier generally allows stuff to get through that the brain needs, like water, oxygen and glucose while keeping stuff like bacteria out. Here’s a diagram of the Blood Brain Barrier that shows how it’s a wall that lines the blood vessels that are directed through the brain. Some of the parts of the blood brain barrier that are important to know about are Endothelial Cells (these line the blood vessel and act to form a seal of sorts) and Astrocytes (these are like Oligodenrocytes in that they are part of the brain support cell group referred to as glial, see midpage ). Here’s a page that has a nice illustration of the blood brain barrier.

Central Nervous System
The Central Nervous System (CNS) is composed of two parts, the brain and the spinal cord. This is where the Oligodendrocytes and Myelin are found. In the football game example the CNS are the stands where the fans watch the game. The key here is that it’s an area that is segregated from the players by the blood brain barrier.

Seventh Point: The Anatomy of a Best Guess

Obviously the body is designed to be healthy wherein the players and the equipment are supposed to come together and play a game for the benefit of the spectators. In MS, the players gain access to the stands and use their equipment to beat-up the fans. Why?

No one knows with certainly, but there are widely accepted guesses. Now my goal is to try and put all the above information into practice. Can I better understand the medical language of MS? Here’s my objective – to more fully comprehend a predominate hypothesis of how MS happens. Here’s the hypothesis (from the UCSF MS Center ):

In this model, the process begins with an infection by a virus or other external antigen (a substance, foreign to the body, that excites an immune response). Once this antigen gets into the blood stream, it is "eaten" by a macrophage, which digests the proteins of the virus or antigen to form smaller particles called peptides. Some of these peptides are then brought to the macrophage cell surface, where they are displayed inside a hand-like structure called an MHC (major histocompatability complex) molecule. In the cartoon, the peptide appears as a small oval ball held in the MHC. This MHC-peptide display can be recognized by special receptors on the surface of a particular white blood cell called the T cell. Only the TH1 subset of T cells that have receptors with a perfect fit for the MHC-peptide complex will recognize this display. Once recognition occurs, the TH1 cell undergoes activation of its cellular functions. This activation results in a proliferation of the number of TH1 cells that are capable of recognizing the MHC-peptide complex and the expression of additional T cell surface receptors that are capable of sticking to the so-called endothelial cells which line the blood vessel wall. Once attached, the TH1 cell secretes chemicals called proteases that facilitate migration through the endothelial cells and into the CNS. Once the TH1 cell arrives in the CNS, it may encounter a glial cell. Like the macrophage in the blood stream, the glial cell is also capable of presenting a MHC-peptide complex to T-cells. In MS, there is reason to believe that the peptide presented by the glial cell is a breakdown product of myelin, which is indistinguishable from the original viral peptide recognized by the TH1 cell. This "mistaken identity” restimulates the TH1 cell to proliferate and undergo further activation of cellular function. This activation leads to the production of chemicals called cytokines, which are small proteins that have effects on other cells. Some of these cytokines produced by TH1 cells, such as interleukin-2 (IL-2), interferon-gamma (IFN-g), tumor necrosis factor-alpha (TNF-a), and interleukin-1 (IL-1), promote inflammation. Another subset of T-cells called TH2 cells secrete different cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor growth factor-beta (TGF-b), which counteract or regulate pro-inflammatory cytokines. The balance between pro-inflammatory and immuno-modulating cytokines is probably important in regulating disease activity. An imbalance favoring pro-inflammatory cytokines may result in demyelination.

That was a LOT more detailed than the definition we started with. But some of it made sense, yes? I’d hope that more of it made sense than before you started reading this whole narrative. Let’s break it down into parts and try to understand it better.

In this model, the process begins with an infection by a virus or other external antigen (a substance, foreign to the body, that excites an immune response). Once this antigen gets into the blood stream, it is "eaten" by a macrophage, which digests the proteins of the virus or antigen to form smaller particles called peptides. Some of these peptides are then brought to the macrophage cell surface, where they are displayed inside a hand-like structure called an MHC (major histocompatability complex) molecule.

The 4 key terms in this part are Antigen, Macrophage, Peptides and Major Histocompatability Complex (in this case MHC Class 2). One of the structural problems with MS research is that no one really knows exactly what the cause is. In this case an unspecified foreign substance gets in the body, gets consumed by the macrophage and is broken down and some of the parts get made into peptides which can be displayed as part of the MHC Class 2 molecules on the macrophage surface. The next part says:

In the cartoon, the peptide appears as a small oval ball held in the MHC. This MHC-peptide display can be recognized by special receptors on the surface of a particular white blood cell called the T cell. Only the TH1 subset of T cells that have receptors with a perfect fit for the MHC-peptide complex will recognize this display. Once recognition occurs, the TH1 cell undergoes activation of its cellular functions.

I didn’t include the cartoon. But if you follow the link above, you can see it. A lot of the illustrations of peptides make the MHC Class 2 molecule out to look like a hotdog in a bun with the peptide being the hotdog. The white blood cell, T-cell, TH1 subset that is mentioned are all the same cell. See T Lymphocytes above if this is not clear. Here’s another way of seeing how these are grouped:

White Blood Cells
.....T Lymphocytes
..........CD4+ T Cells
...............T Helper 0 Cells
...............T Helper 1 Cells
...............T Helper 2 Cells
..........CD8+ T Cells
.....B Lymphocyes
.....Macrophages

So the T Helper 1 cell has the ability to connect up with the macrophage that is displaying the MHC Class 2 molecule. The T Helper 1 cell is stimulated by this display and wakes up and is activated.

This activation results in a proliferation of the number of TH1 cells that are capable of recognizing the MHC-peptide complex and the expression of additional T cell surface receptors that are capable of sticking to the so-called endothelial cells which line the blood vessel wall. Once attached, the TH1 cell secretes chemicals called proteases that facilitate migration through the endothelial cells and into the CNS.

Once activated the T Helper 1 cells multiply. The T Helper 1 cells also have the ability to attach to the lining of the veins that run through the brain. This lining is the endothelial cells. Ordinarily the T Helper 1 cells cannot penetrate the endothelial cells, but in MS it is believed that they do. Once this happens the blood brain barrier has been breached.

Once the TH1 cell arrives in the CNS, it may encounter a glial cell. Like the macrophage in the blood stream, the glial cell is also capable of presenting a MHC-peptide complex to T-cells. In MS, there is reason to believe that the peptide presented by the glial cell is a breakdown product of myelin, which is indistinguishable from the original viral peptide recognized by the TH1 cell. This "mistaken identity” restimulates the TH1 cell to proliferate and undergo further activation of cellular function.

We’re not sure about the glial cell, they are mentioned above regarding blood brain barrier and Oligadendrocytes. In this hypothesis the T Helper 1 cell encounters a glial cell which unfortunately has an MHC Class 2 molecule on its surface that contains a peptide made from myelin. This causes the T Helper 1 cell to recognize myelin as an antigen, meaning the T Helper 1 cell now thinks myelin is a foreign invader like bacteria. This causes the T Helper 1 cell to activate again and initiate a process of multiplying to “wipe out” the myelin.

This activation leads to the production of chemicals called cytokines, which are small proteins that have effects on other cells. Some of these cytokines produced by TH1 cells, such as interleukin-2 (IL-2), interferon-gamma (IFN-g), tumor necrosis factor-alpha (TNF-a), and interleukin-1 (IL-1), promote inflammation. Another subset of T-cells called TH2 cells secrete different cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor growth factor-beta (TGF-b), which counteract or regulate pro-inflammatory cytokines. The balance between pro-inflammatory and immuno-modulating cytokines is probably important in regulating disease activity. An imbalance favoring pro-inflammatory cytokines may result in demyelination.

Cytokines are a huge area of interest in MS. In the example the T Helper 1 cell emits cytokines and these send the message to other cells that it’s important to be activated against myelin. I’ll need to take a closer look at Cytokines in a separate writing. The overall point here is that you can understand doctor speak.

There are other theories, this is not set in stone. Here’s another idea about the cause of MS.

Eighth Point: There are Multiple Points

First of all I did this because I wanted to understand MS better and have a basis for assessing a lot of the claims that are made about supplements. I couldn’t find all this information in one place and it took me about 2 weeks to assemble this. So, if it was this much work for me, then I figure I’m helping someone by typing this all up and putting in the links to some of the stuff I looked at. The main thing I observed about MS information is that authoritative sites, like universities and medical journals really lack beginning to end plain English explanations of things. I understand that they are not going to adopt the football analogy, but the medical folks need to know that they are not serving the patient by keeping all the information in this coded language I call doctor speak.

Secondly, I hope that you might take this information and use it as a launch pad to gain more information. Be careful about where you get your information. I’ve been careful to put in links so you can assess the accuracy of the information yourself. Sites that hype supplements or that provide testimonials are not very authoritative, they might be attractively persuasive, and they might even have a quote from a doctor, but please learn to discern the examined information from hype.

Thirdly, I know I have not got a complete picture here and that there are some holes. I found other topics that I want to look into like the entire Cytokines thing. I want to know more about Protease, Monocytes and Integrin too. I’d also like to find more understandable pictures. There are also a bunch of minor medical terms that ought to be defined. The word “Mediate” comes to mind as being splashed all over this stuff.

Fourthly, I hope to be corrected. Yes, I admit to being fallible. I will edit this post from your comments. Please post stuff that includes links. Think about the second point before you click the post button. Drop me a message, or post a reply and tell me what you think. napay

Other similar posts on my road to understanding MS:

Understanding MS 101: Doctor Talk and People Talk
Understanding MS 102: My Doctor is Expressing Cytokines: Code Cipher Training
A Layman’s Review of Glyconutrients – not good
Turmeric, Curcumin and IL-12 - good
C is for Controversy – good

Most definitions begin with the idea that MS is an autoimmune disease. Some people here (and even some researchers) disagree; they believe that work by two men in Australia (John Prineas and Barnett) points to some trigger and THEN the immune system comes into it.

I believe MS was first diagnosed in 1868, though it had been known since the 14th century; I find it incredible that there is still a question about WHAT it is!

I applaud your research, notasperfectasyou, and I thank you for putting it in terms understandable by me.

I know you prefer links and legitimate sources with information and I don't have those today--just some questions for you. I start with the basic definition of this disease: "autoimmune." You wrote in one post, "I refuse to assume anything." What evidence is there that MS is autoimmune? Aren't we assuming that is so? Even scientists seem divided on this. And, of course, the pharmaceutical companies will promote the idea--that's the problem they have drugs for!

As you will recall, I am the "inflammation/insulin" proponent. (It seems to "fit" my case so well.) I know that insulin is caustic. After causing cell damage, wouldn't the macrophages clean up and put "pieces of the jerseys" out there, thereby getting other cells of the immune system to go after "self?" Since insulin ferries glucose to the cells where it is used for energy, does it cross the blood-brain barrier when glucose is used by the brain? Couldn't an excess cause damage there?

How do I find these answers? How do I find a scientist who might know or look into these things?

I've been away. I'm going to post the 102 post now. A lot has happened in 2 months. I dropped my MS researching hat to plan a family vacation to Boston, a city that does not believe in street signs. We're also off Avonex and have transitioned to Copaxone and done one of eight starting Novantrone. We also got permission from the church to get married and we're deep in wedding planning. It's a lot. This is why I have been away. I'm posting up the 102 post incomplete. It's more important to get it up than to finish it. napay

NOTASPERFECTASYOU: YOU ARE AN AMAZING FIENCE TO WHOM I AM HONORED TO CALL MYSELF YOURE BRIDE TO BE! YOU WORK FEVERISHLY ON MY/OUR JOURNEY AND HOW YOU MAKE ME SMILE ALL THE WAY THRU IT!!!! KEEP UP YOUR TEACHING/TRAINING AS I KNOW YOU HAVE TOUCHED US ALL!!!! I LOVE YOU! K

This post has languished as Ken has expanded his research and Kim is now on an antibiotic protocol. It deserves a bump, though, just for some insight into the common thinking (much of which I think is incorrect) on the subject of MS.

Actually, I think this is good and valuable - in that, it's part of the journey as it has unfolded. In terms of our view of MS and what causes it, no. But, folks just getting into it need to know the language. I big giant copy of McAlpines says nothing about ABX. Ken

I am new here and have never before heard the antibiotic theory. Please could you tell me where best to find a simple explanation of what I need to do? Could it help once the MS has reached secondary progressive stage??