Multiple sclerosis is primarily considered a disease of demyelination. More specifically, it is considered to be a myelinoclastic disease in which normal healthy myelin tissue (the outside sheath of a nerve cell) starts to break down. The cause of the breakdown is unknown.
The pathology of MS is also not fully understood because although it is considered to be a demyelinating disease more research has shown that the axon located inside the myelin sheath may break down as well. Lastly, the breakdown of myelin only occurs in select areas of the brain, and other areas of myelin in the brain are spared.
Myelin makes up the bulk of the white matter portion of the brain. It provides structure, support and insulation. Myelin is mostly fat, which is what makes it a good insulator. There is a layer of protein sandwiched in the middle of the fat layer to give it strength. Since most of the brain is white matter, most of the brain is made up of fats making it the fattest organ in the body.
The cause of demyelination in multiple sclerosis is still believed to be an internal agent, such as an overactive immune system, an inflammatory reaction, or an attack from an external foreign agent, such as a virus or toxin.
However, according to Dr. Franz Schelling, an Austrian physician and an expert on the subject of multiple sclerosis, there has been very little evidence in the way of white blood cells, such as immunocytes, lymphocytic infiltrations or scavenger cells associated with multiple sclerosis to support the immunological or inflammatory theories. This includes sources from environmental triggers, dietary or other causes. Some researchers believe that when immunological and inflammatory evidence is found, it is more likely to be a reaction to the disease process rather than the cause of it. Dr. Schelling is also known for his theory on backjets.
While demyelination is still considered to be the hallmark of multiple sclerosis, recent research shows that contrary to long held beliefs, it may not be the primary problem. As was stated above, it has been shown that the portion of the nerve inside the myelin sheath, called the axon, may start to breakdown well before the myelin does. In addition, studies have connected demyelination to Alzheimer’s and Parkinson’s and other neurodegenerative diseases implying that it is part of the general neurodegenerative process rather than the cause. Lastly, viruses tend to attack tissues and cause them to breakdown from the outside in. The nerves in MS, on the other hand, tend to breakdown from the inside out.
Location of MS Lesions
The lesions of MS show up as hyperintensity signals, which look like bright white spots on brain scans. For the most part the myelin breakdown in MS occurs in the brain and sometimes in the cervical cord. Interestingly, the areas where demyelinated lesions are typically found tend to be around the larger veins in the brain. They get progressively smaller and fewer in number as you follow the bloods vessels counter current to progressively smaller and smaller veins and back to the arteries.
This doesn’t make sense in light of viral attacks. Viruses have no muscles for locomotion. They simply follow the blood stream. If they didn’t they would have to grow muscles, which would make them bigger and less effective in getting where they do. This begs the question as to why the lesions are found toward the terminal (smaller) end rather than toward the beginning point of the circulatory routes.
In addition to being located around the larger veins, the lesions seen in the brain tend to be located above the covering over the cerebellum, or hindbrain. This covering is called the tentorium cerebelli. The location of MS lesions are typically surpratentorial, meaning above the tentorium.
Lesions also tend to be located around the large chambers in the middle of the brain, called ventricles. The ventricles contain cerebrospinal fluid called CSF. The lesions in MS are often found in the periventricular area of the chamber.
In contrast to the lesions in the brain, which are found around the chambers in its core, the lesions seen in the cervical cord tend to show up along its outer flanks.
The picture on the right shows lesions (brown spots) on the cerebellum and cervical cord.
Mysteriously, these lesions stop at the shoulders and spare the rest of the myelin in the cord. This doesn’t make sense if the problem is immunological or inflammatory in nature. It should continue down the cord as there is no disconnect between the nerves and myelin at this level.
The fact is, conditions associated with demyelination don’t stop at the shoulders. There are similar diseases of demyelination that occur in the lower cord from the shoulders down. One fairly well known condition is amyotrophic lateral sclerosis, more commonly called Lou Gehrig’s disease. Other conditons include Devic’s disease and progressive lateral sclerosis (PLS).
From a patient’s point of view, however, it doesn’t matter which part of the nerve breaks down first, or where the demyelination fits into the degenerative process. The outcome for the patient is the same in terms of disability.
But for the scientist and or the physician if the demyelination is not caused by viruses, immunological or inflammatory reactions, then what could possibly cause the myelin to breakdown?
As will be discussed in detail below, Dr. Zamboni suggests that the cause of multiple sclerosis is due to venous drainage issues in the brain he calls CCSVI. The success of his surgical liberation procedure further bolsters his theory. Moreover, venous flow in the brain affects CSF production and flow. Therefore, venous drainage issues can affect CSF flow and pressure in the brain.
The demographics of MS are just as mysterious as everything else about the condition. In the picture below, the areas depicted in blue have a high risk for MS. The red area has a probable high risk for MS. The dark and light yellow areas have low and probable low risks respectively. The areas in green are the geographic dividing line between risks associated with living in northern versus more southern climates closer to the tropics. For instance MS affects people living in northern temperate climates more than people living in southern climates. The incidence is very low in tropical regions.
Another interesting fact about demographics is, if you move a child from southern to northern climates their incidence increases to the same level as if they were born there. Conversely, if you move a child from north to south their incidence of getting MS drops to the same level as if they were born in the south. On the other hand, moving adults from north to south and south to north has no affect on their chance of getting MS.
An additional demographic finding is that regardless of where they live, Asians have a very low incidence of MS. Furthermore, Eskimos, who are ethnic descendants of Asians living in the most extreme northern environments hardly get any MS at all. But, Asians living in the white areas are associated with other risks in that they don’t get classic MS but they do get a variant of MS called Devic’s disease or neuromyelitis optica (NMO). Could it be that the demographics of MS are associated with weather related trauma and differences in racial designs of the skull? Certainly people living in snowier and icier climates have significantly higher incidence of slips and falls and winter related motor vehicle and sports related whiplash type injuries. Skiers are prime candidates for serious falls and trauma. Hockey is another high risk sport.
A New Cause of MS called CCSVI
As mentioned above, multiple sclerosis has a new theory regarding its cause called chronic cerebrospinal venous insufficiency, or CCSVI. CCSVI is more than just a new theory about the cause of multiple sclerosis. It also offers fresh hope for a cure for those afflicted with this devastating condition.
The theory and term was proposed by vascular surgeon Paulo Zamboni of the University of Ferrara in Italy. Dr. Zamboni blames the cause of CCSVI on stenosis in jugular and thoracic veins.
What is promising is that, Dr. Zamboni has been having remarkable success treating patients with multiple sclerosis using venous balloon angioplasty to open up the constricted veins. He initially called it the liberation procedure. Mutliple sclerosis patients soon embraced the term, not so much because it frees the venous congestion as envisioned by Zamboni, but because it frees them from the prison of their oftentimes terribly disabling symptoms.
The examination and procedure has spread to other countries and is now being offered to patients outside Italy. There have been some problems, but so far, not many considering the number of surgeries performed. Some problems are lack of improvement in symptoms and nonlasting relief of symptoms. The procedure is still new, though, and has room to grow and improve. There is also debate amongst the surgeons about the preference of using venous stents as opposed to balloon angioplasty. In any case, even considering the problems, the results have been stunning. More than that, the new direction points to a cure for an age old mystery.
Interestingly, the scientific community hasn’t totally embraced this new theory for the cause of multiple sclerosis. They are skeptical about the long-term benefits of the surgical cure.
Depite the fact that the theory makes sense and surgery appears to work well, there are some problems with the theory. The first is that it fails to explain the unusual demographics associated with multiple sclerosis. The second is that it fails to explain the peculiar location and nature of the lesions seen in multiple sclerosis. See the MS treatment page for addtional information on treatment.
Optic neuritis is covered on a separate page. You may also find the following pages interesting due to their relationship with MS: Ehlers Danlos, Brain Cooling and the Cranial Veins and dysautonomia.