Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis, or encephalomyelitis disseminata) is an idiopathic disease of suspected autoimmune causation, where the body’s immune responses attacks a person’s central nervous system (brain and spinal cord) leading to demyelination[1]. Onset of the disease usually occurs in early adulthood and tends to be more common in females. Prevalence of the disease ranges between two (2) and 150 per 100,000 people.

MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other. This communication occurs when electrical signals called action potentials travel down long fibers known as axons that are wrapped in an insulating substance called myelin. In a person with MS, their immune system attacks and damages the myelin; the result is that the damaged axons can no longer conduct signals. The name – Multiple sclerosis – refers to the scars (scleroses – better known as plaques or lesions) in the white matter of both the brain and spinal cord, which is primarily composed of myelin. Although much is known regarding the mechanisms involved in the disease process, the exact cause is still unknown. Theories as to the cause include genetics or infection, however, different environmental risk factors have also been found.

One of the intriguing things about MS is that almost any neurological symptom can appear with the disease, and often progresses to both physical and cognitive disability. Patients can also suffer from neuropsychiatric disorders[2]. MS can take several forms with new symptoms occurring either in discrete attacks (relapsing form) or slowly accumulating over time (progressive form). Between these attacks, symptoms might go away completely, however, permanent neurological problems often occur – especially as the disease progresses.

Currently, there is no known cure for MS. Treatment attempts to restore function following an attack, prevent future attacks, and prevent disability. MS medications can have adverse effects and/or be poorly tolerated; for that reason many patients pursue alternative treatments, despite the lack of supporting scientific study. The prognosis of a patient with MS can be difficult to predict; it depends on the subtype of the disease, initial symptoms, and the degree of disability the person experiences as the disease progresses. For example, when country musician Clay Walker was first diagnosed with MS in 1996, doctors told him that he would be wheelchair bound in four (4) years and dead by 2004. Instead, he has been in remission since 1998. Overall the life expectancy of people with MS is nearly the same as that of the unaffected population.

How is MS classified?

Several subtypes (patterns) of progression have been identified. These subtypes use the past course of the disease as a guide to identify how it will behave in the future. These patterns are also important for helping the person’s medical team to make therapeutic decisions. In 1996, the United States National Multiple Sclerosis Society standardized four (4) subtype definitions: relapsing-remitting, secondary-progressive, primary-progressive, and progressive-relapsing[3].

Relapsing-remitting

This subtype of MS is characterized by unpredictable relapses followed by months – or even years – of relative quiet (remission) with no new signs of disease activity. Deficits suffered during attacks can either resolve or leave sequelae. This describes the initial course experienced by 85 – 90% of individuals with MS. In cases where deficits always resolve between attacks, it is sometimes referred to as benign MS[4].

Secondary-progressive

This subtype of MS describes those patients with initial remitting MS, who then begin to have progressive neurological decline between acute attacks without a definite period of remission. Occasional relapses and minor remissions can appear. The median time between disease onset and conversion from relapsing-remitting to secondary-progressive MS is 19 years.

Primary-progressive

This subtype is used to described the approximately 10% - 15% of people who never experience a remission following their initial MS symptoms[5]. It is characterized by the progression of disability from onset, with either no or only occasional and minor remissions and improvements. Interestingly, the age of onset for this subtype is later than that seen with other subtypes.

Progressive-relapsing

Individuals with this subtype experience steady neurological decline from the onset of the disease as clearly defined superimposed attacks.

Cases with non-standard behavior have also been described. Sometimes referred to as borderlines forms of MS, these include Devic’s disease[6] (pictured at right), Balo concentric sclerosis, Schilder’s diffuse sclerosis, and Marburg multiple sclerosis. There is some debate as to whether these are atypical variants of MS or a total different disease.

 Are there risk factors for MS?

Although the exact cause of MS remains unknown, it is believed that it might have a number of genetic, environmental, and immune factors. In addition, there is a hypothesis that states that individuals with a genetic predisposition who become infected with certain viruses induce an immune response that attacks their own nerve cells. The following are also known risk factors for MS:

Latitude

Latitude is more closely related to MS than any other risk factor. The risk of developing MS increases, the further away from the equator a person lives.

Family history

A person with a first-degree relative who has MS is fifteen (15) times more likely to develop the disease than the general public. Twins from the same egg (monozygotic) are more likely to have MS than those from separate eggs (dizygotic) if one twin is affected.

Sex

Females are more likely to develop MS than males. The reason for this difference is unknown.

Race

MS presents more often in populations of northern European ancestry.

Vitamin D level

Low vitamin D level has been shown to increase the risk of developing multiple sclerosis.

What is the pathophysiology of MS?

MS is an auto-immunological disease

It is believed that MS is an immune-mediated disorder that could initially be triggered by a virus etiology.  The damage is believed to be caused by the person’s own immune system which attacks the nervous system – possibly as the result of exposure to a molecule with a similar structure as its own.

Lesions

 The name multiple sclerosis refers to the scars (scleroses – also known as plaques or lesions) that form in the nervous system. These lesions most commonly involve white matter areas close to the ventricles in the cerebellum (pictured at left), brain stem, basal ganglia, and spinal cord; it can also affect the optic nerve. The function of these white matter areas – specifically the cells – is to carry signals between grey matter areas (where processing takes place) and the remainder of the body. Also, it should be noted, MS rarely affects the peripheral nervous system.

MS destroys oligodendrocytes – the cells responsible for creating and maintaining the myelin sheath. The disease causes the thinning or, in some cases, the complete loss of myelin and, as it progresses, the transection (cutting) of the neuron’s extensions or axons. A repair process – known as remyelination – takes places during the early phase of the disease, however, the myelin sheath can’t be completely rebuilt. As a person suffers repeated MS attacks, the number of effective remyelinations becomes fewer and fewer until a scar-like plaque is built up around the damaged axons.

Blood-brain barrier breakdown

The blood-brain barrier is a capillary system that should (emphasis added) prevent the entrance of T cells into the nervous system. Under normal circumstances, the blood-brain barrier is not permeable by these types of cells unless triggered by an infection or virus, which decreases the integrity of the tight junction forming the barrier. Once the blood-brain barrier regains its integrity – after the infection or virus has cleared – the T cells remain trapped in the brain.

Inflammation

Apart from demyelination, the other pathologic hallmark of the disease is inflammation. Looking at it from a strictly immunological standpoint, the inflammation is the result of T cells that are a type of lymphocyte. What happens is that the T cells recognize myelin as a foreign body and attack it. This triggers the inflammatory process, stimulating other immune cells and soluble factors such as cytokines and antibodies. It also causes leaks to form in the blood-brain barrier that results in a number of other damaging effects such as swelling, activation of macrophages, and other destructive proteins.

How is MS diagnosed?

MS can be difficult to diagnose since its signs and symptoms can be similar to many other medical conditions. Because of this, medical organizations have created diagnostic criteria to standardize the process. Historically, both the Schumacher and Poser criteria were popular. Currently, the McDonald criterion focuses on a demonstration with clinical, laboratory, and radiological data of the dissemination of MS lesions in time and space. A diagnosis cannot be made until other possible conditions have been ruled out AND there is evidence of demyelinating events that are separated both anatomically and in time.

Clinical data alone can be sufficient for a diagnosis of MS if the individual has suffered separate episodes of neurological symptoms characteristic of MS. The most commonly used diagnostic tools for MS are neuro-imaging, analysis of cerebrospinal fluid, and evoked potentials. Gadolinium can be administered intravenously (as a contrast) to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the time the MRI is being done.

Testing of cerebrospinal fluid (CSF) obtained from a lumbar puncture (pictured at left) can provide evidence of chronic inflammation of the central nervous system. The CSF is tested for oligoclonal bands, a type of inflammation found in 75% - 80% of people with MS. Since there is no known test perfectly specific to MS, only biopsies or post-mortem examination can give an absolutely certain diagnosis.

How is MS treated?

Although there is not a known cure for multiple sclerosis, several therapies have proven helpful. The primary goals of therapy are to restore function following an attack, prevent new attacks, and preventing disability. As with medical treatment, medications used in the treatment of MS have several adverse effects.

Management of acute attacks

During symptomatic attacks, the administration of high doses of intravenous corticosteroids – such as methylprednisolone – is the routine therapy for acute relapses. The aim of this type of treatment is to end the attack sooner and leave the patient with fewer lasting deficits. Although it has proven generally effective in the short term for relieving MS symptoms, these treatments do not appear to have a significant impact on long-term recovery. Potential side effects from the corticosteroids include osteoporosis and impaired memory – the latter being reversible. For severe cases that do not respond to the corticosteroids, plasmapheresis is an option.