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Multiple Sclerosis

Pathology || Signs and Symptoms || Diagnosis || Treatment || Overview ||
Related Articles || References and Resources || Leave a Comment || Search

Pathology





If we break the term multiple sclerosis down, we literally get "multiple scars". And in multiple sclerosis the scaring takes place in the central nervous system. The pathology of why multiple sclerosis occurs is not yet fully understood. We do know that it is an autoimmune condition in which the body attacks itself.

The object of that attack in multiple sclerosis is myelin. Myelin is a fatty substance that insulates neuronal axons. You can think of myelin as the rubber coating around electrical wiring. The insulating role of myelin helps axons send information rapidly from one neuron to the next. Interestingly, multiple sclerosis only affects myelin created by oligodendrocytes, which are glial cells (ie: neuron support cells) found in the central nervous system. Multiple sclerosis does not affect myelin formed by Schwann cells, which are located in the peripheral nervous system.

The damage to myelin is thought to be caused by T-cells. T-cells are a branch of the adaptive immune system. Usually T-cells do not invade the central nervous system, but in multiple sclerosis some antecedent event (possibly infection) allows T-cells to gain access to the CNS. In genetically susceptible people these trapped T-cells "see" myelin as a foreign substance and attack it with resulting inflammation and scaring (in the brain, scaring is called "gliosis").

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Signs and Symptoms

The classic case of a multiple sclerosis patient is multiple neurological complaints spaced out in time. These neurological symptoms can be highly variable. Often times patients will have blurred vision or blindness if demyelination occurs at the optic nerve. This is known as optic neuritis and is a common feature in multiple sclerosis patients.

In addition, weakness of an extremity can occur and can be partial (paresis) or complete (paralysis). Difficulty speaking and swallowing can occur, as can bowel and bladder incontinence. Sensory deficits such as numbness and tingling are also common symptoms. If the cerebellum or spinocerebellar tracts in the spinal cord are involved loss of coordination can occur (ataxia).

There are many other symptoms that can be seen in multiple sclerosis depending on which part of the central nervous system is involved. Ultimately, if a patient returns with several neurological complaints spaced out in time, then multiple sclerosis should be high on the list of possible diagnoses, and the patient should be referred to a neurologist who specializes in diagnosing multiple sclerosis.

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Diagnosis

The diagnosis of multiple sclerosis is based on clinical and supporting laboratory evidence. There is no single test that can determine if you have the disease for sure, but there is a set of guidelines that can help the clinician determine if multiple sclerosis is the most likely diagnosis.

These guidelines include:

(1) Signs and symptoms referable to the central nervous system.
    (a) Symptomatic episodes should last at least 24 hours.
    (b) Two or more symptomatic episodes at least one month apart.
(2) Two or more lesions (ie: "scars") seen on MRI of the brain (see image below).
(3) Physical exam findings supporting central nervous system disease.
(4) Cerebrospinal fluid results consistent with a diagnosis of multiple sclerosis.
(5) No other disease that could explain the symptoms and findings.

MRI of Multiple Sclerosis

Many other tests are often performed to rule out other causes for a patient's symptoms. Testing for systemic lupus erythematosis, Lyme disease, neuro-syphilis, vitamin B12 deficiency, and thyroid disease are common adjunctive tests.

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Treatment

There is currently no cure for multiple sclerosis. However, like many other autoimmune disorders, there are several disease modifying medications that can slow its progression.

The first class of modifying medications are known as the "interferons". Interferon is believed to act through several different mechanisms. It inhibits white blood cell proliferation (T-cells are one type of white blood cell) and decreases antigen presentation by immune cells. It also reduces T-cell migration and switches the body towards an anti-inflammatory state. These effects help decrease the inflammation associated with multiple sclerosis. There are currently three different formulations of interferon on the market for multiple sclerosis. The first two are interferon β-1a formulations known as Avonex and Rebif. The third is an interferon β-1b formulation known as Betaseron.

Another medication known as glatiramer acetate (aka: Copaxone) acts as a possible myelin "mimick", protecting normal myelin from attack. Copaxone is a synthetic polymer of four amino acids (ie: the building blocks of protein) found in normal human myelin. The exact mechanism of Copaxone's actions are unknown.

Natalizumab (aka: Tysabri) was approved for use in multiple sclerosis. It is a monoclonal antibody that binds to, and inhibits the function of α4-integrin. α4-integrin is a cell adhesion molecule found on white blood cells that normally allows them to move into body tissues to fight infection. By blocking this movement, natalizumab is thought to decrease the number of T-cells that enter the central nervous system.

Another medication known as mitoxantrone is also used in the treatment of multiple sclerosis. It was originally designed as a cancer medication. Its mechanism of action is to disrupt DNA synthesis and repair by inhibiting a protein known as topoisomerase.

Patients who are acutely symptomatic (ie: having a "flair") are treated with intravenous steroids. Methylprednisolone is the most common steroid used in patients with the acute onset of neurological symptoms.

The goal of all of these medications is to dampen the immune response and prevent the abnormal inflammation occuring in the central nervous system. Because of this, many of these medications have serious side effects that include the risk of major infections.

Finally, depending on a patient's symptoms, therapies designed to mitigate them may be used as well. Medications like baclofen are commonly used for spasticity; dalfampridine (Ampyra) can help patients walk longer distances. It is important to not forget to prescribe medications that help reduce the symptoms of multiple sclerosis.

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Overview

Multiple sclerosis is considered an autoimmune condition in which the body attacks the myelin surrounding axons (ie: the "insulation around the wires"). This process only occurs in the central nervous system. Symptoms are numerous and depend on what area of the brain and/or spinal cord a "flair" occurs. Everything from weakness to blindness can occur. Diagnosis is based on clinical signs and symptoms, as well as supporting evidence such as MRI findings and cerebrospinal fluid abnormalities. Treatment is with disease modifying agents like copaxone and various interferons.

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Related Articles

- Lyme disease (borrelia burgdorferi)

- Introduction to the nervous system

- Vitamin B12

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References and Resources

(1) Baehr M, Frotscher M. Duus' Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. Fourth Edition. Stuttgart: Thieme, 2005.

(2) Simon RP, Aminoff MJ, Greenberg DA. Clinical Neurology, Seventh Edition (LANGE Clinical Medicine). Seventh Edition. New York: McGraw Hill, 2009.

(3) Flynn JA. Oxford American Handbook of Clinical Medicine (Oxford American Handbooks of Medicine). First Edition. Oxford University Press, 2007.

(4) Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2010 Oct 12. [Epub ahead of print] Dutta R, Trapp BD.

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Lumbar puncture (ie: "spinal tap") is sometimes done to obtain a cerebrospinal fluid sample in multiple sclerosis patients. The CSF in MS will often show elevated IgG (a protein involved in immune system reactions).

A process known as protein electrophoresis is performed on the CSF sample; the various IgG proteins and protein fragments migrate at different rates on a laboratory gel matrix. This is called oligoclonal banding, which is seen in several diseases including MS. However, CSF results cannot definitively diagnosis MS; the findings, if present, can only support the diagnosis.