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Multiple Sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system. The vast majority of patients are mildly affected, but in the worst cases MS can render a person unable to write, speak, or walk. During an MS attack, inflammation occurs in areas of the white matter of the central nervous system in random patches called plaques. This process is followed by destruction of myelin, the fatty covering that insulates nerve cell fibers in the brain and spinal cord. Myelin facilitates the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body; when it is damaged, neurological transmission of messages may be slowed or blocked completely, leading to diminished or lost function. The name "multiple sclerosis" signifies both the number (multiple) and condition (sclerosis, from the Greek term for scarring or hardening) of the demyelinated areas in the central nervous system.

No one knows exactly how many people have MS. It is believed that, currently, there are approximately 250,000 to 350,000 people in the United States with MS diagnosed by a physician. This estimate suggests that approximately 200 new cases are diagnosed each week.

Symptoms

Symptoms of MS may be mild or severe, of long duration or short, and may appear in various combinations, depending on the area of the nervous system affected. Complete or partial remission of symptoms, especially in the early stages of the disease, occurs in approximately 70 percent of MS patients.

The initial symptom of MS is often blurred or double vision, red-green color distortion, or even blindness in one eye. Inexplicably, visual problems tend to clear up in the later stages of MS. Inflammatory problems of the optic nerve may be diagnosed as retrobulbaror optic neuritis. Fifty-five percent of MS patients will have an attack of optic neuritis at some time or other and it will be the first symptom of MS in approximately 15 percent. This has led to general recognition of optic neuritis as an early sign of MS, especially if tests also reveal abnormalities in the patient's spinal fluid.

Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance at some time during the course of the disease. These symptoms may be severe enough to impair walking or even standing. In the worst cases, MS can produce partial or complete paralysis. Spasticity - the involuntary increased tone of muscles leading to stiffness and spasms - is common, as is fatigue. Fatigue may be triggered by physical exertion and improve with rest, or it may take the form of a constant and persistent tiredness.

Most people with MS also exhibit paresthesias, transitory abnormal sensory feelings such as numbness, prickling, or "pins and needles" sensations; uncommonly, some may also experience pain. Loss of sensation sometimes occurs. Speech impediments, tremors, and dizziness are other frequent complaints. Occasionally, people with MS have hearing loss.

Approximately half of all people with MS experience cognitive impairments such as difficulties with concentration, attention, memory, and poor judgment, but such symptoms are usually mild and are frequently overlooked. In fact, they are often detectable only through comprehensive testing. Patients themselves may be unaware of their cognitive loss; it is often a family member or friend who first notices a deficit. Such impairments are usually mild, rarely disabling, and intellectual and language abilities are generally spared.

Cognitive symptoms occur when lesions develop in brain areas responsible for information processing. These deficits tend to become more apparent as the information to be processed becomes more complex. Fatigue may also add to processing difficulties. Scientists do not yet know whether altered cognition in MS reflects problems with information acquisition, retrieval, or a combination of both. Types of memory problems may differ depending on the individual's disease course (relapsing-remitting, primary-progressive, etc.), but there does not appear to be any direct correlation between duration of illness and severity of cognitive dysfunction.

Depression, which is unrelated to cognitive problems, is another common feature of MS. In addition, about 10 percent of patients suffer from more severe psychotic disorders such as manic-depression and paranoia. Five percent may experience episodes of inappropriate euphoria and despair - unrelated to the patient's actual emotional state - known as "laughing/weeping syndrome." This syndrome is thought to be due to demyelination in the brainstem, the area of the brain that controls facial expression and emotions, and is usually seen only in severe cases.

As the disease progresses, sexual dysfunction may become a problem. Bowel and bladder control may also be lost.

In about 60 percent of MS patients, heat - whether generated by temperatures outside the body or by exercise - may cause temporary worsening of many MS symptoms. In these cases, eradicating the heat eliminates the problem. Some temperature-sensitive patients find that a cold bath may temporarily relieve their symptoms. For the same reason, swimming is often a good exercise choice for people with MS.

Diagnosis

There is no single test that unequivocally detects MS. When faced with a patient whose symptoms, neurological exam results, and medical history suggest MS, physicians use a variety of tools to rule out other possible disorders and perform a series of laboratory tests which, if positive, confirm the diagnosis.

Imaging technologies such as MRI can help locate central nervous system lesions resulting from myelin loss. MRI is painless, noninvasive, and does not expose the body to radiation. It is often used in conjunction with the contrast agent gadolinium, which helps distinguish new plaques from old. However, since these lesions can also occur in several other neurological disorders, they are not absolute evidence of MS.

Several new MRI techniques may help quantify and characterize MS lesions that are too subtle to be detected using conventional MRI scans. While standard MRI provides an anatomical picture of lesions, magnetic resonance spectroscopy (MRS) yields information about the brain's biochemistry; specifically, it can measure the brain chemical N-acetyl aspartate. Decreased levels of this chemical can indicate nerve damage.

Magnetization transfer imaging (MTI) is able to detect white matter abnormalities before lesions can be seen on standard MRI scans by calculating the amount of "free" water in tissues. Demyelinated tissues and damaged nerves show increased levels of free" (versus "bound") water particles.

Diffusion-tensor magnetic resonance imaging (DT-MRI or DTI) measures the random motion of water molecules. Individual water molecules are constantly in motion, colliding with each other at extremely high speeds. This causes them to spread out, or diffuse. DT-MRI maps this diffusion to produce intricate, three-dimensional images indicating the size and location of demyelinated areas of the brain. Changes in this process can then be measured and correlated with disease progression.

Functional MRI (fMRI) uses radio waves and a strong magnetic field to measures the correlation between physical changes in the brain (such as blood flow) and mental functioning during the performance of cognitive tasks.

Other tests that may be used to diagnosis MS include visual evoked potential (VEP) tests and studies of cerebrospinal fluid (the colorless liquid that circulates through the brain and spinal cord). VEP tests measure the speed of the brain's response to visual stimuli. VEP can sometimes detect lesions that the scanners miss and is particularly useful when abnormalities seen on MRI do not meet the specific criteria for MS. Auditory and sensory evoked potentials have also been used in the past, but are no longer believed to contribute significantly to the diagnosis of MS. Like imaging technologies, VEP is helpful but not conclusive because it cannot identify the cause of lesions.

Causes

Scientists have learned a great deal about MS in recent years; still, its cause remains elusive. Many investigators believe MS to be an autoimmune disease - one in which the body, through its immune system, launches a defensive attack against its own tissues. In the case of MS, it is the nerve-insulating myelin that comes under assault. Such assaults may be linked to an unknown environmental trigger, perhaps a virus.

Treatment

There is as yet no cure for MS. Many patients do well with no therapy at all, especially since many medications have serious side effects and some carry significant risks. Naturally occurring or spontaneous remissions make it difficult to determine therapeutic effects of experimental treatments; however, the emerging evidence that MRIs can chart the development of lesions is already helping scientists evaluate new therapies.

In the past, the principal medications physicians used to treat MS were steroids possessing anti-inflammatory properties; these include adrenocorticotropic hormone (better known as ACTH), prednisone, prednisolone, methylprednisolone, betamethasone, and dexamethasone. Studies suggest that intravenous methylprednisolone may be superior to the more traditional intravenous ACTH for patients experiencing acute relapses; no strong evidence exists to support the use of these drugs to treat progressive forms of MS. Also, there is some indication that steroids may be more appropriate for people with movement, rather than sensory, symptoms.

While steroids do not affect the course of MS over time, they can reduce the duration and severity of attacks in some patients. The mechanism behind this effect is not known; one study suggests the medications work by restoring the effectiveness of the blood/brain barrier. Because steroids can produce numerous adverse side effects (acne, weight gain, seizures, psychosis), they are not recommended for long-term use.

One of the most promising MS research areas involves naturally occurring antiviral proteins known as interferons. Three forms of beta interferon (Avonex, Betaseron, and Rebif) have now been approved by the Food and Drug Administration for treatment of relapsing-remitting MS. Beta interferon has been shown to reduce the number of exacerbations and may slow the progression of physical disability. When attacks do occur, they tend to be shorter and less severe. In addition, MRI scans suggest that beta interferon can decrease myelin destruction.

Investigators speculate that the effects of beta interferon may be due to the drug's ability to correct an MS-related deficiency of certain white blood cells that suppress the immune system and/or its ability to inhibit gamma interferon, a substance believed to be involved in MS attacks. Alpha interferon is also being studied as a possible treatment for MS. Common side effects of interferons include fever, chills, sweating, muscle aches, fatigue, depression, and injection site reactions.

Scientists continue their extensive efforts to create new and better therapies for MS. Goals of therapy are threefold: to improve recovery from attacks, to prevent or lessen the number of relapses, and to halt disease progression.

 

Reference:

National Institute of Neurological Disorders and Stroke, USA.