JOHNS HOPKINS HOSPITAL: CLICK TO READ MORE"Multiple sclerosis (MS) is a disorder characterized by destruction of the protective outer casings of the nerves within the central nervous system (the brain, optic nerves, and spinal cord). The nerve casings, known as myelin sheaths, are composed mostly of fats; they insulate the nerves and preserve the speed of electrical transmissions. In MS, patchy areas of the sheaths are destroyed (demyelinated) and replaced by scar tissue (called plaques)-a process known as sclerosis-at multiple sites throughout the central nervous system (hence the name of the disorder). Sclerosis impairs electrical conduction, thus reducing or eliminating transmission of nerve impulses within the affected areas. When severe, the disease may destroy the inner cables of the nerves (axons), causing irreversible damage.

Symptoms wax and wane unpredictably and vary widely from patient to patient. For example, sclerosis of the optic nerves may cause vision disturbances, and sclerosis of the nerves that control the muscles may lead to spasticity, weakness, muscle spasms, or paralysis. Different symptoms may occur in combination and may vary greatly over time.

The initiating cause is unknown; however, current research indicates that MS is an autoimmune disorder, in which the immune system attacks some of the body's own cells, mistaking them for foreign invaders. MS is rare in children and in people over 60; the first episode usually occurs between the ages of 20 and 50.

MS occurs in two major forms. In relapsing/ remitting MS, which afflicts about 70 percent of MS patients, a series of flare-ups or attacks are separated by periods of normal or near-normal health. Such remissions may be short or may last for months or years. In a few cases, remission is permanent, but many patients gradually accumulate permanent neurological deficits.

The other type of MS, chronic/progressive, gradually worsens without remission. Rarely is progression so rapid or severe that survival is limited to only months or a few years. Women are affected more often than men. Average survival after diagnosis is more than 35 years, but destruction of the myelin sheaths eventually results in a combination of nerve, muscle, and, occasionally, brain damage. However, many people retain much of their function for years and are able to pursue a wide range of normal activities with the help of supportive therapy. Current treatment is aimed at reducing the frequency and severity of attacks, relieving the problems caused by neurological deficits, and providing psychological support."

NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE: CLICK TO READ MORE"An unpredictable disease of the central nervous system, multiple sclerosis (MS) can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted. 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.

Most people experience their first symptoms of MS between the ages of 20 and 40; the initial symptom of MS is often blurred or double vision, red-green color distortion, or even blindness in one eye. Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance. These symptoms may be severe enough to impair walking or even standing. In the worst cases, MS can produce partial or complete paralysis. Most people with MS also exhibit paresthesias, transitory abnormal sensory feelings such as numbness, prickling, or "pins and needles" sensations. Some may also experience pain. 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. Depression is another common feature of MS.

Is there any 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. However, 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. The FDA also has approved a synthetic form of myelin basic protein, called copolymer I (Copaxone), for the treatment of relapsing-remitting MS. Copolymer I has few side effects, and studies indicate that the agent can reduce the relapse rate by almost one third. An immunosuppressant treatment, Novantrone (mitoxantrone ), is approved by the FDA for the treatment of advanced or chronic MS.

While steroids do not affect the course of MS over time, they can reduce the duration and severity of attacks in some patients. Spasticity, which can occur either as a sustained stiffness caused by increased muscle tone or as spasms that come and go, is usually treated with muscle relaxants and tranquilizers such as baclofen, tizanidine, diazepam, clonazepam, and dantrolene. Physical therapy and exercise can help preserve remaining function, and patients may find that various aids -- such as foot braces, canes, and walkers -- can help them remain independent and mobile. Avoiding excessive activity and avoiding heat are probably the most important measures patients can take to counter physiological fatigue. If psychological symptoms of fatigue such as depression or apathy are evident, antidepressant medications may help. Other drugs that may reduce fatigue in some, but not all, patients include amantadine (Symmetrel), pemoline (Cylert), and the still-experimental drug aminopyridine. Although improvement of optic symptoms usually occurs even without treatment, a short course of treatment with intravenous methylprednisolone (Solu-Medrol) followed by treatment with oral steroids is sometimes used.


What is the prognosis?
A physician may diagnose MS in some patients soon after the onset of the illness. In others, however, doctors may not be able to readily identify the cause of the symptoms, leading to years of uncertainty and multiple diagnoses punctuated by baffling symptoms that mysteriously wax and wane. The vast majority of patients are mildly affected, but in the worst cases, MS can render a person unable to write, speak, or walk. MS is a disease with a natural tendency to remit spontaneously, for which there is no universally effective treatment.


What research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct research in laboratories at the NIH and also support additional research through grants to major medical institutions across the country. Scientists continue their extensive efforts to create new and better therapies for MS. One of the most promising MS research areas involves naturally occurring antiviral proteins known as interferons. 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, there are a number of treatments under investigation that may curtail attacks or improve function. Over a dozen clinical trials testing potential therapies are underway, and additional new treatments are being devised and tested in animal models."

NATIONAL MS SOCIETY: CLICK TO READ MORE"MS is thought to be an autoimmune disease that affects the central nervous system (CNS). The CNS consists of the brain, spinal cord, and the optic nerves. Surrounding and protecting the nerve fibers of the CNS is a fatty tissue called myelin, which helps nerve fibers conduct electrical impulses.


In MS, myelin is lost in multiple areas, leaving scar tissue called sclerosis. These damaged areas are also known as plaques or lesions. Sometimes the nerve fiber itself is damaged or broken.


Myelin not only protects nerve fibers, but makes their job possible. When myelin or the nerve fiber is destroyed or damaged, the ability of the nerves to conduct electrical impulses to and from the brain is disrupted, and this produces the various symptoms of MS.




People with MS can expect one of four clinical courses of disease, each of which might be mild, moderate, or severe.




MS is a chronic, unpredictable neurological disease that affects the central nervous system.

MS is not contagious and is not directly inherited.

Most people with MS have a normal or near-normal life expectancy.

The majority of people with MS do not become severely disabled.

There is no cure for MS yet, but drugs can help slow the course and/or symptoms in some patients.

The above is from the brochure Just the Facts: 2005-2006.


Relapsing-Remitting
Characteristics: People with this type of MS experience clearly defined flare-ups (also called relapses, attacks, or exacerbations). These are episodes of acute worsening of neurologic function. They are followed by partial or complete recovery periods (remissions) free of disease progression.
Frequency: Most common form of MS at time of initial diagnosis. Approximately 85%.
Primary-Progressive
Characteristics: People with this type of MS experience a slow but nearly continuous worsening of their disease from the onset, with no distinct relapses or remissions. However, there are variations in rates of progression over time, occasional plateaus, and temporary minor improvements.
Frequency: Relatively rare. Approximately 10%.

Secondary-Progressive
Characteristics: People with this type of MS experience an initial period of relapsing-remitting disease, followed by a steadily worsening disease course with or without occasional flare-ups, minor recoveries (remissions), or plateaus.
Frequency: 50% of people with relapsing-remitting MS developed this form of the disease within 10 years of their initial diagnosis, before introduction of the “disease-modifying” drugs. Long-term data are not yet available to demonstrate if this is significantly delayed by treatment.
Progressive-Relapsing
Characteristics: People with this type of MS experience a steadily worsening disease from the onset but also have clear acute relapses (attacks or exacerbations), with or without recovery. In contrast to relapsing-remitting MS, the periods between relapses are characterized by continuing disease progression.
Frequency: Relatively rare. Approximately 5%."

UNIVERSITY OF MARYLAND MEDICAL CENTER: CLICK TO READ MORE"Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. Its cause is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

The primary characteristic of this disease is the destruction of myelin, a fatty insulation covering the nerve fibers. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)


Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

Another important feature in the disease is destruction of axons -- the long filaments that carry electric impulses away from a nerve cell -- which is now considered to be a major factor in the permanent disability that occurs with MS.
The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting.
Chronic-progressive MS, which is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing MS.
Recent evidence is strongly suggesting that the disease process starts long before symptoms begin, and by the time symptoms appear, there are already signs of brain and spinal cord atrophy.

Relapsing-Remitting Multiple Sclerosis

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (e.g., facial pain, Lhermitte's sign, or bladder instability) that lasts at least 24 hours (and typically several days). Such attacks are fairly mild in about half of patients with this form of MS. [For a description of symptoms see What Are the Symptoms of Multiple Sclerosis.]
The disease then goes into remission (when symptoms improve or disappear), usually for about four to eight weeks. At least 30 days should separate one attack from another to be considered a remission. Remission periods may be spontaneous or induced by immunosuppressive drugs. (A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.)
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability. The average number of relapses per year range from 0.14 to 1.1.
Some patients with relapsing-remitting MS can experience little or no progression for long periods of time, although by 25 years most patients have converted to a progressive phase [see below].

Chronic-Progressive Multiple Sclerosis

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Primary-Progressive MS (PPMS) -- progresses continuously and gradually without remission. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Secondary-Progressive MS (SPMS) -- occurs after the initial relapsing-remitting phase in about half of patients during the first 10 years and nearly all of them within 25 years. It is follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Progressive-Relapsing MS (PRMS) -- is progressive from the start with acute symptom flare-ups and continued deterioration between relapses. It occurs in less than 5% of patients.
Because the natural courses of primary progressive and progressive relapsing MS are similar, some experts believe this distinction is unnecessary. "

MAYO CLINIC: CLICK TO READ MORE"Multiple sclerosis

Overview
Multiple sclerosis (MS) is a chronic, potentially debilitating disease that affects the central nervous system, which is made up of the brain and spinal cord. Doctors and researchers think the illness is probably an autoimmune disease, which means that your immune system attacks part of your body as if it's a foreign substance.

In multiple sclerosis, the body incorrectly directs antibodies and white blood cells against proteins in the myelin sheath, which surrounds nerves in your brain and spinal cord. This causes inflammation and injury to the sheath and ultimately to the nerves that it surrounds. The result may be multiple areas of scarring (sclerosis). Eventually, this damage can slow or block the nerve signals that control muscle coordination, strength, sensation and vision.

Multiple sclerosis affects more than 1 million people around the world - including twice as many women as men. Most people experience their first symptoms between ages 20 and 40. This disease is unpredictable and varies in severity. In some people, MS is a mild illness, but, for others, it results in permanent disability. Treatments can modify the course of the disease and relieve symptoms."

CLEVELAND CLINIC...CLICK TO READ MORE"What is Multiple Sclerosis (MS)?
Multiple sclerosis (MS) is thought to be an autoimmune disease in which the body’s own immune system mistakenly attacks normal tissues of the body. In MS, these attacks are aimed at the myelin in the Central Nervous System (CNS). The Central Nervous System, which includes the brain and spinal cord, is made up of nerves that act as the body’s messenger system. Each nerve has a fatty covering of myelin that serves as insulation, which helps in the transmission of nerve impulses (messages) between the brain and other parts of the body. Once myelin in a certain area has been damaged, normal nerve function is disturbed and a number of symptoms can be experienced. The types of symptoms, severity of symptoms, and the course of MS varies widely due in part to the sites of the plaques and the extent of demyelination.

The Cause of Multiple Sclerosis
There is no known cause of MS; the disease is probably related to a number of factors. While symptoms relate to problems with the central nervous system, MS appears to be a disease of immune system function. The ultimate consequence of MS is the entrance of immune cells into the CNS, attacks on the myelin, and eventually myelin loss and scarring. The entire process results in the failure of nerve impulses acting properly.

The Course of MS
The course of multiple sclerosis varies from person to person and there is no way to predict how a person’s MS will progress. Four basic types of MS have been defined:

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Relapsing-Remitting: characterized by acute attacks (exacerbations) with full recovery or some neurological symptoms after recovery. The periods between disease relapses are characterized by a lack of disease progression.


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Primary-Progressive: characterized by a gradual but steady progression of disability, without any obvious relapses and remissions.


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Secondary-Progressive: initially begins with a relapsing-remitting course, but later evolves into progression at a variable rate.


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Progressive-Relapsing: characterized by a steady progression in disability with acute attacks that may or may not have some recovery following an acute episode."

"Multiple sclerosis (MS) is a chronic, often disabling disease of the central nervous system (CNS). Converging lines of evidence suggest that the disease is caused by a disturbance in immune function. This disturbance permits cells of the immune system to attack myelin, the insulating sheath that surrounds the nerve fibers (axons) located in the CNS (i.e., the brain and spinal cord). When myelin is damaged, electrical impulses cannot travel quickly along nerve fiber pathways in the brain and spinal cord. Disruption of electrical conductivity results in fatigue and disturbances of vision, strength, coordination, balance, sensations, and bladder and bowel function.

Why was this disease called multiple sclerosis? Physicians during the 19th century noticed that the brains and spinal cords of patients with MS contained many areas where the nervous tissue was hard to the touch and appeared scarred. The Latin word for scar is sclerosis. Thus, the term multiple sclerosis was chosen to describe the appearance of the brain in patients who died with this illness. Pathologists call these scars plaques. When observed microscopically, plaques consist of inflammatory cells, astroglial cells, increased water (edema), and destroyed myelin fragments. Larger plaques may be seen on magnetic resonance imaging (MRI) scans of the brain and spinal cord.

The loss of normal myelin is called demyelination. Demyelination produces a situation analogous to that resulting from cracks or tears in the insulator surrounding an electrical lamp cord. When the insulating surface is disrupted, the lamp will short-circuit and the light bulb will flicker or no longer illuminate. Similarly, loss of myelin surrounding nerve fibers results in short-circuits in nerves traversing the brain and spinal cord that result in symptoms of MS.

In contrast to a single wire pathway in a lamp cord, there are thousands of nerve pathways in the brain and spinal cord, the two components of the CNS. The symptoms of multiple sclerosis depend largely on which particular nerve fiber pathway is involved in the CNS. Tingling, numbness, sensations of tightness, or weakness may result when loss of myelin occurs in the spinal cord. If the nerve fibers to the bladder are affected, urinary incontinence may follow. If the cerebellum of the brain is affected, imbalance or incoordination may result. Since the plaques of MS can arise in any location of the CNS, it is easy to understand why no two MS patients have exactly the same symptoms."CLICK HERE FOR MORE: UCSF Multiple Sclerosis Center