Multiple Sclerosis (MS)

Multiple Sclerosis - Wikipedia

2007-11-06T13:49:00.000-08:00

Multiple sclerosis
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Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory, demyelinating disease that affects the central nervous system (CNS). MS can cause a variety of symptoms, including changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating, and pain. MS will cause impaired mobility and disability in more severe cases.

Multiple sclerosis affects neurons, the cells of the brain and spinal cord that carry information, create thought and perception, and allow the brain to control the body. Surrounding many of these neurons is a fatty layer known as the myelin sheath, which helps neurons carry electrical signals. MS causes gradual destruction of myelin (demyelination) and transection of neuron axons in patches throughout the brain and spinal cord. When the myelin is destroyed, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the multiple scars (or scleroses) on the myelin sheaths. This scarring causes symptoms which vary widely depending upon which signals are interrupted.

The predominant theory today is that MS results from attacks by an individual's immune system on the nervous system and it is therefore usually categorized as an autoimmune disease. There is a minority view that MS is not an autoimmune disease, but rather a metabolically dependent neurodegenerative disease. Although much is known about how MS causes damage, its exact cause remains unknown.

Multiple sclerosis may take several different forms, with new symptoms occurring either in discrete attacks or slowly accruing over time. Between attacks, symptoms may resolve completely, but permanent neurologic problems often persist, especially as the disease advances. MS currently does not have a cure, though several treatments are available that may slow the appearance of new symptoms.

MS primarily affects adults, with an age of onset typically between 20 and 40 years, and is more common in women than in men.

Signs and symptoms
MS can cause a variety of symptoms, including changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression). Lhermitte sign is considered a classic M.S. finding, but it can be seen in several other conditions as well. The main clinical measure of disability progression and severity of the symptoms is the Expanded Disability Status Scale or EDSS.

The initial attacks are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made based on further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (16%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis. Fifteen percent of individuals have multiple symptoms when they first seek medical attention. For some people the initial MS attack is preceded by infection, trauma, or strenuous physical effort.

Diagnosis
Multiple sclerosis is difficult to diagnose in its early stages. In fact, definite diagnosis of MS cannot be made until there is evidence of at least two anatomically separate demyelinating events occurring at least thirty days apart.

Historically different criteria were used. The Schumacher criteria and Poser criteria were both popular. Currently, McDonald criteria represents international efforts to standardize the diagnosis of MS using clinical data, laboratory data, and radiologic data.

Clinical data alone may be sufficient for a diagnosis of MS. If an individual has suffered two separate episodes of neurologic symptoms characteristic of MS, and the individual also has consistent abnormalities on physical examination, a diagnosis of MS can be made with no further testing. Since some people with MS seek medical attention after only one attack, other testing may hasten the diagnosis and allow earlier initiation of therapy.

Magnetic resonance imaging (MRI) of the brain and spine is often used to evaluate individuals with suspected MS. MRI shows areas of demyelination as bright lesions on T2-weighted images or FLAIR (fluid attenuated inversion recovery) sequences. Gadolinium contrast is used to demonstrate active plaques on T1-weighted images. Because MRI can reveal lesions which occurred previously but produced no clinical symptoms, it can provide the evidence of chronicity needed for a definite diagnosis of MS.

Testing of cerebrospinal fluid (CSF) can provide evidence of chronic inflammation of the central nervous system. The CSF is tested for oligoclonal bands, which are immunoglobulins found in 85% to 95% of people with definite MS (but also found in people with other diseases). Combined with MRI and clinical data, the presence of oligoclonal bands can help make a definite diagnosis of MS. Lumbar puncture is the procedure used to collect a sample of CSF.

The brain of a person with MS often responds less actively to stimulation of the optic nerve and sensory nerves. These brain responses can be examined using visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). Decreased activity on either test can reveal demyelination which may be otherwise asymptomatic. Along with other data, these exams can help find the widespread nerve involvement required for a definite diagnosis of MS.

Another test which may become important in the future is measurement of antibodies against myelin proteins such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). As of 2007, however, there is no established role for these tests in diagnosing MS.

The signs and symptoms of MS can be similar to other medical problems, such as neuromyelitis optica, stroke, brain inflammation, infections such as Lyme disease (which can produce identical MRI lesions and CSF abnormalities), tumors, and other autoimmune problems, such as lupus. Additional testing may be needed to help distinguish MS from these other problems.

Disease course and clinical subtypes
The course of MS is difficult to predict, and the disease may at times either lie dormant or progress steadily. Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. Subtypes are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized the following four subtype definitions:

Relapsing-remitting
Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. This subtype is characterized by unpredictable attacks (relapses) followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during the attacks may either resolve or may be permanent. When deficits always resolve between attacks, this is referred to as "benign" MS.
Secondary progressive
Secondary progressive describes around 80% of those with initial relapsing-remitting MS, who then begin to have neurologic decline between their acute attacks without any definite periods of remission. This decline may include new neurologic symptoms, worsening cognitive function, or other deficits. Secondary progressive is the most common type of MS and causes the greatest amount of disability.
Primary progressive
Primary progressive describes the approximately 10% of individuals who never have remission after their initial MS symptoms. Decline occurs continuously without clear attacks. The primary progressive subtype tends to affect people who are older at disease onset.
Progressive relapsing
Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer superimposed attacks; and is the least common of all subtypes

Special cases of the disease with non-standard behavior have also been described although many researchers believe they are different diseases. These cases are sometimes referred to as borderline forms of multiple sclerosis and are Neuromyelitis optica (NMO), Balo concentric sclerosis, Schilder's diffuse sclerosis and Marburg multiple sclerosis.

Factors triggering a relapse
Multiple sclerosis relapses are often unpredictable and can occur without warning with no obvious inciting factors. Some attacks, however, are preceded by common triggers. In general, relapses occur more frequently during spring and summer than during autumn and winter. Infections, such as the common cold, influenza, and gastroenteritis, increase the risk for a relapse. Emotional and physical stress may also trigger an attack, as can severe illness of any kind. Statistically, there is no good evidence that either trauma or surgery trigger relapses. People with MS can participate in sports, but they should probably avoid extremely strenuous exertion, such as marathon running. Heat can transiently increase symptoms, which is known as Uhthoff's phenomenon. This is why some people with MS avoid saunas or even hot showers. However, heat is not an established trigger of relapses.

Pregnancy can directly affect the susceptibility for relapse. The last three months of pregnancy offer a natural protection against relapses. However, during the first few months after delivery, the risk for a relapse is increased 20%–40%. Pregnancy does not seem to influence long-term disability. Children born to mothers with MS are not at increased risk for birth defects or other problems.

Many potential triggers have been examined and found not to influence relapse rates in MS. Influenza vaccination is safe, does not trigger relapses, and can therefore be recommended for people with MS. There is also no evidence that vaccines for hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin (BCG—immunization for tuberculosis) increases the risk for relapse.

Pathophysiology
Although much is known about how multiple sclerosis causes damage, the reasons why multiple sclerosis occurs are not known.

Multiple sclerosis is a disease in which the myelin (a fatty substance which covers the axons of nerve cells) degenerates. According to the view of most researchers, a special subset of lymphocytes, called T cells, plays a key role in the development of MS.

According to a strictly immunological explanation of MS, the inflammatory processes is triggered by the T cells. These lymphocytes recognize myelin as foreign and attack it as if it were an invading virus. That triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood-brain barrier (a capillary system that should prevent entrance of T-cells into the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as matrix metalloproteinases. A deficiency of uric acid has been implicated in this process.
It is known that a repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. The newly-formed myelin sheaths are thinner and often not as effective as the original ones. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons, according to four different damage patterns. The central nervous system should be able to recruit oligodendrocyte stem cells capable of turning into mature myelinating oligodendrocytes, but it is suspected that something inhibits stem cells in affected areas.

The axons themselves can also be damaged by the attacks. Often, the brain is able to compensate for some of this damage, due to an ability called neuroplasticity. MS symptoms develop as the cumulative result of multiple lesions in the brain and spinal cord. This is why symptoms can vary greatly between different individuals, depending on where their lesions occur.

Causes
Although many risk factors for multiple sclerosis have been identified, no definitive cause has been found. MS likely occurs as a result of some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations. Although most accept an autoimmune explanation, several theories suggest that MS is an appropriate immune response to one or several underlying conditions (the etiology could be heterogeneous). The need for alternative theories is supported by the poor results of present therapies, since autoimmune theory predicted greater success.

Environmental
The most popular hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. On a molecular level, this might occur if there is a structural similarity between the infectious virus and some component of the central nervous system, leading to eventual confusion in the immune system.

Since MS seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure and possibly decreased vitamin D production may help cause MS. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator. A large, 2006 study by the Harvard School of Public Health, reported evidence of a link between Vitamin D deficiency and the onset of multiple sclerosis. Other data comes from a 2007 study which concluded that sun exposure during childhood reduces the risk of suffering MS, while controlling for genetic factors.

Other theories, noting that MS is less common in children with siblings, suggest that less exposure to illness in childhood leads to an immune system which is not primed to fight infection and is thus more likely to attack the body. One explanation for this would be an imbalance between the Th1 type of helper T-cells, which fight infection, and the Th2 type, which are more active in allergy and more likely to attack the body.

Other theories describe MS as an immune response to a chronic infection. The association of MS with the Epstein-Barr virus suggests a potential viral contribution in at least some individuals. Still others believe that MS may sometimes result from a chronic infection with spirochetal bacteria, a hypothesis supported by research in which cystic forms were isolated from the cerebrospinal fluid of all MS patients in a small study. When the cysts were cultured, propagating spirochetes emerged. Another bacterium that has been implicated in MS is Chlamydophila pneumoniae; it or its DNA has been found in the cerebrospinal fluid of MS patients by several research laboratories, with one study finding that the oligoclonal bands of 14 of the 17 MS patients studied consisted largely of antibodies to Chlamydophila antigens.

Severe stress may also be a factor—a large study in Denmark found that parents who had lost a child unexpectedly were 50% more likely to develop MS than parents who had not. Smoking has also been shown to be an independent risk factor for developing MS.

Genetic
MS is not considered a hereditary disease. However, increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS:
Some populations, such as the Roma, Inuit, and Bantus, rarely if ever get MS. The indigenous peoples of the Americas and Asians have very low incidence rates.

In the population at large, the chance of developing MS is less than a tenth of one percent. However, if one person in a family has MS, that person's first-degree relatives—parents, children, and siblings—have a one to three percent chance of getting the disease.

For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30%; for fraternal twins (who do not inherit an identical set of genes), the likelihood is closer to that for non-twin siblings, or about 4%. The fact that the rate for identical twins both developing MS is significantly less than 100% suggests that the disease is not entirely genetically controlled. Some (but definitely not all) of this effect may be due to shared exposure to something in the environment, or to the fact that some people with MS lesions remain essentially asymptomatic throughout their lives.

Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS. Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. However, there are other genes in this region which are not related to the immune system.

The HLA patterns of MS patients tend to be different from those of people without the disease. Investigations in northern Europe and America have detected three HLAs that are more prevalent in people with MS than in the general population. Studies of American MS patients have shown that people with MS also tend to exhibit these HLAs in combination—that is, they have more than one of the three HLAs—more frequently than the rest of the population. Furthermore, there is evidence that different combinations of the HLAs may correspond to variations in disease severity and progression.

A large study examining 334,923 single nucleotide polymorphisms (small variations in genes) in 931 families showed that apart from HLA-DRA there were two genes in which polymorphisms strongly predicted MS; these were the IL2RA (a subunit of the receptor for interleukin 2) and the IL7RA (idem for interleukin 7) genes. Mutations in these genes were already known to be associated with diabetes mellitus type 1 and other autoimmune conditions; the findings therefore support the notion that MS is an autoimmune disease.

Studies of families with multiple cases of MS and research comparing proteins expressed in humans with MS to those of mice with EAE suggest that another area related to MS susceptibility may be located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11, 17, 19, and X have also been identified as possibly containing genes involved in the development of MS.

These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene's interactions with other genes and with the environment make an individual susceptible to MS.

Approved treatments
Only approved treatments are covered here. For more information about approved treatments, experimental therapies and medication for symptoms see therapies for multiple sclerosis and therapies under investigation for multiple sclerosis.

There is no known definitive cure for multiple sclerosis. However, several types of therapy have proven to be helpful. Different therapies are used for patients experiencing acute attacks, for patients who have the relapsing-remitting subtype, for patients who have the progressive subtypes, for patients without a diagnosis of MS who have a demyelinating event, and for managing the various consequences of MS attacks. Treatment is aimed at returning function after an attack, preventing new attacks, and preventing disability.

Different disease-modifying treatments have been approved by different countries regulatory agencies, like the USA's Food and Drug Administration (FDA), the European Medicines Agency (EMEA) or the Japanese PMDA. More treatments are being studied and undergoing the approval process.

Interferons:
These are medications derived from human cytokines which help regulate the immune system.

Interferon beta-1a: (trade names Avonex , Rebif and CinnoVex [Biogereric/biosimolar form of Avonex])
beta-1b: (trade name Betaseron [in Europe and Japan Betaferon]). Betaseron has been approved by the FDA for relapsing forms of secondary progressive MS.
Glatiramer acetate: (trade name Copaxone)
A synthetic medication made of four amino acids that are found in myelin. This drug stimulates T cells in the body's immune system to change from harmful, pro-inflammatory agents to beneficial, anti-inflammatory agents that work to reduce inflammation at lesion sites.
Mitoxantrone: (trade name Novantrone)
This medication is effective, but is limited by cardiotoxicity. Novantrone has been approved by the USA's FDA for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS.
Natalizumab: (trade name Tysabri).
This medication is effective and safe alone but in combination with other immunotherapies can lead to PML.

Relapsing-remitting symptomatic attacks can be treated. Patients are typically given high doses of intravenous corticosteroids, such as methylprednisolone, or plasma exchange to end the attack sooner and leave fewer lasting deficits. Patients' self-reporting indicates that many find benefit from a number of other medicines.

There are no approved treatments for primary progressive multiple sclerosis, though several medications are being studied.

Prognosis
The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, race, age, and initial symptoms; and the degree of disability the person experiences. The life expectancy of people with MS is now nearly the same as that of unaffected people. This is due mainly to improved methods of limiting disability, such as physical therapy, occupational therapyand speech therapy, along with more successful treatment of common complications of disability, such as pneumonia and urinary tract infections. Nevertheless half of the deaths in people with MS are directly related to the consequences of the disease, while 15% more are due to suicide.

Individuals with progressive subtypes of MS, particularly the primary
progressive subtype, have a more rapid decline in function. In the primary
progressive subtype, supportive equipment (such as a wheelchair or standing
frame) is often needed after six to seven years. However, when the initial
disease course is the relapsing-remitting subtype, the average time until such
equipment is needed is twenty years. This means that many individuals with MS
will never need a wheelchair. There is also more cognitive impairment in the
progressive forms than in the relapsing-remitting course.

The earlier in life MS occurs, the slower disability progresses.
Individuals who are older than fifty when diagnosed are more likely to
experience a chronic progressive course, with more rapid progression of
disability. Those diagnosed before age 35 have the best prognosis. Females
generally have a better prognosis than males. Although individuals of African
descent tend to develop MS less frequently, they are often older at the time of
onset and may have a worse prognosis.

Initial MS symptoms of visual loss or sensory problems, such as
numbness or tingling, are markers for a relatively good prognosis, whereas
difficulty walking and weakness are markers for a relatively poor prognosis.
Better outcomes are also associated with the presence of only a single symptom
at onset, the rapid development of initial symptoms, and the rapid regression of
initial symptoms.

The degree of disability varies among individuals with MS. In general,
one of three individuals will still be able to work after 15–20 years. Fifteen
percent of people diagnosed with MS never have a second relapse, and these
people have minimal or no disability after ten years. The degree of disability
after five years correlates well with the degree of disability after fifteen
years. This means that two-thirds of people with MS with low disability after
five years will not get much worse during the next ten years. It should be noted
that most of these outcomes were observed before the use of medications such as
interferon, which can delay disease progression for several years.

Currently there are no clinically established laboratory investigations available that can predict prognosis or response to treatment. However, several promising approaches have been proposed. These include measurement of the two antibodies anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein, and measurement of TRAIL (TNF-related apoptosis-inducing ligand).

Epidemiology
In northern Europe, continental North America, and Australasia, about one of every 1000 citizens suffers from multiple sclerosis, whereas in the Arabian peninsula, Asia, and continental South America, the frequency is much lower. In sub-Saharan Africa, MS is extremely rare. With important exceptions, there is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator. Climate, diet, geomagnetism, toxins, sunlight exposure, genetic factors, and infectious diseases have all been discussed as possible reasons for these regional differences. Environmental factors during childhood may play an important role in the development of MS later in life. This idea is based on several studies of migrants showing that if migration occurs before the age of fifteen, the migrant acquires the new region's susceptibility to MS. If migration takes place after age fifteen, the migrant keeps the susceptibility of his home country.

MS occurs mainly in Caucasians. It is twentyfold lower in the Inuit people of Canada than in other Canadians living in the same region. It is also rare in the Native American tribes of North America, Australian Aborigines and the Māori of New Zealand. Scotland appears to have the highest rate of MS in the world. The reasons for this are unknown. These few examples point out that either genetic background or lifestyle and cultural factors play an important role in the development of MS.

As observed in many autoimmune disorders, MS is more common in females than males; the mean sex ratio is about two females for every male. In children (who rarely develop MS) the sex ratio may reach three females for each male. In people over age fifty, MS affects males and females equally. Onset of symptoms usually occurs between fifteen to forty years of age, rarely before age fifteen or after age sixty.

As previously discussed, there is a genetic component to MS. On average one of every 25 siblings of individuals with MS will also develop MS. Almost half of the identical twins of MS-affected individuals will develop MS, but only one of twenty fraternal twins. If one parent is affected by MS, each child has a risk of only about one in forty of developing MS later in life.
Finally, it is important to remark that advances in the study of related diseases have shown that some cases formerly considered MS are not MS at all. In fact, all the studies before 2004 can be affected by the impossibility to distinguish MS and Devic's disease (NMO) reliably before this date. The error can be important in some areas, and is considered to be 30% in Japan.

History
The French neurologist Jean-Martin Charcot (1825–93) was the first person to recognize multiple sclerosis as a distinct, separate disease in 1868. Summarizing previous reports and adding his own important clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad are dysarthria (problems with speech), ataxia (problems with coordination), and tremor. Charcot also observed cognition changes in MS since he described his patients as having a "marked enfeeblement of the memory" and "with conceptions that formed slowly".

Prior to Charcot, Robert Hooper (1773–1835), a British pathologist and practicing physician, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease's clinical details.

After this, several people, such as Eugène Devic (1858–1930), Jozsef Balo (1895–1979), Paul Ferdinand Schilder(1886–1940), and Otto Marburg (1874–1948) found special cases of the disease that some authors consider different diseases and now are called the borderline forms of multiple sclerosis.

There are several historical accounts of people who probably had MS. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first identifiable MS patients. From the age of sixteen until her death at age 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS. Almost a hundred years before there is a story from Iceland of a young woman called Halla. This girl suddenly lost her vision and capacity to talk; but after praying to the saints recovered them seven days after. Augustus Frederick d'Este (1794–1848), an illegitimate grandson of King George III of Great Britain, almost certainly suffered from MS. D'Este left a detailed diary describing his 22 years living with the disease. He began his diary in 1822 and it had its last entry in 1846 (only to remain unknown until 1948). His symptoms began at age 28 with a sudden transient visual loss after the funeral of a friend. During the course of his disease he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life. Another early account of MS was kept by the British diarist W. N. P. Barbellion, who maintained a detailed log of his diagnosis and struggle with MS. His diary was published in 1919 as The Journal of a Disappointed Man.

Cultural references
The German propaganda film Ich klage an (1941) by Wolfgang Liebeneiner had the main character suffering from MS and wishing herself to be killed because she had become unable to do so by herself. In Duet for One, Julie Andrews plays a concert violinist who must sacrifice her career when she is diagnosed with MS.

In the American television series The West Wing, the fictional United States President, Josiah "Jed" Bartlet, has the relapsing-remitting subtype of MS. The storylines have educated many viewers about the nature of MS and have helped to dispel some of the misconceptions about the disease. Another American TV series, Extreme Makeover: Home Edition, aired a two-part episode on February 12, 2006 that featured a new home for Carol Crawford-Smith of Blacksburg, Virginia, a former principal dancer with the Dance Theatre of Harlem who was diagnosed with MS in 2000. Ty Pennington and his team not only built her a new home, but also renovated her Blacksburg dance studio, "The Center of Dance."

In the 2006 film Dreamland the character Callista suffers from Multiple Sclerosis. British cellist Jacqueline du Pré died with MS in 1987 when she was 42. After a long struggle with the disease, she was robbed of her capacity to perform as she progressively lost sensitivity in her fingers, hearing, and muscle coordination. This decline was portrayed in the 1998 film, Hilary and Jackie. The above-mentioned play Duet for One was inspired by du Pre's life.

See also
List of people with multiple sclerosis and the category People with multiple sclerosis
MS fundraisers include the MS Challenge Walk, MS Walk and MS Bike Tour.
Multiple Sclerosis organizations

References
Further reading
The patient's journey: multiple sclerosis Langgartner M, Langgartner I, Drlicek M. The patient's journey: multiple sclerosis.
BMJ. 2005 Apr 16;330(7496):885-8. PMID 15831874.
Multiple Sclerosis Encyclopedia

External links
Database for analysis and comparison of global data on the epidemiology of MS
NIH listing of clinical trials related to MS
Abstract index of the Cochrane Library

To view information on another disease, click on Digestive Diseases Library

Digestive Diseases Library

Multiple Sclerosis -- an Unpredictable Disease

2007-05-11T11:57:00.000-07:00

What is Multiple Sclerosis?
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.

In 2001, the National Academies/Institute of Medicine, a Federal technical and scientific advisory agency, prepared a strategic review of MS research. To read or download the National Academies/Institute of Medicine report, go to: "Multiple Sclerosis: Current Status and Strategies for the Future."

Clinical Trials Select this link to view a list of studies currently seeking patients.

Organizations

Clearinghouse on Disability Information
Special Education & Rehabilitative Services Communications & Customer Service Team
550 12th Street, SW, Rm. 5133
Washington, DC 20202-2550
http://www.ed.gov/about/offices/list/osers
Tel: 202-245-7307 202-205-5637 (TTD)
Fax: 292024507636

International Essential Tremor Foundation
P.O. Box 14005
Lenexa, KS 66285-4005
http://www.essentialtremor.org
Tel: 913-341-3880 888-387-3667
Fax: 913-341-1296

Multiple Sclerosis Association of America
706 Haddonfield Road
Cherry Hill, NJ 08002
msaa@msaa.com
http://www.msaa.com
Tel: 856-488-4500 800-532-7667
Fax: 856-661-9797

Multiple Sclerosis Foundation
6350 North Andrews Avenue
Ft. Lauderdale, FL 33309-2130
support@msfocus.org
http://www.msfocus.org
Tel: 954-776-6805 888-MSFOCUS (673-6287)
Fax: 954-351-0630

National Rehabilitation Information Center (NARIC)
4200 Forbes Boulevard
Suite 202
Lanham, MD 20706-4829
naricinfo@heitechservices.com
http://www.naric.com
Tel: 301-459-5900/301-459-5984 (TTY) 800-346-2742
Fax: 301-562-2401

National Ataxia Foundation (NAF)
2600 Fernbrook Lane North
Suite 119
Minneapolis, MN 55447-4752
naf@ataxia.org
http://www.ataxia.org
Tel: 763-553-0020
Fax: 763-553-0167

National Multiple Sclerosis Society
733 Third Avenue
6th Floor
New York, NY 10017-3288
nat@nmss.org
http://www.nationalmssociety.org
Tel: 212-986-3240 800-344-4867 (FIGHTMS)
Fax: 212-986-7981

American Autoimmune Related Diseases Association
22100 Gratiot Avenue
Eastpointe
East Detroit, MI 48201-2227
aarda@aarda.org
http://www.aarda.org
Tel: 586-776-3900 800-598-4668
Fax: 586-776-3903

National Organization for Rare Disorders (NORD)
P.O. Box 1968
(55 Kenosia Avenue)
Danbury, CT 06813-1968
orphan@rarediseases.org
http://www.rarediseases.org
Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
Fax: 203-798-2291

Well Spouse Association
63 West Main Street
Suite H
Freehold, NJ 07728
info@wellspouse.org
http://www.wellspouse.org
Tel: 800-838-0879 732-577-8899
Fax: 732-577-8644

Paralyzed Veterans of America (PVA)
801 18th Street, NW
Washington, DC 20006-3517
info@pva.org
http://www.pva.org
Tel: 202-USA-1300 (872-1300) 800-424-8200
Fax: 202-785-4452

Accelerated Cure Project for Multiple Sclerosis
300 Fifth Avenue
Waltham, MA 02451
info@acceleratedcure.org
http://www.acceleratedcure.org
Tel: 781-487-0008
Fax: 781-487-0009

Related NINDS Publications and Information

Multiple Sclerosis: Hope Through Research
Multiple Sclerosis (MS) information sheet compiled by the National Institute of Neurological Disorders and Stroke (NINDS).

Neurological Diagnostic Tests and Procedures
Fact sheet on neurological diagnosis and testing, prepared by the National Institute of Neurological Disorders and Stroke (NINDS).

Small Trial Shows Daclizumab Add-On Therapy Improves Multiple Sclerosis Outcome
May 2004 press release on a clinical trial showing improved patient outcome after use of the drug daclizumab.

Old Drug, New Use: New Research Shows Common Cholesterol-Lowering Drug Reduces Multiple Sclerosis Symptoms in Mice
January 2003 news summary on studies suggesting that statin drugs may be useful for multiple sclerosis.

Brain Produces New Cells in Multiple Sclerosis
February 2002 news summary on brain repair in multiple sclerosis.

Biomarkers in Multiple Sclerosis - Workshop Summary
Biomarkers in Multiple Sclerosis - Workshop Summary

Genetics and Multiple Sclerosis: Future Prospects Workshop
Genetics and Multiple Sclerosis: Future Prospects Workshop

Multiple Sclerosis and Chemokines: Prospects for Therapeutic and Prophylactic Intervention
Health Disparities Working Group Meeting: Cognitive and Emotional Health Multiple Sclerosis and Chemokines: Prospects for Therapeutic and Prophylactic Intervention

NINDS Seeks Patients with Multiple Sclerosis
Lay-language descriptions of new program announcements and clinical trials seeking patient volunteers.

NINDS Accepts Organ Donations for Multiple Sclerosis Research
Lay-language descriptions of new program announcements and clinical trials seeking patient volunteers.

Publicaciones en Español

Esclerosis Múltiple: Esperanza en la Investigacion
A Spanish-language public information booklet on multiple sclerosis/Informacion de la Enfermadad de Esclerosis

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892
..
NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.
..
All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.
..
Last updated December 01, 2006
..

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Research: stem cells In the Subventicular Zone (SVZ), Deep in the Brain

2007-05-11T11:14:00.001-07:00

Bulletins
Bulletins Archive

Society-Funded Researchers Find Cells that May Promote Myelin Repair in MS

April 20, 2007

Researchers funded in part by the National MS Society’s Promise:2010 campaign report on a potential source of cells in the brain to promote repair of nervous system damage that occurs in multiple sclerosis. Anne Baron-Van Evercooren PhD, and Brahim Nait-Oumesmar PhD (INSERM, Paris) and colleagues report their findings in the Proceedings of the National Academy of Sciences (2007 Mar 13;104[11]:4694-9). Drs. Van-Evercooren and Nait-Oumesmar are members of one of the four international, multidisciplinary teams funded through the Promise:2010 campaign’s Repair and Protection Initiative to accelerate nerve tissue repair from basic research to human clinical trials.

Multiple sclerosis occurs when the immune system mistakenly attacks the myelin insulation of nerve fibers. Nerve fibers themselves also are damaged. Some spontaneous repair occurs via populations of immature stem cells resident in the brain, but this repair is not sufficient. Researchers are searching for ways to stimulate these natural repair resources in people with MS. Drs. Van-Evercooren and Nait-Oumesmar are members of the repair team headed by Professor Charles ffrench-Constant (University of Cambridge, UK), which is focusing on restoring myelin by identifying and amplifying natural repair factors in the brain and by attempting transplantation of replacement cells.

In the current study, the authors investigated an area deep in the brain that may harbor cells capable of promoting repair: the subventricular zone (SVZ). They studied brain tissue obtained from people with MS through autopsy and compared cells found in the SVZ with tissue obtained from people who did not have MS.

The researchers found evidence of two to three times as many stem cells showing molecular signs of being immature myelin-making cells in the SVZ of people with MS as in controls without the disease. In areas (lesions) of active inflammation, the number of cells was eight times more than in areas where there was no inflammation.

These results show expanded capabilities for the SVZ in people with MS to produce cells that have potential to promote myelin repair. It remains to be seen why these cells fail to prevent disease progression, and how any obstacles might be overcome to take full advantage of the cells in therapeutic strategies for people with MS.

A full report on the progress of the Repair and Protection Initiative can be found in the Winter/Spring 2007 issue of “Research Highlights,” at
www.nationalmssociety.org/

-- Research and Clinical Programs Department

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MS Research and Links

2007-05-10T12:21:00.000-07:00

Multiple Sclerosis
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phone: (206) 284-4254
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Research
The National MS Society is the largest private sponsor of MS research in the world. We support research and training projects aimed at finding the cause of MS, better treatments, and a cure. We also identify promising areas of research and promote activity in those areas.

Breaking News: International collaborators identify new genetic risk factors for MS. National MS Society supported the largest whole genome scan for MS.

MS in the Northwest: Information on research initiatives and links to local trials recruiting subjects.

Clinical Trials Recruiting Patients: Learn about local trials in Washington state that are recruiting subjects.

Research Fact Sheet: Quick reference guide of research basics.

Research Highlights: A publication of progress in research published twice a year.

Learn more about the research efforts of the National MS Society

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