Multiple sclerosis

From Wikipedia, the free encyclopedia

You have new messages (last change).
Multiple Sclerosis
Classification & external resources
MRI image showing a bright spot where multiple sclerosis has damaged myelin in the brain
ICD-10 G35.
ICD-9 340
OMIM 126200
MedlinePlus 000737

Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory 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 and protecting some 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. 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 which 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.[1][2]

Contents

[edit] Common symptoms

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, sensitivity to heat and pain. 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.[3][4] Fifteen percent of individuals have multiple symptoms when they first seek medical attention.[5] For some people the initial MS attack is preceded by infection, trauma, or strenuous physical effort.

Other symptoms and physical findings common in multiple sclerosis are flickering eye movements (nystagmus), speech difficulties, tremor, clumsiness of the hands, abnormal muscle spasms, and bladder and bowel difficulties. People with MS may also experience a range of acute and chronic pain syndromes.


[edit] Cognitive and emotional symptoms

Cognitive impairments are common. Neuropsychological studies suggest that 40 to 60 percent of patients have cognitive deficits.[6], being the lowest percentages usually from community-based studies while the highest ones from hospital-based. Some of the most common declines are in recent memory, attention, processing speed, visuoespatial abilities and executive functions.[7] Other cognitive-related symptoms are emotional instability, and fatigue, including purely neurological fatigue.

Emotional symptoms are common and can be the normal response to having a debilitating disease or the result of damage to the nerves that generate and control emotions, clinical depression being the most common condition. Feelings such as anger, anxiety, frustration, and hopelessness are also common, and suicide is a very real threat.

[edit] Further discussion of 3 symptoms

Three clinical entities warrant further discussion because affected individuals are often eventually diagnosed with MS. (However, MS is only one of several potential causes for these entities.)

Optic neuritis
Some individuals experience rapid onset of pain in one eye, followed by blurry vision in part or all of the visual field of that eye. This is a result of involvement of the optic nerve by MS. Only 10% to 50% of patients (depending on the population studied) with optic neuritis go on to develop MS. The blurred vision usually resolves within six months, but individuals are often left with less vivid color vision (especially red) in the affected eye.
Internuclear ophthalmoplegia
Some individuals will experience binocular diplopia (double vision with both eyes open) when looking to one side. Internuclear ophthalmoplegia occurs when MS affects a part of the brain stem called the medial longitudinal fasciculus, which is responsible for communication between the two eyes. This results in the failure of the medial rectus muscle to contract appropriately, so that the eyes do not move equally (called disconjugate gaze).
Transverse myelitis
Some MS patients develop rapid onset of numbness, weakness, bowel or bladder dysfunction, and/or loss of muscle function, typically in the lower half of the body. This is the result of MS attacking the spinal cord. As many as 80% of individuals with transverse myelitis are left with lasting disabilities, even though there is usually some improvement during the first two years.

[edit] 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. The McDonald criteria represent international efforts to standardize the diagnosis of MS using clinical data, laboratory data, and radiologic data.[8]

  • 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). [9] 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.[10]

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[11][12][13][14]), tumors, and other autoimmune problems, such as lupus. Additional testing may be needed to help distinguish MS from these other problems.

[edit] Disease course and clinical subtypes

Graph representing the different types of multiple sclerosis
Graph representing the different types of multiple sclerosis

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. A person diagnosed with a particular subtype may, for unclear reasons, switch from one subtype to another over time. 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:[15]

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.

[edit] 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.[16]

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 hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin (BCG - immunization for tuberculosis) increases the risk for relapse.[17]

[edit] Pathophysiology

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

[edit] How multiple sclerosis causes damage

Multiple sclerosis is a disease in which the myelin surrounding some nerve cells degenerates. Myelin is a fatty substance which covers the axons of nerve cells and is important for proper nerve conduction.

According to the view of most researchers, a special subset of lymphocytes, called T cells, plays a key role in the development of MS. Under normal circumstances, these lymphocytes can distinguish between self and non-self. However, in a person with MS, these cells recognize healthy parts of the central nervous system as foreign and attack them as if they were an invading virus, triggering inflammatory processes and stimulating other immune cells and soluble factors like cytokines and antibodies.

Normally, there is a tight barrier between the blood and brain, called the blood-brain barrier, built up of endothelial cells lining the blood vessel walls. It should prevent the passage of antibodies through it, but in MS patients it does not work. A deficiency of uric acid has been implicated in this process. Uric acid added in physiological concentrations (i.e. achieving normal concentrations) is therapeutic in MS by preventing the breakdown of the blood brain barrier though inactivation of peroxynitrite.[18]. The low level of uric acid found in MS victims is manifestedly causative rather than a consequence of tissue damage.[19]. Nevertheless, whether BBB dysfunction is the cause or the consequence of MS [20] is still disputed.

According to a strictly immunological explanation of MS, the inflammatory processes triggered by the T cells create leaks in the blood-brain barrier. 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. The final result is destruction of myelin, called demyelination.

Repair processes, called remyelination, also play an important role in MS. Remyelination is one of the reasons why, especially in early phases of the disease, symptoms tend to decrease or disappear temporarily. Nevertheless, nerve damage and irreversible loss of neurons occur early in MS. Proton magnetic resonance spectroscopy has shown that there is widespread neuronal loss even at the onset of MS, largely unrelated to inflammation.[21] 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.

The oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. However, the brain can recruit stem cells, which migrate from other unknown regions of the brain, differentiate into mature oligodendrocytes, and rebuild the myelin sheath. These new myelin sheaths are 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. Under laboratory conditions, stem cells are quite capable of differentiating and remyelinating axons; it is therefore suspected that inflammatory conditions or axonal damage somehow inhibit stem cell differentiation in the body.

[edit] Pathophysiology research

Until recently, most of the data available came from post-mortem brain samples and animal models of the disease, such as the experimental autoimmune encephalomyelitis (EAE), an autoimmune disease that can be induced in rodents, and which is considered a possible animal model for multiple sclerosis.[22]

In 1998, the National Multiple Sclerosis Society and the Mayo Clinic launched "The Lesion Project"[23] to describe MS lesions as accurately as possible and to develop an accurate model of the evolution of the disease. They have used brain biopsies apart from the post-mortem samples. Four different damage patterns have been identified in the scars of the brain tissue[24], but the meaning of this fact remains controversial. For some researchers it means that MS is a heterogeneous disease. Other teams maintain that the shape of the scars can change from one type to another and this could be a marker of the disease action time.

The four patterns that were identified are:[25]

Pattern I 
The scar presents T-cells and macrophages around blood vessels, with preservation of oligodendrocytes, but no signs of complement system activation.[26]
Pattern II 
The scar presents T-cells and macrophages around blood vessels, with preservation of oligodendrocytes, as before, but also signs of complement system activation can be found.[27]
Pattern III 
The scars are diffuse with inflammation, distal oligodendrogliopathy and microglial activation. There is also loss of myelin associated glycoprotein (MAG). The scars do not surround the blood vessels, and in fact, a rim of preserved myelin appears around the vessels. There is evidence of partial remyelinization and oligodendrocyte apoptosis.
Pattern IV 
The scar presents sharp borders and oligodendrocyte degeneration, with a rim of normal appearing white matter. There is a lack of oligodendrocytes in the center of the scar. There is no complement activation or MAG loss.

Apart from this, special cases of the disease with non-standard behavior have been described. These cases are[28]: Devic's disease, Balo concentric sclerosis, Schilder disease, Marburg multiple sclerosis, acute disseminated encephalomyelitis or ADEM and autoimmune variants of peripheral neuropathies.

[edit] Why multiple sclerosis occurs

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 an underlying condition. In support of alternative theories is the fact that present therapies have not been as successful as was expected based on the autoimmune theory.[29][30][31]

[edit] 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[32] 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.[33].

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.[34] 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.[35] 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. [36]

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.[37] Smoking has also been shown to be an independent risk factor for developing MS.[38]

[edit] 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 identical gene pools), 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.

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.

[edit] Treatment

Main article: Therapies 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.

Various disease-modifying treatments have been approved by the USA's Food and Drug Administration (FDA) for multiple sclerosis.

These are medications derived from human cytokines which help regulate the immune system. Betaseron has been approved by the FDA for relapsing forms of secondary progressive MS.
Interferon beta-1a: (trade names Avonex and Rebif)
beta-1b: (trade name Betaseron [in Europe and Japan Betaferon]).
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.
This medication is effective, but is limited by cardiac toxicity. Novantrone has been approved by the FDA for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS.
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 in the United States are typically given high doses of intravenous corticosteroids, such as methylprednisolone, to end the attack sooner and leave fewer lasting deficits. Patients' self-reporting indicates that many find benefit from a number of other medicines.[6]

Currently there are no approved treatments for primary progressive multiple sclerosis, though several medications are being studied and are described at Therapies for multiple sclerosis.

[edit] Prognosis

The prognosis (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 and speech therapy, and more successful treatment of common complications of disability, such as pneumonia and urinary tract infections.[39]

  • 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.
  • 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 black individuals 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.[40] 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).[41]

[edit] Epidemiology

World map showing that risk for MS increases with greater distance from the equator
World map showing that risk for MS increases with greater distance from the equator

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[42]. 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.[43]

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. These few examples point out that genetic background plays 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 twenty 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.[44]

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 imposibility to distinguish MS and NMO reliably before this date. The error can be important in some areas, and is considered to be 30% in Japan.[45]

[edit] 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.[46] 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 Multiple sclerosis borderline.

There are several historical accounts of people who probably had MS. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may have been the first identifiable MS patient. 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. 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. 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.

March is Multiple Sclerosis Awareness Month. Throughout the year, and especially during this month, the National Multiple Sclerosis Society encourages people to visit http://www.JoinTheMovement.org, and join the MySpace page at http://www.MySpace.com/MSsociety.

One feature on the site is an interactive "Make Your Mark" tool where visitors can design their own marks against MS to be displayed on a "Wall." There is also video, a send-to-friend feature, easy ways to volunteer and join walk or bike events, 25 user-generated stories, and free MS button artwork (http://www.nationalmssociety.org/jtm_buttons.asp) to increase awareness of how others can help bring about an end to multiple sclerosis.

[edit] Multiple sclerosis in film, television and sports

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."

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.

Actor Vidya Balan played an MS patient in a real-life-based Bollywood movie Guru (2007 film). The character suffers with impaired legs and extreme weakness. The film portrays the problems that people having MS face in their daily life. The character, however, is incorrectly shown as being able to predict her last moments, when in fact, MS is known only to impact the quality, and not the quantity, of life.

Jordan Sigalet, goalie for the Providence Bruins, has MS, and has been getting better and better every year.

Television talk show host Montel Williams was diagnosed with MS in 1999.

[edit] See also

[edit] References

  1. ^ Dangond, F.Multiple sclerosis. eMedicine Neurology. Updated 2005 Apr 25. full text.
  2. ^ Calabresi PA.Diagnosis and management of multiple sclerosis. Am Fam Physician. PMID 15571060full text.
  3. ^ Navarro S, Mondéjar-Marín B, Pedrosa-Guerrero A, Pérez-Molina I, Garrido-Robres J, Alvarez-Tejerina A. "[Aphasia and parietal syndrome as the presenting symptoms of a demyelinating disease with pseudotumoral lesions]". Rev Neurol 41 (10): 601-3. PMID 16288423. 
  4. ^ Jongen P (2006). "Psychiatric onset of multiple sclerosis". J Neurol Sci 245 (1-2): 59-62. PMID 16631798. 
  5. ^ Paty D, Studney D, Redekop K, Lublin F. MS COSTAR: a computerized patient record adapted for clinical research purposes. Ann Neurol 1994;36 Suppl:S134-5. PMID 8017875
  6. ^ Rao S, Leo G, Bernardin L, Unverzagt F (1991). "Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction". Neurology 41 (5): 685-91. PMID 2027484. 
  7. ^ Bobholz J, Rao S (2003). "Cognitive dysfunction in multiple sclerosis: a review of recent developments". Curr Opin Neurol 16 (3): 283-8. PMID 12858063. 
  8. ^ McDonald WI; Compston A; Edan G; Goodkin D; Hartung HP; Lublin FD; McFarland HF; Paty DW; Polman CH; Reingold SC; Sandberg-Wollheim M; Sibley W; Thompson A; van den Noort S; Weinshenker BY; Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001 Jul;50(1):121-7 PMID 11456302
  9. ^ Rudick, RA, Whitaker, JN. Cerebrospinal fluid tests for multiple sclerosis. In Scheinberg, P (Ed). Neurology/neurosurgery update series, Vol. 7, CPEC. Princeton, NJ 1987
  10. ^ Gronseth GS; Ashman EJ. Practice parameter: the usefulness of evoked potentials in identifying clinically silent lesions in patients with suspected multiple sclerosis (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000 May 9;54(9):1720-5. PMID 10802774
  11. ^ Garcia-Monco JC; Miro Jornet J; Fernandez Villar B; Benach JL; Guerrero Espejo A; Berciano JA. [Multiple sclerosis or Lyme disease? a diagnosis problem of exclusion] Med Clin (Barc) 1990 May 12;94(18):685-8. PMID 2388492
  12. ^ Hansen K; Cruz M; Link H. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1990 Jun;161(6):1194-202. PMID 2345300
  13. ^ Schluesener HJ; Martin R; Sticht-Groh V. Autoimmunity in Lyme disease: molecular cloning of antigens recognized by antibodies in the cerebrospinal fluid. Autoimmunity 1989 2(4):323-30. PMID 2491615
  14. ^ Kohler J; Kern U; Kasper J; Rhese-Kupper B; Thoden U. Chronic central nervous system involvement in Lyme borreliosis Neurology 1988 Jun;38(6):863-7. PMID 3368066
  15. ^ Lublin FD; Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996 Apr;46(4):907-11. PMID 8780061
  16. ^ Worthington J; Jones R; Crawford M; Forti A. Pregnancy and multiple sclerosis--a 3-year prospective study. J Neurol 1994 Feb;241(4):228-33. PMID 8195822
  17. ^ Confavreux C; Suissa S; Saddier P; Bourdes V; Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med 2001 Feb 1;344(5):319-26. PMID 11172162
  18. ^ The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity[1]
  19. ^ Serum uric acid and multiple sclerosis[2]
  20. ^ Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis [3]
  21. ^ Fillipi M, Bozzali M, Rovaris M, et al. "Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis" Brain 2003;126:433–437
  22. ^ Experimental Autoimmune Encephalomyelitis. All About Multiple Sclerosis (08/13/2003). Retrieved on 2006-05-10.
  23. ^ The MS Lesion Project - Is MS More Than One Disease?. National Multiple Sclerosis Society (December 14, 2005). Retrieved on 2006-05-10.
  24. ^ Lucchinetti, C. Bruck, W. Parisi, J. Scherhauer, B. Rodriguez, M. Lassmann, H.Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination Ann Neurol, 2000; 47(6):707-17. PMID 10852536
  25. ^ Wilner, Andrew (August 2002). Unraveling The Mystery Of The MS Lesion - Pathogenic Clues And Therapeutic Hints. Neurology Reviews.com. Retrieved on 2006-05-10.
  26. ^ Holmes, Nick (15 November 2001). Part 1B Pathology: Lecture 11 - The Complement System. Retrieved on 2006-05-10.
  27. ^ Lucchinetti, Claudia; Wolfgang Brück, Joseph Parisi, Bernd Scheithauer, Moses Rodriguez and Hans Lassmann (December 1999). "A quantitative analysis of oligodendrocytes in multiple sclerosis lesions - A study of 113 cases". Brain 122 (12): 2279-2295. Retrieved on 2006-05-10. 
  28. ^ Borderline forms of MS, Fontaine, B., Federation de Neurologie, INSERM U546, Groupe Hospitalier, Faculte de Medecine Pitie-Salpetriere, Paris [4]
  29. ^ Peter Behan and Abhijit Chaudhuri (2002). "The pathogenesis of multiple sclerosis revisited". J R Coll Physicians Edinb 32: 244-265. 
  30. ^ Abhijit Chaudhuri and Peter Behan (2004). "Multiple Sclerosis Is Not an Autoimmune Disease". Archives of Neurology 61: 1610-2. 
  31. ^ Abhijit Chaudhuri and Peter Behan (2005). "Evaluating the Evidence for Multiple Sclerosis as an Autoimmune Disease--In reply". Archives of Neurology 62: 688-9. 
  32. ^ van der Mei, IA, Ponsonby, AL, Dwyer, T, et al. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 2003; 327:316. PMID 12907484
  33. ^ Munger KL. , Levin, LI,Hollis BW , Howard, NS , Ascherio A (2006). "High Levels of Vitamin D In the Body May Decrease the Risk of Multiple Sclerosis". Journal of the American Medical Association 296 (23): 2832-2838. 
  34. ^ Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A. Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA. 2005 May 25;293(20):2496-500. PMID 15914750
  35. ^ Brorson O; Brorson SH; Henriksen TH; Skogen PR; Schoyen R; Association between multiple sclerosis and cystic structures in cerebrospinal fluid. Infection. 2001 Dec;29(6):315-9. PMID 11787831
  36. ^ Yao SY, Stratton CW, Mitchell WM, Sriram S, CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens. Neurology. 2001 May 8;56(9):1168-76. PMID 11342681
  37. ^ http://news.bbc.co.uk/2/hi/health/3542257.stm
  38. ^ Franklin, GM, Nelson, L. Environmental risk factors in multiple sclerosis: Causes, triggers, and patient autonomy. Neurology 2003; 61:1032. PMID 14581658
  39. ^ Weinshenker BG. Natural history of multiple sclerosis. Ann Neurol 1994;36 Suppl:S6-11. PMID 8017890
  40. ^ Pittock SJ; McClelland RL; Mayr WT; Jorgensen NW; Weinshenker BG; Noseworthy J; Rodriguez M. Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study Ann Neurol 2004 Aug;56(2):303-6. PMID 15293286
  41. ^ Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med. 2003 Jul 10;349(2):139-45. PMID 12853586
  42. ^ Epidemiology and multiple sclerosis. a personal review
  43. ^ Marrie, RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol. 2004 Dec;3(12):709-18. Review. PMID 15556803
  44. ^ Sadovnick, AD, Ebers, GC, Dyment, DA, Risch, NJ. Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet 1996; 347:1728. PMID 8656905
  45. ^ Differences between optic-spinal and classic MS in Japanese patients [5]
  46. ^ Charcot, J. Histologie de la sclerose en plaques. Gazette des hopitaux, Paris, 1868; 41: 554-555.

[edit] Further reading

[edit] External links

Resources:

Organizations:

Retrieved from "http://en.wikipedia.org../../../m/u/l/Multiple_sclerosis.html"