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Multiple sclerosisClassification and external resources

Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion.

Original scale 1:100ICD-10 G 35 ICD-9 340OMIM 126200DiseasesDB 8412MedlinePlus 000737

eMedicineneuro/228 oph/179 emerg/321 pmr/82 radio/461

MeSH D009103

GeneReviews Multiple Sclerosis Overview

Multiple sclerosis (MS), also known as "disseminated sclerosis" or "encephalomyelitis disseminata", is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms.[1] Disease onset usually occurs in young adults, and it is more common in women.[1] It has a prevalence that ranges between 2 and 150 per 100,000.[2] MS was first described in 1868 by Jean-Martin Charcot.[3]

MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals.[4] The name multiple sclerosis refers to scars (sclerae-—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.[3] Although much is known about the

mechanisms involved in the disease process, the cause remains unknown. Theories include genetics or infections. Different environmental risk factors have also been found.[4][5]

Almost any neurological symptom can appear with the disease, and the disease often progresses to physical and cognitive disability.[4] MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or accumulating over time (progressive forms).[6] Between attacks, symptoms may go away completely, but permanent neurological deficits often occur, especially as the disease advances.[6]

There is no known cure for multiple sclerosis. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability.[4] MS medications can have adverse effects or be poorly tolerated, and many people pursue alternative treatments, despite the lack of supporting scientific study. The prognosis is difficult to predict; it depends on the subtype of the disease, the individual's disease characteristics, the initial symptoms and the degree of disability the person experiences as time advances.[7] Life expectancy of people with MS is 5 to 10 years lower than that of the unaffected population.[1]

Contents

1 Signs and symptoms 2 Causes

o 2.1 Geneticso 2.2 Environmental factorso 2.3 Infections

3 Pathophysiology o 3.1 Autoimmunology o 3.2 Blood–brain barrier breakdown

4 Diagnosis o 4.1 Clinical courses

5 Management o 5.1 Acute attackso 5.2 Disease-modifying treatmentso 5.3 Management of the effects of MSo 5.4 Alternative treatments

6 Prognosis 7 Epidemiology 8 History

o 8.1 Medical discoveryo 8.2 Historical cases

9 Research o 9.1 Therapieso 9.2 Disease biomarkerso 9.3 Chronic cerebrospinal venous insufficiency

10 See also 11 References

12 Further reading 13 External links

Signs and symptoms

Main article: Multiple sclerosis signs and symptoms

Main symptoms of multiple sclerosis

A person with MS can suffer almost any neurological symptom or sign, including changes in sensation such as loss of sensitivity or tingling, pricking or numbness (hypoesthesia and paresthesia), muscle weakness, clonus, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis including phosphenes,[8][9] or diplopia), fatigue, acute or chronic pain, and bladder and bowel difficulties.[1] Cognitive impairment of varying degrees and emotional symptoms of depression or unstable mood are also common.[1] Uhthoff's phenomenon, an exacerbation of extant symptoms due to an exposure to higher than usual ambient temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS although not specific.[1] The main clinical measure of disability progression and symptom severity is the Expanded Disability Status Scale or EDSS.[10]

Symptoms of MS usually appear in episodic acute periods of worsening (called relapses, exacerbations, bouts, attacks, or "flare-ups"), in a gradually progressive deterioration of neurologic function, or in a combination of both.[6] Multiple sclerosis relapses are often unpredictable, occurring without warning and without obvious inciting factors with a rate rarely above one and a half per year.[1] Some attacks, however, are preceded by common triggers.

Relapses occur more frequently during spring and summer.[11] Viral infections such as the common cold, influenza, or gastroenteritis increase the risk of relapse.[1] Stress may also trigger an attack.[12] Pregnancy affects the susceptibility to relapse, with a lower relapse rate at each trimester of gestation. During the first few months after delivery, however, the risk of relapse is increased.[1] Overall, pregnancy does not seem to influence long-term disability. Many potential triggers have been examined and found not to influence MS relapse rates. There is no evidence that vaccination and breast feeding,[1] physical trauma,[13] or Uhthoff's phenomenon[11] are relapse triggers.

Causes

Most likely MS occurs as a result of some combination of genetic, environmental and infectious factors,[1] and possibly other factors like vascular problems.[14] Epidemiological studies of MS have provided hints on possible causes for the disease. Theories try to combine the known data into plausible explanations, but none has proved definitive.

Genetics

HLA region of Chromosome 6. Changes in this area increase the probability of suffering MS.

MS is not considered a hereditary disease. However, a number of genetic variations have been shown to increase the risk of developing the disease.[15]

The risk of acquiring MS is higher in relatives of a person with the disease than in the general population, especially in the case of siblings, parents, and children.[4] The disease has an overall familial recurrence rate of 20%.[1] In the case of monozygotic twins, concordance occurs only in about 35% of cases, while it goes down to around 5% in the case of siblings and even lower in half-siblings. This indicates susceptibility is partly polygenically driven.[1][4] It seems to be more common in some ethnic groups than others.[16]

Apart from familial studies, specific genes have been linked with MS. Differences in the human leukocyte antigen (HLA) system—a group of genes in chromosome 6 that serves as the major histocompatibility complex (MHC) in humans—increase the probability of suffering MS.[1] The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6.[1] Other loci have shown a protective effect, such as HLA-C554 and HLA-DRB1*11.[1]

Environmental factors

Different environmental factors, both of infectious and non-infectious origin, have been proposed as risk factors for MS. Although some are partly modifiable, only further research—especially clinical trials—will reveal whether their elimination can help prevent MS.[17]

MS is more common in people who live farther from the equator, although many exceptions exist.[1] Decreased sunlight exposure has been linked with a higher risk of MS.[17] Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun.[17][18][19]

Severe stress may be a risk factor although evidence is weak.[17] Smoking has also been shown to be an independent risk factor for developing MS.[18] Association with occupational exposures and toxins—mainly solvents—has been evaluated, but no clear conclusions have been reached.[17] Vaccinations were investigated as causal factors for the disease; however, most studies show no association between MS and vaccines.[17] Several other possible risk factors, such as diet [20] and hormone intake, have been investigated; however, evidence on their relation with the disease is "sparse and unpersuasive".[18]

Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in people with MS as compared to normal individuals. This led to the theory that uric acid protects against MS, although its exact importance remains unknown.[21]

Infections

Many microbes have been proposed as potential infectious triggers of MS, but none have been substantiated.[4] Moving at an early age from one location in the world to another alters a person's subsequent risk of MS.[5] An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare pathogen, is the origin of the disease.[5] There are a number of proposed mechanisms, including the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to several infectious agents early in life is protective against MS, the disease being a response to a later encounter with such agents.[1]

The prevalence hypothesis proposes that the disease is due to a pathogen more common in regions of high MS prevalence where in most individuals it causes an asymptomatic persistent infection. Only in a few cases and after many years does it cause demyelination.[5][22] The hygiene hypothesis has received more support than the prevalence hypothesis.[5]

Evidence for viruses as a cause includes the presence of oligoclonal bands in the brain and cerebrospinal fluid of most people with MS, the association of several viruses with human demyelination encephalomyelitis, and induction of demyelination in animals through viral infection.[23] Human herpes viruses are a candidate group of viruses linked to MS. Individuals who have never been infected by the Epstein-Barr virus have a reduced risk of having the disease, and those infected as young adults have a greater risk than those who had it at a younger age.[1][5] Although some consider that this goes against the hygiene hypothesis, since the noninfected have probably experienced a more hygienic upbringing,[5] others believe that there is no contradiction since it is a first encounter at a later moment with the causative virus that is the trigger for the disease.[1] Other diseases that have also been related with MS are measles, mumps, and rubella.[1]

Pathophysiology

Main article: Pathophysiology of multiple sclerosis

Demyelination in MS. On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).

Autoimmunology

MS is believed to be an immune-mediated disorder mediated by a complex interaction of the individual's genetics and as yet unidentified environmental insults.[4] Damage is believed to be caused by the person's own immune system attacking the nervous system. Possible targets of the immune response include myelin basic protein (MBP) and proteolipid protein (PLP). The commonly prescribed MS drug Copaxone was designed to mimic MBP and therefore act as a decoy for autoreactive immune cells. Even so, the role of MBP in MS is controversial; it is buried within the myelin sheath (rather than on the surface), where immune cells would not be able to recognize it.

Recent data suggest a role for myelin lipids in MS.[24] Historically, researchers have assumed the myelin target was a protein, even though the myelin sheath is nearly 80% lipid. Furthermore,

lipids are known to be the target of another prominent nervous system autoimmune condition, Guillain-Barre Syndrome.

Whether the autoantigen is a protein or a lipid, autoimmunity may arise when immune cells recognizing a foreign antigen cross-react with self antigens. This process is known as molecular mimicry.[4][25]

Lesions

The name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. MS lesions most commonly involve white matter areas close to the ventricles of the cerebellum, brain stem, basal ganglia and spinal cord; and the optic nerve. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.[4]

More specifically, MS destroys oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials).[4] MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron's axons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.[4] A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cell's myelin sheath.[26] Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons.[26] Different lesion patterns have been described.[27]

Inflammation

Apart from demyelination, the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by T cells, a kind of lymphocyte. Lymphocytes are cells that play an important role in the body's defenses.[4] In MS, T cells gain entry into the brain via disruptions in the blood–brain barrier. Evidence from animal models also point to a role of B cells in addition to T cells in development of the disease.[28]

The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Further leaks form in the blood–brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.[4]

Blood–brain barrier breakdown

The blood–brain barrier is a part of the capillary system that prevents the entry of T cells into the central nervous system.[4] However, it may become permeable to these types of cells because of an infection or a virus.[4] When the blood–brain barrier regains its integrity, typically after the infection or virus has cleared, the T cells are trapped inside the brain.[4]

Diagnosis

Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to other medical problems.[1][29] Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process especially in the first stages of the disease.[1] Historically, the Schumacher and Poser criteria were both popular.[30]

Currently, the McDonald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space for non-invasive MS diagnosis, though some have stated that the only proved diagnosis of MS is autopsy, or occasionally biopsy, where lesions typical of MS can be detected through histopathological techniques.[1][31][32]

Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate episodes of neurologic symptoms characteristic of MS.[31] Since some people seek medical attention after only one attack, other testing may hasten and ease the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.[31][33] Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.[31][34] The nervous system of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.[35]

Clinical courses

Progression of MS subtypes

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. They are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized four clinical courses:[6]

1. relapsing remitting,2. secondary progressive,3. primary progressive, and4. progressive relapsing.

The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during attacks may either resolve or leave sequelae, the latter being more common as a function of time.[1] This describes the initial course of 80% of individuals with MS.[1] When deficits always resolve between attacks, this is sometimes referred to as benign MS,[36] although people will still accrue some degree of disability in the long term.[1] The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis.[1][37] However only 30 to 70% of persons experiencing CIS later develop MS.[37]

Nerve axon with myelin sheath

Secondary progressive MS describes around 65% of those with an initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission.[1][6] Occasional relapses and minor remissions may appear.[6] The median time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.[38] The primary progressive subtype describes the approximately 10–15% of individuals who never have remission after their initial MS symptoms.[39] It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.[6] The age of onset for the primary progressive subtype is later than for the relapsing-remitting, but similar to mean age of progression between the relapsing-remitting and the secondary progressive. In both cases it is around 40 years of age.[1]

Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also suffer clear superimposed attacks. This is the least common of all subtypes.[6]

Atypical variants of MS with non-standard behavior have been described; these include Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases.[40] Multiple sclerosis also behaves differently in children, taking more time to reach the progressive stage.[1] Nevertheless they still reach it at a lower mean age than adults.[1]

Management

Main article: Treatment of multiple sclerosis

Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of

MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting, comparable, replicated scientific study.

Acute attacks

During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses,[1] while oral corticosteroids seem to have a similar efficacy and safety profile.[41] Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[42] Consequences of severe attacks which do not respond to corticosteroids might be treated by plasmapheresis.[1]

Disease-modifying treatments

Main article: Treatment of multiple sclerosis#Disease-modifying treatments

Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 1–3 month intervals.

As of January 2013, seven disease-modifying treatments have been approved by regulatory agencies of different countries, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese PMDA. The approved drugs are interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone (an immunosuppressant also used in cancer chemotherapy), natalizumab (a humanized monoclonal antibody immunomodulator), fingolimod and teriflunomide.[1][43][44]

The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for interferon beta-1a. Natalizumab and mitoxantrone are given by intravenous (IV) infusion at monthly intervals in the case of natalizumab and every three months in the case of mitoxantrone.[45] [46][47] In 2010 fingolimod became the first oral drug approved by the FDA,[43] being followed in 2012 by teriflunomide.[44] Fingolimod and teriflunomide are taken through a daily single dose.[44][48]

Most drugs are approved only for the relapsing-remitting course (RRMS). Medications are modestly effective at decreasing the number of attacks in RRMS.[49]

Interferons and glatiramer acetate are roughly equivalent, reducing relapses by approximately 30%.[1] Comparisons to natalizumab show that the most effective is the latter, both in terms of relapse rate reduction and halting disability progression.[50] Mitoxantrone may be the most

effective of them all; however, it is generally not considered as a long-term therapy, as its use is limited by severe secondary effects.[1][51] While more studies of the long-term effects of the drugs are needed,[1][51][52] specially for the newest treatments, existing data on the effects of interferons and glatiramer acetate indicate that early-initiated long-term therapy is safe and it is related to better outcomes.[52][53]

The earliest clinical presentation of RRMS is the clinically isolated syndrome (CIS). Treatment with interferons during an initial attack decreases the chance that a person will develop clinical MS.[1][54] Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in those with secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in short-term follow-up.[55] No treatment has been proven to modify the course of primary progressive MS.[56] Efficacy of most common treatments, interferons and glatiramer acetate, in early-onset MS (before eighteen years of age) has been estimated to be roughly equivalent to adults.[57]

As with many medical treatments, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferon treatments. Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons produce symptoms similar to influenza;[58] some people taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes.[59] More dangerous but much less common are liver damage from interferons,[60] severe cardiotoxicity, infertility, and acute myeloid leukemia of mitoxantrone,[1][51] and the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy.[1] Fingolimod side effects in clinical trials have included cardiovascular conditions, macular edema, infections, liver toxicity and malignancies.[61][62]

Management of the effects of MS

Disease-modifying treatments reduce the progression rate of the disease, but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and disability. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, though neither influences disease progression.[1][63] Some symptoms have a good response to medication, such as unstable bladder and spasticity, while management of many others is much more complicated.[1] As for any person with neurologic deficits, a multidisciplinary approach is key to improving quality of life; however, there are particular difficulties in specifying a 'core team' because people with MS may need help from almost any health profession or service at some point.[1] Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.[64] Due to the paucity of randomized controlled studies, there is limited evidence of the overall efficacy of individual therapy disciplines,[65][65][66] though there is good evidence that specific approaches, such as exercise,[67][68] psychology therapies, particularly cognitive behavioral approaches [69] and energy conservation instruction[70] are effective.

Alternative treatments

Many people with MS use complementary and alternative medicine. Depending on the treatments, the evidence is weak or absent.[71] Examples are a dietary regimen,[72] herbal medicine (including the use of medical cannabis),[73] hyperbaric oxygenation [74] and self-infection with hookworm (known generally as helminthic therapy).[75] Helminthic therapy of infection with Trichuris suis ova is under investigation as of 2013, with expected results of a clinical trial in 2014. Preliminary data indicates that it may be safe and clinically useful.[76][77]

Prognosis

Disability-adjusted life year for multiple sclerosis per 100,000 inhabitants in 2004   no data  <13  13–16  16–19  19–22  22–25  25–28

  28–31  31–34  34–37  37–40  40–43  >43

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, age, and initial symptoms; and the degree of disability the person experiences.[7] The disease evolves and advances over decades, 30 being the mean years to death since onset.[1]

Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.[7][78]

The life expectancy of people with MS is 5 to 10 years lower than that of unaffected people.[1] Almost 40% of people with MS reach the seventh decade of life.[78] Nevertheless, two-thirds of the deaths in people with MS are directly related to the consequences of the disease.[1] Suicide also has a higher prevalence than in the healthy population, while infections and complications are especially hazardous for the more disabled ones.[1]

Although most people lose the ability to walk before death, 90% are still capable of independent walking at 10 years from onset, and 75% at 15 years.[78][79]

Epidemiology

Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at a given time. Prevalence is known to depend not only on incidence, but also on survival rate and migrations of affected people. MS has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population.[2] Studies on populational and geographical patterns of epidemiological measures have been very common in MS,[22] and have led to the proposal of different etiological (causal) theories.[5][17][18][22]

MS usually appears in adults in their thirties but it can also appear in children.[1] The primary progressive subtype is more common in people in their fifties.[39] As with many autoimmune disorders, the disease is more common in women, and the trend may be increasing.[1][80] The CDC data suggest that MS is three times more common in women than in men in the United States.[81] In children, the sex ratio difference is higher,[1] while in people over fifty, MS affects males and females almost equally.[39]

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.[1][80] Climate, sunlight and intake of vitamin D have been investigated as possible causes of the disease that could explain this latitude gradient.[18] However, there are important exceptions to the north–south pattern and changes in prevalence rates over time;[1] in general, this trend might be disappearing.[80] This indicates that other factors such as environment or genetics have to be taken into account to explain the origin of MS.[1] MS is also more common in regions with northern European populations.[1] But even in regions where MS is common, some ethnic groups are at low risk of developing the disease, including the Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori.[82]

Environmental factors during childhood may play an important role in the development of MS later in life. Several studies of migrants show that if migration occurs before the age of 15, the migrant acquires the new region's susceptibility to MS. If migration takes place after age 15, the migrant retains the susceptibility of his home country.[1][17] However, the age–geographical risk for developing multiple sclerosis may span a larger timescale.[1] A relationship between season of birth and MS has also been found which lends support to an association with sunlight and vitamin D. For example fewer people with MS are born in November as compared to May.[83]

History

Medical discovery

Detail of Carswell's drawing of MS lesions in the brain stem and spinal cord (1838)

The French neurologist Jean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.[84] Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad 1 are nystagmus, intention tremor, and telegraphic speech (scanning speech), though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a "marked enfeeblement of the memory" and "conceptions that formed slowly".[3]

Before Charcot, 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, but did not identify it as a separate disease.[84] Specifically, Carswell described the injuries he found as "a remarkable lesion of the spinal cord accompanied with atrophy".[1] Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.[85][86]

After Charcot's description, Eugène Devic (1858–1930), Jozsef Balo (1895–1979), Paul Ferdinand Schilder (1886–1940), and Otto Marburg (1874–1948) described special cases of the disease. During all the 20th century there was an important development on the theories about the cause and pathogenesis of MS while efficacious treatments began to appear in 1990.[1]

Historical cases

There are several historical accounts of people who lived before or shortly after the disease was described by Charcot and probably had MS.

A young woman called Halldora who lived in Iceland around 1200 suddenly lost her vision and mobility but, after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of 16 until her death at 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS.[87] Both cases have led to the proposal of a 'Viking gene' hypothesis for the dissemination of the disease.[88]

Augustus Frederick d'Este (1794–1848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George   III of the United Kingdom , almost certainly suffered from MS. D'Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) 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.[89][90]

Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle with MS.[90] His diary was published in 1919 as The Journal of a Disappointed Man.[91]

Research

Main article: Therapies under investigation for multiple sclerosis

Therapies

Chemical structure of alemtuzumab

Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments.[92] A number of treatments that may curtail attacks or improve function are under investigation. Emerging agents for RRMS that had shown promise in phase 2 trials before 2009 included[92] alemtuzumab, daclizumab,[93] rituximab,[94] dirucotide, BHT-3009, cladribine, dimethyl fumarate, estriol, laquinimod, PEGylated interferon-β-1a,[95] minocycline, statins, temsirolimus and teriflunomide.

Since MS has been related to vitamin D deficiency it has been proposed that vitamin D could be used to treat the disease.[96] Clinical trials have been scarce, of low quality and have not shown clear indication of benefit.[97]

While there is anecdotal evidence of benefit for low dose naltrexone,[98] only results from a pilot study in primary progressive MS have been published.[99][100]

Disease biomarkers

The variable clinical presentation of MS and the lack of diagnostic laboratory tests lead to delays in diagnosis and the impossibility of predicting diagnosis. New diagnostic methods are being investigated. These include work with anti-myelin antibodies, analysis of microarray gene expression and studies with serum and cerebrospinal fluid but none of them has yielded reliable positive results.[101]

Currently there are no clinically established laboratory investigations available that can predict prognosis. However, several promising approaches have been proposed. Investigations on the prediction of evolution have centered on monitoring disease activity. Disease activation biomarkers include interleukin-6, nitric oxide and nitric oxide synthase, osteopontin, and fetuin-A.[101] On the other hand since disease progression is the result of neurodegeneration the roles of proteins indicative of neuronal, axonal, and glial loss such as neurofilaments, tau and N-acetylaspartate are under investigation.[101]

A final investigative field is work with biomarkers that distinguish between medication responders and nonresponders.[101]

Chronic cerebrospinal venous insufficiency

Main article: Chronic cerebrospinal venous insufficiency

In 2008, Italian vascular surgeon Paolo Zamboni reported research suggesting that MS involves a vascular disease process he referred to as chronic cerebrospinal venous insufficiency (CCSVI, CCVI), in which veins from the brain are constricted. He found CCSVI in the majority of people with MS, performed a surgical procedure to correct it and claimed that 73% of people improved.[102] Concern has been raised with Zamboni's research as it was neither blinded nor controlled[103] and further studies have had variable results.[104] This has raised serious objections to the hypothesis of CCSVI originating multiple sclerosis.[105] The neurology community currently

recommends not to use the proposed treatment unless its effectiveness is confirmed by controlled studies, the need for which has been recognized by the scientific bodies engaged in MS research.[106]

See also

List of multiple sclerosis organizations List of people with multiple sclerosis

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106. ̂ Khan O, Filippi M, Freedman MS, Barkhof F, Dore-Duffy P, Lassmann H, Trapp B, Bar-Or A, Zak I, Siegel MJ, Lisak R (2010-02-12). "Chronic cerebrospinal venous insufficiency and multiple sclerosis". Annals of neurology (Annals of Neurology) 67 (3): 286–90. doi:10.1002/ana.22001. PMID 20373339.

2. Multiple sclerosis (MS) is a potentially debilitating disease in which your body's immune system eats away at the protective sheath (myelin) that covers your nerves. Damage to myelin causes interference in the communication between your brain, spinal cord and other areas of your body. This condition may result in deterioration of the nerves themselves, a process that's not reversible.

3. Symptoms vary widely, depending on the amount of damage and the nerves that are affected. People with severe cases of multiple sclerosis may lose the ability to walk or speak clearly. Multiple sclerosis can be difficult to diagnose early in the course of the disease because symptoms often come and go — sometimes disappearing for months.

4. Multiple sclerosis has no cure. However, treatments may help treat MS attacks, manage symptoms and reduce progress of the disease.

People with multiple sclerosis (MS) tend to have their first symptoms between the ages of 20 and 40. Usually the symptoms get better, but then come back. Some may come and go, while others linger.

The unpredictable course of MS can make it hard to get a diagnosis quickly. Keep track of your symptoms to help your doctor know whether MS or another condition is to blame.

Recommended Related to Multiple Sclerosis

CCSVI and Multiple Sclerosis

People with a lifelong condition like multiple sclerosis (MS) are always on the lookout for a new treatment that might improve, or even cure, their disease. In the last few years, there's been a lot of buzz about a vein condition called CCSVI and its possible connection to MS. However, this connection is very controversial. Some researchers say treating CCSVI can relieve MS symptoms. Others say CCSVI isn't even real. They compare it to the snake venom, bee stings, and other dubious "cures" that...

Read the CCSVI and Multiple Sclerosis article > >

You can manage and treat most symptoms of MS.

Whether you have a diagnosis or are worried about symptoms, know that MS doesn't have to control your life. You can work with your doctor to treat and manage your symptoms so you can stay healthy and continue to live the life you want.

Early Symptoms of MS

Blurred or double vision Thinking problems Clumsiness or a lack of coordination Loss of balance Numbness Tingling Weakness in an arm or leg.

No two people have exactly the same symptoms of MS.

You may have a single symptom, and then go months or years without any others. A problem can also happen just one time, go away, and never return. For some people, the symptoms become worse within weeks or months.

Common Symptoms of MS

These are the most common changes to the mind and body.

Abnormal sensations: People with MS often say they feel a "pins and needles" sensation. They may also have numbness, itching, burning, stabbing, or tearing pains. About half of people with MS have these uncomfortable symptoms. Fortunately, they can be managed or treated.

Bladder problems: About 8 in 10 people have bladder problems, which can be treated. You may need to pee often, urgently, need to go at night, or have trouble emptying your bladder fully. Bowel problems, especially constipation, are also common.

Difficulty walking: MS can cause muscle weakness or spasms, which make it harder to walk. Balance problems, numb feet, and fatigue can also make walking difficult.

Dizziness: It's common to feel dizzy or lightheaded. You usually won't have vertigo, or the feeling that the room is spinning.

Fatigue: About 8 in 10 people feel very tired. It often comes on in the afternoon and causes weak muscles, slowed thinking, or sleepiness. It's usually not related to the amount of work you do. Some people with MS say they can feel tired even after a good night's sleep.

Muscle spasms: They usually affect the leg muscles. For about 40% of people they are an early symptom of MS. In progressive MS, muscle spasms affect about 6 in 10 people. You might feel mild stiffness or strong, painful muscle spasms.

Sexual difficulties: These include vaginal dryness in women and erection problems in men. Both men and women may be less responsive to touch, have a lower sex drive, or have trouble reaching orgasm.

Common Symptoms of MS continued...

Speech problems: Sometimes MS can cause people to pause a long time in between words and have slurred or nasal speech. Some people also develop swallowing problems in more advanced stages of MS.

Thinking problems: About half of people with MS have trouble concentrating that comes and goes. For most, this means slowed thinking, poor attention, or fuzzy memory. Rarely, people can have severe problems that make it hard to do daily tasks. MS usually does not change your intellect and ability to read and understand conversation.

Tremors: About half of people with MS have tremors. They can be minor shakes or make it hard to manage everyday activities.

Vision problems: Problems with your eyes tend to be one of the first symptoms. They usually affect only one eye and go away on their own. Your sight may be blurry, gray, or have a dark spot in the center. You may suddenly have eye pain and temporary vision loss.

Very rarely, people with MS may have breathing problems or seizures.

What Causes MS Symptoms?

Doctors divide the symptoms into three groups: primary, secondary, and tertiary.

Primary symptoms come from damage to the protective sheath around the nerves in your spine or brain. The damage is called demyelination. It causes scarring, which makes it harder for signals to travel between the brain and the body.

This process can lead to bladder or bowel problems, loss of balance, numbness, paralysis, tingling, tremors, vision problems, or weakness.

Medicine, rehabilitation, and other treatments can keep many of these problems under control.

Secondary symptoms follow the main problems of MS. For instance, not being able to empty your bladder can lead to a bladder infection.

Doctors can treat secondary symptoms, but the goal is to avoid them by treating the primary symptoms.

Tertiary symptoms are the social, psychological, and job-related problems of coping with MS. For instance, if MS makes it hard for you to walk or drive, you may not be able to do your job well. 

Because MS varies so much, it's best not to compare yourself with other people who have MS. Your experience is likely to be different. Most people learn to manage their symptoms and can keep leading full, active lives.

Multiple Sclerosis research: the thalamus moves into the spotlight

This 3D view shows a composite of the thalamus of healthy controls (outlined in red) and MS patients (magenta). The whole thalamus is generally smaller in MS due to atrophy, and is also shifted (as seen in blue) slightly beyond the position of the normal thalamus due to atrophy of other parts of the brain.

Atrophy of the thalamus is an important predictor of clinically definite MS, study shows

By: Ellen Goldbaum

Release Date: March 21, 2013

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Print “The location of the thalamus in the brain, its unique function and its vulnerability to changes wrought by the disease make the thalamus a critical barometer of the damage that MS causes to the brain.”Robert Zivadinov, professor of neurology

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BUFFALO, N.Y. – A growing body of research by multiple sclerosis (MS) investigators at the University at Buffalo and international partners is providing powerful new evidence that the brain’s gray matter reflects important changes in the disease that could allow clinicians to diagnose earlier and to better monitor and predict how the disease will progress.

Over the past three years, the UB researchers and their partners around the world, supported by an active fellowship program at UB’s Buffalo Neuroimaging Analysis Center (BNAC), have published journal papers and given presentations demonstrating that the thalamus region, in particular, is key to a host of issues involving MS.

“The thalamus is providing us with a new window on MS,” says Robert Zivadinov, MD, PhD, UB professor of neurology, BNAC director and leader of the research team. “In our recent studies, we have used large datasets to investigate the evolution of atrophy of the thalamus and its association with clinical impairment in MS, starting with the earliest stages of the disease. The location of the thalamus in the brain, its unique function and its vulnerability to changes wrought by the disease make the thalamus a critical barometer of the damage that MS causes to the brain.”

Zivadinov and UB professor of neurology Ralph Benedict discuss the new research in a video at (http://youtu.be/QhsaHeBjZrA).

At the annual meeting of the American Academy of Neurology today, Zivadinov will discuss a study he performed in collaboration with colleagues from Charles University in Prague. The study found that atrophy of the thalamus, determined with MRI, can help identify which patients with clinically isolated syndrome (CIS), a patient’s first episode of MS, are at risk for developing clinically definite MS. Such a tool would be immensely helpful to clinicians, Zivadinov notes.

“This study, which included more than 200 patients, shows that thalamic atrophy is one of the most important predictors of clinically definite MS,” says Dana Horakova, MD, PhD, the principal investigator at Charles University.

“Therefore, based on these findings, we think MRI should be used to determine which patients are at highest risk for a second attack,” explains Zivadinov.

MS is traditionally viewed as a disease of the brain’s white matter, in which myelin, the fatty material surrounding neurons that allows them to signal effectively, is gradually destroyed. The UB researchers are now revealing how the thalamus and other parts of the brain’s gray matter, play a key role as well.

Central to a wide variety of neurologic functions, the thalamus is involved in motor and sensory function, the regulation of sleep and wakefulness, memory, emotion, consciousness, awareness and attention. It functions as a kind of relay center in the brain, taking in sensory information and sending it to the cerebral cortex; it also processes information coming from the cortex.

Another study, which the UB researchers conducted in collaboration with Stavanger University Hospital in Norway, is the first to look at the evolution of thalamic atrophy over a 10-year period in MS patients. Results also will be presented at the AAN meeting.

This study of 81 patients found that atrophy in the cortex and subcortical deep grey matter, including the thalamus, was significantly related to patients’ declining cognitive abilities. “We found that cognitive dysfunction appears early in the course of MS and that thalamic atrophy plays a central role in predicting cognitive deterioration over the long-term,” says Zivadinov.

In a review paper published earlier this year in Neurology, Zivadinov and co-authors note that gray matter injury can not only be detected in the disease’s earliest stages but that this injury is associated with a wide range of symptoms from cognitive decline and motor deficits to fatigue and chronic pain.

The UB findings reveal that atrophy of the thalamus, determined through routine magnetic resonance imaging (MRI), can be an important tool in detecting, evaluating and predicting the course of MS in children and adults; it also may become a valuable method of evaluating new MS treatments.

Loss of thalamic volume and its tissue integrity can also predict cognitive impairment in MS patients, according to a study recently published in Multiple Sclerosis Journal led by UB neurology professor Ralph Benedict in collaboration with Jeroen JG Geurts, PhD, from VU University Medical Center in Amsterdam, the Netherlands.

Research currently in press by the UB team and performed in collaboration with colleagues from Charles University in Prague also was the first prospective, longitudinal study to investigate and find associations between grey matter atrophy and physical disability progression in patients with relapsing-remitting MS, the most common and most disabling type of MS.

The five-year study, which covered 180 patients, also found that thalamic atrophy has p0tential as a way to evaluate novel therapies for MS, according to Eva Havrdova, MD, PhD, principal investigator.

“Since progressive pathology of the thalamus has been shown in all different MS disease types, including in pediatric MS patients, we must look at the thalamus as a biomarker for assessing new therapies,” says Zivadinov. “Measurement of thalamic atrophy may become an ideal MRI outcome for MS clinical trials.

“Atrophy in MS patients happens in the thalamus more rapidly than in other brain structures,” Zivadinov continues. “It is detectable very early in the disease and it is less affected by fluid shifts in the brain, an effect of anti-inflammatory drugs used in MS. This feature in particular, makes thalamic atrophy an ideal candidate for assessing novel therapies.”

These findings, says Zivadinov, are just the beginning. “Until now, existing information about thalamic involvement in MS has stemmed mainly from neuropathologic and neuroimaging studies with a limited number of subjects that contain no clear practical implications for clinicians. The team at UB, of researchers and fellows, together with our global partners, is planning to undertake larger, longitudinal studies in order to comprehensively determine how best to apply these very promising findings.”

The BNAC, part of the UB Department of Neurology, is located in the Buffalo General Medical Center on the Buffalo Niagara Medical Campus.

UB co-authors with Zivadinov on these studies are: Ralph Benedict, Bianca Weinstock-Guttman, Murali Ramanathan, Michael G. Dwyer and Niels Bergsland. Co-authors at VU University Medical Center are Jeroen JG Geurts, Hanneke E Hulst and Menno M Schoonheim; at Charles University in Prague: Dana Horakova, Eva Havrdova, Michaela Tyblova, Zdenek Seidl, Manuela Vaneckova, Jan Krasensky and Tomas Kalincik.

Other co-authors are Alireza Minagar, Louisiana State University; Michael H. Barnett, University of Sydney, Australia; Daniel Pelletier, Yale University; Mohamad Ali Sahraian, Tehran University of Medical Sciences; Istvan Pirko, the Mayo Clinic; Elliott Frohman, UT Southwestern Medical Center; Cecilie Jacobsen, Turi O Dalaker, Elisabeth Farbu, Jan Petter Larsen and Kirsten Lode of Stavanger University Hospital; and Kjell-Morten Myhr and Harald Nyland, Haukeland University Hospital.

Multiple sclerosis (MS) is a disease affecting nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision.

Each nerve fibre in the brain and spinal cord is surrounded by a layer of protein called myelin, which protects the nerve and helps electrical signals from the brain travel to the rest of the body. In MS, the myelin becomes damaged.

This disrupts the transfer of these nerve signals, causing a wide range of potential symptoms, such as:

loss of vision – usually only in one eye spasticity – muscle stiffness that can lead to uncontrolled muscle movements ataxia – difficulties with balance and co-ordination fatigue – feeling very tired during the day

Read more about the symptoms of multiple sclerosis.

Types of multiple sclerosis

Around 8 out of 10 people with MS will have the relapsing remitting type of MS.

Someone with relapsing remitting MS will have periods of time where symptoms are mild or disappear altogether. This is known as remission and can last for days, weeks or sometimes months.

Remission will be followed by a sudden flare-up of symptoms, known as a relapse. Relapses can last from a few weeks to few months.

Usually after around 10 years, around half of people with relapsing remitting MS will go on to develop secondary progressive MS.

In secondary progressive MS, symptoms gradually worsen and there are fewer or no periods of remission.

The least common form of MS is primary progressive MS. In this type, symptoms gradually get worse over time and there are no periods of remission.

Treatment

There is currently no cure for MS but there are a number of treatments that can help.

Relapsing remitting MS and secondary progressive MS can be treated with disease-modifying drugs. These are designed to slow the progression of the disease and reduce the number of relapses. But they are not suitable for all people with MS.

For example at the moment, there is no treatment that can slow the progress of primary progressive MS.

There are also a wide range of treatments, including steroid injections and physiotherapy, that can help relieve symptoms and make day-to-day living easier.

Read more about the treatment of multiple sclerosis.

Causes

MS is known as an autoimmune condition. This is where something goes wrong with the immune system (the body’s defence against infection) and it mistakenly attacks healthy body tissue – in this case, the myelin covering of nerves.

This can cause multiple sections of the brain and spinal column to become damaged and hardened (sclerosis), which can disrupt the nerve signals passing through these areas.

Exactly what causes the immune system to act in this way is unclear, but most experts think a combination of genetic and environmental factors are involved.

Read more about the possible risk factors and causes of multiple sclerosis.

Who is affected

It is estimated that there are currently around 100,000 people with MS in the United Kingdom.

Symptoms usually first develop between the ages of 15 and 45, with the average age of diagnosis being about 30.

For reasons that are unclear, MS is twice as common in women than men, and more common in white people than black and Asian people

Outlook

MS can be a challenging and frustrating condition to live with but new treatments over the past 20 years have considerably improved the quality of life of people with the disease.

MS is not fatal, but some complications which can arise from more severe MS, such as pneumonia, can be.

As a result, the average life expectancy for people with MS is around 10 years lower than the population at large.

Multiple sclerosis, also known as MS, is a chronic disease that attacks the central nervous system, i.e. the brain, spinal cord and optic nerves. In severe cases the patient becomes paralyzed and/or blind, while in milder cases there may be numbness in the limbs.

Over 350,000 people have MS in the USA. The Cleveland Clinic says that MS-related health care costs are thought to be over $10 billion per year in the United States.

According to the National Health Service, UK, approximately 100,000 people live with multiple sclerosis in Great Britain. Symptoms usually appear initially between 15 and 45 years of age. Women are twice as likely to get MS than men.

The term Multiple Sclerosis comes from the Latin multus plus plica meaning "fold", and the Greek sklerosis meaning "hardening".

According to MediLexicon's medical dictionary, Multiple Sclerosis (MS) is:

"a common demyelinating disorder of the central nervous system, causing patches of sclerosis (plaques) in the brain and spinal cord; occurs primarily in young adults, and has protean clinical manifestations, depending on the location and size of the plaque; typical symptoms include visual loss, diplopia, nystagmus, dysarthria, weakness, paresthesias, bladder abnormalities, and mood alterations; characteristically, the plaques are "separated in time and space" and clinically the symptoms show exacerbations and remissions".

With MS the central nervous system (CNS) is attacked by the person's own immune system. That is why MS is known as an auto-immune disease.

Nerve fibers are surrounded by myelin, which protects them. Myelin also helps conduct electrical signals (impulses) - i.e. myelin facilitates a good flow of electricity along the nervous system from the brain. Myelin regulates a key protein involved in sending long-distant signals.

The myelin of a patient with MS disappears in multiple areas. This leaves a scar (sclerosis). Multiple Sclerosis means "Scar Tissue in Multiple Areas". The areas where there is either not enough or no myelin are called plaques or lesions. As the lesions get worse the nerve fiber can break or become damaged.

When a nerve fiber has less myelin the electrical impulses received from the brain do not flow smoothly to the target nerve - when there is no myelin the nerve fibers cannot conduct the electrical impulses at all. The electrical impulses are instructions from the brain to carry out actions, such as to move a muscle. With MS, you cannot get your body to do what your brain wants it to do.

Who Can Develop Multiple Sclerosis?

MS can affect people of all ages.

It is more common among people aged from 20 to 50 years.

More women develop MS than men.

People of European descent are more likely to develop MS, compared to other people. However, people of all ancestries can get it.

You can inherit a greater susceptibility of getting MS from your parents.

In 2007 the World Health Organization (WHO) estimated that approximately 2.5 million people had MS.

Multiple sclerosis rates are higher the further away you live from the equator. This leads many to believe that exposure to sunlight impacts on MS risk.

What Are The Causes Of MS?

Although experts are still uncertain, most of them say that the person's own immune system attacks the myelin as if it were an undesirable foreign body - in the same way our immune system might attack a virus or bacteria.

Why might our immune system attack the myelin?

The reasons could be:

Genetic - some studies have shown that the genes we inherit from our parents may, in part, impact on our risk of developing MS. If you have a parent, sibling, or grandparent who has/had MS, your risk of developing it yourself is greater than average.

Several genes are most likely involved in influencing multiple sclerosis risk, experts say. Scientists believe that a set of gene variants we are born with, plus exposure to some environmental trigger(s), affect the immune system of some people which eventually leads to MS symptoms.

We are probably not that far from identifying those gene variants. The largest MS genetic study ever undertaken, involving 250 scientists from around the world and led by the Universities of Cambridge and Oxford, reported in the journal Nature in August 2011 that over 50 genes had been identified and associated with MS.

Environmental - MS prevalence varies according to geographical area and population groups. MS is much more common in northern Europe than southern Europe, northern USA than southern USA. It seems that the more exposure to sunlight we have, the lower our MS risk is. The more sunlight we are exposed to, the less likely we are to have low levels of vitamin D - therefore, long-term vitamin D levels probably play a role in MS risk.

Italian scientists explained in July 2012 at the 22nd Meeting of the European Neurological Society (ENS) in Prague, Czech Republic, that people with high vitamin D levels are less likely to develop MS.

In the USA, Caucasian people have a higher risk of developing MS than other racial groups; regardless of geographical location.

Studies indicate that people who move from a higher-risk area to a lower-risk one only acquire the risk of the new area if they move before they reach adolescence. This means that there is something in the environment we are exposed to early in life which influences risk.

Exposure to a toxic substance, such as a heavy metal or solvent has been suggested, but no clear conclusions have been reached.

People with MS are less likely to suffer from gout. MS patients have lower-than-average levels of uric acid in their system, which leads scientists to believe that uric acid protects from MS.

It is unlikely there is just one trigger, experts say, but rather MS is probably triggered by multiple factors.

Infections - doctors and researchers have often mentioned viruses, such as Epstein-Barr (mononucleosis), varicella zoster, as possible MS triggers; however, this theory has not been backed up scientifically.

Too much salt - too much salt may trigger the immune system, causing autoimmune diseases, researchers from the Massachusetts Institute of Technology reported in the journal Nature (March 2013 issue). The excessive consumption of salt might increase our risk of developing multiple sclerosis.

What Are The Signs And Symptoms Of MS?

MS affects the central nervous system, which controls all the actions in the body. When nerve fibers which carry messges to and from the brain are damaged, symptoms may occur in any part of the body.

In most cases, signs and symptoms generally appear between the ages of 20 and 40. For some patients, they are so mild that they do not notice anything until much later in the course of the disease. Others may be aware of them very early on

The most common symptoms are:

Bladder problems - patients may have difficulty emptying their bladder completely, needing to go to the toilet more frequently. Urge incontinence (suddenly dying to go, or unintentional passing of urine), and Nocturia (needing to go frequently during the night) are also common symptoms.

Bowel problems - half of all MS patients are frequently affected with constipation, which can sometimes be serious (fecal impaction). If the fecal impaction is not resolved, the problem may lead to bowel incontinence.

Cognitive Function - according to the Multiple Sclerosis Resource Center, UK, about 50% of people with MS say they experience cognitive problems to some extent,

increasing to 80% among the most severe cases. The most commonly reported cognitive abnormalities include problems with memory, abstraction, attention and word finding.

In March 2012, researchers from the Kessler foundation reported on a study they carried out which showed that warmer weather has a negative effect on the cognitive performance of patients with MS.

Depression - researchers from UCLA say MS patients have a 50% chance of developing depression. They add that depression among MS patients is not psychological, but linked to atrophy in part of the hippocampus.

Emotional Changes - MS may have a profound emotional effect on the individual when a diagnosis is first made. It may be hard to adjust to the diagnosis of such an unpredictable disorder, which carries a risk of some level of physical disability. Also, demyelination and nerve fiber damage in the brain can cause emotional changes. In short, a person with MS may experience emotional changes for either psychological or physical reasons, or both.

Researchers from the LSU Health Sciences Center New Orleans, USA, showed that stress management treatment reduced the formation of new brain lesions in people with MS considerably.

Fatigue - this is one of the most common symptoms of MS, and affects approximately 80% of patients. The person's ability to function properly at work and at home may be seriously undermined by fatigue. It is the main reason MS patients leave their jobs.

Dizziness and Vertigo - people with MS commonly experience dizziness and problems with balance. Vertigo is not the same as dizziness; it is a sensation that the room around you is moving or spinning.

Head movements may cause electric-shock like sensations.

Numbness or weakness - usually in one or more limbs, and typically affects just one side of the body at a time, or just the bottom half of the body.

Pain or tingling in some parts of the body.

Sexual Dysfunction - loss of interest in sex is common for people with MS. Males commonly find it difficult to reach or maintain an erection; they may also find it takes longer to ejaculate. Females may find achieving orgasm more difficult.

Spasticity and muscle spasms - damaged nerve fibers in the spinal cord and brain can cause muscles to tightly and painfully contract (spasms). Muscles might get stiff and be resistant to movement (spasticity).

Tremor - involuntary quivering movements

Vision Problems - Double vision or blurring vision. There may be partial or total loss of vision, which usually affects one eye at a time. When the eye moves there is pain (optic neuritis, inflammation of the optic nerve)

Gait - gait can be a problem for people with MS. Gait refers to the way you walk. MS can change the way people walk, because their muscles are weaker, they may have problems with balance and dizziness, plus fatigue.

These symptoms are less common, but also possible:

Headache Hearing Loss Itching Respiration / Breathing Problems Seizures Speech Disorders Swallowing Problems Tremor

As the MS advances these symptoms may appear:

Alterations in perception and thinking

Fatigue Heat sensitivity Muscle spasm Sexual dysfunction

MS is an unpredictable disease. Each individual will experience it in different ways.. For some, MS starts with a subtle sensation, and it could take months and even years without any MS progression being noticed. For others, however, symptoms worsen much more rapidly - within weeks or months.

MS is very much an individual disease. People are encouraged not to compare what affects them against what other patients might experience.

The Four Courses Of Multiple Sclerosis

There are 4 courses of the disease. In each case, the MS may be mild, moderate or severe.

Relapsing-Remitting MS (RRMS): Over 80% of patients start off with this type.

Relapsing - there are acute and unpredictable "exacerbations" (acute attacks, also called "flare-ups"). During this period symptoms get worse.

Remitting - and then there are periods of full or partial recovery. Sometimes there is no recovery.

The attacks may evolve over days or even weeks, and recovery can take weeks, or even months. In between the attacks there is calm, and symptoms do not worsen.

Primary-Progressive MS (PPMS): About 15% of patients have this type.

There are no clear relapses or remissions. The progression of the disease is steady. It is the most common form of MS in those who develop the disease after 40 years of age.

Secondary-Progressive MS (SPMS):

Starts off as a relapsing-remitting type of MS. Relapses and partial recoveries occur. However, in between cycles the disability does not go away. Eventually it becomes a progressive disease with no cycles. The progressive stage may start very early on, years, or even decades later.

Progressive-Relapsing MS (PRMS): The least common form.

Symptoms worsen progressively, steadily There are acute attacks. Some recovery may follow, or may not. In the early stage, it seems the patient has primary progressive MS.

How Is MS Diagnosed?

It is still not yet possible to diagnose MS by sending samples to a lab or collecting physical findings.

The doctor needs to use several strategies to decide whether a patient meets the criteria for an MS diagnosis. To do this, other possible causes of the symptoms need to be ruled out.

The doctor will talk to the patient, carefully look at his/her medical history, carry out a neurolgic exam, order imaging scans, visual evoked potentials (VEP), spinal fluid analysis, and perhaps some further tests.

The health care professional needs to do the following before diagnosing MS:

Detect evidence of damage in two or more separate parts of the CNS (central nervous system). The CNS includes the spinal cord, brain and optic nerves.

and

Have proof that the CNS damage happened at least one month apart

and

Eliminate other potential diagnoses

In 2001, the International Panel on the Diagnosis of Multiple Sclerosis revised the criteria to include precise instructions for using magnetic resonance imaging (MRI), visual evoked potentials (VEP) and cerebrospinal fluid analysis to hasten the diagnostic process. These tests can be used to look for a second area of damage in a person who has experienced only one episode of MS-like symptoms - referred to as a clinically-isolated syndrome (CIS). A person with CIS might not develop MS. The criteria were revised again in 2005 - it is now known as The Revised McDonald Criteria, and has improved the process.

Gauging MS progression through the patient's eyes

A person's multiple sclerosis progression can be determined by measuring how much their retina has thinned, researchers from Johns Hopkins MS Center reported in Neurology. The authors specified that a layer of the retina in the eyes thins when MS progresses.

The researchers wrote "This study suggests that retinal thinning, measured by in-office eye scans, called OCT, may occur at higher rates in people with earlier and more active MS."

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What Are The Treatment Options For MS?

There is no cure for MS yet. Existing treatments focus on suppressing the autoimmune response and managing symptoms. Some MS patients do not need treatment because their symptoms are so mild, while others do.

The most common drugs used for treating MS; plus some new ones and a supplement that apparently does not help

Corticosteroids - these drugs reduce inflammation. During a MS relapse inflammation can become problematic. Corticosteroids are the most commonly prescribed drugs for MS patients.

Prednisone can be taken orally while methylprednisolone is administered intravenously.

During a relapse there is a breakdown of the blood-brain-barrier (BBB) - harmful substances from the bloodstream might cross this barrier and make their way to the brain and spinal cord.

Steroids stabilize the BBB and help prevent harmful substances leaking through. These drugs are also immunosuppressive - they help stop our body's immune system from attacking itself.

Interferons - these medicines seem to slow down the progression of worsening MS symptoms. However, they must be used with care as they can also cause liver damage.

Interferon alpha is used for treating some cancers, but has no effect on multiple sclerosis. Interferon gamma was also found to have no beneficial effect on multiple sclerosis. However, interferon beta has shown effectiveness as a multiple sclerosis treatment (A Canadian study contradicts this, see below). While the exact method by which interferon beta 1a achieves its beneficial effects in multiple sclerosis remains unknown, some researchers believe it may reduce inflammation. Studies looking at how interferon beta behaves in the lab suggest it may stop harmful cells from entering the brain. However, this is just a theory.

Canadian scientists reported in JAMA in July 2012 that Interferon Beta may not slow long-term progression of MS. They had carried out a study with participants who had

relapsing-remitting MS. They concluded that there was no clear evidence showing that Beta A had any measurable effect on the long-term disability progression of MS.

Copaxone (Glatiramer) - this drug is aimed at stopping the immune system from attacking myelin. It is a combination of four amino acids (proteins). It is injected once a day, subcutaneously (under the skin). The patient may experience flushing and shortness of breath after receiving the injection.

Tysabri (Natalizumab) - this drug is used on patients who either cannot tolerate other treatments or did not experience any benefits from them. It increases the patient's chances of developing multifocal leukoencephalopathy, a fatal brain infection. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood-brain barriers.

Mitoxantrone (Novantrone) - usually used only for patients with advanced MS. It is an immunosuppressant medication that can damage the heart.

Novantrone was approved for the treatment of some cancer about 15 years ago. MS patients may find the idea of using chemotherapy cancer treatment disconcerting. In 2000 the Food and Drug Administration (FDA) approved Novantrone as the "only treatment for worsening MS". The recommended treatment schedule for Novantrone usage in MS is much less intensive than for cancer treatment.

For MS patients whose illness is rapidly progressing and getting worse despite other therapies, Novantrone can help slow down the progression of disability and help preserve the patient's independence.

Cannabis extract - a Phase III trial found that MS patients who took cannabis extract (tetrahydrocannabinol) had improvements in their symptoms of pain, muscle stiffness and insomnia.

Aubagio (teriflunomide), a once-daily tablet for adults with relapsing forms of MS was approved by the FDA in September 2012. Clinical trials showed that those on Aubagio had relapse rates 30% lower compared to those on placebo.

Do omega-3 fatty acid supplements help MS patients? - according to scientists at Haukeland University Hospital in Bergen, Norway, who carried out a double blind, placebo-control trial, omega-3 fatty acids do not help MS patients.

Rehabilitation

Rehabilitation is designed to help the MS patient improve or maintain his/her ability to perform effectively at home and at work. The focus is on general fitness and energy management, while at the same time dealing with the problems related to mobility and accessibility, speech and swallowing, memory, thinking and perception.

For an MS patient to achieve good quality health care, rehabilitation is usually a crucial component.

Rehabilitation programs generally include:

Physical therapy (UK term is physiotherapy) - aims to provide people with the skills to maintain and restore maximum movement and functional ability.

Occupational therapy - The therapeutic use of work, self-care, and play activities to increase development and prevent disability. It may include adaptation of task or environment to achieve maximum independence and to enhance the quality of life (American Occupational Therapy Association).

Speech and swallowing therapy - professionals who are trained to assess speech and language development and to treat speech and language disorders are called Speech Language Pathologists, or Speech Therapists. They are also trained to help people with swallowing disorders.

Cognitive rehabilitation - assists in the management of specific problems in thinking and perception. The patient learns and practices skills and strategies to improve function and/or make up for deficits that remain.

Vocational rehabilitation - helps people with disabilities make career plans, learn job skills, get and keep a job.

Plasma exchange (plasmapheresis)

Plasmapheresis involves withdrawing whole blood from the patient. The plasma is removed from the blood and replaced with new plasma. Then the blood, with all its red and white blood cells is transfused back into the patient. This process is effective in treating patients with autoimmune diseases because it takes out the antibodies in the blood that are attacking parts of the patients body they should not be attacking.

However, whether plasmapheresis is of benefit to MS patients is unclear. Studies using plasmapheresis on patients with primary and secondary progressive MS have had mixed results.

Beware of fertility treatment - researchers from the Raúl Carrea Institute for Neurological Research in Buenos Aires, Argentina reported that females with MS who undergo ART (assisted reproduction technology) infertility treatment may risk increased disease activity.

Research Into Multiple Sclerosis

Over the last ten years, there has been a great deal of research into multiple sclerosis. Below are some examples:

Lemtrada (alemtuzumab), a medication used for the treatment of a type of leukemia, was shown to help MS patients in two Phase III trials. Lemtrada appears to "reboot" the immune system in MS cases that had not responded to first-line therapy; it reduced the risk of brain shrinkage and disability. Researchers from the University of Cambridge reported in the November 1, 2012, issue of The Lancet that alemtuzumab helped people with early MS who relapsed on previous treatments, as well as those who were treatment naïve (had not yet received any treatment).

Repairing Multiple Sclerosis Damage May be Possible - researchers at Oregon Health & Science University reported in Annals of Neurology (November 2012 issue) that they may be able to repair the damage to the central nervous system associated with multiple sclerosis by blocking an enzyme in the brain called hyaluronidase.

In animal experiments, the scientists blocked the activity of hyaluronidase in mice with MS-like disease, and found that myelin-forming cell differentiation was restored. In other words, remyelination (myelin repair) started to occur.

The authors added that the drug they used on the mice to block hyaluronidase activity would not work on humans, because of the serious side effects. However, they believe that creating one that is suitable for humans is feasible. Any therapy that promotes remyelination would completely change the lives of millions of MS sufferers around the world.

Nanoparticles to trick the immune system and protect the myelin sheath - researchers from Northwestern University Feinberg School of Medicine successfully used nanoparticles covered with proteins that tricked the immune systems of mice so that they stopped attacking myelin and halting MS progression. The mice had relapsing remitting MS.

The scientists say their breakthrough also has the potential for treatment for patients with type 1 diabetes, asthma, and other auto-immune diseases.

They reported in Nature Biotechnology (November 18th, 2012 issue) that MS relapses were prevented in mice for up to 100 days. In human terms, this is equivalent to several years.

The nanoparticles seem to be as effective as using the human body's own white blood cells to deliver the antigen. Phase I/II trials are currently underway on humans with MS. Nanoparticles are much cheaper and easier to use, the authors added.

BG-12 (dimethyl fumarate) - in September 2012, the results of two Phase III clinical trials that evaluated oral dimethyl fumarate, found that it may reduce relapses and disability progression in patients with relapsing-remitting MS.

Alzheimer's molecule reverses paralysis and inflammation - scientists from Stanford University School of Medicine found that a molecule known as the main culprit in Alzheimer's disease surprisingly reversed paralysis and inflammation in mice with multiple sclerosis.

Sodium accumulation - a French study revealed that sodium buildup is linked to MS disability. MRI scans detected the accumulation of sodium in certain parts of the brain among patients with early-stage MS, and throughout the entire brain in those with advanced MS. The scientists say sodium may be a biomarker for the degeneration of nerve cells that occurs in MS.

High Vitamin D levels protects mother but not baby from MS - pregnant women have a smaller risk of developing MS if their vitamin D levels are high. Scientists from Umeå University Hospital added that the developing fetus does not appear to receive the same protection if the mother's vitamin D levels are high. They reported their findings in the journal Neurology.

Jonatan Salzer, MD., neurologist and study author, said: "In our study, pregnant women and women in general had a lower risk for MS with higher levels of the vitamin, as expected. However, a mother's levels of vitamin D during early pregnancy did not have an effect on MS risk for her baby."

MS And Life Expectancy

The lifespan of a person with MS is usually about the same as a healthy person who does not have MS. In rare cases the MS may be so malignant that it is terminal.

Written by Christian Nordqvist

View drug information on Novantrone.

Copyright: Medical News Today

Multiple Sclerosis

Also called: MS Email this page to a friend Share on facebook Share on twitter Bookmark & Share Printer-friendly version Subscribe to RSS   

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down or blocks messages between your brain and your body, leading to the symptoms of MS. They can include

Visual disturbances Muscle weakness Trouble with coordination and balance Sensations such as numbness, prickling, or "pins and needles" Thinking and memory problems

No one knows what causes MS. It may be an autoimmune disease, which happens when your body attacks itself. Multiple sclerosis affects women more than men. It often begins between the ages of 20 and 40. Usually, the disease is mild, but some people lose the ability to write, speak or walk. There is no cure for MS, but medicines may slow it down and help control symptoms. Physical and occupational therapy may also help.

NIH: National Institute of Neurological Disorders and Stroke