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T1- MRI image showing four bright spots (plaques) where multiple sclerosis has damaged myelin in the brain
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(abbreviated '''MS''', also known as '''disseminated sclerosis''' or '''encephalomyelitis disseminata''') is a
Chronic ,
Inflammatory ,
Demyelinating Disease that affects the
Central Nervous System (CNS) . MS can cause a variety of
Symptom s, 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
Neuron s, the cells of the
Brain and
Spinal Cord that carry information, create thought and perception, and allow the brain to control the body. Surrounding many of these neurons is a fatty layer known as the
Myelin sheath, which helps neurons carry
Electrical Signal s. MS causes gradual destruction of myelin (
Demyelination ) and transection of neuron
Axons in patches throughout the brain and spinal cord. When the myelin is destroyed, the neurons can no longer effectively conduct their electrical signals. The name ''multiple sclerosis'' refers to the multiple scars (or scleroses) on the myelin sheaths. This scarring causes symptoms which vary widely depending upon which signals are interrupted.
The predominant theory today is that MS results from attacks by an individual's
Immune System on the
Nervous System and it is therefore usually categorized as an
Autoimmune Disease . There is a minority view that MS is not an autoimmune disease, but rather a metabolically dependent neurodegenerative disease. Although much is known about how MS causes damage, its exact cause remains unknown.
Multiple sclerosis may take several different forms, with new symptoms occurring either in discrete attacks or slowly accruing over time. Between attacks, symptoms may resolve completely, but permanent neurologic problems often persist, especially as the disease advances. MS currently does not have a cure, though several treatments are available that may slow the appearance of new symptoms.
MS primarily affects adults, with an age of onset typically between 20 and 40 years, and is more common in women than in men.Dangond, F.''Multiple sclerosis.'' eMedicine Neurology. Updated 2005 Apr 25.
full text .Calabresi PA.''Diagnosis and management of multiple sclerosis.''
Am Fam Physician . PMID 15571060
full text .
See Also: Multiple sclerosis signs and symptoms
MS can cause a variety of symptoms, including changes in sensation (
Hypoesthesia ), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance (
Ataxia ); problems in speech (
Dysarthria ) or swallowing (
Dysphagia ), visual problems (
Nystagmus ,
Optic Neuritis , or
Diplopia ),
Fatigue and acute or chronic
Pain syndromes,
Bladder and
Bowel difficulties,
Cognitive impairment, or emotional symptomatology (mainly
Depression ). The main clinical measure of disability progression and severity of the symptoms is the
Expanded Disability Status Scale or EDSS.
1
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 ,
Trauma , or strenuous physical effort.
scans (post-contrast) of same brain slice at monthly intervals. Bright spots indicate active lesions.]]
Multiple sclerosis is difficult to
Diagnose in its early stages. In fact, definite diagnosis of MS cannot be made until there is evidence of at least two
Anatomically separate demyelinating events occurring at least thirty days apart.
Historically different criteria were used. The
Schumacher Criteria and
Poser Criteria were both popular. Currently,
McDonald Criteria represents international efforts to standardize the diagnosis of MS using clinical data, laboratory data, and radiologic data.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
- 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 Lesion s 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 Band s, which are Immunoglobulin s found in 85% to 95% of people with definite MS (but also found in people with other diseases).Rudick, RA, Whitaker, JN. ''Cerebrospinal fluid tests for multiple sclerosis.'' In Scheinberg, P (Ed). Neurology/neurosurgery update series, Vol. 7, CPEC. Princeton, NJ 1987 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 Potential s (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.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
Another test which may become important in the future is measurement of
Antibodies against myelin
Protein s 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 ,
Infection s such as
Lyme Disease (which can produce identical MRI lesions and CSF abnormalitiesGarcia-Monco JC; Miro Jornet J; Fernandez Villar B; Benach JL; Guerrero Espejo A; Berciano JA. ''
sclerosis or Lyme disease? a diagnosis problem of exclusion '' Med Clin (Barc) 1990 May 12;94(18):685-8. PMID 2388492Hansen 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 2345300Schluesener 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 2491615Kohler 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),
Tumor s, and other autoimmune problems, such as
Lupus . Additional testing may be needed to help distinguish MS from these other problems.
The course of MS is difficult to predict, and the disease may at times either lie dormant or progress steadily. Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to
Predict the future course. Subtypes are important not only for
Prognosis but also for therapeutic decisions. In 1996 the
United States National Multiple Sclerosis Society standardized the following four subtype definitions: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
;Relapsing-remitting
:Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. This subtype is characterized by unpredictable attacks (
Relapse s) followed by periods of months to years of relative quiet (
Remission ) with no new signs of disease activity. Deficits suffered during the attacks may either resolve or may be permanent. When deficits always resolve between attacks, this is referred to as "
Benign " MS.
;Secondary progressive
:Secondary progressive describes around 80% of those with initial relapsing-remitting MS, who then begin to have neurologic decline between their acute attacks without any definite periods of remission. This decline may include new neurologic symptoms, worsening
Cognitive function, or other deficits. Secondary progressive is the most common type of MS and causes the greatest amount of
Disability .
;Primary progressive
:Primary progressive describes the approximately 10% of individuals who never have remission after their initial MS symptoms. Decline occurs continuously without clear attacks. The primary progressive subtype tends to affect people who are older at disease onset.
;Progressive relapsing
:Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer superimposed attacks; and is the least common of all subtypes
Special cases of the disease with non-standard behavior have also been described although many researchers believe they are different diseases. These cases are sometimes referred to as
Borderline Forms Of Multiple Sclerosis and are
Neuromyelitis Optica (NMO),
Balo Concentric Sclerosis ,
Schilder's Diffuse Sclerosis and
Marburg Multiple Sclerosis .Borderline forms of MS, Fontaine, B., Federation de Neurologie, INSERM U546, Groupe Hospitalier, Faculte de Medecine Pitie-Salpetriere, Paris
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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.
4
Emotional and physical stress may also trigger an attack,
567 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
Sport s, 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
Sauna s or even hot showers.
However, heat is not an established trigger of relapses.
8
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 Defect s or other problems.
9
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.
10
See Also: Pathophysiology of multiple sclerosis
Although much is known about how multiple sclerosis causes damage, the reasons why multiple sclerosis occurs are not known.
Multiple sclerosis is a disease in which the
Myelin (a
Fatty substance which covers the
Axon s of
Nerve Cells ) degenerates. According to the view of most researchers, a special subset of
Lymphocyte s, called
T Cell s, plays a key role in the development of MS.
According to a strictly immunological explanation of MS, the inflammatory processes triggered by the T cells create leaks in the
Blood-brain Barrier (a capillary system that should prevent entrance of T-cells into the nervous system). These leaks, in turn, cause a number of other damaging effects such as
Swelling , activation of
Macrophages , and more activation of cytokines and other destructive
Protein s such as
Matrix Metalloproteinase s. A deficiency of
Uric Acid has been implicated in this process.
11
In a person with MS, these
Lymphocyte s recognize myelin as foreign and attack it as if it were an invading virus. That triggers
Inflammatory processes, stimulating other immune cells and soluble factors like
Cytokine s and
Antibodies .
It is known that a repair process, called remyelination, takes place in early phases of the disease, but the s capable of turning into mature myelinating oligodendrocytes, but it is suspected that something inhibits stem cells in affected areas.
Also the axons are damaged by the attacks.
12 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
Lesion s in the brain and
Spinal Cord . This is why symptoms can vary greatly between different individuals, depending on where their lesions occur.
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. The need for alternative theories is supported by the poor results of present therapies, since autoimmune theory predicted greater success.
