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Multiple sclerosis
Classification and external resources
MRI FLAIR sequence showing four bright spots (plaques) where multiple sclerosis has damaged myelin in the brain
ICD-10 G35.
ICD-9 340
OMIM 126200
DiseasesDB 8412
MedlinePlus 000737
eMedicine neuro/228  oph/179 emerg/321 pmr/82 radio/461
MeSH D009103

Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. A demyelinating disease is any Disease of the Nervous system in which the Myelin sheath of Neurons is damaged It may cause numerous physical and mental symptoms, and often progresses to physical and cognitive disability. Disease onset usually occurs in young adults, is more common in women, and has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population. In Epidemiology, the prevalence of a Disease in a Statistical population is defined as the total number of cases of the disease in the population at a given [1] MS was first described in 1835 by Jean-Martin Charcot. Jean-Martin Charcot ( 29 November 1825 – 16 August 1893) was a French Neurologist and professor of Anatomical pathology

MS affects the areas of the brain and spinal cord known as the white matter. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The spinal cord is a long thin tubular bundle of Nerves that is an extension of the Central nervous system from the brain and is enclosed in and protected White matter is one of the three main solid components of the Central nervous system. White matter cells carry signals between the grey matter areas, where the processing is done, and the rest of the body. More specifically, MS destroys oligodendrocytes which are the cells responsible for creating and maintaining a fatty layer, known as the myelin sheath, which helps the neurons carry electrical signals. Origin Oligodendroglia arise during development from an Oligodendrocyte precursor cell, which can be identified by its expression of a number of Antigens, including Myelin is an electrically-insulating Dielectric Phospholipid layer that surrounds only the Axons of many Neurons It is an outgrowth See also Electrophysiology In Biology, a signal or biopotential is an Electric quantity (voltage or current or field strength caused MS results in a thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron's extensions or axons. An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell When the myelin is lost, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the scars (scleroses - better known as plaques or lesions) in the white matter. Loss of myelin in these lesions causes some of the symptoms, which vary widely depending upon which signals are interrupted. However, more advanced forms of imaging are now showing that much of the damage happens outside these regions. Almost any neurological symptom can accompany the disease. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from

MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms). Most people are first diagnosed with relapsing-remitting MS but develop secondary-progressive MS (SPMS) after a number of years. Between attacks, symptoms may go away completely, but permanent neurological problems often persist, especially as the disease advances.

Although much is known about the mechanisms involved in the disease process, the cause remains elusive: the most widely-held being that the condition results from attacks to the nervous system by the body's own immune system. The nervous system is a Network of specialized cells that communicate information about an animal's surroundings and itself An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Some believe it is a metabolically dependent disease while others think that it might be caused by a virus such as Epstein-Barr. The Epstein-Barr Virus ( EBV) also called Human herpesvirus 4 (HHV-4 is a Virus of the herpes family (which includes Herpes Still others believe that its virtual absence from tropical areas points to a deficiency of vitamin D during childhood. Vitamin D is a group of fat-soluble Prohormones, the two major forms of which are vitamin D2 (or Ergocalciferol) and vitamin D3 (or [2]

This disease does not have a cure, but several therapies have proven helpful. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability. MS medications can have adverse effects or be poorly tolerated, and many patients pursue alternative treatments, despite the paucity of supporting scientific study. Many candidate therapies are still under investigation.

The prognosis, or expected course of the disease, depends on the subtype of the disease, the individual patient's disease characteristics, the initial symptoms, and the degree of disability the person experiences as time advances. Prognosis (older Greek πρόγνωσις modern Greek πρόγνωση - literally fore-knowing foreseeing) is a medical term denoting the Life expectancy of patients, however, is nearly the same as that of the unaffected population, and in some cases a near-normal life is possible. Life expectancy is the average number of years of life remaining at a given age

Contents

Signs and symptoms

Main article: Multiple sclerosis signs and symptoms

MS presents with 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, and bladder and bowel difficulties. Multiple sclerosis can cause a variety of symptoms including paranoid delusions changes in sensation ( Hypoesthesia) muscle weakness abnormal muscle spasms or difficulty Hypoesthesia refers to a reduced sense of Touch or sensation or a partial loss of sensitivity to sensory stimuli. Ataxia (from Greek α- as a negative prefix + -τάξις, meaning "lack of order" is a neurological sign and symptom consisting Dysarthria is a motor Speech disorder resulting from neurological injury, characterised by poor articulation (cf Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder Nystagmus is a type of eye movement characterized by alternating slow phase movements in one direction and Saccade -like quick phases in the other direction Optic Neuritis is the Inflammation of the Optic nerve that may cause a complete or partial loss of vision Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Chronic pain is defined as Pain that persists longer than the temporal course of natural healing associated with a particular type of injury or disease process In Anatomy, the urinary bladder is a hollow muscular, and distensible (or elastic organ that sits on the Pelvic floor in Mammals It is the In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists Cognitive impairment of varying degrees, or emotional symptomatology in the form of depression or pseudobulbar affect[3] are also common. Cognition is a concept used in different ways by different disciplines but is generally accepted to mean the process of awareness or thought Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Labile affect or pseudobulbar affect refers to the pathological expression of Laughter, Crying or smiling. Neuropathic pain is usual, and this can be in the form of Lhermitte's sign. Lhermitte's Sign, sometimes called the Barber Chair phenomenon, is an electrical sensation that runs down the back and into the limbs and is produced by bending the neck forward Neuropathic pain is the most common, distressing and intractable of the pain syndromes in MS. This pain is described as constant, boring, burning or tingling intensely. It usually occurs in the legs. Paraesthesias include pins and needles; tingling; shivering; burning pains; feelings of pressure; and areas of skin with heightened sensitivity to touch. Paresthesia (pron /ˌpɛɹɪsˈθiʒə/ paraesthesia in British English, pron The pains associated with these can be aching, throbbing, stabbing, shooting, gnawing, tingling, tightness and numbness. [4] The main clinical measure of disability progression and severity of the symptoms is the Expanded Disability Status Scale or EDSS. The Kurtzke Expanded Disability Status Scale (EDSS is a method of quantifying disability in Multiple sclerosis. [5]

The initial attacks (also known as exacerbations or relapses) are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made based on further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (16%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis. In Psychology, sensation is the first stage in the biochemical and neurologic events that begins with the impinging of a stimulus upon the receptor cells of a Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic [6][7] Fifteen percent of individuals have multiple symptoms when they first seek medical attention. [8] Optic neuritis or focal leg weakness may lead to falls and other serious accidents[9]. Optic Neuritis is the Inflammation of the Optic nerve that may cause a complete or partial loss of vision For some people the initial MS attack is preceded by infection, trauma, or strenuous physical effort. An infection is the detrimental Colonization of a host Organism by a foreign Species. Treatment of physical trauma is described here and in First aid.

Diagnosis

T1-weighted MRI scans (post-contrast) of same brain slice at monthly intervals. Bright spots indicate active lesions.
T1-weighted MRI 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. Diagnosis is the identification by Process of elimination, of the nature of anything In fact, a definite diagnosis cannot be made until other disease processes (differential diagnoses) have been ruled out and, in the case of relapsing-remitting MS, there is evidence of at least two anatomically separate demyelinating events separated by at least thirty days. Anatomy (from the Greek anatomia, from ana separate apart from and temnein, to cut up cut open is a branch of Biology that is the consideration In the case of primary progressive, a slow progression of signs and symptoms over at least 6 months is required.

Historically, different criteria were used and the Schumacher and Poser criteria were both popular. Currently, the McDonald criteria represent international efforts to standardize the diagnosis of MS using clinical, laboratory and radiologic data. The McDonald criteria are diagnostic criteria for Multiple sclerosis. [10]

Another test, which may become important in the future, is measurement of antibodies against myelin proteins such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Myelin Oligodendrocyte Glycoprotein (MOG is a Glycoprotein believed to be important in the process of Myelinization of Nerves in the Central Myelin basic protein ( MBP) is a Protein believed to be important in the process of myelination of Nerves in the Central nervous system As of 2007, however, there is no established role for these tests in diagnosing MS. Optical coherence tomography of the eye's retina is also under study,[13] mainly as a tool to measure response to medication and axonal degeneration. Optical coherence tomography (OCT is an optical signal acquisition and processing method allowing extremely high-quality micrometre-resolution three-dimensional images from within optical Eyes are organs that detect Light, and send signals along the Optic nerve to the visual areas of the brain The vertebrate retina is a light sensitive part inside the inner layer of the Eye. [14]

The signs and symptoms of MS can be similar to other medical problems, such as neuromyelitis optica, stroke, brain inflammation, infections such as Lyme disease (which can produce identical MRI lesions and CSF abnormalities[15][16][17][18]), tumors, and other autoimmune problems, such as lupus. Devic's disease, also known as Devic's syndrome or neuromyelitis optica (NMO, is an autoimmune, inflammatory disorder in which a person's own A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Acute disseminated encephalomyelitis ( ADEM) is an immune mediated Disease of the brain. Lyme disease, or borreliosis, is an Emerging infectious disease caused by at least three Species of Bacteria belonging to the Genus See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Additional testing may be needed to help distinguish MS from these other problems.

Disease course and clinical subtypes

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

The course of MS is difficult to predict, and the disease may at times either lie dormant or progress steadily. Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. A prediction is a statement or claim that a particular Event will occur in the Future in more certain terms than a forecast. 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:[19]

Relapsing-remitting
Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. The United States of America —commonly referred to as the The National Multiple Sclerosis Society, a United States -based Non-profit organization, and its network of chapters nationwide promote research educate advocate This subtype is characterized by unpredictable attacks (relapses) followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. A relapse (etymologically "who falls again" occurs when a person is affected again by a condition that affected them in the past Remission is the state of absence of Disease activity in patients with known Chronic illness. 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. Neurocognitive is a term used to describe Cognitive functions closely linked to the function of particular areas Neural pathways or cortical networks in 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

Nevertheless the earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). In CIS, there is a subacute attack suggestive of demyelination but the person does not fulfill the criteria for multiple sclerosis. A demyelinating disease is any Disease of the Nervous system in which the Myelin sheath of Neurons is damaged [20] Several studies have shown that starting treatment with interferons during the initial attack can decrease the chance that a patient will develop clinical MS. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents [21][22][23]. Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS[24]. Preclinical MS refers to cases after the CIS but before the confirming second attack[25].

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. Idiopathic Inflammatory Demyelinating Diseases (IIDDs sometimes known as Borderline forms of multiple sclerosis, is a collection of Multiple sclerosis variants Balo concentric sclerosis is one of the borderline forms of multiple sclerosis. This article deals with the MS variant known as diffuse myelinoclastic sclerosis. Marburg multiple sclerosis, also known as malignant, acute or fulminant Multiple sclerosis, is considered one of the Multiple sclerosis [26]

Factors triggering a relapse

Multiple sclerosis relapses are often unpredictable and can occur without warning with no obvious inciting factors. Some attacks, however, are preceded by common triggers. In general, relapses occur more frequently during spring and summer than during autumn and winter. Infections, such as the common cold, influenza, and gastroenteritis, increase the risk for a relapse. Acute viral nasopharyngitis or acute coryza, usually known as the common cold, is a highly contagious viral Infectious disease of the Gastroenteritis (also known as gastro, gastric flu, and stomach flu, although unrelated to Influenza) is Inflammation of the [27] Emotional and physical stress may also trigger an attack,[28][29][30] as can severe illness of any kind. Statistically, there is no good evidence that either trauma or surgery trigger relapses. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental [31] People with MS can participate in sports, but they should probably avoid extremely strenuous exertion, such as marathon running. Sport is an Activity that is governed by a set of rules or Customs and often engaged in competitively The marathon is a long-distance foot race with an official distance of 42 Heat can transiently increase symptoms, which is known as Uhthoff's phenomenon. Uhthoff's phenomenon is the worsening of neurologic Symptoms in Multiple sclerosis after periods of Exercise and increased body Heat This is why some people with MS avoid saunas or even hot showers. A sauna (ˈsɔːnə or as Finnish) is a small room or house designed as a place to experience dry or wet heat sessions or an establishment with one or more of these and auxiliary However, heat is not an established trigger of relapses. [32]

Pregnancy can directly affect the susceptibility for relapse. Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female The last three months of pregnancy offer a natural protection against relapses. However, during the first few months after delivery, the risk for a relapse is increased 20%–40%. Pregnancy does not seem to influence long-term disability. Children born to mothers with MS are not at increased risk for birth defects or other problems. A congenital disorder is a disease or disorder that is present at birth [33]

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. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease There is also no evidence that vaccines for hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin (BCG—immunization for tuberculosis) increases the risk for relapse. Evidence in its broadest sense includes anything that is used to determine or demonstrate the Truth of an assertion Chickenpox is a highly contagious illness caused by primary infection with Varicella zoster virus (VZV Tetanus is a medical condition that is characterized by a prolonged contraction of Skeletal muscle fibres Bacillus Calmette-Guérin (or Bacille Calmette-Guérin, BCG) is a vaccine against Tuberculosis that is prepared from a strain of the attenuated Tuberculosis (abbreviated as TB for tubercle bacillus or T u' b' erculosis Bacillus --> is a common [34]

Pathophysiology

Main article: Pathophysiology of multiple sclerosis
Demyelinization in MS. On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).
Demyelinization in MS. Multiple sclerosis is a disease in which the Myelin (a fatty substance which covers the Axons of nerve cells, important for proper nerve conduction On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).
Demyelinization in MS. Immunohistochemstry for CD68 demonstrates Macrophages (brown) in the area of the lesion(Original scale 1:100).
Demyelinization in MS. Immunohistochemstry for CD68 demonstrates Macrophages (brown) in the area of the lesion(Original scale 1:100). CD68 ( '''C'''luster of '''D'''ifferentiation '''68''') is a Glycoprotein which binds to Low density lipoprotein. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that

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

Multiple sclerosis is a disease in which the myelin (a fatty substance which covers the axons of nerve cells) degenerates. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information According to the view of most researchers, a special subset of lymphocytes, called T cells, plays a key role in the development of MS. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.

According to a strictly immunological explanation of MS, the inflammatory process is triggered by the T cells. T cells gain entry into the brain via the blood-brain barrier (a capillary system that should prevent entrance of T-cells into the nervous system). The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic The blood brain barrier is normally not permeable to these types of cells, unless triggered by either infection or a virus, where the integrity of the tight junctions forming the blood-brain barrier is decreased. Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtual impermeable barrier When the blood brain barrier regains its integrity (usually after infection or virus has cleared) the T cells are trapped inside the brain. These lymphocytes recognize myelin as foreign and attack it as if it were an invading virus. That triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Leaks form in the blood-brain barrier. These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as matrix metalloproteinases. Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Matrix metalloproteinases (MMPs are Zinc -dependent Endopeptidases other family members are Adamalysins Serralysins and Astacins A deficiency of uric acid has been implicated in this process. Uric acid (or urate) is an Organic compound of Carbon, Nitrogen, Oxygen and Hydrogen with the formula C5H4N4O3 [35]

It is known that a repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. Myelin is an electrically-insulating Dielectric Phospholipid layer that surrounds only the Axons of many Neurons It is an outgrowth The newly-formed myelin sheaths are thinner and often not as effective as the original ones. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons, according to four different damage patterns. Multiple sclerosis is a disease in which the Myelin (a fatty substance which covers the Axons of nerve cells, important for proper nerve conduction [36] The central nervous system should be able to recruit oligodendrocyte stem cells capable of turning into mature myelinating oligodendrocytes, but it is suspected that something inhibits stem cells in affected areas. Stem cells are cells found in most if not all multi-cellular Organisms.

The axons themselves can also be damaged by the attacks. [37] Often, the brain is able to compensate for some of this damage, due to an ability called neuroplasticity. Neuroplasticity (variously referred to as brain plasticity, cortical plasticity or cortical re-mapping) refers to the changes that occur in MS symptoms develop as the cumulative result of multiple lesions in the brain and spinal cord. This is why symptoms can vary greatly between different individuals, depending on where their lesions occur.

Causes

Although many risk factors for multiple sclerosis have been identified, no definitive cause has been found. MS likely occurs as a result of some combination of both environmental and genetic factors. An ecosystem is a natural unit consisting of all plants animals and micro-organisms( Biotic factors in an area functioning together with all of the non-living physical ( Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is Various theories try to combine the known data into plausible explanations. Although most accept an autoimmune explanation, several theories suggest that MS is an appropriate immune response to one or several underlying conditions (the etiology could be heterogeneous[38]). Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues Etiology (alternatively aetiology, aitiology) is the study of causation. The need for alternative theories is supported by the poor results of present therapies, since autoimmune theory predicted greater success. [39][40][41]

Environmental

The most popular hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable A retrovirus is any Virus belonging to the viral family Retroviridae. On a molecular level, this might occur if there is a structural similarity between the infectious virus and some component of the central nervous system, leading to eventual confusion in the immune system. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by

Since MS seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure[42] and possibly decreased vitamin D production may help cause MS. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator. Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as A large, 2006 study by the Harvard School of Public Health, reported evidence of a link between vitamin D deficiency and the onset of multiple sclerosis. [2] Other data comes from a 2007 study which concluded that sun exposure during childhood reduces the risk of suffering MS, while controlling for genetic factors. [43]

Other theories, noting that MS is less common in children with siblings, suggest that less exposure to illness in childhood leads to an immune system which is not primed to fight infection and is thus more likely to attack the body. One explanation for this would be an imbalance between the Th1 type of helper T-cells, which fight infection, and the Th2 type, which are more active in allergy and more likely to attack the body. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or Allergy is a disorder of the Immune system often also referred to as Atopy.

Other theories describe MS as an immune response to a chronic infection. The association of MS with the Epstein-Barr virus suggests a potential viral contribution in at least some individuals[44]. Human endogenous retroviruses could also be involved, specially one called MSRV (MS associated retrovirus)[45]. Endogenous retroviruses are Retroviruses derived from ancient infections of Germ cells in Humans Mammals and other vertebrates as such their Still others believe that MS may sometimes result from a chronic infection with spirochetal bacteria, a hypothesis supported by research in which cystic forms were isolated from the cerebrospinal fluid of all MS patients in a small study. Spirochaetes is a phylum of distinctive Gram-negative bacteria, which have long helically coiled cells [46] When the cysts were cultured, propagating spirochetes emerged. Another bacterium that has been implicated in MS is Chlamydophila pneumoniae; it or its DNA has been found in the cerebrospinal fluid of MS patients by several research laboratories, with one study finding that the oligoclonal bands of 14 of the 17 MS patients studied consisted largely of antibodies to Chlamydophila antigens. Oligoclonal bands are bands of Immunoglobulins that are seen when a patient's Blood plasma or Cerebrospinal fluid (CSF is analyzed by Protein electrophoresis [47]. Varicella zoster virus is also suspected to be involved[48]. Varicella zoster virus ( VZV) is one of eight herpes viruses known to infect humans (and other vertebrates

Severe stress may also be a factor—a large study in Denmark found that parents who had lost a child unexpectedly were 50% more likely to develop MS than parents who had not. [49] Smoking has also been shown to be an independent risk factor for developing MS. Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette. [50]

Genetic

MS is not considered a hereditary disease. However, increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS:

Some populations, such as the Roma, Inuit, and Bantus, rarely if ever develop MS. The Romani people (singular Rom, plural Roma as a Noun; also known as Romanies or Roma people) are an ethnic group with origins Inuit (plural the singular Inuk, means "man" or "person" is a general term for a group of culturally similar Indigenous peoples inhabiting Bantu may refer to Bantu expansion, a series of migrations of Bantu speakers Bantu languages Bantu people The indigenous peoples of the Americas and Asians have very low incidence rates. For indigenous peoples in the United States other than Hawaii and Alaska see also Native Americans in the United States. Asian or Asiatic is a Demonym for people from Asia. However the use of the term varies by country and person often referring to people from a particular

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

For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30%. Twins are Offspring resulting from the same Pregnancy, either of the same or opposite Sex. For fraternal twins (who do not inherit an identical set of genes), the likelihood is closer to that for non-twin siblings, at about 4%. This pattern suggests that, while genetic factors clearly help determine the risk of MS, other factors such as environmental effects or random chance are also involved. The actual correlation may be somewhat higher than reported by these numbers as people with MS lesions remain essentially asymptomatic throughout their lives.

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

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

A large study examining 334,923 single nucleotide polymorphisms (small variations in genes) in 931 families showed that apart from HLA-DRA there were two genes in which polymorphisms strongly predicted MS; these were the IL2RA (a subunit of the receptor for interleukin 2) and the IL7RA (idem for interleukin 7) genes. A single nucleotide polymorphism ( SNP, pronounced snip) is a DNA sequence variation occurring when a single Nucleotide - A, T History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance The interleukin-2 receptor (IL-2R is heterotrimeric protein expressed on the surface of certain immune cells such as Lymphocytes that binds and responds to In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response Interleukin 7 receptor ( IL7R) also known as CD127 ( C luster of D ifferentiation 127) is a Type I cytokine receptor. Interleukin 7 ( IL7) is a hematopoietic Growth factor secreted by the stromal cells of the red marrow and thymus capable of stimulating the proliferation of Lymphoid Mutations in these genes were already known to be associated with diabetes mellitus type 1 and other autoimmune conditions; the findings circumstantially support the notion that MS is an autoimmune disease. Diabetes mellitus type 1 (Type 1 diabetes Type I diabetes T1D T1DM IDDM juvenile diabetes is a form of Diabetes mellitus. [51]

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

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

Treatment

Main article: treatment of multiple sclerosis

Although there is no known cure for multiple sclerosis, several therapies have proven helpful. Several therapies for Multiple sclerosis (MS exist although there is no known cure 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, and many possible therapies are still under investigation. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery. At the same time different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study. The term alternative medicine, as used in the modern western world encompasses any healing practice "that does not fall within the realm of conventional Medicine.

Management of acute attacks

During symptomatic attacks administration of high doses of intravenous corticosteroids, such as methylprednisolone,[52][53] is the routine therapy for acute relapses. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. Methylprednisolone is a synthetic Glucocorticoid drug It is sold in the USA and Canada under the brand names Medrol and Solu-Medrol The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits in the patient. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. [54] Potential side effects include osteoporosis[55] and impaired memory, the latter being reversible. [56]

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

The earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). Several studies have shown that treatment with interferons during an initial attack can decrease the chance that a patient will develop MS. [57][58][23]

As of 2007, six disease-modifying treatments have been approved by regulatory agencies of different countries for relapsing-remitting MS. Three are interferons: two formulations of interferon beta-1a (trade names Avonex and Rebif) and one of interferon beta-1b (U. Interferon beta-1a is a drug in the Interferon family used to treat Multiple sclerosis (MS Interferon beta-1b (tradenames Betaferon, Betaseron (North America and Extavia) is a drug in the Interferon family used to treat S. trade name Betaseron, in Europe and Japan Betaferon). A fourth medication is glatiramer acetate (Copaxone). Glatiramer Acetate is the generic name for the Drug Copaxone or Copolymer 1, developed by Teva Pharmaceuticals. The fifth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy, is approved only in the USA and largely for SPMS. Mitoxantrone is an Anthracenedione (not an anthracycline Antineoplastic agent used in the treatment of certain types of cancer mostly metastatic Breast cancer An immunosuppressant is a substance that performs Immunosuppression of the Immune system. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Finally, the sixth is natalizumab (marketed as Tysabri). Natalizumab is a humanized Monoclonal antibody against the Cellular adhesion molecule α4-integrin. All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, although they differ in their efficacy rate and studies of their long-term effects are still lacking. [59][60][61][62] Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, both in terms of relapse rate reduction and halting disability progression[63]; it has also been shown to reduce the severity of MS[64]. Mitoxantrone may be the most effective of them all;[65] however, it is generally considered not as a long-term therapy as its use is limited by severe cardiotoxicity. Cardiotoxicity is the occurrence of heart muscle damage The heart becomes weaker and is not as efficient in pumping and therefore circulating blood [66]

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 Avonex. Interferon beta-1a is a drug in the Interferon family used to treat Multiple sclerosis (MS Natalizumab and mitoxantrone are given by IV infusion at monthly intervals. Natalizumab is a humanized Monoclonal antibody against the Cellular adhesion molecule α4-integrin.

Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in patients with a secondary progressive and progressive relapsing courses. Mitoxantrone is an Anthracenedione (not an anthracycline Antineoplastic agent used in the treatment of certain types of cancer mostly metastatic Breast cancer It is moderately effective in reducing the progression of the disease and the frequency of relapses in patients in short-term follow-up. [62] On the other hand no treatment has been proven to modify the course of primary progressive MS. [67]

As with any medical treatment, 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. Lipoatrophy is the term describing the localized loss of fat tissue Interferons also produce symptoms similar to influenza;[68] while some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes. [60]. More dangerous are liver damage of interferons and mitoxantrone,[69][70][71][72][73] the immunosuppressive effects and cardiac toxicity of the latter;[73] or the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy in patients who had taken it in combination with interferons. Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i Progressive multifocal leukoencephalopathy (PML also known as progressive multifocal leukoencephalitis is a rare and usually fatal viral disease that is characterized by progressive [74][75]

Management of the effects of MS

Disease-modifying treatments only 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 handicap. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, even though neither influence disease progression. Neurorehabilitation is a complex medical process which aims to aid recovery from a Nervous system injury and to minimize and/or compensate for any functional alterations resulting [76] As for any patient with neurologic deficits, a multidisciplinary approach is key to limiting and overcoming disability; 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. In Academia, Pedagogy, Physical sciences, Earth sciences, Human sciences and Social sciences [77] Similarly for each symptom there are different treatment options. Treatments should therefore be individualized depending both on the patient and the physician

Therapies under investigation

Main article: Therapies under investigation for multiple sclerosis

Scientists continue their extensive efforts to create new and better therapies for MS. Scientists continue their efforts to create new and better therapies for Multiple sclerosis. There are a number of treatments under investigation that may improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for MS. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.

Alternative treatments

Different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study. Examples are dietary regimens,[78] herbal medicine, including the use of medical cannabis to help alleviate symptoms,[79][80] or hyperbaric oxygenation. Swank Multiple Sclerosis diet The Swank Multiple Sclerosis Herbalism is a traditional Medicinal or Folk medicine practice based on the use of Plants and Plant extracts Herbalism is also known as Medical cannabis refers to the use of the Cannabis plant as a physician-recommended Herbal therapy as well as synthetic THC and Cannabinoids Hyperbaric medicine, also known as hyperbaric oxygen therapy (HBOT is the medical use of Oxygen at a higher than Atmospheric pressure. [81] On the other hand the therapeutic practice of martial arts such as tai chi, relaxation disciplines such as yoga, or general exercise, seem to mitigate fatigue and improve quality of life. Martial arts Therapy refers to the usage of Martial arts as an alternative or complementary therapy for a medical disorder. Tai chi chuan (is an internal Chinese martial art often practiced for Health reasons Yoga ( Sanskrit: योग, IAST: yóga, joːgə refers to traditional physical and mental disciplines originating in India, to the [82]

Prognosis

The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, race, age, and initial symptoms; and the degree of disability the person experiences. The life expectancy of people with MS, at least for earlier years, is now nearly the same as that of unaffected people. Life expectancy is the average number of years of life remaining at a given age This is due mainly to improved methods of limiting disability, such as physical therapy, occupational therapy and speech therapy, along with more successful treatment of common complications of disability, such as pneumonia and urinary tract infections. Occupational Therapy, often abbreviated "OT", is the "use of productive or creative activity in the treatment or rehabilitation of physically cognitively or Speech-language pathology is the study of disorders that affect a person's Speech, Language, cognition voice swallowing ( Dysphagia) and the rehabilitative Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal A urinary tract infection ( UTI) is a bacterial Infection that affects any part of the Urinary tract. [83] Nevertheless, half of the deaths in people with MS are directly related to the consequences of the disease, while 15% more are due to suicide. [84]

Currently there are no clinically established laboratory investigations available that can predict prognosis or response to treatment. A medical laboratory or clinical laboratory is a Laboratory where tests are done on clinical specimens in order to get information about the Health However, several promising approaches have been proposed. These include measurement of the two antibodies anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein, and measurement of TRAIL (TNF-related apoptosis-inducing ligand). Tumor necrosis factors (or the TNF-family) refers to a group of Cytokines family that can cause Apoptosis. In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally [86]

Epidemiology

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

Epidemiology is, among other things, the study of prevalence and incidence of diseases, incidence being the percentage of cases reported each year and prevalence the total percentage of cases in the population. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Prevalence is known to depend not only to incidence, but also to survival rate and migrations of affected people[87].

In northern Europe, continental North America, and Australasia, about one of every 1000 people suffers from multiple sclerosis, whereas in the Arabian peninsula, Asia, and continental South America, the frequency is much lower. Australasia is a Region of Oceania: New Zealand, Australia, Papua New Guinea, and neighbouring Islands in the Pacific The Arabian Peninsula (in Arabic: شبه الجزيرة العربية šibh al-jazīra al-ʻarabīya or جزيرة العرب jazīrat al-ʻarab) South America is a Continent of the Americas, situated entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a In sub-Saharan Africa, MS is extremely rare. Sub-Saharan Africa is a geographical term used to describe the area of the African continent which lies south of the Sahara, or those African countries With important exceptions, there is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator. [88] Climate, diet, geomagnetism, toxins, sunlight exposure, genetic factors, and infectious diseases have all been discussed as possible reasons for these regional differences. Climate encompasses the temperatures humidity rainfall atmospheric particle count and numerous other meteorogical factors in a given region over long periods of This article is primarily about the human diet For a discussion of animal diets see List of feeding behaviours. Earth 's magnetic field (and the surface magnetic field) is approximately a Magnetic dipole, with one pole near the North pole (see A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low Sunlight, in the broad sense is the total spectrum of the Electromagnetic radiation given off by the Sun. An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic Environmental factors during childhood may play an important role in the development of MS later in life. This idea is based on several studies of migrants showing that if migration occurs before the age of fifteen, the migrant acquires the new region's susceptibility to MS. If migration takes place after age fifteen, the migrant keeps the susceptibility of his home country. [89] However other works suggest that the age/geographical risk for developing multiple sclerosis spans a larger timescale than just the first 15 years of life. [90]

MS occurs mainly in Caucasians. The Caucasian race, sometimes the Caucasoid race, is a term of Racial classification, coined around 1800 by Johann Friedrich Blumenbach for the " It is twentyfold lower in the Inuit people of Canada than in other Canadians living in the same region. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page It is also rare in the Native American tribes of North America, Australian Aborigines and the Māori of New Zealand. Native Americans in the United States are the indigenous peoples from the regions of North America now encompassed by the continental United States This is an article about a class of people as identified and defined within Australian law This article discusses the Māori people of New Zealand For their language see Māori language, and for other meanings see Māori (disambiguation. New Zealand is an Island country in the south-western Pacific Ocean comprising two main landmasses (the North Island and the South Island Scotland appears to have the highest rate of MS in the world. Scotland ( Gaelic: Alba) is a Country in northwest Europethat occupies the northern third of the island of Great Britain. [91] The reasons for this are unknown. These few examples point out that either genetic background or lifestyle and cultural factors play an important role in the development of MS.

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

As previously discussed, there is a genetic component to MS. On average one of every 25 siblings of individuals with MS will also develop MS. Almost half of the identical twins of MS-affected individuals will develop MS, but only one of twenty fraternal twins. Twins are Offspring resulting from the same Pregnancy, either of the same or opposite Sex. If one parent is affected by MS, each child has a risk of only about one in forty of developing MS later in life. [92]

Finally, it is important to remark that advances in the study of related diseases have shown that some cases formerly considered MS are not MS at all. In fact, all the studies before 2004 can be affected by the impossibility to distinguish MS and Devic's disease (NMO) reliably before this date. Devic's disease, also known as Devic's syndrome or neuromyelitis optica (NMO, is an autoimmune, inflammatory disorder in which a person's own The error can be important in some areas: 30% of cases diagnosed as MS in Japan may have been NMO. [93]

History

The French neurologist Jean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct, separate disease in 1868. This article is about the country For a topic outline on this subject see List of basic France topics. Jean-Martin Charcot ( 29 November 1825 – 16 August 1893) was a French Neurologist and professor of Anatomical pathology A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Summarizing previous reports and adding his own important clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad are dysarthria (problems with speech), ataxia (problems with coordination), and tremor. Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body Charcot also observed cognition changes in MS since he described his patients as having a "marked enfeeblement of the memory" and "with conceptions that formed slowly". [94]

Prior to Charcot, Robert Hooper (1773–1835), a British pathologist and practicing physician, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease's clinical details. The Kingdom of Great Britain, also known as the United Kingdom of Great Britain, was a State in northwest Europe, in existence from 1707 to 1800 A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and Jean Cruveilhier (born 1791 in Limoges, France; died 1874 in Sussac) was a French Anatomist.

After this, several people, such as Eugène Devic (1858–1930), Jozsef Balo (1895–1979), Paul Ferdinand Schilder (1886–1940), and Otto Marburg (1874–1948) found special cases of the disease that some authors consider different diseases and now are called the borderline forms of multiple sclerosis. Eugène Devic (1858-1930 was a French Neurologist who was a native of La Cavalerie a village in the department of Aveyron. Austrian doctor and researcher Was born in Vienna in 1886 Graduated there in medicine in 1909 Dr Otto Marburg (1874-1948 was a doctor who was born in Vienna Austria

There are several historical accounts of people who probably had MS. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first identifiable MS patients. Saint Lidwina (Lydwine Lydwid Lidwid Liduina of Schiedam ( Schiedam, March 18 1380 – Schiedam, April 14 1433) was Schiedam is a city and municipality in the province of South Holland in the Netherlands and is part of the Rotterdam The Netherlands ( Dutch:, ˈnedərlɑnt is the European part of the Kingdom of the Netherlands, which consists of the Netherlands the Netherlands A Nun is a Woman who has taken special vows committing her to a religious life From the age of sixteen until her death at age 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS. Almost a hundred years before there is a story from Iceland of a young woman called Halla. Iceland, officially the Republic of Iceland ( ( Ísland or Lýðveldið Ísland ( This girl suddenly lost her vision and capacity to talk; but after praying to the saints recovered them seven days after. [95] Augustus Frederick d'Este (1794–1848), an illegitimate grandson of King George III of Great Britain, almost certainly suffered from MS. Augustus Frederick d'Este (1794-1848 was the son of Prince Augustus Frederick Duke of Sussex and Lady Augusta Murray and the grandson of George III. George III (George William Frederick 4 June 1738 George III's long reign was marked by a series of military conflicts involving his kingdom much of the rest of Europe and places D'Este left a detailed diary describing his 22 years living with the disease. He began his diary in 1822 and it had its last entry in 1846 (only to remain unknown until 1948). His symptoms began at age 28 with a sudden transient visual loss after the funeral of a friend. During the course of his disease he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life. [96] Another early account of MS was kept by the British diarist W. N. P. Barbellion, who maintained a detailed log of his diagnosis and struggle with MS. W(ilhelm N(ero P(ilate Barbellion was the Nom-de-plume of Bruce Frederick Cummings ( September 7, 1889 - October 22, 1919 His diary was published in 1919 as The Journal of a Disappointed Man.

See also

References

  1. ^ Rosati G (2001). List of Multiple Sclerosis Organizations in different countries around the world International Multiple Sclerosis International Federation - "The prevalence of multiple sclerosis in the world: an update". Neurol. Sci. 22 (2): 117–39. doi:10.1007/s100720170011. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11603614.  
  2. ^ a b Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A (2006). "Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis". JAMA 296 (23): 2832-8. doi:10.1001/jama.296.23.2832. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17179460.  
  3. ^ de Seze J, Zephir H, Hautecoeur P, Mackowiak A, Cabaret M, Vermersch P (2006). "Pathologic laughing and intractable hiccups can occur early in multiple sclerosis". Neurology 67 (9): 1684-6. doi:10.1212/01.wnl.0000242625.75753.69. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17101907.  
  4. ^ Multiple Sclerosis Resource Centre Pain. Retrieved on 2008-04-07. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 529 - First draft of Corpus Juris Civilis (a fundamental work in Jurisprudence) is issued by Eastern Roman Emperor
  5. ^ Kurtzke JF (1983). "Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)". Neurology 33 (11): 1444-52. PMID 6685237.  
  6. ^ Navarro S, Mondéjar-Marín B, Pedrosa-Guerrero A, Pérez-Molina I, Garrido-Robres J, Alvarez-Tejerina A. "[Aphasia and parietal syndrome as the presenting symptoms of a demyelinating disease with pseudotumoral lesions]". Rev Neurol 41 (10): 601-3. PMID 16288423.  
  7. ^ Jongen P (2006). "Psychiatric onset of multiple sclerosis". J Neurol Sci 245 (1–2): 59–62. doi:10.1016/j.jns.2005.09.014. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16631798.  
  8. ^ Paty D, Studney D, Redekop K, Lublin F (1994). "MS COSTAR: a computerized patient record adapted for clinical research purposes". Ann. Neurol. 36 Suppl: S134-5. PMID 8017875.  
  9. ^ Brønnum-Hansen H, Hansen T, Koch-Henriksen N, Stenager E (2006). "Fatal accidents among Danes with multiple sclerosis". Mult. Scler. 12 (3): 329-32. doi:10.1191/135248506ms1280oa. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16764347.  
  10. ^ 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
  11. ^ Rudick, RA, Whitaker, JN. Cerebrospinal fluid tests for multiple sclerosis. In Scheinberg, P (Ed). Neurology/neurosurgery update series, Vol. 7, CPEC. Princeton, NJ 1987
  12. ^ 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
  13. ^ Gordon-Lipkin E, Chodkowski B, Reich DS et al (Oct 2007). "Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. ". Neurology 69 (16): 1603-09. doi:10.1212/01.wnl.0000295995.46586.ae. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17938370.  
  14. ^ Albrecht P, Fröhlich R, Hartung HP, Kieseier BC, Methner A (2007). "Optical coherence tomography measures axonal loss in multiple sclerosis independently of optic neuritis". J Neurol Online: 1595. doi:10.1007/s00415-007-0538-3. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17987252.  
  15. ^ Garcia-Monco JC; Miro Jornet J; Fernandez Villar B; Benach JL; Guerrero Espejo A; Berciano JA. [Multiple sclerosis or Lyme disease? a diagnosis problem of exclusion] Med Clin (Barc) 1990 May 12;94(18):685-8. PMID 2388492
  16. ^ Hansen K; Cruz M; Link H. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1990 Jun;161(6):1194-202. PMID 2345300
  17. ^ Schluesener HJ; Martin R; Sticht-Groh V. Autoimmunity in Lyme disease: molecular cloning of antigens recognized by antibodies in the cerebrospinal fluid. Autoimmunity 1989 2(4):323-30. PMID 2491615
  18. ^ Kohler J; Kern U; Kasper J; Rhese-Kupper B; Thoden U. Chronic central nervous system involvement in Lyme borreliosis Neurology 1988 Jun;38(6):863-7. PMID 3368066
  19. ^ 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
  20. ^ Miller D, Barkhof F, Montalban X, Thompson A, Filippi M (2005). "Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis". Lancet neurology 4 (5): 281–8. doi:10.1016/S1474-4422(05)70071-5. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15847841.  
  21. ^ Jacobs LD; Beck RW; Simon JH; Kinkel RP; Brownscheidle CM; Murray TJ; Simonian NA; Slasor PJ; Sandrock AW. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000 September 28;343(13):898–904. PMID 11006365
  22. ^ Comi G; Filippi M; Barkhof F; Durelli L; Edan G; Fernandez O; Hartung H; Seeldrayers P; Sorensen PS; Rovaris M; Martinelli V; Hommes OR. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001 May 19;357(9268):1576–82. PMID 11377645
  23. ^ a b Kappos L, Freedman MS, Polman CH, et al (2007). "Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study". Lancet 370 (9585): 389–97. doi:10.1016/S0140-6736(07)61194-5. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17679016.  
  24. ^ Hakiki B, Goretti B, Portaccio E, Zipoli V, Amato MP. (2008). "Subclinical MS: follow-up of four cases". PMID 18507677.  
  25. ^ Lebrun C, Bensa C, Debouverie M, et al (2008). "Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile". J Neurol Neurosurg Psychiatry 79 (2): 195–198. doi:10.1136/jnnp.2006.108274. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18202208.  
  26. ^ Borderline forms of MS, Fontaine, B. , Federation de Neurologie, INSERM U546, Groupe Hospitalier, Faculte de Medecine Pitie-Salpetriere, Paris [1]
  27. ^ Confavreux C (2002). "Infections and the risk of relapse in multiple sclerosis". Brain 125 (Pt 5): 933-4. doi:10.1093/brain/awf146. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11960883.  
  28. ^ Buljevac D, Hop WC, Reedeker W, et al (2003). "Self reported stressful life events and exacerbations in multiple sclerosis: prospective study". BMJ 327 (7416): 646. doi:10.1136/bmj.327.7416.646. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14500435.  
  29. ^ Brown RF, Tennant CC, Sharrock M, Hodgkinson S, Dunn SM, Pollard JD (2006). "Relationship between stress and relapse in multiple sclerosis: Part I. Important features". Mult. Scler. 12 (4): 453-64. PMID 16900759.  
  30. ^ Brown RF, Tennant CC, Sharrock M, Hodgkinson S, Dunn SM, Pollard JD (2006). "Relationship between stress and relapse in multiple sclerosis: Part II. Direct and indirect relationships". Mult. Scler. 12 (4): 465-75. PMID 16900760.  
  31. ^ Martinelli V (2000). "Trauma, stress and multiple sclerosis". Neurol. Sci. 21 (4 suppl 2): S849-52. doi:10.1007/s100720070024. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11205361.  
  32. ^ Tataru N, Vidal C, Decavel P, Berger E, Rumbach L (2006). "Limited impact of the summer heat wave in France (2003) on hospital admissions and relapses for multiple sclerosis". Neuroepidemiology 27 (1): 28-32. doi:10.1159/000094233. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16804331.  
  33. ^ Worthington J, Jones R, Crawford M, Forti A (1994). "Pregnancy and multiple sclerosis--a 3-year prospective study". J. Neurol. 241 (4): 228-33. doi:10.1007/BF00863773. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8195822.  
  34. ^ Confavreux C, Suissa S, Saddier P, Bourdès V, Vukusic S (2001). "Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group". N. Engl. J. Med. 344 (5): 319-26. PMID 11172162.  
  35. ^ Rentzos M, Nikolaou C, Anagnostouli M, Rombos A, Tsakanikas K, Economou M, Dimitrakopoulos A, Karouli M, Vassilopoulos D (2006). "Serum uric acid and multiple sclerosis". Clinical neurology and neurosurgery 108 (6): 527-31. doi:10.1016/j.clineuro.2005.08.004. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16202511.  
  36. ^ Lucchinetti, C. Bruck, W. Parisi, J. Scherhauer, B. Rodriguez, M. Lassmann, H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination Ann Neurol, 2000; 47(6):707-17. PMID 10852536
  37. ^ Pascual AM, Martínez-Bisbal MC, Boscá I, et al (2007). "Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis". Neurology 69 (1): 63-7. doi:10.1212/01.wnl.0000265054.08610.12. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17606882.  
  38. ^ Lassmann H (2007). "Experimental models of multiple sclerosis". Rev. Neurol. (Paris) 163 (6-7): 651-5. PMID 17607184.  
  39. ^ Peter Behan and Abhijit Chaudhuri (2002). "The pathogenesis of multiple sclerosis revisited". J R Coll Physicians Edinb 32: 244–265.  
  40. ^ Chaudhuri A, Behan P (2004). "Multiple sclerosis is not an autoimmune disease". Arch. Neurol. 61 (10): 1610–2. doi:10.1001/archneur.61.10.1610. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15477520.  
  41. ^ Altmann D (2005). "Evaluating the evidence for multiple sclerosis as an autoimmune disease". Arch. Neurol. 62 (4): 688; author reply 688-9. doi:10.1001/archneur.62.4.688-a. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15824275.  
  42. ^ van der Mei IA, Ponsonby AL, Dwyer T, et al (2003). "Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study". BMJ 327 (7410): 316. doi:10.1136/bmj.327.7410.316. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12907484.  
  43. ^ Islam T, Gauderman WJ, Cozen W, Mack TM (2007). "Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins". Neurology 69 (4): 381–8. doi:10.1212/01.wnl.0000268266.50850.48. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17646631.  
  44. ^ Levin LI, Munger KL, Rubertone MV, et al (2005). "Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis". JAMA 293 (20): 2496-500. doi:10.1001/jama.293.20.2496. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15914750.  
  45. ^ Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A. (2007). "Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6". PMID 17170460.  
  46. ^ Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schøyen R (2001). "Association between multiple sclerosis and cystic structures in cerebrospinal fluid". Infection 29 (6): 315-9. doi:10.1007/s15010-001-9144-y. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11787831.  
  47. ^ Yao SY, Stratton CW, Mitchell WM, Sriram S (2001). "CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens". Neurology 56 (9): 1168-76. PMID 11342681.  
  48. ^ Sotelo J, Martínez-Palomo A, Ordoñez G, Pineda B (2008). "Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis". Ann. Neurol. : 303. doi:10.1002/ana.21316. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18306233.  
  49. ^ Li J, Johansen C, Bronnum-Hansen H, Stenager E, Koch-Henriksen N, Olsen J (2004). "The risk of multiple sclerosis in bereaved parents: A nationwide cohort study in Denmark. ". Neurology 62 (5): 726-9. PMID 15007121.  
  50. ^ Franklin GM, Nelson L (2003). "Environmental risk factors in multiple sclerosis: causes, triggers, and patient autonomy". Neurology 61 (8): 1032-4. PMID 14581658.  
  51. ^ "Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study" (2007). N Engl J Med: 851. doi:10.1056/NEJMoa073493. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17660530.  
  52. ^ Methylprednisolone Oral. US National Library of Medicine (Medline) (2003-04-01). Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. Events 527 - Byzantine Emperor Justin I names his nephew Justinian I as co-ruler and successor to the throne Retrieved on 2007-09-01. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 462 - Possible start of first Byzantine indiction cycle.
  53. ^ Methylprednisolone Sodium Succinate Injection. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-09-01.
  54. ^ Brusaferri F, Candelise L (2000). "Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials". J. Neurol. 247 (6): 435–42. doi:10.1007/s004150070172. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10929272.  
  55. ^ Dovio A, Perazzolo L, Osella G, et al (2004). "Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis". J. Clin. Endocrinol. Metab. 89 (10): 4923–8. doi:10.1210/jc.2004-0164. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15472186.  
  56. ^ Uttner I, Müller S, Zinser C, et al (2005). "Reversible impaired memory induced by pulsed methylprednisolone in patients with MS". Neurology 64 (11): 1971–3. doi:10.1212/01.WNL.0000163804.94163.91. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15955958.  
  57. ^ Jacobs LD, Beck RW, Simon JH, et al. (2000). "Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group". N Engl J Med 343 (13): 898–904. The New England Journal of Medicine ( N Engl J Med or NEJM) is an English-language Peer-reviewed Medical journal published PMID 11006365.  
  58. ^ Comi G, Filippi M, Barkhof F, et al. (2001). "Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study". Lancet 357 (9268): 1576–82. This article is about the journal For other uses of the term "lancet" see Lancet (disambiguation. PMID 11377645.  
  59. ^ Ruggieri M, Avolio C, Livrea P, Trojano M (2007). "Glatiramer acetate in multiple sclerosis: a review". CNS Drug Rev 13 (2): 178–91. doi:10.1111/j.1527-3458.2007.00010.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17627671.  
  60. ^ a b Munari L, Lovati R, Boiko A (2004). "Therapy with glatiramer acetate for multiple sclerosis". Cochrane Database Syst Rev (1): CD004678. doi:10.1002/14651858.CD004678. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14974077.  
  61. ^ Rice GP, Incorvaia B, Munari L, et al (2001). "Interferon in relapsing-remitting multiple sclerosis". Cochrane Database Syst Rev (4): CD002002. doi:10.1002/14651858.CD002002. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11687131.  
  62. ^ a b Martinelli Boneschi F, Rovaris M, Capra R, Comi G (2005). "Mitoxantrone for multiple sclerosis". Cochrane Database Syst Rev (4): CD002127. doi:10.1002/14651858.CD002127.pub2. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16235298.  
  63. ^ Johnson KP (2007). "Control of multiple sclerosis relapses with immunomodulating agents". J. Neurol. Sci. 256 Suppl 1: S23–8. doi:10.1016/j.jns.2007.01.060. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17350652.  
  64. ^ Natalizumab reduces MS severity - http://www.abstracts2view.com/aan2008chicago/view.php?nu=AAN08L_P04.169}}
  65. ^ Gonsette RE (2007). "Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis". Expert opinion on pharmacotherapy 8 (8): 1103–16. doi:10.1517/14656566.8.8.1103. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17516874.  
  66. ^ Murray TJ (2006). "The cardiac effects of mitoxantrone: do the benefits in multiple sclerosis outweigh the risks?". Expert opinion on drug safety 5 (2): 265–74. doi:10.1517/14740338.5.2.265. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16503747.  
  67. ^ Leary SM, Thompson AJ (2005). "Primary progressive multiple sclerosis: current and future treatment options". CNS drugs 19 (5): 369–76. PMID 15907149.  
  68. ^ Sládková T, Kostolanský F (2006). "The role of cytokines in the immune response to influenza A virus infection". Acta Virol. 50 (3): 151–62. PMID 17131933.  
  69. ^ Primetherapeutics - serious liver damage per FDA - http://www.primetherapeutics.com/DrugNews/flash/Avonex.pdf Primetherapeutics]
  70. ^ Betaseron [package insert]. Montville, NJ: Berlex Inc; 2003
  71. ^ Rebif [package insert]. Rockland, MA: Serono Inc; 2005.
  72. ^ Avonex [package insert]. Cambridge, MA: Biogen Inc; 2003
  73. ^ a b Fox EJ (2006). "Management of worsening multiple sclerosis with mitoxantrone: a review". Clinical therapeutics 28 (4): 461–74. doi:10.1016/j.clinthera.2006.04.013. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16750460.  
  74. ^ Kleinschmidt-DeMasters BK, Tyler KL (2005). "Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis". N Engl J Med 353 (4): 369–74. doi:10.1056/NEJMoa051782. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15947079.   Free full text with registration
  75. ^ Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D (2005). "Progressive multifocal leukoencephalopathy in a patient treated with natalizumab". N Engl J Med 353 (4): 375–81. doi:10.1056/NEJMoa051847. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15947078.   Free full text with registration
  76. ^ Kesselring J, Beer S (2005). "Symptomatic therapy and neurorehabilitation in multiple sclerosis". Lancet neurology 4 (10): 643–52. doi:10.1016/S1474-4422(05)70193-9. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16168933.  
  77. ^ The Royal College of Physicians (2004). Multiple Sclerosis. National clinical guideline for diagnosis and management in primary and secondary care. Salisbury, Wiltshire: Sarum ColourView Group. ISBN 1 86016 182 0.  Free full text (2004-08-13). "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " Events 3114 BC - According to the Lounsbury correlation the start of the Maya calendar. Retrieved on 2007-10-01. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 331 BC - Alexander the Great defeats Darius III of Persia in the Battle of Gaugamela.
  78. ^ Farinotti M, Simi S, Di Pietrantonj C, et al. (2007). "Dietary interventions for multiple sclerosis". Cochrane database of systematic reviews (Online) (1): CD004192. doi:10.1002/14651858.CD004192.pub2. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17253500.  
  79. ^ Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E (2006). "Cannabis use in patients with multiple sclerosis". Mult. Scler. 12 (5): 646–51. doi:10.1177/1352458506070947. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17086912.  
  80. ^ Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ (2005). "Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up". J. Neurol. Neurosurg. Psychiatr. 76 (12): 1664–9. doi:10.1136/jnnp.2005.070136. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16291891.  
  81. ^ Bennett M, Heard R (2004). "Hyperbaric oxygen therapy for multiple sclerosis". Cochrane database of systematic reviews (Online) (1): CD003057. doi:10.1002/14651858.CD003057.pub2. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14974004.  
  82. ^ Oken BS, Kishiyama S, Zajdel D, et al. (2004). "Randomized controlled trial of yoga and exercise in multiple sclerosis". Neurology 62 (11): 2058–64. PMID 15184614.  
  83. ^ Weinshenker BG. Natural history of multiple sclerosis. Ann Neurol 1994;36 Suppl:S6–11. PMID 8017890
  84. ^ Stern M (2005). "Aging with multiple sclerosis". Physical medicine and rehabilitation clinics of North America 16 (1): 219-34. doi:10.1016/j.pmr.2004.06.010. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15561552.  
  85. ^ Pittock SJ; McClelland RL; Mayr WT; Jorgensen NW; Weinshenker BG; Noseworthy J; Rodriguez M. Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study Ann Neurol 2004 Aug;56(2):303-6. PMID 15293286
  86. ^ Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med. 2003 Jul 10;349(2):139-45. PMID 12853586
  87. ^ Prevalence Calculations and Presentations [2]
  88. ^ Epidemiology and multiple sclerosis. a personal review
  89. ^ Marrie, RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol. 2004 Dec;3(12):709-18. Review. PMID 15556803
  90. ^ Hammond SR, English DR, McLeod JG (2000). "The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia". Brain 123 ( Pt 5): 968–74. PMID 10775541.  
  91. ^ Rothwell PM, Charlton D (1998). "High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition". J. Neurol. Neurosurg. Psychiatr. 64 (6): 730-5. PMID 9647300.  
  92. ^ Sadovnick, AD, Ebers, GC, Dyment, DA, Risch, NJ. Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet 1996; 347:1728. PMID 8656905
  93. ^ Weinshenker B (2005). "Western vs optic-spinal MS: two diseases, one treatment?". Neurology 64 (4): 594-5. PMID 15728277.  
  94. ^ Charcot, J. Histologie de la sclerose en plaques. Gazette des hopitaux, Paris, 1868; 41: 554–555.
  95. ^ Poser C (1994). "The dissemination of multiple sclerosis: a Viking saga? A historical essay". Ann. Neurol. 36 Suppl 2: S231-43. PMID 7998792.  
  96. ^ Firth, D (1948). The Case of August D`Esté. Cambridge: Cambridge University Press.  

Further reading

External links

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Dictionary

multiple sclerosis

-noun

  1. (pathology) A chronic disease of the brain and spinal cord characterized by changes in sensation, visual problems, weakness, depression, difficulties with coordination and speech, impaired mobility and disability.
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