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== Overview ==
== Overview ==
Multiple sclerosis is a [[disease]] of the [[central nervous system]] and it’s known to be multi factorial. The most common [[risk factors]] in the development of multiple sclerosis are [[smoking]], [[genetic]], [[Ethnic group|ethnic]], [[infection]], low [[vitamin D]], and [[Stress (medicine)|stress]]. Whatever the [[trigger]] is, it will lead to an acquired [[immune response]] followed by [[Inflammation|inflammatory]] reactions. These reactions lead to secretion of [[cytokines]] in the [[CNS]] [[parenchyma]] and activation of resident [[microglia]]. [[Microglia]] cells activate [[astrocytes]] to release more [[Inflammation|inflammatory]] [[cytokines]], leading to recruitment and [[Infiltration (medical)|infiltration]] of circulatory [[leukocytes]]. This burst events cause destruction of [[myelin sheath]] and forms focal sclerotic [[white matter]] plaques, which are characteristic of multiple sclerotic disease. The onset of [[symptoms]] is mostly between the age of fifteen to forty years, rarely before age fifteen or after age sixty and include [[fatigue]], [[mood]] problems, [[spasticity]], [[bowel]] and [[bladder]] [[dysfunction]], [[cognitive impairment]], [[Ophthalmoplegia|eye movement problems]], heat sensitivity, [[incoordination]], [[pain]], [[sexual dysfunction]], [[Sleep disorders|sleep disorder]], [[vertigo]] and [[visual loss]]. There is no single diagnostic study of choice for the [[Diagnosis-related group|diagnosis]] of multiple sclerosis, but multiple sclerosis can be diagnosed based on [[History and Physical examination|clinical presentation]],  [[cerebral]] plaques on [[MRI]] , and [[oligoclonal bands]] in [[CSF analysis]]. The predominant [[therapy]] for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis,  [[Immunosuppression|immunosuppressive threpay]] in progressive multiple sclerosis and [[Glucocorticoid]] [[therapy]] in [[acute]] exacerbation.


'''Multiple sclerosis''' (abbreviated '''[[MS]]''', formerly known as '''disseminated sclerosis''' or '''encephalomyelitis disseminata''') is a [[chronic (medicine)|chronic]], [[Inflammation|inflammatory]], [[demyelinating disease]] that affects the [[Central Nervous System|central nervous system (CNS)]]. Disease onset usually occurs in young adults, is more common in women and the disease has a [[prevalence]] that ranges between 2 and 150 per 100,000 depending on the country or specific population.<ref name="pmid11603614">{{cite journal |author=Rosati G |title=The prevalence of multiple sclerosis in the world: an update|journal=Neurol. Sci. |volume=22 |issue=2 |pages=117–39 |year=2001 |pmid=11603614 |doi=}}</ref> MS was first described in 1868 by [[Jean-Martin Charcot]].
==Historical Perspective==
 
Multiple sclerosis was first described by a [[neurologist]], Dr. Jean Martin Charcot in 1868 and named sclerose en plaque. The [[signs]] and [[symptoms]] including [[dysarthria]], [[ataxia]] and [[tremor]] were called [[Charcot's triad|charcot’s triad]].
MS affects the [[neuron]]s in the areas of the [[brain]] and [[spinal cord]] known as the [[white matter]]. These cells carry signals in between the [[grey matter]] areas, where the processing is done, and between these and the rest of the body. More specifically, MS destroys [[oligodendrocyte]]s which are the cells responsible for creating and maintaining a fatty layer, known as the [[myelin]] sheath, which helps the neurons carry electrical [[Signal (biology)|signal]]s. MS results in a thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron's extensions or [[axons]]. 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 that may vary widely depending upon which signals are interrupted. However, more advanced forms of [[MRI|imaging]] are now showing that much of the damage happens outside these regions. A consequence of this course of action is that almost any neurological [[symptom]] can accompany the disease.
 
Multiple sclerosis may take 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 resolve 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 theory with the most adherents is that it results from attacks to the [[nervous system]] by the body's own [[immune system]]. Some believe it is a metabolically dependent  disease while others think that it might be caused by a virus such as [[Epstein-Barr virus|Epstein-Barr]]. Still other people believe that its virtual absence from the tropics points to a deficiency of vitamin D during childhood.
The disease currently does not have a cure, but several therapies have proven helpful. The aims of treatment are returning function after an attack, preventing new attacks, and preventing disability. As with any treatment, medications have several adverse effects, and many therapies are still under investigation. At the same time different alternative treatments are pursued by many patients, despite the paucity of supporting scientific study.
The [[prognosis]], or expected course of the disease, for a person depends on the subtype of the disease; the characteristics of the individual, the initial symptoms; and the degree of disability the person experiences as time advances. However [[life expectancy]] of patients is nearly the same as that of the unaffected population and in many cases a normal life is possible.
==Historical Perspective==
*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
==Classification==
==Classification==
[[Multiple sclerosis]] may be classified into four groups according to [[clinical]] course of the [[disease]].
Multiple sclerosis may be classified into four groups according to [[clinical]] course of the [[disease]] including relapsing-remitting, secondary-progressive,
#'''Relapsing-remitting'''
primary-progressive and progressive-relapsing. other variants of Multiple sclerosis include clinically isolated syndrome and radiologically isolated syndrome.
#'''secondary-progressive'''
#'''primary-progressive'''
#'''progressive-relapsing'''<ref name=":0">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</ref>
Other variants of Multiple sclerosis include clinically isolated syndrome and radiologically isolated syndrome.


==Pathophysiology==
==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
Multiple sclerosis is a [[disease]] of the [[central nervous system]] and it’s known to be multi factorial. Whatever the trigger is, it will lead to an acquired [[immune response]] followed by [[inflammatory]] reactions. These reactions lead to secretion of [[cytokines]] in the [[CNS]] [[parenchyma]] and activation of resident [[microglia]]. [[Microglia]] cells activate [[astrocytes]] to release more [[Inflammation|inflammatory]] [[cytokines]], leading to recruitment and [[Infiltration (medical)|infiltration]] of circulatory [[leukocytes]]. This burst events cause destruction of [[myelin sheath]] and forms focal sclerotic [[white matter]] plaques, which are characteristic of multiple sclerotic disease. There is some evidence proving [[genetic]] involvement in onset of [[MS]] so that it increases the risk of developing [[MS]] from 0.1% in general population to 3% in those who have siblings with [[MS]] and 25% in those with a mono-zygote [[twin]] affected. Based on studies performed on [[post mortem]] [[brain tissue]] of patients with multiple sclerosis, there are four types of [[white matter]] lesion pathology. Damage to [[myelin sheath]] is prominent in type 1 and 2 while type 3 and 4 characteristic is dying [[Oligodendrocyte|oligodendrocytes]]. the [[etiology]] of [[Oligodendrocyte|oligodendrocytes]] death known to be multi-factorial or followed by [[hypoxia]], [[mitochondrial]] dysfunction and [[Macrophage|macrophages]].
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
==Causes==
==Causes==
* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
Multiple sclerosis may be caused by different categories of causes include: [[Autoimmunity]], [[genetic]], [[infectious]] and [[Degeneration (medical)|degeneration]].
* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
* There are no established causes for [disease name].


==Differentiating Multiple Sclerosis from other Diseases==
==Differentiating Multiple Sclerosis from other Diseases==
The signs and symptoms of MS can be similar to other medical problems, such as [[Devic's disease|neuromyelitis optica]], [[stroke]], [[acute disseminated encephalomyelitis|brain inflammation]],[[infection]]s such as [[Lyme disease]] (which can produce identical MRI lesions and CSF abnormalities<ref>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</ref><ref>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</ref><ref>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</ref><ref>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</ref>), [[tumor]]s, and other autoimmune problems, such as [[lupus erythematosus|lupus]]. Additional testing may be needed to help distinguish MS from these other problems.
Multiple sclerosis must be differentiated from other diseases that can mimic this disease [[Clinical|clinically]] or [[Radiological|radiologically]] such as [[systemic lupus erythematosis]], [[Sjögren’s syndrome]], [[vasculitis]], neuro-[[Behçet's disease|behçet’s disease]], [[sarcoidosis]], [[Antiphospholipid syndrome|antiphospholipid (Hughes) syndrome]] , [[Susac's syndrome|susac syndrome]], [[lyme disease]], [[syphilis]], [[HTLV-1|HTLV-1 infection]], [[HIV]]-Related Disorders of the [[CNS]], [[migraine]], [[cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy]], [[Leber's hereditary optic neuropathy|leber’s hereditary optic neuropathy]], [[vitamin B12 deficiency]], [[metachromatic leukodystrophy]], [[Fabry's disease|Fabry’s disease]], [[Krabbe disease|Krabbe’s disease]], [[adrenoleukodystrophy]], [[Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes|mitochondrial encephalopathy epilepsy lactic acidosis and stroke like episode]], [[stroke]], [[primary CNS lymphoma]] , and [[dural arteriovenous fistula]] and true malformations.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
The majority of multiple sclerosis cases are reported in northern Europe, continental North America, and Australasia, which is about one of every 1000 citizens. Factors including sunlight exposure, climate, [[diet]], [[toxins]], [[genetic]] factors, geomagnetism, Childhood environmental factors and [[infections]] have been proved to cause these differences in [[MS]] [[prevalence]]. [[MS]] is at least two times more common among [[women]] than [[men]]. The onset of [[symptoms]] is mostly between the age of fifteen to forty years, rarely before age fifteen or after age sixty.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
 
===Age===
*Patients of all age groups may develop [disease name].
*[Disease name] is more commonly observed among patients aged [age range] years old.
*[Disease name] is more commonly observed among [elderly patients/young patients/children].
===Gender===
*[Disease name] affects men and women equally.
*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
===Race===
*There is no racial predilection for [disease name].
*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].
==Risk Factors==
==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
Common [[risk factors]] in the development of multiple sclerosis are [[smoking]], [[genetic]], [[Ethnic group|ethnic]], [[infection]], low [[vitamin D]], and [[stress]]. Less common [[risk factors]] in the development of multiple sclerosis include African Americans, Mexicans, Japanese, Chinese and Filipinos race and [[Epstein Barr virus|Epstein-Barr virus]].
 
== Natural History, Complications and Prognosis==
== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
Multiple sclerosis usually start between age of fifteen to forty years, rarely before age fifteen or after age sixty with [[symptoms]] such as [[optic neuritis]], [[diplopia]], [[Sensory loss|sensory]] or [[Muscle weakness|motor loss]], [[vertigo]] and [[Balance disorder|balance]] problems. It may be classified into four groups according to [[clinical]] course of the [[disease]] including relapsing-remitting, secondary-progressive, primary-progressive, and progressive-relapsing. [[Complications]] that can develop as a result of multiple sclerosis are: [[medication]] [[complication]], [[Fatigue]], [[mood]] problems, [[Spasticity]], [[Bowel]] and [[bladder]] dysfunction, [[Cognitive impairment]], Heat sensitivity., [[Incoordination]], [[Pain]], [[Sexual dysfunction]], [[Sleep disorder|Sleep disorders]], [[vertigo]], [[visual loss]]. there are some factors associated with a particularly poor [[prognosis]] among [[patients]] with multiple sclerosis such as: Relapsing versus progressive disease, early symptoms, Demographics, Sex, [[Smoking]].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
 
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].
== Diagnosis ==
== Diagnosis ==
===Diagnostic Criteria===
 
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
=== Diagnostic Study of choice ===
:*[criterion 1]
There is no single diagnostic study of choice for the [[diagnosis]] of multiple sclerosis, but multiple sclerosis can be diagnosed based on [[History and Physical examination|clinical presentation]], [[MRI]] findings, and [[CSF analysis]]. Sequence of diagnostic studies are [[History and Physical examination|history and physical examination]], [[imaging]], and [[CSF analysis]]. The findings are [[cerebral]] plaques which are [[demyelinating]] areas on [[MRI]] and an elevated concentration of [[CSF]] [[oligoclonal bands]]. The diagnostic criteria for multiple sclerosis is [[McDonald criteria]].
:*[criterion 2]
 
:*[criterion 3]
===History and Symptoms===
:*[criterion 4]
The most common [[symptoms]] of multiple sclerosis include: [[Fatigue]], [[Mood disorder|mood problems]], [[spasticity]], [[bowel]] and [[bladder]] dysfunction, [[cognitive impairment]], [[Ophthalmoplegia|eye movement problems]], heat sensitivity, [[incoordination]], [[pain]], [[sexual dysfunction]], [[Sleep disorders|sleep disorder]], [[vertigo]] and [[visual loss]].
 
=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Symptoms of [disease name] may include the following:
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]
=== Physical Examination ===
=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
[[Physical examination]] of patients with multiple sclerosis is usually remarkable for [[lhermitte's sign]], [[spasticity]], increased [[reflexes]], [[internuclear ophthalmoplegia]], [[optic neuritis]], [[gait disturbance]], and [[urinary incontinence]].
*Physical examination may be remarkable for:
 
:*[finding 1]
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]
=== Laboratory Findings ===
=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].
An elevated concentration of [[CSF]] [[oligoclonal bands]] is [[diagnostic]] of multiple sclerosis.
 
=== Electrocardiogram ===
An [[ECG]] may be helpful in the [[diagnosis]] of multiple sclerosis. Findings on an [[ECG]] suggestive of multiple sclerosis include [[atrial fibrillation]], [[ventricular arrhythmia]], shortened or [[Long PR interval|longed P-R interval]], tall waves or peaked waves, [[U waves]], and [[Q waves]].
 
=== X-ray ===
There are no [[x-ray]] findings associated with multiple sclerosis.
 
=== Echocardiography and Ultrasound ===
There are no [[echocardiography]]/[[ultrasound]] findings associated with multiple sclerosis.
 
=== CT scan ===
Findings on [[CT scan]] suggestive of multiple sclerosis include [[brain atrophy]] and some contrast enhancing plaques. Findings on an Double delayed high dose CT scan suggestive of Multiple sclerosis include enhanced [[lesions]] in double delayed high dose [[CT scan]] which are indicators of [[blood brain barrier]] disruption.
 
=== MRI ===
On [[MRI]], multiple sclerosis is characterized by [[cerebral]] plaques disseminating in space and time which are characteristic of [[demyelinating]] areas. These [[Lesion|lesions]] are commonly void, and located in periventricular [[white matter]], [[cerebellum]], and the [[brain stem]]. These lesions are hyperintense on T2 sections of a [[MRI]].
 
=== Other Imaging Findings ===
There is no other [[imaging]] findings associated with multiple sclerosis.


*A  [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].
*[Imaging study 1] is the imaging modality of choice for [disease name].
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
[[Visual evoked potential|Visual evoked potential studies]], anti[[myelin]] [[antibodies]], and optimal coherence tomography may be helpful in the [[diagnosis]] of multiple sclerosis.
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis,  [[Immunosuppression|immunosuppressive threpay]] in progressive multiple sclerosis and [[Glucocorticoid]] therapy in acute exacerbation.


===Prevention===
=== Surgery ===
Surgery can be helpful in controlling [[trigeminal neuralgia]], [[tremor]], and [[ataxia]].


====Secondary Prevention====
=== Alternative Therapies ===
A physiotherapist can help to reduce spasticity and avoid the development of [[contracture]]s with techniques such as passive stretching.<ref name="pmid10871810">{{cite journal |author=Cardini RG, Crippa AC, Cattaneo D |title=Update on multiple sclerosis rehabilitation |journal=J. Neurovirol. |volume=6 Suppl 2|issue= |pages=S179–85|year=2000 |pmid=10871810 |doi=}}</ref>
Alternative [[treatments]] for multiple sclerosis are: [[Diet (nutrition)|Dietary]] regimens [[herbal medicine]] ( [[marijuana]] ) [[hyperbaric oxygenation]] [[Martial arts therapy|therapeutic practice of martial arts.]]


=== Primary Prevention ===
Effective measures for the [[primary prevention]] of multiple sclerosis include: [[Vitamin D]] supplement, [[smoking]] cessation, early exposure to [[infection]]<nowiki/>s.


===Alternative Therapies===
=== Secondary Prevention ===
Different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study. Examples are [[Diet (nutrition)|dietary]] regimens,<ref name="pmid17253500">{{cite journal |author=Farinotti M, Simi S, Di Pietrantonj C, ''et al.''|title=Dietary interventions for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD004192 |year=2007 |pmid=17253500|doi=10.1002/14651858.CD004192.pub2}}</ref>, [[herbal medicine]], including the use of [[marijuana]] to help alleviate symptoms,<ref>{{cite journal |author=Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E |title=Cannabis use in patients with multiple sclerosis |journal=Mult. Scler. |volume=12 |issue=5|pages=646–51|year=2006 |pmid=17086912 |doi=}}</ref><ref>{{cite journal |author=Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ |title=Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up |journal=J. Neurol. Neurosurg. Psychiatr. |volume=76 |issue=12 |pages=1664–9 |year=2005|pmid=16291891|doi=10.1136/jnnp.2005.070136}}</ref> or [[hyperbaric oxygenation]].<ref name="pmid14974004">{{cite journal |author=Bennett M, Heard R|title=Hyperbaric oxygen therapy for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1|pages=CD003057|year=2004 |pmid=14974004 |doi=10.1002/14651858.CD003057.pub2}}</ref>
There is no established method for [[secondary prevention]] of multiple sclerosis.
On the other hand the [[Martial arts therapy|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.<ref name="pmid15184614">{{cite journal |author=Oken BS, Kishiyama S, Zajdel D, ''et al.''|title=Randomized controlled trial of yoga and exercise in multiple sclerosis |journal=Neurology|volume=62|issue=11 |pages=2058–64 |year=2004 |pmid=15184614 |doi=}}</ref>
 
=== Tertiary Prevention ===
Tertiary: There is strong evidence that [[exercise]] therapy can improve [[muscle]] function and [[mobility]] in multiple sclerosis patients.


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}


[[Category:Primary care]]
[[Category:Neurology]]
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{{WS}}

Latest revision as of 22:48, 29 July 2020

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Multiple sclerosis Microchapters

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Overview

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Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview

Multiple sclerosis is a disease of the central nervous system and it’s known to be multi factorial. The most common risk factors in the development of multiple sclerosis are smoking, genetic, ethnic, infection, low vitamin D, and stress. Whatever the trigger is, it will lead to an acquired immune response followed by inflammatory reactions. These reactions lead to secretion of cytokines in the CNS parenchyma and activation of resident microglia. Microglia cells activate astrocytes to release more inflammatory cytokines, leading to recruitment and infiltration of circulatory leukocytes. This burst events cause destruction of myelin sheath and forms focal sclerotic white matter plaques, which are characteristic of multiple sclerotic disease. The onset of symptoms is mostly between the age of fifteen to forty years, rarely before age fifteen or after age sixty and include fatigue, mood problems, spasticity, bowel and bladder dysfunction, cognitive impairment, eye movement problems, heat sensitivity, incoordination, pain, sexual dysfunction, sleep disorder, vertigo and visual loss. There is no single diagnostic study of choice for the diagnosis of multiple sclerosis, but multiple sclerosis can be diagnosed based on clinical presentation, cerebral plaques on MRI , and oligoclonal bands in CSF analysis. The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis, immunosuppressive threpay in progressive multiple sclerosis and Glucocorticoid therapy in acute exacerbation.

Historical Perspective

Multiple sclerosis was first described by a neurologist, Dr. Jean Martin Charcot in 1868 and named sclerose en plaque. The signs and symptoms including dysarthria, ataxia and tremor were called charcot’s triad.

Classification

Multiple sclerosis may be classified into four groups according to clinical course of the disease including relapsing-remitting, secondary-progressive, primary-progressive and progressive-relapsing. other variants of Multiple sclerosis include clinically isolated syndrome and radiologically isolated syndrome.

Pathophysiology

Multiple sclerosis is a disease of the central nervous system and it’s known to be multi factorial. Whatever the trigger is, it will lead to an acquired immune response followed by inflammatory reactions. These reactions lead to secretion of cytokines in the CNS parenchyma and activation of resident microglia. Microglia cells activate astrocytes to release more inflammatory cytokines, leading to recruitment and infiltration of circulatory leukocytes. This burst events cause destruction of myelin sheath and forms focal sclerotic white matter plaques, which are characteristic of multiple sclerotic disease. There is some evidence proving genetic involvement in onset of MS so that it increases the risk of developing MS from 0.1% in general population to 3% in those who have siblings with MS and 25% in those with a mono-zygote twin affected. Based on studies performed on post mortem brain tissue of patients with multiple sclerosis, there are four types of white matter lesion pathology. Damage to myelin sheath is prominent in type 1 and 2 while type 3 and 4 characteristic is dying oligodendrocytes. the etiology of oligodendrocytes death known to be multi-factorial or followed by hypoxia, mitochondrial dysfunction and macrophages.

Causes

Multiple sclerosis may be caused by different categories of causes include: Autoimmunity, genetic, infectious and degeneration.

Differentiating Multiple Sclerosis from other Diseases

Multiple sclerosis must be differentiated from other diseases that can mimic this disease clinically or radiologically such as systemic lupus erythematosis, Sjögren’s syndrome, vasculitis, neuro-behçet’s disease, sarcoidosis, antiphospholipid (Hughes) syndrome , susac syndrome, lyme disease, syphilis, HTLV-1 infection, HIV-Related Disorders of the CNS, migraine, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, leber’s hereditary optic neuropathy, vitamin B12 deficiency, metachromatic leukodystrophy, Fabry’s disease, Krabbe’s disease, adrenoleukodystrophy, mitochondrial encephalopathy epilepsy lactic acidosis and stroke like episode, stroke, primary CNS lymphoma , and dural arteriovenous fistula and true malformations.

Epidemiology and Demographics

The majority of multiple sclerosis cases are reported in northern Europe, continental North America, and Australasia, which is about one of every 1000 citizens. Factors including sunlight exposure, climate, diet, toxins, genetic factors, geomagnetism, Childhood environmental factors and infections have been proved to cause these differences in MS prevalence. MS is at least two times more common among women than men. The onset of symptoms is mostly between the age of fifteen to forty years, rarely before age fifteen or after age sixty.

Risk Factors

Common risk factors in the development of multiple sclerosis are smoking, genetic, ethnic, infection, low vitamin D, and stress. Less common risk factors in the development of multiple sclerosis include African Americans, Mexicans, Japanese, Chinese and Filipinos race and Epstein-Barr virus.

Natural History, Complications and Prognosis

Multiple sclerosis usually start between age of fifteen to forty years, rarely before age fifteen or after age sixty with symptoms such as optic neuritis, diplopia, sensory or motor loss, vertigo and balance problems. It may be classified into four groups according to clinical course of the disease including relapsing-remitting, secondary-progressive, primary-progressive, and progressive-relapsing. Complications that can develop as a result of multiple sclerosis are: medication complication, Fatigue, mood problems, Spasticity, Bowel and bladder dysfunction, Cognitive impairment, Heat sensitivity., Incoordination, Pain, Sexual dysfunction, Sleep disorders, vertigo, visual loss. there are some factors associated with a particularly poor prognosis among patients with multiple sclerosis such as: Relapsing versus progressive disease, early symptoms, Demographics, Sex, Smoking.

Diagnosis

Diagnostic Study of choice

There is no single diagnostic study of choice for the diagnosis of multiple sclerosis, but multiple sclerosis can be diagnosed based on clinical presentation, MRI findings, and CSF analysis. Sequence of diagnostic studies are history and physical examination, imaging, and CSF analysis. The findings are cerebral plaques which are demyelinating areas on MRI and an elevated concentration of CSF oligoclonal bands. The diagnostic criteria for multiple sclerosis is McDonald criteria.

History and Symptoms

The most common symptoms of multiple sclerosis include: Fatigue, mood problems, spasticity, bowel and bladder dysfunction, cognitive impairment, eye movement problems, heat sensitivity, incoordination, pain, sexual dysfunction, sleep disorder, vertigo and visual loss.

Physical Examination

Physical examination of patients with multiple sclerosis is usually remarkable for lhermitte's sign, spasticity, increased reflexes, internuclear ophthalmoplegia, optic neuritis, gait disturbance, and urinary incontinence.

Laboratory Findings

An elevated concentration of CSF oligoclonal bands is diagnostic of multiple sclerosis.

Electrocardiogram

An ECG may be helpful in the diagnosis of multiple sclerosis. Findings on an ECG suggestive of multiple sclerosis include atrial fibrillation, ventricular arrhythmia, shortened or longed P-R interval, tall waves or peaked waves, U waves, and Q waves.

X-ray

There are no x-ray findings associated with multiple sclerosis.

Echocardiography and Ultrasound

There are no echocardiography/ultrasound findings associated with multiple sclerosis.

CT scan

Findings on CT scan suggestive of multiple sclerosis include brain atrophy and some contrast enhancing plaques. Findings on an Double delayed high dose CT scan suggestive of Multiple sclerosis include enhanced lesions in double delayed high dose CT scan which are indicators of blood brain barrier disruption.

MRI

On MRI, multiple sclerosis is characterized by cerebral plaques disseminating in space and time which are characteristic of demyelinating areas. These lesions are commonly void, and located in periventricular white matter, cerebellum, and the brain stem. These lesions are hyperintense on T2 sections of a MRI.

Other Imaging Findings

There is no other imaging findings associated with multiple sclerosis.

Other Diagnostic Studies

Visual evoked potential studies, antimyelin antibodies, and optimal coherence tomography may be helpful in the diagnosis of multiple sclerosis.

Treatment

Medical Therapy

The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis, immunosuppressive threpay in progressive multiple sclerosis and Glucocorticoid therapy in acute exacerbation.

Surgery

Surgery can be helpful in controlling trigeminal neuralgia, tremor, and ataxia.

Alternative Therapies

Alternative treatments for multiple sclerosis are: Dietary regimens herbal medicine ( marijuana ) hyperbaric oxygenation therapeutic practice of martial arts.

Primary Prevention

Effective measures for the primary prevention of multiple sclerosis include: Vitamin D supplement, smoking cessation, early exposure to infections.

Secondary Prevention

There is no established method for secondary prevention of multiple sclerosis.

Tertiary Prevention

Tertiary: There is strong evidence that exercise therapy can improve muscle function and mobility in multiple sclerosis patients.

References

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