Multiple sclerosis overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Multiple sclerosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT Scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Alternative Therapies

Primary Prevention

Secondary Prevention

Tertiary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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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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