Multiple Sclerosis (MS): Causes, Symptoms and Treatments

Multiple sclerosis

1. Introduction:

Neurology deals with complex and rare disorders. One of the most common neurodegenerative disorders is multiple sclerosis.[1] Multiple sclerosis is a disorder of central nervous system. It is characterized by demyelination, mononuclear cell inflammation and axonal injury. Axonal injury is rarely observed.[2] MS sclerosis is generally categorized under autoimmune disorders. Its causes are unknown.[3] Genetic as well as environmental factors play an important role in development of MS.[1] Elvin Cabalt was the first person to recognize the immune mediated infflamatory response in central nervous system of MS patients. He also found that oligoclonal immunoglobulins are present in cerebrospinal fluid of MS patients.[3]MS affects young adults more than any other age group.[4] It affects females more than males. 2.5 million individuals are affected with MS amongst which 70% are females.MS affects. The incidence of occurrence of MS in individuals varies amongst different regions. It affects northern European population more than the Asian and African population.[5] There is no much sensitive and specific diagnostic test or method for diagnosis of multiple sclerosis.[6]

2. pathological process in MS:

Inflammation

gliosis

Oligodendrocyte axonal toxicity axonal and neuronal

Toxicity and axonal loss loss

Remyelination

Central adaptation and plasticity

Ref 1.

3. Classification Multiple sclerosis:

Multiple sclerosis can be classified as symptomic multiple sclerosis and asymptomic multiple sclerosis. Symptoms are not seen in case of asymptomic MS whereas symptoms are seen in case of symptomic Sclerosis.[2] symptomic multiple sclerosis can be further classified as

1. Relapsing MS: Relapses are the most important features for diagnosis of multiple sclerosis. Relapses may produce complete i.e permanent or temporary loss of function.[8]

2. Primary progressive MS : Primary progressive multiple sclerosis occurs most probably after the age of35. It involves spinal cord atrophy and difficulty in walking. MRI of brain shows less damage as compared to secondary progressive MS.[9] Primary progressive MS can be differentiated from relapsing-remitting MS by Magnetic resonance spectroscopic imaging(MRSI)[10]

3. Secondary progressive MS : secondary progressive MS is more severe than primary progressive MS. Cerebrospinal fluid of patients with secondary progressive multiple sclerosis shows increased level oligoclonal immunoglobulins(most probably IgG)[9].Patients with secondary progressive MS also have increased level of uric acid in their body.[11]

4. progressive relapsing MS:

5. Transitional MS.[7]

The relative proportion of all the types of MS was studied in American population. The observations are as follows:

Type % individuals suffering

RRMS 55%

SSMS 31%

PPMS 9%

PRMS 5%

4. Causes of multiple sclerosis:

The exact cause of the disease i.e multiple sclerosis is still unknown.[3] It is generally thought that multiple sclerosis is initiated by an autoimmune response against myelin sheath and mononuclear cells of nervous system.[2]Both genetic as well as environmental factors are involved in the development of multiple sclerosis.[1]

Genetic factors:

The involvement of genetic factors in development of MS is confirmed by the fact that 10-12% of the people suffering from MS also have their family members suffering from this disorder. The incidence of occurrence of MS in case of monozygotic twins(28%) also confirms the involvement of genetic factors in development of MS.[7] However there are many cases where only one of the monozygotic twins is suffering from MS, this supports the involvement of environmental factors in development of MS.[2]multiple sclerosis do not show Mendelian pattern of inheritance. This is may be because number of genes involved in the development of MS are more than multiple.[12] The important genetic susceptibility locus involved in development of MS resides in the HLA-DRB gene. Presence of this haplotype increases the risk of development of MS 2-4 times more than the normal individuals[2].

Environmental factors:

There are many environmental factors involved in the development of MS.

  1. Deficiency of vitamin D: Low levels of vitamin D are thought to be involved in the development of MS.[13]the amount of vitamin D present in individuals system will depend on the amount of sunlight reaching that area. So we can say that latitude also plays an important role in development of MS.[12]
  2. Smoking: Cigarette smoking increases the risk of development of MS[2]. It has proven by the survey in Northern America that more than 50% of patients suffering from MS are smokers.[12]
  3. Surgery: It has been observed that, individuals history of surgery may increase the risk of development of MS as compared to other individuals.[14]There is significant association between tonsillectomy , appendectomy and development of MS[1,14]
  4. Obesity: obesity during during young adulthood may be associated in the development of MS[2]
  5. Infection with certain viruses and bacteria : infection with certain viruses have been proven to increase the risk of development of MS{1,4,15]These viruses include Epstein Barr Virus,Herpes,Hepititis B virus and Chlamydia pneumonia[2,14]
  6. Latitude effect: It has been observed that as we go away from the latitude the percentage of individuals suffering through MS increases.[5]

5. Symptoms of multiple sclerosis:

Early symptoms:

  • Blurred vision
  • Weakness in the arm or leg
  • Tinging
  • Loss of balance
  • Thinking problems[1,4,16]

Common symptoms:

  • Tremor and ataxia: This has been observed in 75% of the patients suffering from MS. It is caused due to the degeneration of myelin sheath.[17]
  • Bladder problems: people suffering through multiple sclerosis many times face bladder problems such as frequent urination, involuntary sphincter muscles.[16]
  • Dizziness[1,3]
  • Sexual trouble: Patients may have difficulty in having sexual intercourse.[1]
  • Fatigue[1,3,4,16]
  • Unusual sensation: patients may feel unusual sensations like itching, tearing , burning etc[16]
  • Speech problems: people suffering through MS may sometimes develop speech problems.
  • Swallowing problems: People with advanced stage of MS develop swallowing problems.

It is important to know that the clinical symptoms of two different individuals suffering through MS differ from each other.

6. Diagnosis of Multiple sclerosis:

The clinical symptoms of MS match with other common neurological disorders therefore it is difficult to diagnose MS at its early stage.[3]migraine may sometimes coexist with MS in case of females[6]therefore sensitive techniques are required for incorrect diagnosis MS .[6] some of the diagnosis methods are as fpllows:

  1. Magnetic Resonance Imaging: This is the most commonly used method for diagnosis of MS[3].MRI can detect presence of characteristic lesions of MS present in periventricular,infratentorial and juxtracortical region of the brain.[17]one of the limitations of MRI is that it cannot diagnose MS lesions in the early stage.[1] If a period of 3 months has elapse between the first MRI scan and the second MRI scan then the presence of progressive lesions is sufficient to dignose MS.[3] IT should be noted by all the physicians and radiologist that the diagnostic imaging crieteria is most effective when combined with standardise MRI protocols published by International Consortium of Multiple Sclerosis centres .[17]
  2. Presence of oligoclonal immunoglobulins: presence of oligoclonal IgG in the cerebrospinal fluid indicates the presence of MS lesions.[4] The presence of oligoclonal immunoglobulins is detected by electrophoresis. the bands obtained after electrophoresis can be isolated for further analysis.[1]
  3. Alkaline phosphatase method and peroxidase method for detecting presence of oligoclinal antibodies: It has been found that the alkaline phosphatase method is more sensitive than the peroxidase method for detecting the presence of oligoclonal bands.[18]
  4. Fluorescence Activated Cell Sorting: the is the advanced method of diagnosis of MS. The cerebrospinal fluid of suspected individuals is checked by FACS. These samples are checked for the presence of cell surface markers such as CD4, CD25, CD20, CD40, CD25,CCR6 and CD45. It has been observed that B-cells/monocytes (CD20/CD14) ratio differs between MS patients and patients suffering through common inflammatory disease.

Biomarkers used for diagnosis:

  1. Differential microRNA expression: microRNA’s are differentially expressed in MS patients. microRNA145 is the potential diagnostic biomarker. [18]
  2. Myelin Binding Protein (MBP): MBP is basically found in myelin sheath of a neuron. Presence of MBP in the surrounding cerebrospinal fluid indicates the presence of neurodegenerative disorder such as MS[2]
  3. Neurospecific enolase: increased level of this enzyme in cerebrospinal fluid may indicate presence of MS. This enzyme is found in the cytosol of the neurons.[1]
  4. Inflammatory markers:
  5. Glial Fibrillary acidic Protein: This protein is the major component of intermediate filaments of glial cells.[19] It increases when glial cells are associated with astrocytes. This can be used as potential biomarker for diagnosis of MS[9]
  6. Biomarkers for remyelination and repair: These biomarkers are not been systematically evaluated. Potential candidates for this type of biomarkers include Neuronal cell adhesion factors(NCAF)[20]
  7. Marker for astrocyte activation and gliosis: S-100 is a calcium binding protein found in astrocytes and Schwann cells. Its presence in CSF indicates the presence of neurodegenerative disorder.[19]

7. Treatment of MS:

1. Use of anti-CD20 antibodies: Rituximab is used to treat mostly the patients suffering from primary and relapsing remmiting MS.[20]

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