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Multiple Sclerosis

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Last Update: July 12, 2019.

Introduction

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by chronic inflammation, demyelination, gliosis, and neuronal loss. The course may be relapsing-remitting or progressive in nature. Lesions in the CNS occur at different times and in different CNS locations. Because of this, multiple sclerosis lesions are sometimes said to be "disseminated in time and space." The clinical course of the disease is quite variable ranging from a stable chronic disease to a rapidly evolving and debilitating illness. The most common form of the disease is relapsing-remitting multiple sclerosis; however, several other forms exist.[1][2][3]

Etiology

The specific cause of multiple sclerosis is unknown. The most widely accepted theory is that multiple sclerosis is an autoimmune disease that preferentially destroys the CNS while the peripheral nervous system is spared. Demyelination causes the symptoms of multiple sclerosis. Damage to myelin, the protective fatty tissue around the nerves that aids conduction of impulses along the nerves, leads to symptomatic flares in multiple sclerosis. These damaged areas often do not fully recover leading to areas of scarring, damage, and ongoing symptoms.  Over time, these cumulative areas of damage can lead to disability. Of note, patients can also develop subclinical areas of damage that are detectable early in the disease course only by radiographic studies.[4][5][6]

Epidemiology

Approximately 350,000 individuals in the United States and 2.5 million individuals worldwide have multiple sclerosis. The disease is 3-fold more common in females than in males. While the age of onset is usually between 20 to 40 years, the disease can present at any age. Almost 10% of the cases present before the age of 18.[7]

Classically, multiple sclerosis is more common in populations who live farther from the equator. The highest prevalence of multiple sclerosis is found in Orkney islands north of Scotland. In other temperate areas like North America, northern Europe, southern Australia and southern New Zealand the prevalence of the multiple sclerosis is significantly higher than in areas closer to the equator.

A variety of risk factors for multiple sclerosis have been suggested. In addition to increasing risk with increasing distance from the equator, genetic associations, sunlight exposure, vitamin-D levels, tobacco smoking, viral transmission, and other theories have been evaluated.  No theory has been proven.

Pathophysiology

Early lesions of multiple sclerosis show mononuclear infiltrate with perivenular cuffing and surrounding white matter infiltration. The blood-brain barrier is disrupted at inflammatory sites. However, the vessel wall is preserved. The humoral immune system may also play a significant role in disease pathogenesis as evident by the presence of B-cells at active sites. The pathological hallmark of multiple sclerosis is demyelination which is often the earliest sign noted in affected neurons. Oligodendrocyte precursor cells usually survive and are often present in greater number when compared to the surrounding normal tissue, but, these cells fail to differentiate into mature oligodendrocytes. In some lesions, there is partial remyelination of surviving neurons, known as shadow plaques. With the evolution of a lesion, astrocytes proliferate resulting in gliosis.

Myelin is known to aid in the conduction of nerve impulses. Because multiple sclerosis is a demyelinating disease resulting in damage to this myelin, conduction speed is often slowed along affected nerves leading to the symptoms seen in multiple sclerosis.

Histopathology

When hematoxylin and eosin (HE) stain is done, the plaques of multiple sclerosis appear pale when compared to normal white matter. Active lesions are also cellular as they contain inflammatory cells like macrophages, lymphocytes, and astrocytes. Often, activity is confined to the borders of the plaques and myelin staining shows complete loss of myelin or palor of the myelin sheaths. The inflammatory cells of the lesions include CD8 T lymphocytes, macrophages, microglia, and astrocytes. B lymphocytes, plasma cells, antibodies, and complement proteins have also been identified in the lesions. Lesions are most frequently found in the periventricular white matter, optic nerves, and the spinal cord in multiple sclerosis.  Lesions in the periventricular white matter often caused "Dawson's fingers."

History and Physical

The presentation of multiple sclerosis is variable. Classic presentations include sensory changes, weakness, or visual changes. The most common presenting symptoms are unilateral sensory disturbances. Unilateral visual changes, often in the form of optic neuritis, are also quite common.

Often patients will present with a history of sensory, weakness, or visual changes which have occurred and resolved. Because symptoms often resolve without specific medical intervention, patients may have a history of several different events prior to presenting for formal medical evaluation.

As stated, sensory changes are common. These can affect any part of the body but are often unilateral. Likewise, weakness may affect any part of the body. Optic neuritis presents with decreased visual activity, dimness of vision, and decreased color perception known as red desaturation. Abnormality of the affected pupil to respond to light called afferent pupillary defect is often seen in cases of optic neuritis. Another common visual complaint is of abnormal eye movement known as internuclear ophthalmoplegia (INO). Patients often complain of diplopia. INO results from a demyelinating lesion of the medial longitudinal fasciculus.

Patients with a history of demyelinating damage may state that symptoms worsen in extreme heat. This is known as Uthoff's phenomenon. Patients may also complain of electrical sensation moving through the spine and limbs. This is known as Lhermitte's sign.

Multiple sclerosis is a complex disease. In addition to sensory changes, weakness, and visual changes, coordination problems or spasticity can be seen. Other complaints related to general health include bladder and bowel dysfunction, cognitive impairment, depression, fatigue, sexual dysfunction, sleep problems, and vertigo.

Evaluation

The diagnosis of multiple sclerosis is a clinical diagnosis. No one test is diagnostic for the disease. Evidence of lesions which have occurred at different times in different locations must be found. This evidence can be clinical or radiographic. When evaluating clinical flares, flares are traditionally defined as symptoms that last for at least 24 hours. The McDonald Criteria is a set of criteria outlining different ways that a patient can meet the criteria for a definite diagnosis of multiple sclerosis.[8][9][10]

MRI is the radiologic study of choice. MRI should be completed with and without contrast to help differentiate old lesions from new, active lesions. Cerebrospinal fluid (CSF) analysis may be helpful in pointing toward a diagnosis of multiple sclerosis. Specifically, the presence of oligoclonal bands present in the cerebrospinal fluid which are not present in the serum is concerning for an underlying diagnosis such as multiple sclerosis. It is important to evaluate for other mimickers of multiple sclerosis as well. These include a wide variety of other neurologic diseases, rheumatologic diseases, and infectious diseases.

Treatment / Management

At least partial recovery from acute exacerbations or flares is expected. However, as discussed above, repair of damaged myelin may be incomplete.[11][12][13]

Flares are often treated with steroids. Steroids lead to a faster recovery from an acute attack but do not change the ultimate extent of recovery. Furthermore, steroids do not prevent future attacks.

The primary goal in the treatment of multiple sclerosis is to prevent areas of damage by using maintenance therapies. Early maintenance therapies were injectables and first became available in the 1990s. Rapid growth has occurred in this area in the past several years with injection therapies, oral therapies, and infusion therapies now available. Therapies have largely targeted relapsing-remitting multiple sclerosis, the most common form of the disease. However, in 2017, the first therapy was approved for another form of the disease, primary progressive.[14][15]

Differential Diagnosis

The differential diagnosis for multiple sclerosis is broad. Other related neurologic diseases such as neuromyelitis optica must be ruled out. A wide variety of rheumatologic diseases and infectious diseases must also be screened for when a diagnosis of multiple sclerosis is considered.

Enhancing Healthcare Team Outcomes

Multiple sclerosis is a complex disease. In addition to sensory changes, weakness, and visual changes, coordination problems or spasticity can be seen. Other complaints related to general health include bladder and bowel dysfunction, cognitive impairment, depression, fatigue, sexual dysfunction, sleep problems, and vertigo. Because of the shortened life expectancy and multisystem involvement, the disorder is best managed by a multidisciplinary team that includes a neurologist, therapist, pain specialist, nurse specialist, ophthalmologist, mental health nurse, gastroenterologist and a urologist. Because there is no cure, it is vital to ensure that the patient's quality of life is not eroded. Social work must be involved early in the care and the patient provided with all the possible supportive assistance.[16] (Level V)

Questions

To access free multiple choice questions on this topic, click here.

References

1.
Konuskan B, Anlar B. Treatment in childhood central nervous system demyelinating disorders. Dev Med Child Neurol. 2019 Apr 16; [PubMed: 30993677]
2.
Kaur J, Ghosh S, Sahani AK, Sinha JK. Mental imagery training for treatment of central neuropathic pain: a narrative review. Acta Neurol Belg. 2019 Jun;119(2):175-186. [PubMed: 30989503]
3.
Pape K, Tamouza R, Leboyer M, Zipp F. Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol. 2019 Jun;15(6):317-328. [PubMed: 30988501]
4.
Cree BAC, Mares J, Hartung HP. Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm. Curr. Opin. Neurol. 2019 Jun;32(3):365-377. [PubMed: 30985372]
5.
Ryan P, Xu M, Davey AK, Danon JJ, Mellick GD, Kassiou M, Rudrawar S. O-GlcNAc Modification Protects against Protein Misfolding and Aggregation in Neurodegenerative Disease. ACS Chem Neurosci. 2019 May 15;10(5):2209-2221. [PubMed: 30985105]
6.
Schweitzer F, Laurent S, Fink GR, Barnett MH, Reddel S, Hartung HP, Warnke C. Age and the risks of high-efficacy disease modifying drugs in multiple sclerosis. Curr. Opin. Neurol. 2019 Jun;32(3):305-312. [PubMed: 30985373]
7.
Magyari M, Sorensen PS. The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis. Curr. Opin. Neurol. 2019 Jun;32(3):320-326. [PubMed: 30925518]
8.
Sherif M, Bergin C, Borruat FX. Normal Visual Recovery after Optic Neuritis Despite Significant Loss of Retinal Ganglion Cells in Patients with Multiple Sclerosis. Klin Monbl Augenheilkd. 2019 Apr;236(4):425-428. [PubMed: 30999347]
9.
Schmierer K, Campion T, Sinclair A, van Hecke W, Matthews PM, Wattjes MP. Towards a standard MRI protocol for multiple sclerosis across the UK. Br J Radiol. 2019 May 14;:20180926. [PMC free article: PMC6732926] [PubMed: 30994035]
10.
Hartung HP, Graf J, Aktas O, Mares J, Barnett MH. Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change. Curr. Opin. Neurol. 2019 Jun;32(3):327-337. [PubMed: 30985371]
11.
Van Der Walt A, Nguyen AL, Jokubaitis V. Family planning, antenatal and post partum care in multiple sclerosis: a review and update. Med. J. Aust. 2019 Mar 27; [PubMed: 30919466]
12.
Hočevar K, Ristić S, Peterlin B. Pharmacogenomics of Multiple Sclerosis: A Systematic Review. Front Neurol. 2019;10:134. [PMC free article: PMC6399303] [PubMed: 30863357]
13.
Kim Y, Lai B, Mehta T, Thirumalai M, Padalabalanarayanan S, Rimmer JH, Motl RW. Exercise Training Guidelines for Multiple Sclerosis, Stroke, and Parkinson Disease: Rapid Review and Synthesis. Am J Phys Med Rehabil. 2019 Jul;98(7):613-621. [PMC free article: PMC6586489] [PubMed: 30844920]
14.
Ömerhoca S, Akkaş SY, İçen NK. Multiple Sclerosis: Diagnosis and Differential Diagnosis. Noro Psikiyatr Ars. 2018;55(Suppl 1):S1-S9. [PMC free article: PMC6278620] [PubMed: 30692847]
15.
Krasniuk S, Classen S, Morrow SA, Tippett M, Knott M, Akinwuntan A. Clinical Determinants of Fitness to Drive in Persons With Multiple Sclerosis: Systematic Review. Arch Phys Med Rehabil. 2019 Jan 26; [PubMed: 30690007]
16.
Gullo HL, Fleming J, Bennett S, Shum DHK. Cognitive and physical fatigue are associated with distinct problems in daily functioning, role fulfilment, and quality of life in multiple sclerosis. Mult Scler Relat Disord. 2019 Jun;31:118-123. [PubMed: 30981190]
Copyright © 2019, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license, and any changes made are indicated.

Bookshelf ID: NBK499849PMID: 29763024

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