Multiple Sclerosis

Woojun Kim; Ho Jin Kim

doi:10.5124/jkma.2009.52.7.665

J Korean Med Assoc > Volume 52(7); 2009 > Article

Kim and Kim: Multiple Sclerosis

Focused Issue of This Month

Autoimmune Disease

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2009; 52(7): 665-676.

Published online: July 31, 2009

DOI: http://dx.doi.org/10.5124/jkma.2009.52.7.665

Multiple Sclerosis

Woojun Kim, MD, Ho Jin Kim, MD

Department of Neurology, National Cancer Center, Korea. hojinkim@ncc.re.kr

Abstract

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.

Multiple sclerosis; Epidemiology; Immunopathology; Diagnosis; Treatment

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Figure 1

APC = antigen presenting cell, IFN = interferon, MBP = myelin basic protein, MHC = major histocompatibility complex, MMP = matrix metalloproteinase, NOI = nitric oxide intermediates, ROI = reactive oxygen intermediates, TCR = T cell receptor, TNF = tumor necrosis factor, VCAM = vascular cell adhesion molecule, VLA = very late antigen.

The five key immunopathogenic processes in multiple sclerosis (MS) targeted by MS therapies (10). (A) T cell activation and differentiation into T-helper (Th) -1 cells, (B) interleukin (IL)-2-induced proliferation of activated Th1 cells, (C) recruitment of B cells and monocytes by activated Th1 cells, (D) activated Th1 cell trafficking across the blood- brain barrier (BBB), (E) T cell reactivation and induction of immune cell-mediated demyelination.

Figure 2

Diagram representing the different types of multiple sclerosis.

Figure 3

Representing MRI of multiple sclerosis.

(A) Fluid-attenuated inversion recovery (FLAIR) MRI demonstrates typical multiple perpendicular-axis periventricular white matter lesions called "Dawson's fingers".

(B) Gadolinium enhanced T1-weighted MRI shows well-enhancing MS plaque.

Table 1

2005 Revisions to the McDonald Diagnostic Criteria for Multiple Sclerosis (25)

If criteria indicated are fulfilled and there is no better explanation for the clinical presentation, the diagnosis is MS; if suspicious, but the criteria are not completely met, the diagnosis is "possible MS" ; if another diagnosis arises during the evaluation that better explains the entire clinical presentation, then the diagnosis is "not MS".

^a An attack is defined as an episode of neurological disturbance for which causative lesions are likely to be inflammatory and demyelinating in nature. There should be subjective report (backed up by objective findings) or objective observation that the event lasts for at least 24 hours.

^b No additional tests are required; however, if tests (MRI, CSF) are undertaken and are negative, extreme caution needs to be taken before making a diagnosis of MS. Alternative diagnoses must be considered. There must be no better explanation for the clinical picture and some objective evidence to support a diagnosis of MS.

^c MRI demonstration of space dissemination must fulfill the criteria derived from Barkhof and colleagues and Tintoré and coworkers.

^d Positive CSF determined by oligoclonal bands detected by established methods (isoelectric focusing) different from any such bands in serum, or by an increased IgG index.

^e MRI demonstration of time dissemination must fulfill the criteria in Table 3.

^f Abnormal VEP of the type seen in MS.

MS = multiple sclerosis, MRI = magnetic resonance imaging, CSF = cerebrospinal fluid, VEP = visual- evoked potential

Table 2

MRI criteria to demonstrate brain abnormality and demonstration of dissemination in space

NOTE: A spinal cord lesion can be considered equivalent to a brain infratentorial lesion: an enhancing spinal cord lesion is considered to be equivalent to an enhancing brain lesion, and individual spinal cord lesions can contribute together with individual brain lesions to reach the required number of T2 lesions.

Table 3

MRI criteria to demonstrate dissemination of lesions in time

Table 4

List of US food and drug administration-approved disease-modifying therapies

CBC = complete blood count with platelets, CIS = clinically isolated syndrome, DMT = disease-modifying therapy, LFT = liver function tests, LVEF = left ventricular ejection fraction, MS = multiple sclerosis, PML = progressive multifocal leukoencephalopathy, PR = progressive-relapsing, q = every, qOD = every other day, RR = relapsing-remitting, SC = subcutaneous, SP = secondary progressive, TFT = thyroid function tests, TIW = 3 times a week