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Multiple Sclerosis: Clinical Features, Immunopathogenesis, and Treatment

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Inflammatory Disorders of the Nervous System

Part of the book series: Current Clinical Neurology ((CCNEU))

Abstract

Classically, multiple sclerosis (MS) is characterized by relapses of neurological deficits followed by remission. At present mechanisms of progressive aspects of the disease are currently undergoing increasing attention. Updated diagnostic criteria and improved diagnostic techniques, particularly in the field of magnetic resonance imaging (MRI), have facilitated diagnosis and monitoring of MS patients. Advances in immunology, particularly regarding the role of Th17 helper cells and B cells, together with increasing insight into genetics of MS, continue to improve our knowledge of the disease mechanisms underlying MS.

Symptomatic treatment of MS represents an important aspect of comprehensive care. These include a multitude of symptoms ranging from fatigue, cognitive, and mood disorders to disorders of gait, spasticity, pain, and bladder and bowel abnormalities, as well as less common paroxysmal manifestations. These symptoms necessitate a myriad of treatment approaches tailored to individual patient needs. A boom in the development of disease-modifying therapies for MS has resulted in 14 currently FDA-approved medications for relapsing-remitting MS in 2016 compared to just a handful in the early 2000s.

The pivotal clinical trials are reviewed in regard to safety and efficacy for each of these medications. Of particular concern is the risk of progressive multifocal leukoencephalopathy (PML) with increasingly effective therapies. Such cases have been most commonly been associated with natalizumab (Tysabri®), but a very low incidence of this disorder has been associated with two new drugs, dimethyl fumarate (Tecfidera®) and fingolimod (Gilenya®).

Available data for medications in development is also briefly discussed, with a focus on B-cell therapy disability measures, progressive disease, and repair including remyelination. Development of these new targeted therapies represents an exciting next frontier in MS treatment.

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Abbreviations

ACTH:

Corticotrophin

APC:

Antigen-presenting cell

CIS:

Clinically isolated syndrome

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CT:

Computerized tomography

DIR:

Double inversion recovery

DTI:

Diffusion tensor imaging

EAE:

Experimental allergic encephalomyelitis

EDSS:

Expanded disability status scale

GFAP:

Glial fibrillary acidic protein

HIV:

Human immunodeficiency virus

IL:

Interleukin

MBP:

Myelin basic protein

MHC:

Major histocompatibility class

MOG:

Myelin oligodendrocyte glycoprotein

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

NEDA:

No evidence of disease activity

PCR:

Polymerase chain reaction

PML:

Progressive multifocal leukoencephalopathy

PPMS:

Primary progressive multiple sclerosis

RRMS:

Relapsing-remitting multiple sclerosis

SLE:

Systemic lupus erythematosus

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Authors and Affiliations

  1. Miller School of Medicine University of Miami, Miami, FL, USA

    Alexis A. Lizarraga MD & William A. Sheremata MD, FRCPC, FACP, FAAN

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  2. William A. Sheremata MD, FRCPC, FACP, FAAN
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Correspondence to Alexis A. Lizarraga MD .

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  1. Department of Neurology, LSU Health Sciences Center, Shreveport, Louisiana, USA

    Alireza Minagar

  2. Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana, USA

    J. Steven Alexander

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Lizarraga, A.A., Sheremata, W.A. (2017). Multiple Sclerosis: Clinical Features, Immunopathogenesis, and Treatment. In: Minagar, A., Alexander, J. (eds) Inflammatory Disorders of the Nervous System. Current Clinical Neurology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-51220-4_2

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