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Understanding Multiple Sclerosis Pathophysiology

Posted on June 01, 2021
Medically reviewed by
Joseph V. Campellone, M.D.
Article written by
Amanda Agazio, Ph.D.

The word “pathophysiology” refers to the changes a person’s tissues and bodily functions undergo due to a disease or an injury. Pathophysiology can also refer to the hallmarks of a disease that lead to these functional changes. For example, one pathophysiological hallmark of multiple sclerosis (MS) includes demyelination — damage to the protective covering of nerve cells. Another is the formation of lesions — damage or scarring — in the central nervous system (CNS). The pathophysiology also includes the MS symptoms related to dysfunction of motor, sensory, and cognitive abilities.

Learning more about the pathophysiology of MS can improve the way you manage your symptoms. It may also open the door to useful conversations with doctors and other people living with the disease. This article will review the basics of the central nervous system and the pathophysiology of MS.

Understanding the Central Nervous System

MS is an autoimmune disorder that affects different parts of the central nervous system. Understanding the basics of the CNS can better help you understand the pathophysiology of MS.

The CNS is made up of the brain and spinal cord. This also includes the cranial nerves and associated optic nerves. Neurons are the basic units of the nervous system. They’re responsible for transmitting motor, sensory, and cognitive information in the body. There are approximately 86 billion neurons in the brain.

Each neuron is made up of:

  • A cell body — The core part of the neuron
  • Dendrites — Extensions of the cell body that receive electrical impulses
  • Axons — The parts of the nerve cell that send electrical impulses

Neurons transmit information through their axons to other neurons. Each axon is covered with a myelin sheath. The myelin sheath allows electrical impulses to move quickly through the axon. In the CNS, myelin is produced by specialized cells called oligodendrocytes.

The brain is composed of two different types of substances, commonly called “white matter” and “gray matter.” White matter and gray matter are related to the different parts of the neuron. Gray matter is composed of the neuron cell bodies, whereas white matter is composed of the axons with their myelin sheaths. The term “white matter” was derived from the brain tissue’s white color. That color comes from the myelin in those areas.

The Pathophysiology of MS

MS is a neurodegenerative disease caused by the autoimmune destruction of the protective myelin sheath covering axons. An autoimmune disease refers to a condition where a person’s immune system reacts to and attacks its own tissues and cells. The exact cause of MS is still unknown, and researchers do not completely understand what causes the autoimmune response against the CNS. However, it is thought that several steps occur during the course of MS to lead to this autoimmune destruction.

Immune Cells Cross the Blood-Brain Barrier

The blood-brain barrier (BBB) is in place to prevent certain cells, substances, and disease-causing agents — such as viruses and bacteria — from entering the brain through the blood. It is made up of a tightly packed layer of cells that act as a barrier, crossing over from the blood vessels and into the brain. Some researchers believe MS may start when immune cells, such as lymphocytes (a type of white blood cell), cross into the BBB. This puts immune cells in a place that they should not be, thus creating the risk for an autoimmune reaction.

Immune Cells Respond to Self-Antigens

Antigens are molecules or substances that can trigger an immune response when an immune cell recognizes them. Your immune system is programmed to know the difference between self-antigens and foreign antigens, in order to prevent autoimmune reactions against the body’s tissues. However, in MS, the immune system recognizes (detects and reacts to) self-antigens located within the myelin sheath covering axons. Once an autoreactive lymphocyte is in the brain, it can recognize the self-antigen on myelin. When this happens, it will initiate an immune response against the tissues.

There are two types of lymphocytes, B cells and T cells. T cells can produce inflammatory proteins, known as cytokines, in response to recognizing a self-antigen. These cytokines lead to inflammatory damage to neurons. Cytokines can also recruit more immune cells to the area.

B cells produce proteins known as antibodies that can bind to antigens. These antibodies oversee the destruction of the antigens. In MS, B cells produce autoantibodies that bind to self-antigens, thereby causing autoimmune damage to the CNS. B cells can also act as antigen-presenting cells, which are cells that display an antigen for recognition by the immune system. From there, antigen-presenting cells can activate T cells against self-antigens. This is another way in which B cells can lead to an autoimmune reaction.

Lesions Form in the CNS

The pathological hallmark of MS is the formation of lesions within the CNS. These lesions are often located in the brain, spinal cord, and optic nerves.

But what actually defines a lesion? Lesions are simply areas of damage caused by the destruction of the myelin in your CNS. Often, these lesions will show signs of inflammation and neurodegeneration. A doctor can detect MS lesions using an MRI scan of your brain and spinal cord. Depending on the size of the lesions and whether any new lesions have appeared, your doctor can determine if your disease is active or not.

Most of the damage caused during MS attacks occurs in the white matter, as it’s made up of axons coated in myelin. However, there is also some evidence that damage occurs in the gray matter too.

Types of MS and Pathophysiology

According to the National Multiple Sclerosis Society, one commonality among all forms of MS is the autoimmune destruction of the myelin sheath that protects nerve fibers. However, there are some slight differences in pathophysiology depending on the type of MS a person has been diagnosed with.

Relapsing-Remitting MS

People living with relapsing-remitting MS (RRMS) will experience periods of disease activity, known as a relapse. This is then followed by periods of remission. During remission, some remyelination by oligodendrocytes may occur. People with RRMS tend to have more brain lesions than spinal cord lesions.

Primary Progressive MS

Individuals living with primary progressive MS (PPMS) do not experience clear periods of relapse and remission. Rather, their symptoms gradually accumulate over the course of the disease. People with PPMS generally have more lesions located in their spinal cord compared to their brain.

Secondary Progressive MS

Individuals with relapsing-remitting MS often have disease progression to secondary progressive MS (SPMS). SPMS is characterized by no clear period of remission and relapse. There is sometimes a gradual worsening of disease, but in some people, the disease can remain inactive.

Information is Power

Knowing more about your diagnosis and understanding the pathophysiology of MS can be empowering. It can also help you to improve your overall well-being. As we learn more about the pathophysiology of MS and gain a better understanding of the disease and neurology, doctors may develop better treatment options for MS. Information is a powerful tool and is one of the pieces to the puzzle to living your best life with a chronic illness.

Talk With Others Who Understand

MyMSTeam is the social network for people with MS and their loved ones. On MyMSTeam, more than 168,000 members come together to ask questions, give advice, and share their stories with others who understand life with MS.

Are you living with MS? Share your experience in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Joseph V. Campellone, M.D. is board-certified in neurology, neuromuscular disease, and electrodiagnostic medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Amanda Agazio, Ph.D. completed her doctorate in immunology at the University of Colorado Anschutz Medical Campus. Her studies focused on the antibody response and autoimmunity. Learn more about her here.

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