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Multiple sclerosis (MS) is a complex and highly unpredictable disease that affects people differently. In MS, the immune system specifically attacks the central nervous system (CNS) and, over time, wears down the protective cover on the nerves. This permanent damage is called sclerosis. In fact, the term multiple sclerosis means “many scars.” 


This section provides some history and basic explanations, and explores how MS affects the body's nervous system.


Click on these headings to be taken directly to the associated content :

Age, gender and nationality

Although MS can occur at any age, it is commonly diagnosed between the ages of 20 and 40, although onset may be earlier or later.

References: O’Connor, Paul. Multiple Sclerosis: The Facts You Need. 5th ed. Library and Archives Canada Cataloguing in Publication; 2014.

Multiple Sclerosis Society of Canada (MSSC). What is MS? https://beta.mssociety.ca/about-ms/what-is-ms. Accessed October 26, 2107.


MS is three times as likely to occur in women than in men.


Reference: Multiple Sclerosis Society of Canada (MSSC). What is MS? https://beta.mssociety.ca/about-ms/what-is-ms. Accessed October 26, 2107.


It is estimated that MS affects more than two million people worldwide, most commonly people of northern European background. Canada has the highest rate of MS in the world, currently affecting approximately 100,000 Canadians.


References: Multiple Sclerosis Society of Canada (MSSC). What is MS? https://beta.mssociety.ca/about-ms/what-is-ms. Accessed October 26, 2107.

Multiple Sclerosis International Federation. Atlas of MS. http://www.msif.org/about-us/advocacy/atlas/. Accessed October 26, 2107.

MS and the body

MS is an autoimmune disease of the central nervous system (CNS), made up of the brain and spinal cord, and its course and symptoms vary considerably from person to person.

MS causes inflammation, or swelling, around blood vessels in the brain and spinal cord, and leads to the formation of small damaged areas in the brain and spinal cord called “lesions.” This inflammation appears to be caused by the immune system, which normally protects the body against viruses, bacteria and other biological invaders. Although MS can occur at any age, it is commonly diagnosed between the ages of 20 and 40, although onset may be earlier or later.

WHITE BLOOD CELLS

In individuals with MS, white blood cells are able to leave the circulatory system and enter the nervous system, where they are not supposed to be.

DEMYELINATION

When white blood cells encounter the nerve cells in the brain or spinal cord, they may attack the protective covering of nerve fibres outside of the nerve, an area called the myelin sheath.

 

INFLAMMATION AND DAMAGE

The inflammation and damage of myelin and nerve fibres that occur in MS weaken the transmission of nerve impulses sent between the brain, the spinal cord and the rest of the body.

When the brain cannot communicate with the nerves and muscles the way it is supposed to, various symptoms of MS (such as vision problems and difficulty with muscle movement, coordination, and balance) can occur. 

The complex nature of MS

Despite a great deal of research, scientists have not yet pinpointed the exact cause(s) of MS. However, the best current evidence suggests that a combination of lifestyle , environmental , genetic and biological factors may all be at play.

GENETICS

While it is not hereditary, MS does appear
to be genetic to some extent. 

  • The risk of developing MS is low for the general population.
  • Some researchers speculate that MS develops because a person is born with a genetic tendency to react to some environmental agent that, upon exposure, triggers an immune-mediated response. 
  • Studies have shown that certain genes appear more often in people with higher rates of MS. Common genetic factors have also been found in some families where there is more than one family member with MS.

VIRUS

A great deal of research has investigated the links between MS and many kinds of viruses.  

  • MS is not contagious, but the possibility of a virus triggering the disease cannot be ruled out. 
  • To date, researchers have not been able to pinpoint a single virus as the cause for MS. Several viruses have been studied, but many steps are needed in order to prove that a particular virus⁣⁣ triggers MS.
  • Researchers must show that the virus is in the body before MS develops, and that the virus actually causes the disease and is not just happening alongside the disease.
  • A likely possibility is that MS only develops in people with certain genetic codes that put them at risk, but the onset of the disease itself is a response to outside factors.

CLIMATE

Climate may play a role in the development of MS. 

  • MS most commonly affects Caucasians, particularly in North America, Europe and Australia. 
  • Mounting evidence suggests that vitamin D plays a key role. Vitamin D is believed to support immune function and may help protect against immune-mediated diseases like MS.
  • People living closer to the equator are exposed to greater amounts of sunlight year-round, and so they tend to have higher levels of naturally produced vitamin D.

The four types of MS and how they may affect the body

In MS, not only can the course of illness and range of symptoms vary from person to person, but there are very different types of the disease as well. Some are considered relapsing types of MS, while others are considered progressive.

With the relapsing types of MS, people will experience periods of visible disease activity (relapses) alternating with periods of remission or recovery. Others will experience only a gradual and steady progression of disability, called progressive MS.



There are four types of MS and a condition known as clinically isolated syndrome.

Clinically isolated syndrome (CIS)

When a person has experienced a single episode of MS-like symptoms, there may not be enough evidence for a complete diagnosis of MS.

  • This is called clinically isolated syndrome, and it is typically the first stage of MS.
  • Treatment can begin at this stage, before another event occurs, in order to delay the progression of MS.

Relapsing-remitting MS (RRMS)

 

RRMS is the most common type of MS and is most commonly seen when people are first diagnosed.

  • This type of MS shows clearly defined relapses with some amount of recovery. It affects around 85% of all people with MS.
  • There are periods of relapses or exacerbations (attacks of symptoms) followed by recovery (remission) between relapses. The amount of recovery varies – some people may have full recovery between relapses, while others have only partial recovery.
  • Relapses may last anywhere from one day to a few weeks.
  • About half of the people with RRMS will develop secondary-progressive MS within 10-20 years of being diagnosed with RRMS.

Secondary-progressive MS (SPMS)

The majority of people who get diagnosed with relapsing-remitting MS will eventually transition to SPMS in which there is a progressive worsening of symptoms and disability over time. SPMS is characterized as either active (evidence of relapse) or not active, as well as with progression (worsening of symptoms) or without progression.

  • While technically a type of progressive MS, SPMS acts more like a relapsing type of MS in its early-to-mid stage, with relapses and remissions being quite common.
  • Eventually a more continuous loss of physical and cognitive functions starts to take over, and relapses become less common.

Primary-progressive MS (PPMS)

This type of MS affects about 10% of all people with MS and is generally diagnosed after the age of 40.

  • This type of MS shows no defined relapses (attacks or flare-ups), but over a period of years, there is a steady, gradual loss of physical and cognitive functions.
  • There may be small improvements or plateaus (when the symptoms stay stable), but overall, symptoms tend to get gradually worse.

Progressive-relapsing MS (PRMS)

 

PRMS is the least common of the four MS disease stages.

  • Approximately 5% of people with MS have this type of the disease.
  • This type of MS has relapses (attacks or flare-ups) but also steadily gets worse between relapses.
  • People with this form of MS may or may not experience some recovery following these attacks – the disease continues to progress without remissions.

Progression of MS

The central nervous system (CNS) is made up of the brain and the spinal cord. From the CNS, nerves spread out throughout the body to make up the peripheral nervous system. It is important to note that MS affects only the CNS.

Here is a closer look at the complexity of the CNS and how it might be affected by MS:

ROLE OF THE CNS

Essentially, the CNS is a big processing centre that helps coordinate activity in all parts of the body:   

● Walking

● Speaking

● Balance

● Vision

● Memory

● Eye and muscle control

HOW THE CNS FUNCTIONS

  • Nerve cells and fibres are the building blocks of the CNS.
  • These cells communicate with other parts of the body via tiny electric signals.
  • These signals travel along the nerve fibres (also called axons) to other parts of the body.
  • Much in the way telephone signals travel along a phone wire, this messaging process is repeated in billions of locations in each person’s central nervous system, all day, every day.
  • The myelin sheath insulates and protects the axons and helps signals travel efficiently to and from the brain, telling the body what to do.


  • MS is called a demyelinating disease because in MS the myelin protein gets damaged and the damage is known as demyelination.

The immune system and MS

  • The immune system works on the assumption that there are “self” tissues – which are of the body – and “nonself” tissues – which are not of the body.
  • The immune system does not allow for “nonself” or foreign tissues to remain in the body and tries to destroy them relentlessly.
  • For no known reason, in MS, the immune system sporadically attacks the body’s own myelin (self tissue).
  • The location and intensity of the attacks are hard to predict and are very different, not only within a person but from one person to another.
  • Generally, a person’s symptoms reflect the extent of the myelin damage.

 

Understanding the impact of MS

THE SYMPTOMATIC PROCESS

In early MS, your nervous system will usually repair the myelin damage caused by a relapse (also referred to as an “attack” or “flare-up”). As MS progresses, the nervous system can repair most of the damage, but not all. Because of this incomplete recovery, leftover symptoms accumulate and disability progresses.

  • When someone experiences a relapse (attack or flare-up), it means the MS is active.
  • The symptoms experienced from relapse are due to the damage caused to the central nervous system (CNS); this damaged area is called a lesion.

  • Relapses are characterized by the development of new MS symptoms and/or the significant worsening of symptoms a person may already have.
  • The symptoms one may experience will depend on the part of the CNS that has been damaged and the severity of the damage.

Exploring how MS progresses over time

The symptoms of MS become worse over time as more nerves become damaged.

The progression of MS varies depending on how much nerve damage there is, how quickly it happens and where it occurs. Research shows that MS continues to progress, even when a person is not having relapses. This happens because MS has two components: the invisible disease and the visible results of it.


The invisible aspect of MS is the ongoing inflammation in the brain and spinal cord, causing scarring and loss of nerve tissue, which leads to the visible effects of MS:

●     Relapses: temporary episodes of problems with walking, speech or vision

●     Physical disability: sensory, motor or other neurological problems that persist or continue to progress

●     Cognitive dysfunction: problems with memory and other thinking skills



MS progresses and can become more disabling. It moves into another stage, called secondary-progressive MS.

When this happens, a person’s level of disability steadily increases, without periods of relapse and remission. The damage to the nervous system worsens and symptoms become more limiting when MS is untreated.

  • It is very important to treat MS as early as possible, even if the disease is in the invisible phase, to slow the progression of disability.
  • Treating early can help slow the progression of disability in MS, preventing damage from occurring as quickly.
  • Medicines using interferon have been used to slow the progression of disability in relapsing-remitting and secondary-progressive MS.

History of MS

Drawings from as early as 1838 clearly show what is now recognized as MS. In 1868, Jean- Martin Charcot, a professor at the University of Paris who has been dubbed “the father of neurology,” outlined a condition called “la sclérose en plaques” – in effect, multiple sclerosis. Charcot wrote a complete description of the disease and the changes in the brain and spinal cord that accompany it, having identified the condition’s gradual development in a maid employed in his house.



Charcot’s further scientific exploration of MS paralleled the creation of neurology, the specialty branch of medicine that deals with diseases of the nervous system. In those early days, the only way to determine what was going on in a person was through neurological examination – that is, by having the person demonstrate how well certain functions of the nervous system (vision, balance, reflexes and so on) were working.

In the time since Charcot's initial research, many new discoveries have helped medical professionals better understand and treat MS. New advancements continue to provide insight into better therapeutic treatments and help shape the medical community's awareness of MS.



SIGNIFICANT CHRONOLOGICAL MOMENTS IN THE HISTORY OF MS ARE LISTED BELOW 

1920-1930: Early discoveries

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Ten years after World War I, MS research became more advanced.

  • Abnormalities in spinal fluid were recognized for the first time in 1919.
  • Cells that make myelin (oligodendrocytes) were discovered in 1928.
  • Dr. Thomas Rivers proved that immune cells and not viruses produced the MS-like illness in 1935.

It would take many years before a connection between the immune system and MS was established.

1940-1950: Myelin composition

World War II directed the energies of scientists towards new technologies.

  • 1943: The physical composition of myelin was discovered.
  • 1946: The National Multiple Sclerosis Society was established. It was created to connect neurologists around the United States who treated MS and to raise money to fund MS research.

Research into every aspect of MS ranged from description and diagnosis to causes and cures

1950-1960: DNA structure

  • Strong geographical gradient discovered: the occurrence and frequency of MS increased consistently as one moved north, away from the equator.
  • Doctors who treated people with MS in the 1950s suspected the cause of MS was impaired blood flow and prescribed circulation stimulators as the main treatment.
  • In 1953, Nobel Prize-winning description of DNA structure by Francis Crick and James Watson allows for clearer understanding of the way in which genes control biologic functions – including how the immune system is regulated by sequences of genes.
  • Myelin was further broken down – scientists studied B-cells, T‑cells, genes and myelin but without discovering a clear unifying thread to guide MS treatment.

Treatments depended more on opinions than facts.

1960-1970: The immune system

  • By 1960, the National MS Society had created 114 chapters.
  • The National MS Society funds a panel of experts, led by Dr. George Schumacher, to create standard guidelines for MS diagnosis.
  • Rating scale is developed by Dr. John Kurtzke to figure out the level of disability and the parts of the nervous system afflicted by MS.

Thanks to the ability to make accurate diagnoses and measure how therapies affected disability, it became possible to begin scientifically testing MS treatments.


Scientific research points to two big ideas that:

  1. Led scientists to examine the possibility that MS entails a direct immune system attack on myelin.
  2. Reignited older ideas that MS could be caused by a virus, but not as a viral infection directly damaging the CNS, but more as affecting the immune system and trigger it to damage myelin.

Both ideas remain closely tied today: MS may be a combination of both an infectious and an autoimmune disease.

1970-1980: Laboratory advances

  • First CAT (computed axial tomography) scans, X-ray tests in which a computer generates cross-section views of a patient’s brain, performed on people with MS in 1978.
  • Diagnosis of MS also improved with the introduction of brain wave tests called “evoked potentials” (which measure nerve conduction throughout the optic nerves, brain and spinal cord, and often identify hidden areas of scarring and damage).
  • Steroids used to hold immune activity in check.
  • First small studies were conducted using interferons, and in the late 1970s, the first studies of beta interferon for MS began.

1980-1990: MRI diagnosis

Explosion of new drug trials

Under the guidance of the National MS Society, an organization based in the Unites States, scientists reached an agreement on how research for new treatments was to be designed and conducted, and dozens of different therapies were tested in an attempt to control or cure MS.

1981: First MRI (magnetic resonance imaging) scans of people with MS performed.

1982: First use of MRI to image MS lesions in living patients.

1984: MRI scans show MS attacks within the brain – including those which did not have any actual symptoms.

1988: Sequential MRI scans changed the entire way we look at MS by showing that it is a constant, ongoing disease, even though relapses with symptoms occur only sporadically.

  • Determination is made (by way of the first studies of identical and fraternal twins) that genes determine only part of the MS risk.
  • Psychosocial and mental-health issues, as well as cognitive changes due to MS, which had been previously neglected, finally begin receiving research attention.

1990-2000: Research breakthroughs and new treatments

Advances fuelled by the incredible power of new technology

  • Enhancements to MRI allowed it to detect MS plaques earlier and more accurately, leading to more rapid diagnosis of the disease.
  • Studies of a series of MRI scans taken over time showed how MS plaques actually develop and allowed researchers to track the “burden of the disease” (total plaque area) in individual patients.
  • MRI scanning offered researchers faster and more sophisticated ways of testing drugs to treat MS, allowing the benefits of a new drug to be seen on MRI scans before they could be seen in the patients themselves.
  • The Internet brings faster, better communications and data analysis to MS doctors and researchers from all over the world, leading to powerful coalitions.
  • Large databases to track and analyze thousands of patient histories are created and used to clarify their disease variations and responses to treatment.
  • Characteristic patterns of MS begin to emerge.
  • Advent of disease-modifying therapies (DMTs).
  • Research reveals the many ways in which MS can affect the mind, e.g., slowing down thinking and memory.
  • Refinements in rehabilitation, exercise and physical therapy benefit people with MS.
  • Years of research culminated in the creation of BETASERON® (beta interferon 1-b) in 1993 and AVONEX® (beta interferon 1-a) and COPAXONE® (glatiramer acetate) in 1996, later to be followed by REBIF® (variation of beta interferon 1-a) in 2002.

MS clinics and research laboratories are now linked, able to share and analyze new findings.

2000-present: More new treatments

  • By the mid 2000s, a new class of drugs called monoclonal antibodies was introduced.
  • 2006: TYSABRI® (natalizumab).

  • 2011: Oral treatment options – GILENYA® (fingolimod), TECFIDERA® (dimethyl fumarate) and AUBAGIO® (teriflunomide).
  • 2012: FAMPYRA® (fampridine).
  • 2014: LEMTRADA® (alemtuzumab), an infusion therapy.
  • 2015: PLEGRIDY® (peginterferon beta-1a), an injectable.
  • 2017: OCREVUS® (ocrelizumab), an infusion and MAVENCLAD® (cladribine), a tablet.
  • 2020: Mayzent™ (siponimod), an oral treatment for SPMS (Secondary Progressive Multiple Sclerosis) only.

Glossary

Much of the material on this website may be new for readers, and as such, an expansive glossary has been created to help define technical terms and concepts. The goal of this glossary is to enhance the understanding of MS and MS-related topics.

See the glossary located within the RESOURCES section