Multiple Sclerosis Overview

Living with Multiple Sclerosis

Multiple sclerosis is a disease that affects your nervous system.
It can radically alter your life and indirectly affect those who care for you.

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MS affects approximately 2.8 million people worldwide.[1]

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MS is a disease of the central nervous system (CNS), including your brain, spinal cord and optic nerves, that disturbs the normal flow of information and can result in severe impairments in body functioning.[2][3]
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The progress, the severity and the specific symptoms that a person living with MS experiences cannot be predicted because MS affects each person differently.[3][4]
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Currently, there is no known cure for MS but over the last decades treatment options have expanded and ongoing research continues to address MS, its symptoms and its causes.[5][6]

What is MS?

MS is an autoimmune, neurological disease in which your own immune cells attack your CNS, resulting in lesions.[7][5]
• Normally, the cells of the immune system patrol for signs of infectious agents (such as viruses and bacteria). When they find one, they attack it.
• In MS, for exact reasons that remain unknown, our immune cells attack the outer covering of nerve cells, called myelin, and cause inflammation in the CNS.[7]

When you talk to your healthcare team about your MS, they may refer to two types of blood cells (lymphocytes) that play an important role in this process. These cells are known as B-cells and T-cells and they belong to our body’s immune system.

You might hear certain words during your appointments - click here to learn more

Inflammation: Inflammation is a protective response of your body to a harmful stimuli, such as pathogens, damaged cells or irritants. The function of inflammation is usually to eliminate the initial cause of cell injury, clear out damaged tissues and initiate tissue repair.[8] In MS, there is abnormal inflammation which causes damage to the central nervous system.[9]

B-cells and T-cells: Many different cells are involved in the normal immune response. Generally, B-cells make antibodies that help the immune system recognise the foreign infectious substance, and T-cells attack the foreign infectious substance and help control the immune response. In MS, these cells move into the CNS causing lesions.[5]


Myelin: Myelin is a substance that forms a protective layer over neurons in the CNS. This helps neurons send signals rapidly.[10] When myelin is damaged or destroyed, in demyelinating diseases such as MS, it becomes harder for the neurons to communicate with each other quickly and effectively. The neurons themselves can also be damaged in MS.[9][10]


MS lesions: Areas where inflammation has damaged or destroyed myelin are called lesions. These lesions can occur in the brain, optic nerve and spinal cord. Your doctor can often see these lesions by using magnetic resonance imaging (MRI).[11]

How does MS impact communication in the CNS?

The CNS communicates by sending signals through the nerve cells, also called neurons. These neurons help you process and respond to the world around you.[12]

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Groups of neurons interconnect to form neuronal networks that are like well-maintained highways throughout the CNS.[13] This allows your brain to receive and process information that you receive from the world around you.

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With MS, these highways become ‘damaged’ and over time may become disconnected.[14][12] This can cause signals to move more slowly and less efficiently within neural networks.[14]

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The CNS can build new connections to try and repair damage. However, its ability to build these new connections decreases over time.[15][16]

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As the brain tries to build new connections, it can become less efficient. Think of it like taking a detour—you may still get to your destination, but it usually takes longer.[15][17]

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There is no single symptom, physical finding or laboratory test that can definitively diagnose MS, so healthcare professionals must use a variety of methods to evaluate patients before a diagnosis is made. They will take a detailed medical history, perform a neurological examination, and request additional investigations including blood tests, spinal fluid tests (sometimes called spinal tap or lumbar puncture), and imaging procedures including Magnetic Resonance Imaging (MRI).[18]

An MS diagnosis will only be given if the results of these tests and examinations meet certain criteria (known as McDonald Criteria).[19]

A person may be given a diagnosis of radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS).

Radiologically isolated syndrome (RIS)
People with RIS had an MRI that showed an abnormality in their brain or spinal cord that looked similar to an MS lesion. These individuals have no past or current neurologic symptoms at the time the abnormality is found.[20]
People with CIS have a first episode of neurologic symptoms caused by inflammation in the CNS and damage to myelin. The signs and symptoms of CIS are similar to those of MS but don’t yet meet the full criteria for an MS diagnosis.[20]

A diagnosis of MS can include the identification of its subtypes. Main subtypes are relapsing-remitting MS, secondary progressive MS with or without relapses, and primary progressive MS.[21][22]

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Primary progressive MS (PPMS)
Example of disease activity in a person with PPMS[20]
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PPMS is a type of MS in which symptoms and the neurological function gradually and progressively get worse over time without periods of relapse and remission in between. PPMS can also be characterised as active (with some relapses and/or evidence of new MRI activity in a specified period of time) or not active, as well as with progression (evidence of disability accumulation over time, with or without relapse or new MRI activity) or without progression.This type of MS affects approximately 10-15% of newly diagnosed individuals.

Graphic gives an example of the types of activity that can occur in PPMS over time however each person’s experience with PPMS will be unique.

Adapted from the National MS Society, 'Types of MS'.

Example of disease activity in a person with RRMS[23]
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RRMS affects most people with MS (85%) and is characterised by recurring “relapses” followed by a period of recovery or remission. Relapses are episodes of new symptoms or worsening of old symptoms that may occur at the same time as MS lesions in the CNS.2,5,17,18

  • Relapses can vary in intensity from mild to severe, and the symptoms they cause can vary from person to person. After a relapse, the symptoms can disappear completely, but sometimes they don’t. If symptoms continue after a relapse, it can lead to further disability.17,18
  • RRMS can also be characterised as active (with some relapses and/or evidence of new MRI activity in specified period of time) or not active, as well as with worsening (a confirmed increase in disability following relapse) or not worsening.17

Graphic gives an example of the type of disease activity that can occur in RRMS over time, but every person’s experience with RRMS will be unique.

Adapted from the National MS Society, 'Types of MS'.

Example of disease activity in a person with SPMS[23]
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80% of patients with RRMS will eventually progress to SPMS. In this form of MS, the functioning of your CNS and level of disability steadily worsens over time, with or without relapses. SPMS can also be characterised as active (with some relapses and/or evidence of new MRI activity in a specified period of time) or not active, as well as with progression (evidence of disability accumulation over time, with or without relapse or new MRI activity) or without progression.2,5,17

Graphic gives an example of the types of activity that can occur in SPMS over time however each person’s experience with SPMS will be unique.

Adapted from the National MS Society, 'Types of MS'.

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References

The Multiple Sclerosis International Federation, Atlas of MS, 3rd Edition (September 2020).
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15(9): 545-558. doi:10.1038/nri3871.
National MS Society/What is MS. Accessed September 25, 2020. https://www.nationalmssociety.org/What-is-MS.
National MS Society/ Symptoms and Diagnosis/MS Symptoms. Accessed June 29, 2020. https://www.nationalmssociety.org/ Symptoms and Diagnosis/MS Symptoms.
Filippi M, Bar-Or A, Piehl F, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1): 43. doi:10.1038/s41572-018-0041-4.
National MS Society/ Symptoms and Diagnosis/MS Symptoms. Accessed June 29, 2020. https://www.nationalmssociety.org/ Symptoms and Diagnosis/MS Symptoms.
Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol. 2007; 147(2): 227-235. doi:10.1111/j.1365-2249.2006.03261.x
National MS Society/What is MS. Accessed September 25, 2020.https://www.nationalmssociety.org/What-is-MS.
National MS Society/What is MS/Definition of MS/Myelin. Accessed August 24, 2020.https://www.nationalmssociety.org/What-is-MS/Definition-of-MS/Myelin
Dendrou CA, Fugger L, Friese MA.
Di Filippo M, Portaccio E, Mancini A, Calabresi P. Multiple sclerosis and cognition: synaptic failure and network dysfunction. Nat Rev Neurosci. 2018; 19(10): 599-609. doi:10.1038/s41583-018-0053-9.
Li Y, Jewells V, Kim M, et al. Diffusion tensor imaging based network analysis detects alterations of neuroconnectivity in patients with clinically early relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2013; 34(12): 3376-3391. doi:10.1002/hbm.22158.
Bassi M, Iezzi E, Pavone L, et al. Modeling Resilience to Damage in Multiple Sclerosis: Plasticity Meets Connectivity. Int J Mol Sci. 2019; 21(1): 143. doi:10.3390/ijms21010143.
Cerqueira JJ, Compston DAS, Geraldes R, et al. Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J Neurol NeurosurgPsychiatry. 2018; 89(8): 844-850. doi:10.1136/jnnp-2017-317509.
Li Y, Jewells V, Kim M, et al. Diffusion tensor imaging based network analysis detects alterations of neuroconnectivity in patients with clinically early relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2013; 34(12): 3376-3391. doi:10.1002/hbm.22158.
Kerschensteiner M, Bareyre FM, Buddeberg BS, et al. Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J Exp Med. 2004; 200(8): 1027-1038. doi: 10.1084/jem.20040452.
National MS Society/Symptoms-Diagnosis/Diagnosis MS. Accessed August 26, 2020. https://www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-MS.
Cerqueira JJ, Compston DAS,
National MS Society/What is
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15(9): 545-558. doi:10.1038/nri3871.
Filippi M, Bar-Or A, Piehl F, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1): 43. doi:10.1038/s41572-018-0041-4.
National MS Society/What is MS/Types of MS. Accessed August 26, 2020. https://www.nationalmssociety.org/What-is-MS/Types-of-MS.
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