Multiple sclerosis

Multiple sclerosis (MS) is a condition that is characterized by areas of injury (lesions) in the brain and spinal cord (central nervous system). These lesions are associated with damage to the myelin sheath, which is the covering that protects nerves and allows them to transmit impulses efficiently. “Sclerosis” is the medical term for the scar tissue that forms when the myelin sheath is damaged. These damaged areas can be seen on a magnetic resonance imaging (MRI) scan.

The specific features seen in people with MS and the course of the disease vary widely. The signs and symptoms of MS usually begin between the ages of 20 and 40. Affected individuals often have sensory disturbances in the arms, legs, or face, including a prickling or tingling sensation (paresthesia), numbness, or pain. Some people with this condition experience an electrical shock-like sensation that runs down the back and into the arms or legs (Lhermitte’s sign). This sensation usually occurs when the head is bent forward.

Problems with muscle control are common in people with MS. Affected individuals may experience muscle stiffness (spasticity), muscle weakness, or balance and coordination problems (ataxia). This can make standing and walking difficult. Some people with MS develop partial or complete paralysis.

Additional signs and symptoms of MS can include dizziness; poor bladder or bowel control; and difficulties with speech, concentration, memory, or judgement. MS is also associated with vision problems, such as blurred vision or double vision. Affected individuals may have optic neuritis, which is an inflammation of the nerve that carries signals from the eye to the brain (the optic nerve). Optic neuritis can cause eye pain and vision loss. Infections or fever can make the signs and symptoms of MS worse.

MS can be broadly classified into relapsing-remitting MS (RRMS) and progressive MS. Most people with MS receive a diagnosis of RRMS. These individuals typically have periods during which they experience symptoms (relapses) followed by periods of partial or complete recovery (remission). Up to 15 percent of people receive a diagnosis of progressive MS, which is characterized by symptoms that gradually worsen over time, without the typical periods of relapses and remissions.

An estimated 2.8 million people worldwide have MS. Approximately 2.1 in 100,000 people receive a diagnosis of MS each year. This condition is more common in women and in white people of northern European descent.

MS is likely caused by a combination of genetic, environmental, and lifestyle factors.

In people with MS, the immune system attacks the body's own tissues and organs. This abnormal immune response triggers inflammation, damaging the myelin sheath that protects the nerves in the brain and spinal cord. The damage impairs the communication between these nerve cells and the rest of the body. Over time, nerve cells that lack myelin are more prone to damage and may begin to die off, creating larger areas of injury in the nervous system.

Common genetic changes in or near hundreds of genes likely contribute to a person's risk of developing MS. Many of these genes provide instructions for making proteins that play a role in the immune system.

Changes in several genes within the human leukocyte antigen (HLA) complex have been associated with MS. These changes produce different versions of many HLA genes. Different versions of a gene are called alleles. Alleles of some HLA genes have been associated with an increased risk of developing MS, while others seem to protect against it.

HLA complex genes help the immune system distinguish between the body's own proteins and proteins made by foreign invaders, such as viruses and bacteria. Each HLA gene has many possible alleles, allowing each person's immune system to respond to a wide range of foreign proteins. The most well-established genetic risk factor for developing MS is an allele of the HLA-DRB1 gene called HLA-DRB1*15:01. The HLA-DRB1 gene provides instructions for making a protein that initiates an immune response. Researchers are working to learn exactly how the HLA-DRB1*15:01 allele interacts with other alleles to influence the risk of developing MS.

Certain environmental and lifestyle factors, such as Epstein-Barr virus infections, a lack of exposure to sunlight, vitamin D deficiency, obesity, smoking, and exposure to secondhand smoke, are believed to increase the risk of developing MS. These factors have an especially strong influence on the risk of developing MS when they are present during childhood or adolescence.

Genetic Testing Information

• Genetic Testing Registry: Multiple sclerosis, susceptibility to

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• MULTIPLE SCLEROSIS, SUSCEPTIBILITY TO; MS

Scientific Articles on PubMed

• PubMed

• Albelo-Martinez M, Rizvi S. Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies. Neurotherapeutics. 2025 Jul;22(4):e00601. doi: 10.1016/j.neurot.2025.e00601. Epub 2025 May 9. Citation on PubMed
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• Balcerac A, Louapre C. Genetics and familial distribution of multiple sclerosis: A review. Rev Neurol (Paris). 2022 Jun;178(6):512-520. doi: 10.1016/j.neurol.2021.11.009. Epub 2022 Feb 9. Citation on PubMed
• Barkhof F, Reich DS, Oh J, Rocca MA, Li DKB, Sati P, Azevedo CJ, Bagnato F, Calabresi PA, Ciccarelli O, Dwyer MG, DeLuca GC, De Stefano N, Enzinger C, Filippi M, Granziera C, Halper J, Henry RG, Gasperini C, Gauthier S, Kappos L, Laule C, Newsome SD, Montalban X, Morrow SA, Schoonheim MM, Sicotte N, Toosy A, Wilken J, Yousry T, Sastre-Garriga J, Traboulsee A, Ontaneda D, Rovira A; Magnetic Resonance Imaging Network in Multiple Sclerosis; Consortium of Multiple Sclerosis Centers; North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group. 2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis. Lancet Neurol. 2025 Oct;24(10):866-879. doi: 10.1016/S1474-4422(25)00304-7. Citation on PubMed
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• International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460):eaav7188. doi: 10.1126/science.aav7188. Citation on PubMed
• International Multiple Sclerosis Genetics Consortium; MultipleMS Consortium. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature. 2023 Jul;619(7969):323-331. doi: 10.1038/s41586-023-06250-x. Epub 2023 Jun 28. Citation on PubMed
• Kiani RA, Wattoo FH, Khan MU, Munir M, Sattar S, Kazmi M, Jamila, Rehman R, Shan MA, Ali Q, Iqbal A, Ali D. Impact of the CYP27B1 p.R389H mutation on protein stability and function: implications for multiple sclerosis pathogenesis. Sci Rep. 2025 Sep 26;15(1):33047. doi: 10.1038/s41598-025-07199-9. Citation on PubMed
• Kuhlmann T, Moccia M, Coetzee T, Cohen JA, Correale J, Graves J, Marrie RA, Montalban X, Yong VW, Thompson AJ, Reich DS; International Advisory Committee on Clinical Trials in Multiple Sclerosis. Multiple sclerosis progression: time for a new mechanism-driven framework. Lancet Neurol. 2023 Jan;22(1):78-88. doi: 10.1016/S1474-4422(22)00289-7. Epub 2022 Nov 18. Citation on PubMed
• Patsopoulos NA. Genetics of Multiple Sclerosis: An Overview and New Directions. Cold Spring Harb Perspect Med. 2018 Jul 2;8(7):a028951. doi: 10.1101/cshperspect.a028951. Citation on PubMed
• Sahi N, Ciccarelli O, Houlden H, Chard DT. Unlocking Multiple Sclerosis Genetics: From Susceptibility to Severity. Neurology. 2025 Oct 21;105(8):e214141. doi: 10.1212/WNL.0000000000214141. Epub 2025 Sep 26. Citation on PubMed
• Sorosina M, Santoro S, Ferre L, Mascia E, Clarelli F, Giordano A, Cannizzaro M, Lucia M, Martinelli V, Filippi M, Esposito F. Risk HLA Variants Affect the T-Cell Repertoire in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 15;10(3):e200093. doi: 10.1212/NXI.0000000000200093. Print 2023 May. Citation on PubMed
• Vitturi BK, Cellerino M, Boccia D, Leray E, Correale J, Dobson R, van der Mei I, Fujihara K, Inglese M. Childhood and Adolescent Environmental Risk Factors for Multiple Sclerosis: A Systematic Review With Meta-Analysis. Eur J Neurol. 2025 Nov;32(11):e70398. doi: 10.1111/ene.70398. Citation on PubMed
• Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Angood Napier C, Rijke N, Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020 Dec;26(14):1816-1821. doi: 10.1177/1352458520970841. Epub 2020 Nov 11. Citation on PubMed
• Ward M, Goldman MD. Epidemiology and Pathophysiology of Multiple Sclerosis. Continuum (Minneap Minn). 2022 Aug 1;28(4):988-1005. doi: 10.1212/CON.0000000000001136. Citation on PubMed