Multiple sclerosis

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Multiple sclerosis (MS) is a chronic, irreversible, autoimmune and neurological disease that affects the central nervous system, including the brain and spinal cord.[1][2] In multiple sclerosis the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, trouble with sensation, or trouble with coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often remain, especially as the disease advances.[citation needed]

Epidemiology[edit | edit source]

MS prevalence.png

Prevalence[edit | edit source]

An estimated 2.3 million people worldwide have multiple sclerosis.

Risk factors[edit | edit source]

  • Latitude, which may be a main cause of vitamin D deficiency

Gender differences[edit | edit source]

Over the last decades, the ratio of women to men with MS has increased markedly, representing a true increase in MS among women but not men.[3]

Disease mechanisms[edit | edit source]

Demyelination of the myelin sheath[edit | edit source]

In multiple sclerosis, the myelin sheath, which is the layers of myelin surrounding the nerves of the brain and spinal cord, is destroyed, disrupting the transmission of signals in the nerves.[4]

Epstein-Barr virus[edit | edit source]

In 2022, clear evidence was found of the role of Epstein-Barr virus infection in triggering multiple sclerosis,[5] the strength of the link was higher than that between smoking and lung cancer.[6]

The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality...This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.[7] — Alberto Ascherio, Harvard Chan School

Genes[edit | edit source]

Genetic factors have been recognized as important in multiple sclerosis, and may combine with certain environmental factors, such as smoking and vitamin D deficiency, as well as Epstein-Barr virus infection.[7]

Immune system[edit | edit source]

In 1997, it was discovered that B cell therapy (eg Rituximab) which reduces the number of B cells, can bring immediate improvement in MS symptoms. This treatment is more effective for the relapsing-remitting variant of MS, and less effective for the primary progressive variant.[8]

Microbiome[edit | edit source]

Specific changes in the gut microbiome might increase the risk of MS[9], and the risk might be reduced using probiotics, antibiotics, a combination, or a change of diet. An International Multiple Sclerosis Microbiome Study commenced in 2015.[8]

Treatments[edit | edit source]

Standard of care[edit | edit source]

Experimental treatments[edit | edit source]

Another discovery was that a commonly available and inexpensive antihistamine, can be used to induce remyelination of the nerve cells.[8]

Dietary tryptophan can help reduce brain inflammation and 'cognitive fog'.[10]

Comparison of Multiple Sclerosis and ME/CFS[edit | edit source]

Multiple sclerosis patients or samples are sometimes used for comparison with in ME/CFS in research studies, for instance at the UK ME/CFS biobank, and both are female predominant diseases of the central nervous system.[11][12][13]

There are many similar features in multiple sclerosis and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including: severe disabling fatigue that worsens after exercise; debilitating autonomic symptoms, including orthostatic intolerance; illness course may be relapsing-remitting or progressive; infections and psychosocial stress causing exacerbation; autoimmunity and auto-inflammatory processes; mitochondria dysfunction; and decreased cerebral blood flow, atrophy of some brain structures.[12]

In the United States, the prevalence rate of chronic fatigue syndrome (CFS) is 0.42% of the population versus MS which has a rate of 0.09%.[14] Approximately 14% of MS patients meet the Fukuda criteria for CFS.[15]

In 2017, a study examined whether network analysis of cytokine production differed between patients with CFS, multiple sclerosis, and healthy controls. The study's model, using a select cytokine profile, showed that immunologic activation in CFS was significantly different from that found in the control and multiple sclerosis groups.[16]

A 2015 study found a markedly disturbed immune signature in the cerebrospinal fluid that is consistent with immune activation in the central nervous system (CNS), and autoimmunity. The MS and ME/CFS groups had markedly different immune signatures, and the ME/CFS group had a greater degree of CNS immune activation than the MS group.[17]

In December 2016, Ohanian, et al, published a study identifying two key immune symptoms that physicians could use to differentiate myalgic encephalomyelitis (ME) and CFS from MS: flu-like symptoms and tender lymph nodes. Subjects included 106 people with MS and 354 people with ME or CFS who completed the DePaul Symptom Questionnaire. The data was analyzed using data mining techniques and machine learning that resulted in correctly categorizing MS and ME or CFS 81.2% of the time. The authors conclude that "because ME or CFS and MS have similar presentations recognizing the importance of immune dysfunction for ME or CFS might be important for healthcare providers."[18]

Differences in symptoms between multiple sclerosis and ME/CFS[edit | edit source]

Ohanian et al. (2016) found that the following five symptoms were significantly more common in patients with ME/CFS compared to patients with multiple sclerosis, with mean scores reported as:

  1. Flu-like symptoms: reported in 51 in ME/CFS patients, and 17 inMS patients
  2. Tender lymph nodes: 37 in ME/CFS patients, 8% in MS patients
  3. Alcohol intolerance: 38 in ME/CFS patients, 9 in MS patients
  4. Inability to tolerate upright position (orthostatic intolerance): 51 in ME/CFS patients, 16 in MS patients
  5. post-exertional symptom exacerbation e.g., next-day soreness after non-strenuous activities: 75 in ME/CFS patients, 46 in MS patients

The presence of just two immune-related symptoms (tender lymph nodes and flu-like symptoms), which are optional symptoms in ME/CFS, was found to correctly classify around 80% of patients with ME/CFS, who did not have MS.[18]

Notable studies comparing ME/CFS and multiple sclerosis[edit | edit source]

  • 2012, Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.[13] - (Full Text)
  • 2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics[12] - (Full Text)
  • 2015, A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[19] - (Full Text)
  • 2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients[20] - (Full Text)
  • 2016, Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis[18] - (Full Text)
  • 2016, Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[21] - (Abstract)
  • 2016, Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison[22] - (Full Text)
  • 2016, Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome[17] - (Abstract)
  • 2017, Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome[23] - (Full Text)
  • 2017, Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis[16] - (Abstract)
  • 2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study[24] - (Full Text)
  • 2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls[25] - (Full Text)

Other studies[edit | edit source]

  • 2015, HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study - (Abstract)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. ↑ Javalkar, Vijaykumar; McGee, Jeanie; Minagar, Alireza (2016). "Clinical Manifestations of Multiple Sclerosis: An Overview". Multiple Sclerosis: A Mechanistic View. Academic Press. pp. 1–12. doi:10.1016/b978-0-12-800763-1.00001-4. ISBN 9780128007631.
  2. ↑ "What is multiple sclerosis?". University College London Hospitals NHS trust. Retrieved April 17, 2019.
  3. ↑ Harbo, Hanne F.; Gold, Ralf; Tintoré, Mar (July 2013). "Sex and gender issues in multiple sclerosis". Therapeutic Advances in Neurological Disorders. 6 (4): 237–248. doi:10.1177/1756285613488434. ISSN 1756-2856. PMC 3707353. PMID 23858327.
  4. ↑ Levin, Michael C. (2023). "Overview of Demyelinating Disorders - Brain, Spinal Cord, and Nerve Disorders". MSD Manual Consumer Version. Retrieved December 30, 2023.
  5. ↑ Bjornevik, Kjetil; Cortese, Marianna; Healy, Brian C.; Kuhle, Jens; Mina, Michael J.; Leng, Yumei; Elledge, Stephen J.; Niebuhr, David W.; Scher, Ann I.; Munger, Kassandra L.; Ascherio, Alberto (January 21, 2022). "Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis". Science. doi:10.1126/science.abj8222.
  6. ↑ Denworth, Lydia (January 13, 2022). "Epstein-Barr Virus Found to Trigger Multiple Sclerosis". Scientific American. Retrieved January 15, 2022.
  7. ↑ 7.0 7.1 "Epstein-Barr virus may be leading cause of multiple sclerosis". Harvard T.H. Chan School of Public Health. January 13, 2022. Retrieved January 15, 2022.
  8. ↑ 8.0 8.1 8.2 Conway, Claire (April 25, 2016). "Wrapping Up Multiple Sclerosis". UC San Francisco News Center.
  9. ↑ "Gut bacteria regulate nerve fibre insulation". The Guardian - Science. April 5, 2016.
  10. ↑ Rothhammer, Veit; Mascanfroni, Ivan D; Bunse, Lukas; Takenaka, Maisa C; Kenison, Jessica E; Mayo, Lior; Chao, Chun-Cheih; Patel, Bonny; Yan, Raymond; Blain, Manon; Alvarez, Jorge I; Kébir, Hania; Anandasabapathy, Niroshana; Izquierdo, Guillermo; Jung, Steffen; Obholzer, Nikolaus; Pochet, Nathalie; Clish, Clary B; Prinz, Marco; Prat, Alexandre; Antel, Jack; Quintana, Francisco J (May 9, 2016). "Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor". Nature Medicine. doi:10.1038/nm.4106. ISSN 1078-8956.
  11. ↑ Lacerda, Eliana M.; Bowman, Erinna W.; Cliff, Jacqueline M.; Kingdon, Caroline C.; King, Elizabeth C.; Lee, Ji-Sook; Clark, Taane G.; Dockrell, Hazel M.; Riley, Eleanor M. (2017). "The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis". Open journal of bioresources. 4. doi:10.5334/ojb.28. ISSN 2056-5542. PMC 5482226. PMID 28649428.
  12. ↑ 12.0 12.1 12.2 Morris, Gerwyn; Maes, Michael (December 2013). "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics". BMC Medicine. 11 (1): 205. doi:10.1186/1741-7015-11-205. ISSN 1741-7015. PMC 3847236. PMID 24229326.
  13. ↑ 13.0 13.1 White, Andrea T.; Light, Alan R.; Hughen, Ronald W.; VanHaitsma, Timothy A.; Light, Kathleen C. (January 2012). "Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls". Psychosomatic Medicine. 74 (1): 46–54. doi:10.1097/PSY.0b013e31824152ed. ISSN 0033-3174. PMC 3256093. PMID 22210239.
  14. ↑ Jason, Leonard A.; Paavola, Erin; Porter, Nicole; Morello, Morgan L. (2010). "Frequency and content analysis of chronic fatigue syndrome in medical text books". Australian Journal of Primary Health. 16 (2): 174–178. doi:10.1071/py09023. ISSN 1448-7527. PMC 3691015. PMID 21128580.
  15. ↑ Gaber, Tarek A.-Z.K.; Oo, Wah Wah; Ringrose, Hollie (2014). "Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide". NeuroRehabilitation. 35 (3): 529–534. doi:10.3233/NRE-141146. ISSN 1878-6448. PMID 25238862.
  16. ↑ 16.0 16.1 Sorenson, Matthew; Furst, Jacob; Mathews, Herbert; Jason, Leonard A. (2017). "Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis". Fatigue: Biomedicine, Health & Behavior. 5 (3): 145–158. doi:10.1080/21641846.2017.1335237.
  17. ↑ 17.0 17.1 Hornig, M; Gottschalk, CG; Peterson, DL; Knox, KK; Schultz, AF; Eddy, ML; Che, X; Lipkin, WI (February 2016). "Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome". Molecular Psychiatry. 21 (2): 261–269. doi:10.1038/mp.2015.29. ISSN 1359-4184.
  18. ↑ 18.0 18.1 18.2 Ohanian, Diana; Brown, Abigail; Sunnquist, Madison; Furst, Jacob; Nicholson, Laura; Klebek, Lauren; Jason, Leonard (2016). "Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis". EC Neurology. 4.1 (2): 41–45. PMC 5214344. PMID 28066845.
  19. ↑ Brenu, EW; Broadley, S; Nguyen, T; Johnston, S; Ramos, S; Staines, D; Marshall-Gradisnik, S (2016). "A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis" (PDF). Journal of Immunology Research. doi:10.1155/2016/9064529.
  20. ↑ Wong, Naomi; Nguyen, Thao; Brenu, Ekua Weba; Broadley, Simon; Staines, Donald; Marshall-Gradisnik, Sonya (2015). "A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients". International Journal of Clinical Medicine. 6 (10): 769–783. doi:10.4236/ijcm.2015.610103.
  21. ↑ Huth, TK; Brenu, EW; Ramos, S; Nguyen, T; Broadley, S; Staines, D; Marshall-Gradisnik, S (January 2016). "Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis". Scand J Immunol. 83 (1): 44–51. doi:10.1111/sji.12388. PMID 26381393.
  22. ↑ Ramos, S; Brenu, E; Broadley, S; Kwiatek, R; Ng, J; Nguyen, T; Freeman, S; Staines, D; Marshall-Gradisnik, S (March 20, 2016). "Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison" (PDF). Asian Pac J Allergy Immunol (34): 300–305. doi:10.12932/AP0733.
  23. ↑ Jason, LA; Ohanian, D; Brown, A; Sunnquist, M; McManimen, S; Klebek, L; Fox, P; Sorenson, M (2017). "Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome". Insights in Biomedicine. 2 (2). doi:10.21767/2572-5610.100011.
  24. ↑ Polli, Andrea; Willekens, Barbara; Meeus, Mira; Nijs, Jo; Collin, Simon M.; Ickmans, Kelly (2017). "Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study". Pain Physician. 20 (4): E489–E497. PMID 28535557.
  25. ↑ Kingdon, Caroline C.; Bowman, Erinna W.; Curran, Hayley; Nacul, Luis; Lacerda, Eliana M. (December 1, 2018). "Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls". PharmacoEconomics - Open. 2 (4): 381–392. doi:10.1007/s41669-018-0071-6. ISSN 2509-4254. PMID 29536371.
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