Multiple sclerosis resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Moises Romo, M.D.

Synonyms and Keywords: Multiple sclerosis management, Multiple sclerosis workup, Multiple sclerosis approaches, approach to Multiple sclerosis, Multiple sclerosis treatment

Overview

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system and it’s known to be multi-factorial. The onset of symptoms are mostly between the age of fifteen to forty years (rarely before age fifteen or after age sixty), and include fatigue, mood problems, spasticity, bowel and bladder dysfunction, cognitive impairment, eye movement problems, heat sensitivity, incoordination, pain, sexual dysfunction, sleep disorder, vertigo and visual loss. There is no single diagnostic study of choice for Multiple sclerosis. Diagnosis is currently made by the fulfilment of the McDonald criteria, which include clinical presentation, cerebral plaques on MRI , and oligoclonal bands in CSF analysis. Treatment for multiple sclerosis includes disease-modifying medications (DMTs) and immunosuppressors to prevent relapses and Glucocorticoid therapy in acute exacerbations.

Causes

Life-Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Diagnosis

The diagnostic criteria for multiple sclerosis is 2017 McDonald criteria:[10][11]

Clinical presentation Additional Data Needed
  • 2 or more attacks (relapses)
  • 2 or more objective clinical lesions
  • None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS)
  • 2 or more attacks
  • 1 objective clinical lesion
New criteria: Dissemination in space, demonstrated by:
  • MRI
  • Further clinical attack involving different site
  • Presence of 1 or more T2 lesions in at least 2 of 4 of the following areas of the CNS: Periventricular, Juxtacortical, Infratentorial, or spinal cord
  • 1 attack
  • 2 or more objective clinical lesions
Dissemination in time (DIT), demonstrated by:
  • MRI
  • Second clinical attack

New criteria: No longer a need to have separate MRIs run; dissemination in time, demonstrated by: simultaneous presence of asymptomatic gadolinium-enhancing

and non-enhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or await a second clinical attack. [This allows for quicker diagnosis without sacrificing specificity, while improving sensitivity]

  • 1 attack
  • 1 objective clinical lesion (clinically isolated syndrome)
New criteria: Dissemination in space and time, demonstrated by:
  • For DIS: 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord); or await a second clinical attack implicating a different CNS site; and for DIT: simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time; or a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or await a second clinical attack.
  • Insidious neurological progression suggestive of MS (primary progressive MS)
New criteria: One year of disease progression (retrospectively or prospectively determined) and two or three of the following:
  • Evidence for DIS in the brain based on 1 or more T2 lesions in the MS-characteristic (periventricular, juxtacortical, or infratentorial) regions
  • Evidence for DIS in the spinal cord based on 2 or more T2 lesions in the cord

Treatment

Shown below is an algorithm summarizing the treatment of Multiple sclerosis according the the NHS England’s Neuroscience Clinical Reference Group guidelines:[12]


 
 
 
 
 
 
 
Single clinical episode suggestive of MS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Without MRI abnormalities
 
 
 
 
 
 
 
 
 
With MRI abnormalities and fulfilling the McDonald criteria
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Do not treat
 
 
Fulfills the definition of Clinically Isolated Syndrome (CIS)
 
 
 
 
 
 
Patient with relapsing-remitting MS
 
Radiological markers indicative of a poor prognosis for rapidly developing permanent disability
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Do not treat
 
 
 
 
 
 
 
Interferon beta 1a or glatiramer acetate
 
Alemtuzumab or Ocrelizumab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relapse
 
 
 
 
 
 
 
 
 
2 significant relapses in last 2 years
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasmapheresis
 
Alemtuzumab or Ocrelizumab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Poor response
 
 
 
 
 
 
 
 
 
Steroids
 
 
 
Severe relapse or contraindications to high dose-steroids
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Natalizumab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive John Cunningham (JC) virus
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Close MRI follow-up or change to Cladribine

Dos

Don'ts

  • Do not continue disease modifying therapy if adverse effects of the drug are observed, the patient becomes pregnant or they develop progressive disease or fixed disability above EDSS 6.5.[12]
  • Do not prescribe mitoxantrone to people with MS unless the potential therapeutic benefits greatly outweigh the risks, due to high frequency of severe adverse effects.[13]

References

  1. Pette M, Fujita K, Kitze B, Whitaker JN, Albert E, Kappos L, Wekerle H (1990). "Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals". Neurology. 40 (11): 1770–6. PMID 1700336.
  2. Bielekova B, Goodwin B, Richert N, Cortese I, Kondo T, Afshar G, Gran B, Eaton J, Antel J, Frank JA, McFarland HF, Martin R (2000). "Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand". Nat. Med. 6 (10): 1167–75. doi:10.1038/80516. PMID 11017150.
  3. Korn T (2008). "Pathophysiology of multiple sclerosis". J. Neurol. 255 Suppl 6: 2–6. doi:10.1007/s00415-008-6001-2. PMID 19300953.
  4. Compston A, Coles A (2008). "Multiple sclerosis". Lancet. 372 (9648): 1502–17. doi:10.1016/S0140-6736(08)61620-7. PMID 18970977.
  5. Sriram S, Mitchell W, Stratton C (1998). "Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS". Neurology. 50 (2): 571–2. PMID 9484408.
  6. Soldan SS, Jacobson S (2001). "Role of viruses in etiology and pathogenesis of multiple sclerosis". Adv. Virus Res. 56: 517–55. PMID 11450311.
  7. Mechelli R, Manzari C, Policano C, Annese A, Picardi E, Umeton R, Fornasiero A, D'Erchia AM, Buscarinu MC, Agliardi C, Annibali V, Serafini B, Rosicarelli B, Romano S, Angelini DF, Ricigliano VA, Buttari F, Battistini L, Centonze D, Guerini FR, D'Alfonso S, Pesole G, Salvetti M, Ristori G (2015). "Epstein-Barr virus genetic variants are associated with multiple sclerosis". Neurology. 84 (13): 1362–8. doi:10.1212/WNL.0000000000001420. PMC 4388746. PMID 25740864.
  8. Friese MA, Schattling B, Fugger L (2014). "Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis". Nat Rev Neurol. 10 (4): 225–38. doi:10.1038/nrneurol.2014.37. PMID 24638138.
  9. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005). "Cortical demyelination and diffuse white matter injury in multiple sclerosis". Brain. 128 (Pt 11): 2705–12. doi:10.1093/brain/awh641. PMID 16230320.
  10. Gobbin F, Zanoni M, Marangi A, Orlandi R, Crestani L, Benedetti MD, Gajofatto A (January 2019). "2017 McDonald criteria for multiple sclerosis: Earlier diagnosis with reduced specificity?". Mult Scler Relat Disord. 29: 23–25. doi:10.1016/j.msard.2019.01.008. PMID 30658260.
  11. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (July 2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Ann. Neurol. 50 (1): 121–7. PMID 11456302.
  12. 12.0 12.1 12.2 12.3 "www.england.nhs.uk" (PDF).
  13. 13.0 13.1 13.2 Rae-Grant, Alexander; Day, Gregory S.; Marrie, Ruth Ann; Rabinstein, Alejandro; Cree, Bruce A.C.; Gronseth, Gary S.; Haboubi, Michael; Halper, June; Hosey, Jonathan P.; Jones, David E.; Lisak, Robert; Pelletier, Daniel; Potrebic, Sonja; Sitcov, Cynthia; Sommers, Rick; Stachowiak, Julie; Getchius, Thomas S.D.; Merillat, Shannon A.; Pringsheim, Tamara (2018). "Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis". Neurology. 90 (17): 777–788. doi:10.1212/WNL.0000000000005347. ISSN 0028-3878.
  14. Cortese, I.; Chaudhry, V.; So, Y. T.; Cantor, F.; Cornblath, D. R.; Rae-Grant, A. (2011). "Evidence-based guideline update: Plasmapheresis in neurologic disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 76 (3): 294–300. doi:10.1212/WNL.0b013e318207b1f6. ISSN 0028-3878.
  15. Haselkorn, Jodie K.; Hughes, Christina; Rae-Grant, Alex; Henson, Lily Jung; Bever, Christopher T.; Lo, Albert C.; Brown, Theodore R.; Kraft, George H.; Getchius, Thomas; Gronseth, Gary; Armstrong, Melissa J.; Narayanaswami, Pushpa (2015). "Summary of comprehensive systematic review: Rehabilitation in multiple sclerosis". Neurology. 85 (21): 1896–1903. doi:10.1212/WNL.0000000000002146. ISSN 0028-3878.