Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Multiple Sclerosis Workup

  • Author: Christopher Luzzio, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
 
Updated: Jun 16, 2016
 

Approach Considerations

Multiple sclerosis (MS) is diagnosed on the basis of clinical findings and supporting evidence from ancillary tests, such as magnetic resonance imaging (MRI) of the brain and spinal cord and cerebrospinal fluid examination. Clinically, the attack must be compatible with the pattern of neurologic deficits seen in MS, which typically means that the duration of deficit is days to weeks.

Traditionally, MS could not be diagnosed after only a single symptomatic episode, as diagnosis required repeat attacks suggesting the appearance of lesions separated in time and space. In the past, treating physicians were content to "sit back and watch" after a single episode, as it was assumed the disease would "declare" itself. The 2010 McDonald criteria (see Table 1, below) allow diagnosis of MS even with a first clinical episode.[53]

Early diagnosis is important because there is growing evidence that early intervention is useful. It is known through the work of Trapp et al that axonal loss can be present, even in asymptomatic patients, early in the disease process.[54] In addition, studies in patients with a first attack of neurologic symptoms suggestive of MS have demonstrated decreased disability and lower secondary relapse rates with interferon treatment.

Next

McDonald Criteria for MS Diagnosis

The McDonald criteria, which were developed in 2001 by an international expert panel and revised in 2005 and 2010, provide recommendations on the diagnosis of MS, including diagnosis after a single attack.[1, 4, 53] The criteria consist of a combination of clinical, imaging, and paraclinical tests (ie, CSF, evoked potentials).[4] (See Table 1, below.) The 2010 criteria have not yet become widely adopted by clinicians, and it is suggested that the reader consult the original publication.

Table 1. 2010 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis[53] (Open Table in a new window)

Clinical Presentation Additional Data Needed for MS Diagnosis
  • Two or more attacks
  • Objective clinical evidence of 2 or more lesions with reasonable historical evidence of a prior attack
None; clinical evidence will suffice. Additional evidence (eg, brain MRI) desirable,



but must be consistent with MS



  • Two or more attacks
  • Objective clinical evidence of 1 lesion
Dissemination in space demonstrated by MRI or



Await further clinical attack implicating a different site



  • One attack
  • Objective clinical evidence of 2 or more lesions
Dissemination in time demonstrated by



MRI or second clinical attack



  • One attack
  • Objective clinical evidence of 1 lesion (clinically isolated syndrome)
Dissemination in space demonstrated by



MRI or await a second clinical attack implicating a different CNS site



and



Dissemination in time, demonstrated by MRI or second clinical attack



· Insidious neurologic progression suggestive of MS One year of disease progression and dissemination in space, demonstrated by 2 of the following:
  • One or more T2 lesions in brain, in regions characteristic of MS
  • Two or more T2 focal lesions in spinal cord
  • Positive CSF
Notes: An attack is defined as a neurologic disturbance of the kind seen in MS. It can be documented by subjective report or by objective observation, but it must last for at least 24 hours. Pseudoattacks and single paroxysmal episodes must be excluded. To be considered separate attacks, at least 30 days must elapse between onset of one event and onset of another event.
Previous
Next

Blood Studies

Results of blood studies are usually normal in MS patients. Perform blood work to help exclude conditions such as the following:

  • Collagen vascular disease and other rheumatologic conditions
  • Infections (ie, Lyme disease, syphilis)
  • Endocrine abnormalities (eg, thyroid disease)
  • Vitamin B 12 deficiency
  • Sarcoidosis
  • Vasculitis

Neuromyelitis optica (NMO, or Devic disease) can be confirmed by the presence of serum antibodies against aquaporin 4, a water channel expressed at major fluid-tissue barriers across the CNS.[27]

In patients with movement disorders and ocular manifestations, copper studies may be useful. Wilson disease has been misdiagnosed as MS.[55]

Previous
Next

Magnetic Resonance Imaging

Although MRI alone cannot be used to diagnose MS, it remains the imaging procedure of choice for confirming MS and monitoring disease progression in the brain and spinal cord. MRI is not specific, but it is considered the most sensitive imaging modality for diagnosing spinal cord MS, for evaluating its extent, and for following up the response to treatment.[56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66]

The Consortium of Multiple Sclerosis Centers (CMSC) revised its MRI protocol and guidelines in 2015. The revised guidelines recommend using higher-resolution three-dimensional (3D) imaging over two-dimensional (2D) imaging whenever possible. More frequent scanning is recommended to monitor for progressive multifocal leukoencephalopathy in patients taking natalizumab.[67]

MRI is more sensitive for identifying active plaques than is double-dose computed tomography (CT) scanning or clinical examination. MRI far exceeds CT scanning in the ability to demonstrate intramedullary pathology.[68]

MRI shows brain abnormalities in 90-95% of MS patients and spinal cord lesions in up to 75%, especially in elderly patients.[69] T2-weighted images show edema and more chronic lesions, whereas T1-weighted images demonstrate cerebral atrophy and "black holes." These black holes represent areas of axonal death.

One of the limitations of using MRI in patients with MS is the discordance between lesion location and the clinical presentation. In addition, depending on the number and location of findings, MRI can vary greatly in terms of sensitivity and specificity in the diagnosis of MS.

A subset of patients with MS experiences minimal clinical impairment despite significant lesions on MRI. Functional MRI (fMRI) studies detects changes in blood flow related to energy use by brain cells; fMRI studies suggest that increased cognitive control recruitment in the motor system may limit the clinical manifestations of the disease in such cases.[70]

MR spectroscopy is another MRI-based technique that detects a “spectrum” of chemical shifts; this technique appears capable of depicting changes in white matter that are not detected with routine pulse sequences. Because the findings could be correlated with disability scores, the use of MR spectroscopy may prove valuable in monitoring patients after treatment and in formulating their prognosis.[71, 72, 73, 74]

For more information, see Brain Imaging in Multiple Sclerosis and Spine Imaging in Multiple Sclerosis.

Previous
Next

Other Imaging Studies in Multiple Sclerosis

The advent of MRI has limited the role of CT and radiography in the diagnosis and treatment of MS. Occasionally, plain radiographs may be used to exclude mechanical bony lesions.

Angiography also has a limited role, but may occasionally be considered when CNS vasculitis is part of the differential diagnosis in a patient with undifferentiated findings. No positive angiographic findings are specific to MS.

Ultrasonography is not currently used in the investigation of MS. However, Berg et al used transcranial ultrasonography to determine the size of the ventricles in patients with MS and found that increasing ventricular size is correlated with the MRI-determined brain volume, as well as with cognitive dysfunction and clinical disability.[75] Further studies may establish a role for ultrasonography in determining the prognosis and guiding treatment of patients with MS.[76]

Previous
Next

Evoked Potentials

Evoked potentials (ie, recording of the timing of CNS responses to specific stimuli) can be useful neurophysiologic studies for evaluation of MS. These tests, which are used to identify subclinical lesions but which are nonspecific for MS, include the following:

VEPs are performed by having a patient focus on a reversing black-and-white checkerboard pattern. Delays in latencies indicate demyelination in the anterior visual pathways. VEPs are not typically necessary for patients with clear clinical evidence of optic neuritis (ON).

SSEPs evaluate the posterior column of the spinal cord, the brainstem, and the cerebral cortex. Delays in latencies of various peaks indicate demyelination in the correlated pathway of the spinal cord or brain.

BAEPs are performed to evaluate ipsilateral asymptomatic MS lesions in the auditory pathways. They are less sensitive than VEPs and SSEPs.

Previous
Next

Electroencephalography

Electroencephalographic results have been found to be outside the reference range in some patients with MS, but the findings are nonspecific. Nonspecific electroencephalographic abnormalities can also be seen in normal individuals in the general population. A small study by Vazquez-Marrufo et al found that on quantitative electroencephalography, benign MS and relapsing-remitting MS produce different physiologic profiles.[77]

Previous
Next

Lumbar Puncture

Lumbar puncture with CSF analysis is no longer routine in the investigation of MS, but this test may be of use when MRI is unavailable or MRI findings are nondiagnostic. CSF is evaluated for oligoclonal bands (OCBs) and intrathecal immunoglobulin G (IgG) production, as well as for signs of infection.

OCBs are found in 90-95% of patients with MS, and intrathecal IgG production is found in 70-90% of patients. Although these findings are not specific for MS, CSF analysis is the only direct test capable of proving that the patient has a chronic inflammatory CNS condition.

Previous
 
 
Contributor Information and Disclosures
Author

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Fernando Dangond, MD, FAAN Head of US Medical Affairs, Neurodegenerative Diseases, EMD Serono, Inc

Fernando Dangond, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Medical Association

Disclosure: Received salary from EMD Serono, Inc. for employment.

Chief Editor

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

Edmond A Hooker II, MD, DrPH, FAAEM Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association

Disclosure: Nothing to disclose.

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Marjorie Lazoff, MD Editor-in-Chief, Medical Computing Review

Marjorie Lazoff, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Medical Informatics Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Consuelo T Lorenzo, MD Physiatrist, Department of Physical Medicine and Rehabilitation, Alegent Health, Immanuel Rehabilitation Center

Consuelo T Lorenzo, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

William J Nowack, MD Associate Professor, Epilepsy Center, Department of Neurology, University of Kansas Medical Center

William J Nowack, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Electroencephalographic Association, American Medical Informatics Association, and Biomedical Engineering Society

Disclosure: Nothing to disclose.

Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine

Richard Salcido, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Physician Executives, American Medical Association, and American Paraplegia Society

Disclosure: Nothing to disclose.

Daniel D Scott, MD, MA Associate Professor, Department of Physical Medicine and Rehabilitation, University of Colorado School of Medicine; Attending Physician, Department of Physical Medicine and Rehabilitation, Denver Veterans Affairs Medical Center, Eastern Colorado Health Care System

Daniel D Scott, MD, MA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, National Multiple Sclerosis Society, and Physiatric Association of Spine, Sports and Occupational Rehabilitation

Disclosure: Nothing to disclose.

Fu-Dong Shi, MD, PhD Director of Neuroimmunology Laboratory, Barrow Neurological Institute, St Joseph's Hospital and Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Florian P Thomas, MD, MA, PhD, Drmed Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University School of Medicine

Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, and National Multiple Sclerosis Society

Disclosure: Nothing to disclose.

Timothy Vollmer, MD Consulting Staff, Department of Emergency Medicine, Geisinger Medical Center

Disclosure: Nothing to disclose.

Sandra F Williamson, MS, ANP-C, CRRN Clinic Coordinator, Department of Rehabilitation Medicine, Denver Veterans Affairs Medical Center

Sandra F Williamson, MS, ANP-C, CRRN is a member of the following medical societies: Phi Beta Kappa, Phi Kappa Phi, and Sigma Theta Tau International

Disclosure: Nothing to disclose.

References
  1. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec. 58(6):840-6. [Medline].

  2. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar. 13(3):227-31. [Medline].

  3. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr. 46(4):907-11. [Medline].

  4. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul. 50(1):121-7. [Medline].

  5. Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18. 76(3):294-300. [Medline]. [Full Text].

  6. Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-ß-1a (Rebif®): a review of its use in the treatment of relapsing multiple sclerosis. Drugs. 2011 Oct 1. 71(14):1865-91. [Medline].

  7. Betaseron [package insert]. Montville, NJ: Bayer Healthcare Pharmaceuticals Inc. May 2010.

  8. Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, et al. Pegylated interferon ß-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014 Jul. 13(7):657-65. [Medline].

  9. Copaxone [package insert] [package insert]. North Wales, PA: Teva Pharmaceuticals USA. February 2009.

  10. Pucci E, Giuliani G, Solari A, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. 2011 Oct 5. CD007621. [Medline].

  11. Tysabri [package insert]. South San Francisco, CA: Biogen Idec Inc. 2011.

  12. Novantrone [package insert]. Rockland, MA: Serono, Inc. May 2012.

  13. Gilenya [package insert]. East Hanover, NJ: Novartis. September 2010.

  14. Aubagio (teriflunomide) [package insert]. Cambridge, MA: Genentech Corp. September, 2012. Available at [Full Text].

  15. Jeffrey S. FDA approves third oral agent for MS. March 27, 2013. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781450. Accessed: April 2, 2013.

  16. US Food and Drug Administration. FDA approves new multiple sclerosis treatment: Tecfidera. March 27, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345528.htm. Accessed: April 2, 2013.

  17. Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1098-107. [Medline]. [Full Text].

  18. Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1087-97. [Medline]. [Full Text].

  19. Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1819-28. [Medline].

  20. Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1829-39. [Medline].

  21. Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, et al. Alemtuzumab more effective than interferon ß-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3. 78(14):1069-78. [Medline].

  22. Jeffrey S. FDA Approves Interferon Autoinjector for MS. Available at http://www.medscape.com/viewarticle/777065. Accessed: February 20, 2013.

  23. Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med. 1995 Dec 1. 182(6):1985-96. [Medline]. [Full Text].

  24. Huan J, Culbertson N, Spencer L, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005 Jul 1. 81(1):45-52. [Medline].

  25. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008 Jun. 223:87-113. [Medline]. [Full Text].

  26. Minagar A, Jy W, Jimenez JJ, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001 May 22. 56(10):1319-24. [Medline].

  27. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005 Aug 15. 202(4):473-7. [Medline]. [Full Text].

  28. Nielsen NM, Westergaard T, Rostgaard K, et al. Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol. 2005 Oct 15. 162(8):774-8. [Medline].

  29. Nischwitz S, Muller-Myhsok B, Weber F. Risk conferring genes in multiple sclerosis. FEBS Lett. 2011 Dec 1. 585(23):3789-97. [Medline].

  30. Yeo TW, De Jager PL, Gregory SG, et al. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Ann Neurol. 2007 Mar. 61(3):228-36. [Medline]. [Full Text].

  31. Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol. 2009 Jun. 22(3):201-6. [Medline].

  32. Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [Medline].

  33. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20. 296(23):2832-8. [Medline].

  34. Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [Medline].

  35. Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology. 2007 Jul 24. 69(4):381-8. [Medline].

  36. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr. 80(4):392-9. [Medline]. [Full Text].

  37. Zivadinov R, Schirda C, Dwyer MG, et al. Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study. Int Angiol. 2010 Apr. 29(2):158-75. [Medline].

  38. Study To Evaluate Treating Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Multiple Sclerosis Patients. Available at http://clinicaltrials.gov/ct2/show/NCT01089686. Accessed: 10/4/2010.

  39. Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009 Dec. 50(6):1348-58.e1-3. [Medline].

  40. Laupacis A, Lillie E, Dueck A, et al. Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis. CMAJ. 2011 Nov 8. 183(16):E1203-12. [Medline]. [Full Text].

  41. Centers for Disease Control and Prevention. FAQs about Hepatitis B Vaccine (Hep B) and Multiple Sclerosis. [Full Text].

  42. National Multiple Sclerosis Society. Vaccination. Available at http://www.nationalmssociety.org/living-with-multiple-sclerosis/healthy-living/vaccinations/index.aspx. Accessed: November 17, 2011.

  43. Noonan CW, Williamson DM, Henry JP, et al. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis. 2010 Jan. 7(1):A12. [Medline]. [Full Text].

  44. National Multiple Sclerosis Society. Who Gets MS?. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/who-gets-ms/index.aspx. Accessed: 10/04/2010.

  45. Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001 Apr. 22(2):117-39. [Medline].

  46. Aguirre-Cruz L, Flores-Rivera J, De La Cruz-Aguilera DL, Rangel-Lopez E, Corona T. Multiple sclerosis in Caucasians and Latino Americans. Autoimmunity. 2011 Nov. 44(7):571-5. [Medline].

  47. Matsuda PN, Shumway-Cook A, Bamer AM, Johnson SL, Amtmann D, Kraft GH. Falls in multiple sclerosis. PM R. 2011 Jul. 3(7):624-32; quiz 632. [Medline].

  48. Roodhooft JM. Ocular problems in early stages of multiple sclerosis. Bull Soc Belge Ophtalmol. 2009. 65-8. [Medline].

  49. Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010 Aug. 33(8):1061-7. [Medline].

  50. Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Arch Ophthalmol. 1991 Dec. 109(12):1673-8. [Medline].

  51. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov. 33(11):1444-52. [Medline].

  52. Lonergan R, Kinsella K, Duggan M, Jordan S, Hutchinson M, Tubridy N. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?. Mult Scler. 2009 Dec. 15(12):1528-31. [Medline].

  53. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb. 69(2):292-302. [Medline]. [Full Text].

  54. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29. 338(5):278-85. [Medline].

  55. Prashanth LK, Taly AB, Sinha S, Arunodaya GR, Swamy HS. Wilson's disease: diagnostic errors and clinical implications. J Neurol Neurosurg Psychiatry. 2004 Jun. 75(6):907-9. [Medline]. [Full Text].

  56. Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain. 1997 Nov. 120 ( Pt 11):2059-69. [Medline].

  57. Bonhomme GR, Waldman AT, Balcer LJ, et al. Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology. 2009 Mar 10. 72(10):881-5. [Medline].

  58. Filippi M. Enhanced magnetic resonance imaging in multiple sclerosis. Mult Scler. 2000 Oct. 6(5):320-6. [Medline].

  59. Filippi M, Bozzali M, Horsfield MA, et al. A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology. 2000 Jan 11. 54(1):207-13. [Medline].

  60. Filippi M, Yousry TA, Alkadhi H, Stehling M, Horsfield MA, Voltz R. Spinal cord MRI in multiple sclerosis with multicoil arrays: a comparison between fast spin echo and fast FLAIR. J Neurol Neurosurg Psychiatry. 1996 Dec. 61(6):632-5. [Medline]. [Full Text].

  61. Grossman RI, Barkhof F, Filippi M. Assessment of spinal cord damage in MS using MRI. J Neurol Sci. 2000 Jan 15. 172 Suppl 1:S36-9. [Medline].

  62. Neema M, Goldberg-Zimring D, Guss ZD, et al. 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage. 2009 Jul 1. 46(3):633-41. [Medline]. [Full Text].

  63. Poonawalla AH, Hou P, Nelson FA, Wolinsky JS, Narayana PA. Cervical Spinal Cord Lesions in Multiple Sclerosis: T1-weighted Inversion-Recovery MR Imaging with Phase-Sensitive Reconstruction. Radiology. 2008 Jan. 246(1):258-264. [Medline].

  64. Stankiewicz JM, Glanz BI, Healy BC, et al. Brain MRI lesion load at 1.5T and 3T versus clinical status in multiple sclerosis. J Neuroimaging. 2011 Apr. 21(2):e50-6. [Medline]. [Full Text].

  65. Vaneckova M, Seidl Z, Krasensky J, et al. Patients' stratification and correlation of brain magnetic resonance imaging parameters with disability progression in multiple sclerosis. Eur Neurol. 2009. 61(5):278-84. [Medline].

  66. Wattjes MP, Barkhof F. High field MRI in the diagnosis of multiple sclerosis: high field-high yield?. Neuroradiology. 2009 May. 51(5):279-92. [Medline].

  67. [Guideline] Traboulsee, A. et al. Revised Recommendations of the CMSC Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-up of Multiple Sclerosis. Consortim of Multiple Sclerosis Centers. Available at http://c.ymcdn.com/sites/www.mscare.org/resource/collection/9C5F19B9-3489-48B0-A54B-623A1ECEE07B/MRIprotocol2015.pdf. Accessed: August 13, 2015.

  68. Agosta F, Absinta M, Sormani MP, et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain. 2007 Aug. 130:2211-9. [Medline].

  69. Fazekas F, Offenbacher H, Fuchs S, et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology. 1988 Dec. 38(12):1822-5. [Medline].

  70. Colorado RA, Shukla K, Zhou Y, Wolinsky JS, Narayana PA. Multi-task functional MRI in multiple sclerosis patients without clinical disability. Neuroimage. 2012 Jan 2. 59(1):573-81. [Medline]. [Full Text].

  71. Wang J, Xiao Y, Luo M, Zhang X, Luo H. Statins for multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008386. [Medline].

  72. Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr. 14(1):154-9. [Medline].

  73. Henning A, Schar M, Kollias SS, Boesiger P, Dydak U. Quantitative magnetic resonance spectroscopy in the entire human cervical spinal cord and beyond at 3T. Magn Reson Med. 2008 Jun. 59(6):1250-8. [Medline].

  74. Marliani AF, Clementi V, Albini-Riccioli L, Agati R, Leonardi M. Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 Tesla. Magn Reson Med. 2007 Jan. 57(1):160-3. [Medline].

  75. Berg D, Maurer M, Warmuth-Metz M, Rieckmann P, Becker G. The correlation between ventricular diameter measured by transcranial sonography and clinical disability and cognitive dysfunction in patients with multiple sclerosis. Arch Neurol. 2000 Sep. 57(9):1289-92. [Medline].

  76. Walter U, Wagner S, Horowski S, Benecke R, Zettl UK. Transcranial brain sonography findings predict disease progression in multiple sclerosis. Neurology. 2009 Sep 29. 73(13):1010-7. [Medline].

  77. Vazquez-Marrufo M, Gonzalez-Rosa JJ, Vaquero E, et al. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients. BMC Neurol. 2008 Nov 24. 8:44. [Medline]. [Full Text].

  78. Jeffrey S. TOPIC: Teriflunomide Delays Clinically Definite MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803177. Accessed: May 8, 2013.

  79. Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology. 1993 Jun. 43(6):1100-4. [Medline].

  80. Spelman T, Mekhael L, Burke T, Butzkueven H, Hodgkinson S, Havrdova E, et al. Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis. Eur J Neurol. 2016 Jan 19. [Medline].

  81. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993 Apr. 43(4):655-61. [Medline].

  82. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996 Mar. 39(3):285-94. [Medline].

  83. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 7. 352(9139):1498-504. [Medline].

  84. Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology. 2002 Nov 26. 59(10):1496-506. [Medline].

  85. Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clin Ther. 2007 Sep. 29(9):2031-48. [Medline].

  86. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995 Jul. 45(7):1268-76. [Medline].

  87. Johnson KP, Brooks BR, Ford CC, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler. 2000 Aug. 6(4):255-66. [Medline].

  88. Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013 Jun. 73(6):705-13. [Medline].

  89. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2. 354(9):899-910. [Medline].

  90. Cadavid D, Jurgensen S, Lee S. Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis. PLoS One. 2013. 8(1):e53297. [Medline]. [Full Text].

  91. Chun J, Brinkmann V. A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya). Discov Med. 2011 Sep. 12(64):213-28. [Medline].

  92. Hughes S. Shorter washout reduces MS relapse switching off natalizumab. Medscape Medical News. October 7, 2013. [Full Text].

  93. Hughes S. Shorter Washout Better for Natalizumab-to-Fingolimod Switch. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822567. Accessed: April 1, 2014.

  94. Cohen M, Maillart E, Tourbah A, De Sèze J, Vukusic S, Brassat D, et al. Switching From Natalizumab to Fingolimod in Multiple Sclerosis: A French Prospective Study. JAMA Neurol. 2014 Feb 24. [Medline].

  95. O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6. 365(14):1293-303. [Medline].

  96. Semedo, D. Aubagio (Teriflunomide) Slows Brain Atrophy in Patients with Relapsing Multiple Sclerosis. Multiple Sclerosis News Today. Available at http://multiplesclerosisnewstoday.com/2015/10/08/aubagio-teriflunomide-slows-brain-atrophy-patients-relapsing-multiple-sclerosis/. October 8, 2015; Accessed: October 14, 2015.

  97. A study comparing the effectiveness and safety of teriflunomide and interferon beta-1a in patients with relapsing multiple sclerosis (TENERE). 4th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). June 2, 2012 (ClinicalTrials.gov identifier: NCT00883337).

  98. A multicenter double-blind parallel-group placebo-controlled study of the efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis who are treated with interferon-beta. (ClinicalTrials.gov identifier: NCT01252355).

  99. Fox EJ, Sullivan HC, Gazda SK, et al. A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. Eur J Neurol. 2012 Feb. 19(2):307-11. [Medline].

  100. Anderson P. Alemtuzumab Benefits Hard-to-Treat MS Patients. Medscape Medical News. Available at http://www.medscape.com/viewarticle/805173. Accessed: June 12, 2013.

  101. Harrison DM, Gladstone DE, Hammond E, et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012 Feb. 18(2):202-9. [Medline].

  102. Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD006643. [Medline].

  103. Goodkin DE, Rudick RA, VanderBrug Medendorp S, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol. 1995 Jan. 37(1):30-40. [Medline].

  104. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):387-401. [Medline].

  105. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):402-15. [Medline].

  106. Khatri B, Barkhof F, Comi G, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011 Jun. 10(6):520-9. [Medline].

  107. Killestein J, Rudick RA, Polman CH. Oral treatment for multiple sclerosis. Lancet Neurol. 2011 Nov. 10(11):1026-34. [Medline].

  108. Multiple Sclerosis Association of America (MSAA). MS Research Update. Available at http://mymsaa.org/PDFs/MSAA_Research_Update_2013.pdf. Accessed: March 27, 2013.

  109. Bielekova B, Richert N, Herman ML, et al. Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology. 2011 Nov 22. 77(21):1877-86. [Medline]. [Full Text].

  110. Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011 Nov 19. 378(9805):1779-87. [Medline].

  111. Anderson P. Myelin peptide skin patch safe, reduces MS activity. Medscape Medical News. July 29, 2013. [Full Text].

  112. Walczak A, Siger M, Ciach A, Szczepanik M, Selmaj K. Transdermal application of myelin peptides in multiple sclerosis treatment. JAMA Neurol. 2013 Jul 1. 1-6. [Medline].

  113. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998 Jul 30. 339(5):285-91. [Medline].

  114. Tsui A, Lee MA. Multiple sclerosis and pregnancy. Curr Opin Obstet Gynecol. 2011 Dec. 23(6):435-9. [Medline].

  115. Krupp LB, Christodoulou C, Melville P, et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology. 2011 Apr 26. 76(17):1500-7. [Medline]. [Full Text].

  116. Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol. 2004 Apr. 61(4):525-8. [Medline].

  117. MacAllister WS, Krupp LB. Multiple sclerosis-related fatigue. Phys Med Rehabil Clin N Am. 2005 May. 16(2):483-502. [Medline].

  118. Solaro C, Uccelli MM. Management of pain in multiple sclerosis: a pharmacological approach. Nat Rev Neurol. 2011 Aug 16. 7(9):519-27. [Medline].

  119. Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28. 373(9665):732-8. [Medline].

  120. Ampyra [package insert]. Hawthorne, NY: Acorda Therapeutics, Inc. 2010.

  121. Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD004193. [Medline].

  122. US Food and Drug Administration. FDA approves Botox to treat specific form of urinary incontinence. August 25, 2011. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269509.htm. Accessed: November 28, 2011.

  123. Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27. 326(9):581-8. [Medline].

  124. Myhr KM. Vitamin D treatment in multiple sclerosis. J Neurol Sci. 2009 Nov 15. 286(1-2):104-8. [Medline].

  125. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. November 30, 2010. Available at http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed: December 29, 2011.

  126. Summerday NM, Brown SJ, Allington DR, Rivey MP. Vitamin D and multiple sclerosis: review of a possible association. J Pharm Pract. 2012 Feb. 25(1):75-84. [Medline].

  127. Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008422. [Medline].

  128. DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol. 2003 Apr. 60(4):504-9. [Medline].

  129. Confavreux C, Suissa S, Saddier P, Bourdès V, Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med. 2001 Feb 1. 344(5):319-26. [Medline].

  130. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011 Oct. 68(10):1267-71. [Medline].

  131. Azasan [package insert] [package insert]. Wilmington, NC: Salix pharmaceuticals Inc. August 2011.

  132. Cyclophosphamide [package insert]. Deerfield, IL: Baxter Healthcare Corporation. June 2004.

  133. Brooks M. New AAN guideline on psychiatric disorders in MS. Medscape Medical News. January 3, 2014. [Full Text].

  134. Hughes S. New Test to Identify PML Risk With Natalizumab in MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/832504. Accessed: October 7, 2014.

  135. Jeffrey S. No Cognitive Disadvantage in Pediatric- vs Adult-Onset MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/831536. Accessed: September 15, 2014.

  136. Keller DM. Fingolimod Reduces Annual Brain Volume Loss in MS. Medscape Medical News. Jun 6 2014. [Full Text].

  137. Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, et al. Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 Dec 27. [Medline].

  138. Rovira À, Wattjes MP, Tintoré M, Tur C, Yousry TA, Sormani MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol. 2015 Aug. 11 (8):471-82. [Medline].

  139. [Guideline] Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence: A Consensus Paper. The Consortium of Multiple Sclerosis Centers. Available at http://www.mscare.org/?page=dmt. July 2014;

  140. [Guideline] Filippi M, Rocca A, Arnold DL, Bakshi R, Barkhof F, De Stefano N, et al. Use of Imaging in Multiple Sclerosis. Gilhus NE, Barnes MP, Brainin M. European Handbook of Neurological Management. 2nd ed. Oxford (UK): Wiley-Blackwell; 2011. Vol 1: 35-51.

  141. Wattjes MP, Rovira À, Miller D, Yousry TA, Sormani MP, de Stefano MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015 Oct. 11 (10):597-606. [Medline].

  142. Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015 Oct 8. 373 (15):1418-28. [Medline]. [Full Text].

  143. Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Jun 22. 381 (9884):2167-75. [Medline].

 
Previous
Next
 
The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB). T cells are activated following antigen presentation by antigen-presenting cells such as macrophages and microglia, or B cells. Perivascular T cells can secrete proinflammatory cytokines, including interferon gamma and tumor necrosis factor alpha. Antibodies against myelin also may be generated in the periphery or intrathecally. Ongoing inflammation leads to epitope spread and recruitment of other inflammatory cells (ie, bystander activation). The T cell receptor recognizes antigen in the context of human leukocyte antigen molecule presentation and also requires a second event (ie, co-stimulatory signal via the B7-CD28 pathway, not shown) for T cell activation to occur. Activated microglia may release free radicals, nitric oxide, and proteases that may contribute to tissue damage.
MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.
MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. This MRI, performed 3 months after the one in the related image, shows a dramatic decrease in the size of lesions.
Inflammation in multiple sclerosis. Hematoxylin and eosin (H&E) stain shows perivascular infiltration of inflammatory cells. These infiltrates are composed of activated T cells, B cells, and macrophages.
Demyelination in multiple sclerosis. Luxol fast blue (LFB)/periodic acid-Schiff (PAS) stain confers an intense blue to myelin. Loss of myelin is demonstrated in this chronic plaque. Note that absence of inflammation may be demonstrated at the edge of chronic lesions.
Gadolinium-enhanced, T1-weighted image showing enhancement of the left optic nerve (arrow).
Corresponding axial images of the spinal cord showing enhancing plaque (arrow). The combination of optic neuritis and longitudinally extensive spinal cord lesions constitutes Devic neuromyelitis optica.
Table 1. 2010 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis [53]
Clinical Presentation Additional Data Needed for MS Diagnosis
  • Two or more attacks
  • Objective clinical evidence of 2 or more lesions with reasonable historical evidence of a prior attack
None; clinical evidence will suffice. Additional evidence (eg, brain MRI) desirable,



but must be consistent with MS



  • Two or more attacks
  • Objective clinical evidence of 1 lesion
Dissemination in space demonstrated by MRI or



Await further clinical attack implicating a different site



  • One attack
  • Objective clinical evidence of 2 or more lesions
Dissemination in time demonstrated by



MRI or second clinical attack



  • One attack
  • Objective clinical evidence of 1 lesion (clinically isolated syndrome)
Dissemination in space demonstrated by



MRI or await a second clinical attack implicating a different CNS site



and



Dissemination in time, demonstrated by MRI or second clinical attack



· Insidious neurologic progression suggestive of MS One year of disease progression and dissemination in space, demonstrated by 2 of the following:
  • One or more T2 lesions in brain, in regions characteristic of MS
  • Two or more T2 focal lesions in spinal cord
  • Positive CSF
Notes: An attack is defined as a neurologic disturbance of the kind seen in MS. It can be documented by subjective report or by objective observation, but it must last for at least 24 hours. Pseudoattacks and single paroxysmal episodes must be excluded. To be considered separate attacks, at least 30 days must elapse between onset of one event and onset of another event.
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.