Multiple Sclerosis Differential Diagnoses

  • Author: Christopher Luzzio, MD; Chief Editor: B Mark Keegan, MD, FRCPC   more...
 
Updated: Feb 16, 2012
 
 

Diagnostic Considerations

A common misconception is that any attack of CNS demyelination means a diagnosis of acute multiple sclerosis (MS). When a patient has a first attack of demyelination, the physician should not rush to diagnose MS, because the differential diagnosis includes a number of other diseases.

Clinicians who specialize in MS commonly see patients referred for multiple, ill-defined, vague complaints and T2 hyperintense lesions on recent head or spinal magnetic resonance imaging (MRI) scans. Careful questioning in these cases reveals that symptoms have been stereotyped and vague or are consistent with other disorders (eg, scintillating scotomas in a patient with concomitant migraines, or hand symptoms consistent with carpal tunnel syndrome). A history of meningoencephalitis during childhood occasionally emerges.

Another common problem is the presence of small T2 hyperintensities on MRI studies of the CNS, typically referred to as unidentified bright objects (UBOs) by neuroradiologists. These nonspecific lesions are relatively common in the general adult population, and clinical correlation (ie, a high degree of suspicion based on clinical evidence) becomes important in the diagnosis. To confirm MS in these cases, the physician should look for sites of involvement that are rare for UBOs but frequent for MS (eg, the corpus callosum or throughout the spinal cord).

The main differential diagnoses for MS include, but are not limited to, the following:

  • Spinal cord neoplasms (eg, astrocytomas, ependymomas)
  • Acute disseminated encephalomyelitis (ADEM)
  • Schilder disease
  • Baló concentric sclerosis
  • Sarcoidosis
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
  • Transverse myelitis
  • Infarction of the spinal cord
  • Vasculitis
  • Radiation myelitis
  • Arteriovenous fistula
  • Progressive multifocal leukoencephalitis
  • Subacute combined degeneration of the spinal cord (vitamin B12 deficiency)
  • Small-vessel ischemic disease (affecting the brain primarily, and caused by diseases with vascular risk factors, such as diabetes, hypertension, hyperlipidemia, old age)

Spinal cord neoplasms

Both primary and metastatic spinal cord neoplasms must be considered in the differential diagnosis of MS. On imaging studies, the presence of cysts and hemorrhage support the diagnosis of neoplasm.

ADEM

ADEM is considered an isolated postinfectious or postvaccination autoimmune attack on the CNS that leads to diffuse demyelination. ADEM is characterized by acute onset of motor, sensory, cerebellar, and cranial nerve dysfunction with encephalopathy, progressing to coma and eventual death in 30% of cases. Occasionally, ADEM has a fulminant hemorrhagic component, in which case it is termed acute hemorrhagic encephalomyelitis or leukoencephalitis of Weston Hurst.

MRI of the brain may be helpful for showing additional lesions in cases of MS or ADEM. This condition usually responds to steroid therapy; therefore, a treatment trial is often considered before proceeding with biopsy. This process is typically monophasic.

Schilder disease

Schilder disease is characterized in children and young adolescents by massive demyelination, presenting often as asymmetrical foci (often the size of an entire lobe) in the white matter on MRI and with a malignant course (ie, deterioration over months or a few years, with cortical blindness, hemiplegia, or paraplegia). Some patients, however, may respond to steroids and immunosuppressive therapy.

Baló concentric sclerosis

Baló concentric sclerosis is considered by some authors to be a variant of Schilder disease, with MRI lesions showing a characteristic alternating pattern of spared and damaged white matter that suggests progression of the disease process from the ventricles outward. Baló concentric sclerosis is often associated with more inflammatory cerebrospinal fluid (CSF) findings and a more fulminant progression than typical MS.

Sarcoidosis

Sarcoidosis involves the CNS in approximately 5% of cases. Concomitant pial involvement is frequently encountered. Gadolinium enhancement of the pia and white matter lesions on MRI is usually the rule.

CADASIL

CADASIL is an autosomal dominant disease affecting brain blood vessels and characterized by recurrent headaches and strokes or transient ischemic attacks. Mutations in the Notch 3 gene can be demonstrated with current laboratory techniques. In young people with CADASIL who have multiple white matter lesions, CADASIL may be misdiagnosed as MS. A family history of headaches and strokes should prompt a diagnostic workup for CADASIL.

Transverse myelitis

Transverse myelitis is the term usually used for idiopathic inflammatory myelopathy. Swelling and enhancement of the spinal cord may be evident on MRI, often affecting a longer segment than the typical involvement seen with partial myelitis in MS. This also needs to be distinguished from the longitudinally extensive transverse myelitis seen in Devic disease, classically involving multiple spinal cord levels with a linear trajectory.

Infarction of the spinal cord

Infarction of the spinal cord is more common at the thoracic level. Usually, only a single lesion is present. Contrast may be present, although this is not the dominant feature. Signal alteration usually and initially involves the anterior gray matter (anterior spinal artery distribution). The patient's clinical presentation will be acute. Particularly consider this entity if the patient is older and/or has a history of aortic/vascular surgery.

Vasculitic processes

Vasculitic processes such as systemic lupus erythematosus can result in spinal lesions that mimic MS. Often, multiple lesions are present. However, the clinical history is often known and helps to establish the correct diagnosis.

Radiation myelitis

Radiation myelitis generally occurs only in patients who have received doses higher than 4000 cGy. However, chemotherapy may be synergistic (ie, may lead to radiosensitization, triggering myelitis at lower radiation doses.The latency period is 1-3 years. Images may show some peripheral enhancement.

Arteriovenous fistula

Arteriovenous fistula usually occurs at the thoracolumbar level, and patients are usually older than 50 years, with a long history of back pain. The cord signal abnormality can involve a very long segment. Look for a serpiginous flow void along the cord surface.

Differential Diagnoses

Proceed to Workup
 
 
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  Senior Director of Medical Affairs, Neurology, EMD Serono, Inc

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

Disclosure: EMD Serono, Inc. Salary Employment

Chief Editor

B Mark Keegan, MD, FRCPC  Assistant Professor of Neurology, College of Medicine, Mayo Clinic; Master's Faculty, Mayo Graduate School; Consultant, Department of Neurology, Mayo Clinic, Rochester

B Mark Keegan, MD, FRCPC is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Minnesota Medical Association

Disclosure: Novartis Consulting fee Consulting; Bionest Consulting fee Consulting

Additional Contributors

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

  2. Huan J, Culbertson N, Spencer L, Bartholomew R, Burrows GG, Chou YK, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. Jul 1 2005;81(1):45-52. [Medline].

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

  4. Minagar A, Jy W, Jimenez JJ, Sheremata WA, Mauro LM, Mao WW, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. May 22 2001;56(10):1319-24. [Medline].

  5. 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. Aug 15 2005;202(4):473-7. [Medline]. [Full Text].

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

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

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

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

  10. Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. Jul 8 2008;71(2):129-35. [Medline].

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

  12. 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].

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

  14. Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'Ara S, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. Apr 2009;80(4):392-9. [Medline]. [Full Text].

  15. Zivadinov R, Schirda C, Dwyer MG, Haacke ME, Weinstock-Guttman B, Menegatti E, 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. Apr 2010;29(2):158-75. [Medline].

  16. 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.

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

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

  19. Centers for Disease Control and Prevention. FAQs about Hepatitis B Vaccine (Hep B) and Multiple Sclerosis. Accessed 10/04/2010. Available at http://www.cdc.gov/vaccinesafety/Vaccines/multiplesclerosis_and_hep_b.html.

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

  21. Noonan CW, Williamson DM, Henry JP, Indian R, Lynch SG, Neuberger JS, et al. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis. Jan 2010;7(1):A12. [Medline]. [Full Text].

  22. 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.

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

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

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

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

  27. Braley TJ, Chervin RD. Fatigue in Multiple Sclerosis: Mechanisms, Evaluation, and Treatment. Sleep. Aug 2010;33(8):1061-7.

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

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

  30. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. Dec 2005;58(6):840-6. [Medline].

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

  32. 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. Apr 1996;46(4):907-11. [Medline].

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

  34. 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. Dec 2009;15(12):1528-31. [Medline].

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

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

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

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

  39. Bonhomme GR, Waldman AT, Balcer LJ, Daniels AB, Tennekoon GI, Forman S, et al. Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology. Mar 10 2009;72(10):881-5. [Medline].

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

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

  42. 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. Dec 1996;61(6):632-5. [Medline]. [Full Text].

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

  44. Neema M, Goldberg-Zimring D, Guss ZD, Healy BC, Guttmann CR, Houtchens MK, et al. 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage. Jul 1 2009;46(3):633-41. [Medline].

  45. 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. Jan 2008;246(1):258-264. [Medline].

  46. Stankiewicz JM, Glanz BI, Healy BC, Arora A, Neema M, Benedict RH, et al. Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis. J Neuroimaging. Nov 3 2009;[Medline].

  47. Vaneckova M, Seidl Z, Krasensky J, Havrdova E, Horakova D, Dolezal O, 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].

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

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

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

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

  52. Wang J, Xiao Y, Luo M, Zhang X, Luo H. Statins for multiple sclerosis. Cochrane Database Syst Rev. 2010;12:CD008386. [Medline].

  53. 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. Apr 1990;14(1):154-9. [Medline].

  54. Henning A, Schär 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. Jun 2008;59(6):1250-8. [Medline].

  55. 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. Jan 2007;57(1):160-3. [Medline].

  56. Berg D, Mäurer 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. Sep 2000;57(9):1289-92. [Medline].

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

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

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

  60. [Guideline] 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. Jan 18 2011;76(3):294-300. [Medline]. [Full Text].

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

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

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

  64. Pucci E, Giuliani G, Solari A, Simi S, Minozzi S, Di Pietrantonj C, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. Oct 5 2011;CD007621. [Medline].

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

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

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

  68. 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. Apr 1993;43(4):655-61. [Medline].

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

  70. 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. Nov 7 1998;352(9139):1498-504. [Medline].

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

  72. 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. Sep 2007;29(9):2031-48. [Medline].

  73. 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. Jul 1995;45(7):1268-76. [Medline].

  74. Johnson KP, Brooks BR, Ford CC, Goodman A, Guarnaccia J, Lisak RP, 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. Aug 2000;6(4):255-66. [Medline].

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

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

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

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

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

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

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

  82. 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. Jun 2011;10(6):520-529. [Medline].

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

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

  85. Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. Aug 2011;124(2):75-84. [Medline].

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

  87. Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. Nov 19 2011;378(9805):1779-87. [Medline].

  88. 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. Jul 30 1998;339(5):285-91. [Medline].

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

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

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

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

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

  94. [Best Evidence] Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. Feb 28 2009;373(9665):732-8. [Medline].

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

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

  97. 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.

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

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

  100. 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.

  101. Summerday NM, Brown SJ, Allington DR, Rivey MP. Vitamin D and Multiple Sclerosis: Review of a Possible Association. J Pharm Pract. Oct 10 2011;[Medline].

  102. Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. Dec 8 2010;12:CD008422. [Medline].

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

  104. 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. Feb 1 2001;344(5):319-26. [Medline]. [Full Text].

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

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

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

 
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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[35]
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 MSOne 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.
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