Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Clinical features of multiple sclerosis in adults

Michael J Olek, DO
Ram N Narayan, MD
Elliot M Frohman, MD, PhD
Teresa C Frohman, PA-C
Section Editor
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD


Diseases that affect central nervous system (CNS) myelin can be categorized as demyelinating (acquired, inflammatory) and dysmyelinating (abnormal formation of myelin, usually genetic basis) (table 1). The most common immune-mediated inflammatory demyelinating disease of the CNS is multiple sclerosis (MS).

The clinical features and disease course of MS will be reviewed here. Other aspects of MS are discussed separately:

(See "Pathogenesis and epidemiology of multiple sclerosis".)

(See "Clinical course and classification of multiple sclerosis".)

(See "Clinically isolated syndromes suggestive of multiple sclerosis".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: May 2017. | This topic last updated: May 13, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Rice CM, Cottrell D, Wilkins A, Scolding NJ. Primary progressive multiple sclerosis: progress and challenges. J Neurol Neurosurg Psychiatry 2013; 84:1100.
  2. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69:292.
  3. Mowry EM, Deen S, Malikova I, et al. The onset location of multiple sclerosis predicts the location of subsequent relapses. J Neurol Neurosurg Psychiatry 2009; 80:400.
  4. Richards RG, Sampson FC, Beard SM, Tappenden P. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess 2002; 6:1.
  5. DasGupta R, Fowler CJ. Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies. Drugs 2003; 63:153.
  6. Wintner A, Kim MM, Bechis SK, Kreydin EI. Voiding Dysfunction in Multiple Sclerosis. Semin Neurol 2016; 36:34.
  7. Yang CC. Bladder management in multiple sclerosis. Phys Med Rehabil Clin N Am 2013; 24:673.
  8. Frohman TC, Castro W, Shah A, et al. Symptomatic therapy in multiple sclerosis. Ther Adv Neurol Disord 2011; 4:83.
  9. Hennessey A, Robertson NP, Swingler R, Compston DA. Urinary, faecal and sexual dysfunction in patients with multiple sclerosis. J Neurol 1999; 246:1027.
  10. Staff NP, Lucchinetti CF, Keegan BM. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66:1139.
  11. Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol 2008; 7:1139.
  12. Achiron A, Barak Y. Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry 2003; 74:443.
  13. Deloire MS, Salort E, Bonnet M, et al. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2005; 76:519.
  14. Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41:685.
  15. Huijbregts SC, Kalkers NF, de Sonneville LM, et al. Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS. Neurology 2004; 63:335.
  16. Ruet A, Deloire M, Charré-Morin J, et al. Cognitive impairment differs between primary progressive and relapsing-remitting MS. Neurology 2013; 80:1501.
  17. Franklin GM, Heaton RK, Nelson LM, et al. Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis. Neurology 1988; 38:1826.
  18. Hohol MJ, Guttmann CR, Orav J, et al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. Arch Neurol 1997; 54:1018.
  19. Rao SM, Leo GJ, Haughton VM, et al. Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. Neurology 1989; 39:161.
  20. Calabrese M, Agosta F, Rinaldi F, et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 2009; 66:1144.
  21. Amato MP, Bartolozzi ML, Zipoli V, et al. Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 2004; 63:89.
  22. Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 2006; 66:685.
  23. Calabrese M, Rinaldi F, Mattisi I, et al. Widespread cortical thinning characterizes patients with MS with mild cognitive impairment. Neurology 2010; 74:321.
  24. Filippi M, Rocca MA, Benedict RH, et al. The contribution of MRI in assessing cognitive impairment in multiple sclerosis. Neurology 2010; 75:2121.
  25. Mesaros S, Rocca MA, Kacar K, et al. Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis. Neurology 2012; 78:969.
  26. Gilchrist AC, Creed FH. Depression, cognitive impairment and social stress in multiple sclerosis. J Psychosom Res 1994; 38:193.
  27. Mohr DC, Goodkin DE, Gatto N, Van der Wende J. Depression, coping and level of neurological impairment in multiple sclerosis. Mult Scler 1997; 3:254.
  28. Arnett PA, Higginson CI, Randolph JJ. Depression in multiple sclerosis: relationship to planning ability. J Int Neuropsychol Soc 2001; 7:665.
  29. Arnett PA, Higginson CI, Voss WD, et al. Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning. Neuropsychology 1999; 13:434.
  30. Thornton AE, Raz N. Memory impairment in multiple sclerosis: a quantitative review. Neuropsychology 1997; 11:357.
  31. Arnett PA, Higginson CI, Voss WD, et al. Depression in multiple sclerosis: relationship to working memory capacity. Neuropsychology 1999; 13:546.
  32. Zagzag D, Miller DC, Kleinman GM, et al. Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis. Am J Surg Pathol 1993; 17:537.
  33. Rao SM, Reingold SC, Ron MA, et al. Workshop on Neurobehavioral Disorders in Multiple Sclerosis. Diagnosis, underlying disease, natural history, and therapeutic intervention, Bergamo, Italy, June 25-27, 1992. Arch Neurol 1993; 50:658.
  34. Patten SB, Beck CA, Williams JV, et al. Major depression in multiple sclerosis: a population-based perspective. Neurology 2003; 61:1524.
  35. Sadovnick AD, Eisen K, Ebers GC, Paty DW. Cause of death in patients attending multiple sclerosis clinics. Neurology 1991; 41:1193.
  36. Stenager EN, Stenager E. Suicide and patients with neurologic diseases. Methodologic problems. Arch Neurol 1992; 49:1296.
  37. Fredrikson S, Cheng Q, Jiang GX, Wasserman D. Elevated suicide risk among patients with multiple sclerosis in Sweden. Neuroepidemiology 2003; 22:146.
  38. Brønnum-Hansen H, Stenager E, Nylev Stenager E, Koch-Henriksen N. Suicide among Danes with multiple sclerosis. J Neurol Neurosurg Psychiatry 2005; 76:1457.
  39. Sumelahti ML, Tienari PJ, Wikström J, et al. Survival of multiple sclerosis in Finland between 1964 and 1993. Mult Scler 2002; 8:350.
  40. Brønnum-Hansen H, Koch-Henriksen N, Stenager E. Trends in survival and cause of death in Danish patients with multiple sclerosis. Brain 2004; 127:844.
  41. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372:1502.
  42. Patten SB, Metz LM, SPECTRIMS Study Group. Interferon beta1a and depression in secondary progressive MS: data from the SPECTRIMS Trial. Neurology 2002; 59:744.
  43. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS. Lancet 1998; 352:1491.
  44. 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; 39:285.
  45. 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; 352:1498.
  46. Koch M, Uyttenboogaart M, Polman S, De Keyser J. Seizures in multiple sclerosis. Epilepsia 2008; 49:948.
  47. Barnes D, McDonald WI. The ocular manifestations of multiple sclerosis. 2. Abnormalities of eye movements. J Neurol Neurosurg Psychiatry 1992; 55:863.
  48. Frohman EM, Frohman TC, Zee DS, et al. The neuro-ophthalmology of multiple sclerosis. Lancet Neurol 2005; 4:111.
  49. Aschoff JC, Conrad B, Kornhuber HH. Acquired pendular nystagmus with oscillopsia in multiple sclerosis: a sign of cerebellar nuclei disease. J Neurol Neurosurg Psychiatry 1974; 37:570.
  50. Barton JJ, Cox TA. Acquired pendular nystagmus in multiple sclerosis: clinical observations and the role of optic neuropathy. J Neurol Neurosurg Psychiatry 1993; 56:262.
  51. Gresty MA, Ell JJ, Findley LJ. Acquired pendular nystagmus: its characteristics, localising value and pathophysiology. J Neurol Neurosurg Psychiatry 1982; 45:431.
  52. Attarian HP, Brown KM, Duntley SP, et al. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol 2004; 61:525.
  53. Čarnická Z, Kollár B, Šiarnik P, et al. Sleep disorders in patients with multiple sclerosis. J Clin Sleep Med 2015; 11:553.
  54. Tartaglia MC, Narayanan S, Francis SJ, et al. The relationship between diffuse axonal damage and fatigue in multiple sclerosis. Arch Neurol 2004; 61:201.
  55. Braley TJ, Segal BM, Chervin RD. Hypnotic use and fatigue in multiple sclerosis. Sleep Med 2015; 16:131.
  56. Selhorst JB, Saul RF. Uhthoff and his symptom. J Neuroophthalmol 1995; 15:63.
  57. Syndulko K, Jafari M, Woldanski A, et al. Effects of temperature in multiple sclerosis: A review of the literature. Neurorehabil Neural Repair 1996; 10:23.
  58. Davis SL, Wilson TE, White AT, Frohman EM. Thermoregulation in multiple sclerosis. J Appl Physiol (1985) 2010; 109:1531.
  59. Humm AM, Beer S, Kool J, et al. Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study. Clin Neurophysiol 2004; 115:2493.
  60. Rinker JR 2nd, Salter AR, Walker H, et al. Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey. BMJ Open 2015; 5:e006714.
  61. Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler 2004; 10:589.
  62. Thompson AJ, Jarrett L, Lockley L, et al. Clinical management of spasticity. J Neurol Neurosurg Psychiatry 2005; 76:459.
  63. Trompetto C, Marinelli L, Mori L, et al. Pathophysiology of spasticity: implications for neurorehabilitation. Biomed Res Int 2014; 2014:354906.
  64. Drulovic J, Basic-Kes V, Grgic S, et al. The Prevalence of Pain in Adults with Multiple Sclerosis: A Multicenter Cross-Sectional Survey. Pain Med 2015; 16:1597.
  65. Foley PL, Vesterinen HM, Laird BJ, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain 2013; 154:632.
  66. Rae-Grant AD. Unusual symptoms and syndromes in multiple sclerosis. Continuum (Minneap Minn) 2013; 19:992.
  67. Kanchandani R, Howe JG. Lhermitte's sign in multiple sclerosis: a clinical survey and review of the literature. J Neurol Neurosurg Psychiatry 1982; 45:308.
  68. McGraw C, Krieger S, Wong J, Fabian M. The food critic who couldn't taste and 6 other cases of dysgeusia in multiple sclerosis. Neurology 2012; 78(Meeting Abstracts 1):P06.178. www.neurology.org/cgi/content/meeting_abstract/78/1_MeetingAbstracts/P06.178 (Accessed on March 10, 2015).
  69. Lew-Starowicz M, Gianotten WL. Sexual dysfunction in patients with multiple sclerosis. Handb Clin Neurol 2015; 130:357.
  70. Zivadinov R, Zorzon M, Bosco A, et al. Sexual dysfunction in multiple sclerosis: II. Correlation analysis. Mult Scler 1999; 5:428.
  71. Marrie RA, Reider N, Cohen J, et al. A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis. Mult Scler 2015; 21:342.
  72. Tachibana N, Howard RS, Hirsch NP, et al. Sleep problems in multiple sclerosis. Eur Neurol 1994; 34:320.
  73. Brass SD, Duquette P, Proulx-Therrien J, Auerbach S. Sleep disorders in patients with multiple sclerosis. Sleep Med Rev 2010; 14:121.
  74. Stanton BR, Barnes F, Silber E. Sleep and fatigue in multiple sclerosis. Mult Scler 2006; 12:481.
  75. Caminero A, Bartolomé M. Sleep disturbances in multiple sclerosis. J Neurol Sci 2011; 309:86.
  76. Schürks M, Bussfeld P. Multiple sclerosis and restless legs syndrome: a systematic review and meta-analysis. Eur J Neurol 2013; 20:605.
  77. Trojan DA, Da Costa D, Bar-Or A, et al. Sleep abnormalities in multiple sclerosis patients. Mult Scler 2008; 14:S160.
  78. Manconi M, Rocca MA, Ferini-Strambi L, et al. Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage. Mult Scler 2008; 14:86.
  79. Amarenco G, Kerdraon J, Denys P. [Bladder and sphincter disorders in multiple sclerosis. Clinical, urodynamic and neurophysiological study of 225 cases]. Rev Neurol (Paris) 1995; 151:722.
  80. Frohman EM, Zhang H, Dewey RB, et al. Vertigo in MS: utility of positional and particle repositioning maneuvers. Neurology 2000; 55:1566.
  81. Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med 2006; 354:1273.