Encyclopedia of Clinical Neuropsychology

2018 Edition
| Editors: Jeffrey S. Kreutzer, John DeLuca, Bruce Caplan

Relapsing-Remitting Multiple Sclerosis

  • Kathleen L. FuchsEmail author
  • John DeLuca
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-57111-9_518


Exacerbating-remitting multiple sclerosis

Short Description or Definition

Relapsing-remitting multiple sclerosis (RRMS) describes the initial course of approximately 85% of patients diagnosed with MS. There are discrete episodes (aka “relapses,” “attacks,” “flare-ups,” or “exacerbations”) of neurologic dysfunction lasting at least 24 h followed by full or partial recovery and a period in which there is no symptom progression or accumulation of disability (aka “remission”; see Fig. 1). Across individuals with RRMS, there is a great deal of variability in the time between relapses and in the severity of relapse symptoms. Recovery from relapses may be incomplete, and thus a certain amount of residual neurologic dysfunction may persist (see Fig. 2). When symptoms progress outside relapse periods, the person is considered to have entered the secondary progressive stage of the disease.
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References and Readings

  1. Amato, M. P., Langdon, D., Montalban, X., Benedict, R. H. B., DeLuca, J., Krupp, L. B., Thompson, A. J., et al. (2013). Treatment of cognitive impairment in multiple sclerosis: Position paper. Journal of Neurology, 260, 1452–1468.PubMedCrossRefGoogle Scholar
  2. Arnett, P. A., Higginson, C. I., Voss, W. D., Bender, W. I., Wurst, J. M., & Tippin, J. M. (1999). Depression in multiple sclerosis: Relationship to working memory capacity. Neuropsychology, 13, 546–556.PubMedCrossRefGoogle Scholar
  3. Barkhof, F., Scheltens, P., Frequin, S. T., Nauta, J. J., Tas, M. W., Valk, J., et al. (1992). Relapsing-remitting multiple sclerosis: Sequential enhanced MR imaging vs clinical findings in determining disease activity. American Journal of Roentgenology, 159, 1041–1047.PubMedCrossRefGoogle Scholar
  4. Beatty, W. W., Goodkin, D. E., Hertsgaard, D., & Monson, N. (1990). Clinical and demographic predictors of cognitive performance in multiple sclerosis: Do diagnostic type, disease duration, and disability matter? Archives of Neurology, 47, 305–308.PubMedCrossRefGoogle Scholar
  5. Benedict, R. H. B., Fischer, J. S., Archibald, C. J., Arnett, P. A., Beatty, W. W., Bobholz, J., et al. (2002). Minimal neuropsychological assessment of MS patients: A consensus approach. The Clinical Neuropsychologist, 16, 381–397.PubMedCrossRefGoogle Scholar
  6. Benedict, R. H. B., Weinstock-Guttman, B., Fishman, I., Sharma, J., Tjoa, C. W., & Bakshi, R. (2004). Prediction of neuropsychological impairment in multiple sclerosis: Comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Archives of Neurology, 61, 226–230.PubMedCrossRefGoogle Scholar
  7. Bergamaschi, R., Berzuini, C., Romani, A., & Cosi, V. (2001). Predicting secondary progression in relapsing-remitting multiple sclerosis. Journal of the Neurological Sciences, 189, 13–21.PubMedCrossRefGoogle Scholar
  8. Calabrese, M., Atzori, M., Bernardi, V., Morra, A., Romualdi, C., Rinaldi, L., et al. (2007). Cortical atrophy is relevant in multiple sclerosis at clinical onset. Journal of Neurology, 254, 1212–1220.PubMedCrossRefGoogle Scholar
  9. Calabrese, M., Agosta, F., Rinaldi, F., Mattisi, I., Grossi, P., Favaretto, A., et al. (2009). Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Archives of Neurology, 66, 1144–1150.PubMedCrossRefGoogle Scholar
  10. Chiaravalloti, N. D., & DeLuca, J. (2008). Cognitive impairment in multiple sclerosis. Lancet Neurology, 7, 1139–1151.PubMedCrossRefGoogle Scholar
  11. Chiaravalloti, N. D., Wylie, G. R., Leavitt, V. M., & DeLuca, J. (2012). Increased cerebral activation after behavioral treatment for memory deficits in MS. Journal of Neurology, 259, 1337–1346.PubMedCrossRefGoogle Scholar
  12. Chiaravalloti, N. D., Moore, N. B., Nikelshpur, O., & DeLuca, J. (2013). A randomized clinical trial to treat learning impairment in multiple sclerosis: The MEMREHAB trial. Neurology, 81(24), 2066–2072.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Compston, A., Confavreux, C., Lassman, H., McDonald, I., Miller, D., Noseworthy, J., et al. (2005). McAlpine’s multiple sclerosis (4th ed.). Philadelphia: Elsevier.Google Scholar
  14. Confavreux, C., & Compston, A. (2005). The natural history of multiple sclerosis. In A. Compston et al. (Eds.), McAlpine’s multiple sclerosis (4th ed.). Philadelphia: Elsevier.Google Scholar
  15. Costa, S., DeLuca, J., & Chiaravalloti, N. (2016). Information processing speed in multiple sclerosis: Past, present and future. Multiple Sclerosis Journal.  https://doi.org/10.1177/1352458516645869. e-pub.PubMedCrossRefGoogle Scholar
  16. das Nair R., Martin K.J., & Lincoln N.B. (2016). Memory rehabilitation for people with multiple sclerosis. Cochrane Database of Systematic Reviews, 2016(3). Art. No.: CD008754.  https://doi.org/10.1002/14651858.CD008754.pub3.
  17. DeLuca, J., & Nocentini, U. (2011). Neuropsychological, medical and rehabilitative management of persons with multiple sclerosis. NeuroRehabilitation, 29, 197–219.PubMedGoogle Scholar
  18. Dobryakova, E., Wylie, G. R., DeLuca, J., & Chiaravalloti, N. D. (2014). Functional brain activity 6 months after memory retraining in multiple sclerosis: The MEMREHAB trial. Brain Imaging and Behavior, 8, 403–406.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Dobryakova, E., Rocca, M. A., Valsasina, P., Ghezzi, A., Colombo, B., Martinelli, V., Comi, G., DeLuca, J., & Filippi, M. (2016). Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study. Human Brain Mapping, 37(6), 2293–2304.  https://doi.org/10.1002/hbm.23174.CrossRefPubMedGoogle Scholar
  20. Feinstein, A. (2006). Mood disorders in multiple sclerosis and the effects on cognition. Journal of the Neurological Sciences, 245, 63–66.PubMedCrossRefGoogle Scholar
  21. Foong, J., Rozewicz, L., Quaghebeur, G., Thompson, A. J., Miller, D. H., & Ron, M. A. (1998). Neuropsychological deficits in multiple sclerosis after acute relapse. Journal of Neurology, Neurosurgery, & Psychiatry, 64, 529–532.CrossRefGoogle Scholar
  22. Goverover, Y., Strober, L., Chiaravalloti, N., & DeLuca, J. (2015). Factors that moderate activity limitation and participation restriction in people with multiple sclerosis. American Journal of Occupational Therapy, 69, 1–9.CrossRefGoogle Scholar
  23. Goverover, Y., Haas, H., & DeLuca, J. (2016). Money management activities in persons with multiple sclerosis. Archives of Physical Medicine and Rehabilitation, 97(11), 1901–1907.PubMedCrossRefGoogle Scholar
  24. Kalb, R. (2007). The emotional and psychosocial impact of multiple sclerosis relapses. Journal of the Neurological Sciences, 256, S29–S33.PubMedCrossRefGoogle Scholar
  25. Kalmar, J. H., Halper, J., Gaudino, E. A., Moore, N. B., & DeLuca, J. (2008). The relationship between cognitive deficits and everyday functional activities in multiple sclerosis. Neuropsychology, 22, 442–449.PubMedCrossRefGoogle Scholar
  26. Krupp, L. B., Christodoulou, C., Melville, P., Scherl, W. F., MacAllister, W. S., & Elkins, L. E. (2004). Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology, 63, 1579–1585.PubMedCrossRefGoogle Scholar
  27. Langdon, D. W., Amato, M. P., Boringa, J., Brochet, B., Foley, F., Fredrikson, S., Hämäläinen, P., Hartung, H. P., Krupp, L., Penner, I. K., Reder, A. T., & Benedict, R. H. (2012). Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Multiple Sclerosis, 18(6), 891–898.  https://doi.org/10.1177/1352458511431076. Epub 2011 Dec 21.CrossRefPubMedGoogle Scholar
  28. Langer-Gould, A., Popat, R. A., Huang, S. M., Cobb, K., Fontoura, P., Gould, M. K., et al. (2006). Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. Archives of Neurology, 63, 1686–1691.PubMedCrossRefGoogle Scholar
  29. Leavitt, V.M., Wylie, G.R., DeLuca, J., & Chiaravalloti, N.D. (2012). Increased functional connectivity within memory networks following memory rehabilitation in Multiple Sclerosis. Brain Imaging and Behavior. Epub ahead of print, PMID: 22706694.Google Scholar
  30. Lin, X., Tench, C. R., Morgan, P. S., Niepel, G., & Constantinescu, C. S. (2005). ‘Importance sampling’ in MS: Use of diffusion tensor tractography to quantify pathology related to specific impairment. Journal of the Neurological Sciences, 237, 13–19.PubMedCrossRefGoogle Scholar
  31. Lublin, F. D., Reingold, S. C., & for the National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. (1996). Defining the clinical course of multiple sclerosis: Results of an international survey. Neurology, 46, 907–911.PubMedCrossRefGoogle Scholar
  32. Maniero, C., Benner, T., Radding, A., van der Kouwe, A., Jensen, R., Rosen, B. R., et al. (2009). In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI. Neurology, 73, 941–948.CrossRefGoogle Scholar
  33. Mohr, D. C., Boudewyn, A. C., Goodkin, D. E., Bostrom, A., & Epstein, L. (2001). Comparative outcomes for individual cognitive-behavioral therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. Journal of Consulting and Clinical Psychology, 69, 942–949.PubMedCrossRefGoogle Scholar
  34. Mohr, D. C., Hart, S. L., & Tasch, E. S. (2006). Treatment of depression for patients with multiple sclerosis in neurology clinics. Multiple Sclerosis, 12, 204–208.PubMedCrossRefGoogle Scholar
  35. Pardini, M., Ucccelli, A., Grafmna, J., Yaldizli, O., Mancardi, G., & Roccatagliata, L. (2014). Isolated cognitive relapses in multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 85, 1035–1037.PubMedCrossRefGoogle Scholar
  36. Patten, S. B., Metz, L. M., & Reimer, M. A. (2000). Biopsychosocial correlates of major depression in a multiple sclerosis population. Multiple Sclerosis, 6, 115–120.PubMedCrossRefGoogle Scholar
  37. Rao, S. M. (1991). A manual for the brief, repeatable battery of neuropsychological tests in multiple sclerosis. New York: National Multiple Sclerosis Society.Google Scholar
  38. Rao, S. M. (1995). Neuropsychology of multiple sclerosis. Current Opinion in Neurology, 8, 216–220.PubMedCrossRefGoogle Scholar
  39. Rao, S. M., Leo, G. J., Bernardin, L., & Unverzagt, F. (1991a). Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology, 41, 685–691.PubMedCrossRefGoogle Scholar
  40. Rao, S. M., Leo, G. J., Ellington, L., Nauertz, T., Bernardin, L., & Unverzagt, F. (1991b). Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology, 41, 692–696.PubMedCrossRefGoogle Scholar
  41. Rao, S. M., Martin, A. L., Huelin, R., Wissinger, E., Khankhel, Z., Kim, E., & Fahrbach, K. (2014). Correlations between MRI and information processing speed in MS: A meta-analysis. Multiple Sclerosis International, 975803, 1–9.  https://doi.org/10.1155/2014/975803.CrossRefGoogle Scholar
  42. Rocca, M., Torralva, T., Meli, F., Fiol, M., Calcagno, M. L., Carpintiero, S., et al. (2008). Cognitive deficits in multiple sclerosis correlate with changes in fronto-subcortical tracts. Multiple Sclerosis, 14, 364–369.CrossRefGoogle Scholar
  43. Sadovnick, A. D., Remick, R. A., Allen, J., Swartz, E., Yee, I. M. L., Eisen, K., et al. (1996). Depression and multiple sclerosis. Neurology, 46, 628–632.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Sanfilipo, M. P., Benedict, R. H. B., Weinstock-Guttman, B., & Bakshi, R. (2006). Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology, 66, 685–692.PubMedCrossRefGoogle Scholar
  45. Sicotte, N. L., Kern, K. C., Giesser, B. S., Arshanapalli, A., Schultz, A., Montag, M., et al. (2008). Regional hippocampal atrophy in multiple sclerosis. Brain, 131, 1134–1141.PubMedCrossRefGoogle Scholar
  46. Smith, K., McDonald, I., Miller, D., & Lassman, H. (2005). The pathophysiology of multiple sclerosis. In A. Compston et al. (Eds.), McAlpine’s multiple sclerosis (4th ed.). Philadelphia: Elsevier.Google Scholar
  47. Summers, M. M., Fisniku, L. K., Anderson, V. M., Miller, D. H., Cipolotti, L., & Ron, M. A. (2008). Cognitive impairment in relapsing-remitting multiple sclerosis can be predicted by imaging performed several years earlier. Multiple Sclerosis, 14, 197–204.PubMedCrossRefGoogle Scholar
  48. Vollmer, T. (2007). The natural history of relapses in multiple sclerosis. Journal of the Neurological Sciences, 256, S5–S13.PubMedCrossRefGoogle Scholar
  49. Vukusic, S., & Confavreux, C. (2007). Natural history of multiple sclerosis: Risk factors and prognostic indicators. Current Opinion in Neurology, 20, 269–274.PubMedCrossRefGoogle Scholar
  50. Weinshenker, B. G., Bass, B., Rice, G. P., Noseworthy, J., Carriere, W., Baskerville, J., et al. (1989). The natural history of multiple sclerosis: A geographically based study. I. Clinical course and disability. Brain, 112, 133–146.PubMedCrossRefGoogle Scholar
  51. Zivadinov, R., De Masi, R., Nasuelli, D., Monti Bragadin, L., Ukmar, M., Pozzi-Mucelli, R. S., et al. (2001a). MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis. Neuroradiology, 43, 272–278.PubMedCrossRefGoogle Scholar
  52. Zivadinov, R., Sepcic, J., Nasuelli, D., De Masi, R., Monti Bragadin, L., Tommasi, M. A., et al. (2001b). A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. Journal of Neurology, Neurosurgery, & Psychiatry, 70, 773–780.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Virginia Health SystemCharlottesvilleUSA
  2. 2.Research DepartmentKessler FoundationWest OrangeUSA