Semin Neurol 2007; 27(1): 078-085
DOI: 10.1055/s-2006-956758
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Multiple Sclerosis

Ralph H.B Benedict1 , Julie H. Bobholz2
  • 1Department of Neurology, State University of New York (SUNY) at Buffalo, Jacobs Neurological Institute, Buffalo, New York
  • 2Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
Further Information

Publication History

Publication Date:
17 January 2007 (online)

ABSTRACT

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that commonly leads to inflammatory and atrophic brain pathology, often causing cognitive impairment. MS-associated cognitive impairment was first described over a century ago. However, with the advent of standardized neuropsychological testing and quantitative brain imaging, the frequency, quality, and correlates of cognitive impairment are better understood. Dementia is rare in MS, although it is known to occur in 10 to 25% of patients. Our data suggest a frequency of 22% among clinic attendees. In addition to the cognitive impairments evident in MS dementia, changes in personality and social behavior also occur. For example, some patients develop euphoria sclerotica and marked deficiency in social empathy, conditions that in combination with executive dysfunction cause considerable hardship for patients and caregivers. These neuropsychiatric manifestations of MS dementia are correlated with magnetic resonance imaging indicators of brain atrophy, including ventricle enlargement, neocortical volume, and normalized whole brain volume. Recent developments in pharmacological treatment for disease progression and management of cognitive symptoms hold promise for patients suffering from the degenerative aspects of MS.

REFERENCES

  • 1 Cruveilhier J. L'Anatomie Pathologique du Corps Humain. Paris; Bailliere 1842
  • 2 Charcot J M. Lectures on the Diseases of the Nervous System. London; New Sydenham Society 1877
  • 3 Rao S M, Hammeke T A, McQuillen M P et al.. Memory disturbance in chronic progressive multiple sclerosis.  Arch Neurol. 1984;  41 625-631
  • 4 Medaer R, De Smedt L, Swerts M, Geutjens J. Use of rating scales to reflect cognitive and mental functioning in multiple sclerosis.  Acta Neurol Scand Suppl. 1984;  101 65-67
  • 5 Rao S M. Neuropsychology of multiple sclerosis: a critical review.  J Clin Exp Neuropsychol. 1986;  8 503-542
  • 6 Rao S M, Leo G J, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I: frequency, patterns, and prediction.  Neurology. 1991;  41 685-691
  • 7 Heaton R K. Neuropsychological findings in relapsing-remitting and chronic-progressive multiple sclerosis.  J Consult Clin Psychol. 1985;  53 103-110
  • 8 Bobholz J A, Rao S M. Cognitive dysfunction in multiple sclerosis: a review of recent developments.  Curr Opin Neurol. 2003;  16 283-288
  • 9 Benedict R HB, Fischer J S, Archibald C J et al.. Minimal neuropsychological assessment of MS patients: a consensus approach.  Clin Neuropsychol. 2002;  16 381-397
  • 10 Archibald C J, Fisk J D. Information processing efficiency in patients with multiple sclerosis.  J Clin Exp Neuropsychol. 2000;  22 686-701
  • 11 DeLuca J, Johnson S K, Natelson B H. Information processing efficiency in chronic fatigue syndrome and multiple sclerosis.  Arch Neurol. 1993;  50 301-304
  • 12 Demaree H A, DeLuca J, Gaudino E A, Diamond B J. Speed of information processing as a key deficit in multiple sclerosis: implications for rehabilitation.  J Neurol Neurosurg Psychiatry. 1999;  67 661-663
  • 13 Litvan I, Grafman J, Vendrell P, Martinez J. Multiple memory deficits in patients with multiple sclerosis: exploring the working memory system.  Arch Neurol. 1988;  45 607-610
  • 14 Lengenfelder J, Chiaravalloti N D, Ricker J H, DeLuca J. Deciphering components of impaired working memory in multiple sclerosis.  Cogn Behav Neurol. 2003;  16 28-39
  • 15 DeLuca J, Chelune G, Tulsky D S et al.. Is speed of processing or working memory the primary information processing deficit in multiple sclerosis?.  J Clin Exp Neuropsychol. 2004;  26 550-562
  • 16 Arnett P A. Speed of presentation influences story recall in college students and persons with multiple sclerosis.  Arch Clin Neuropsychol. 2004;  19 507-523
  • 17 Rao S M, Hammeke T A, McQuillen M P et al.. Memory disturbance in chronic progressive multiple sclerosis.  Arch Neurol. 1984;  41 625-631
  • 18 DeLuca J, Barbieri-Berger S, Johnson S K. The nature of memory impairments in multiple sclerosis: acquisition versus retrieval.  J Clin Exp Neuropsychol. 1994;  16 183-189
  • 19 Rao S M, Leo G J, St Aubin-Faubert P. On the nature of memory disturbance in multiple sclerosis.  J Clin Exp Neuropsychol. 1989;  11 699-712
  • 20 DeLuca J, Gaudino E A, Diamond B J et al.. Acquisition and storage deficits in multiple sclerosis.  J Clin Exp Neuropsychol. 1998;  20 376-390
  • 21 Ryan L, Clark C M, Klonoff H et al.. Patterns of cognitive impairment in relapsing-remitting multiple sclerosis and their relationship to neuropathology on magnetic resonance images.  Neuropsychology. 1996;  10 176-193
  • 22 Vleugels L, Lafosse C, van Nunen A et al.. Visuoperceptual impairment in multiple sclerosis patients diagnosed with neuropsychological tasks.  Mult Scler. 2000;  6 241-254
  • 23 Beatty W W, Monson N. Problem solving by patients with multiple sclerosis: comparison of performance on the Wisconsin and California Card Sorting Test.  J Int Neuropsychol Soc. 1996;  2 134-140
  • 24 Foong J, Rozewicz L, Quaghebeur G et al.. Executive function in multiple sclerosis: the role of frontal lobe pathology.  Brain. 1997;  120 15-26
  • 25 Achiron A, Barak Y. Cognitive impairment in probable multiple sclerosis.  J Neurol Neurosurg Psychiatry. 2003;  74 443-446
  • 26 Lyon-Caen O, Jouvent R, Hauser S et al.. Cognitive function in recent-onset demyelinating diseases.  Arch Neurol. 1986;  43 1138-1141
  • 27 Amato M P, Ponziani G, Pracucci G et al.. Cognitive impairment in early-onset multiple sclerosis: pattern, predictors, and impact on everyday life in a 4-year follow-up.  Arch Neurol. 1995;  52 168-172
  • 28 Amato M P, Ponziani G, Siracusa G, Sorbi S. Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years.  Arch Neurol. 2001;  58 1602-1606
  • 29 Gronwall D M. Paced auditory serial-addition task: a measure of recovery from concussion.  Percept Mot Skills. 1977;  44 367-373
  • 30 Smith A. Symbol Digit Modalities Test: Manual. Los Angeles; Western Psychological Services 1982
  • 31 Rao S M. Neuropsychological Screening Battery for Multiple Sclerosis. National Multiple Sclerosis Society, unpublished manual 1991
  • 32 Rudick R, Antel J, Confavreux C et al.. Clinical outcomes assessment in multiple sclerosis.  Ann Neurol. 1996;  40 469-479
  • 33 Cutter G R, Baier M L, Rudick R A et al.. Development of a multiple sclerosis functional composite as a clinical trial outcome measure.  Brain. 1999;  122 871-882
  • 34 Fischer J S, Rudick R A, Cutter G R, Reingold S C. The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force.  Mult Scler. 1999;  5 244-250
  • 35 Delis D C, Kramer J H, Kaplan E, Ober B A. California Verbal Learning Test Manual: Adult Version. 2nd ed. San Antonio, TX; Psychological Corporation 2000
  • 36 Benedict R HB. Brief Visuospatial Memory Test-Revised: Professional Manual. Odessa, FL; Psychological Assessment Resources 1997
  • 37 Delis D C, Kaplan E, Kramer J H. Delis-Kaplan Executive Function System. San Antonio, TX; Psychological Corporation 2001
  • 38 Benton A L, Sivan A B, Hamsher K et al.. Contributions to Neuropsychological Assessment. 2nd ed. New York; Oxford University Press 1994
  • 39 Parmenter B A, Zivadinov R, Kerenyi L et al.. Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) sorting tests in multiple sclerosis.  J Clin Exp Neuropsychol. , In press
  • 40 Benedict R H. Effects of using same- versus alternate-form memory tests during short-interval repeated assessments in multiple sclerosis.  J Int Neuropsychol Soc. 2005;  11 727-736
  • 41 Benedict R HB, Cookfair D L, Gavett R et al.. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).  J Int Neuropsychol Soc. 2006;  12 549-558
  • 42 Arnett P A, Rao S M, Bernardin L et al.. Relationship between frontal lobe lesions and Wisconsin Card Sorting Test performance in patients with multiple sclerosis.  Neurology. 1994;  44 420-425
  • 43 Pujol J, Bello J, Deus J et al.. Lesions of the left arcuate fasiculus region and depressive symptoms in multiple sclerosis.  Neurology. 1997;  49 1105-1110
  • 44 Zivadinov R, Sepcic J, Nasuelli D et al.. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis.  J Neurol Neurosurg Psychiatry. 2001;  70 773-780
  • 45 Rovaris M, Comi G, Rocca M A et al.. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications.  Brain. 2001;  124 1803-1812
  • 46 Benedict R HB, Weinstock-Guttman B, Fishman I et al.. Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden.  Arch Neurol. 2004;  61 226-230
  • 47 Fabiano A J, Sharma J, Weinstock-Guttman B et al.. Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study.  J Neuroimaging. 2003;  13 307-314
  • 48 Bakshi R, Benedict R HB, Bermel R A et al.. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study.  Arch Neurol. 2002;  59 62-68
  • 49 Cifelli A, Arridge M, Jezzard P et al.. Thalamic neurodegeneration in multiple sclerosis.  Ann Neurol. 2002;  52 650-653
  • 50 Simon J H, Kinkel R P, Jacobs L et al.. A Wallerian degeneration pattern in patients at risk for MS.  Neurology. 2000;  54 1155-1160
  • 51 Mesulam M M. Large scale neurocognitive networks and distributed processing for attention, language, and memory.  Ann Neurol. 1990;  28 597-613
  • 52 Houtchens M K, Benedict R HB, Killiany R et al.. Thalamic atrophy in multiple sclerosis: clinical-MRI correlations.  Neurology. 2005;  64 A260
  • 53 Benedict R H, Bruce J M, Dwyer M G et al.. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis.  Arch Neurol. 2006;  63 1301-1306
  • 54 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC; American Psychiatric Association 2000
  • 55 Benedict R HB, Priore R L, Miller C et al.. Personality disorder in multiple sclerosis correlates with cognitive impairment.  J Neuropsychiatry Clin Neurosci. 2001;  13 70-76
  • 56 Buchanan R J, Martin R A, Moore L et al.. Nursing home residents with multiple sclerosis and dementia compared to other multiple sclerosis residents.  Mult Scler. 2005;  11 610-616
  • 57 Zarei M, Chandran S, Compston A, Hodges J. Cognitive presentation of multiple sclerosis: evidence for a cortical variant.  J Neurol Neurosurg Psychiatry. 2003;  74 872-877
  • 58 Christodoulou C, Krupp L B, Liang Z et al.. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients.  Neurology. 2003;  60 1793-1798
  • 59 Benedict R H, Shapiro A, Priore R et al.. Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.  Mult Scler. 2000;  6 391-396
  • 60 Finger S. A happy state of mind.  Arch Neurol. 1998;  55 241-250
  • 61 Diaz-Olavarrieta C, Cummings J L, Velazquez J, Cadena C G. Neuropsychiatric manifestations of multiple sclerosis.  J Neuropsychiatry Clin Neurosci. 1999;  11 51-57
  • 62 Fishman I, Benedict R HB, Bakshi R, Priore R. Construct validity and frequency of euphoria sclerotica in multiple sclerosis.  J Neuropsychiatry Clin Neurosci. 2004;  16 350-356
  • 63 Benedict R HB, Carone D, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.  J Neuroimaging. 2004;  14 36S-46S
  • 64 Knight R G, Devereux R C, Godfrey H PD. Psychosocial consequences of caring for a spouse with multiple sclerosis.  J Clin Exp Neuropsychol. 1997;  19 7-19
  • 65 Costa P T, McCrae R R. NEO PI-R Professional Manual. Odessa, FL; Psychological Assessment Resources 1992
  • 66 Costa P T, McCrae R R. Professional Manual for the Revised NEO Personality Inventory and NEO Five-Factor Inventory. Odessa, FL; Psychological Assessment Resources 1992
  • 67 Cummings J L, Mega M, Gray K et al.. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia.  Neurology. 1994;  44 2308-2314
  • 68 Carone D A, Benedict R H, Dwyer M G et al.. Semi-automatic brain region extraction (SABRE) reveals superior cortical and deep gray matter atrophy in MS.  Neuroimage. 2006;  29 505-514
  • 69 Lee M, Reddy H, Johansen-Berg H et al.. The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.  Ann Neurol. 2000;  47 606-613
  • 70 Audoin B, Duong M, Ranjeva J et al.. Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis.  Hum Brain Mapp. 2005;  24 216-228
  • 71 Wishart H A, Saykin A J, McDonald B C et al.. Brain activation patterns associated with working memory in relapsing-remitting MS.  Neurology. 2004;  62 234-238
  • 72 Mainero C, Caramia F, Pozzilli C et al.. FMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis.  Neuroimage. 2004;  21 858-867
  • 73 Fischer J S, Priore R L, Jacobs L D et al.. Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group.  Ann Neurol. 2000;  48 885-892
  • 74 Krupp L B, Christodoulou C, Melville P et al.. Donepezil improves memory in multiple sclerosis in a randomized clinical trial.  Neurology. 2004;  63 1579-1585
  • 75 Geisler M W, Sliwinski M, Coyle P K et al.. The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis.  Arch Neurol. 1996;  53 185-188

Ralph H.B BenedictPh.D. 

Department of Neurology, Suite D-6, Buffalo General Hospital

100 High Street, Buffalo, NY 14203

    >