Introduction by Guest Editor: William H. Stuart, MD, Medical Director, MS Center of Atlanta, Georgia

Neurologists have long equated the major deficits in MS to be in mobility and sensation with Diplopia, and decreased vision a close second.

As MS centers with comprehensive care programs have developed, MS neurologists seeing large numbers of MS patients over extended periods are increasingly aware that several other more subtle aspects of MS are the major contributors to patients' socio-economic decline and loss of social position- including employment.

Fischer, Rao, Munschauer, and others have established the very high frequency of cognitive change in MS. The changes are reported to be present in as many as 60% of patients affected with MS. The unique features of this change include declines in multi-tasking, short-term recall, and executive level tasking.

The end result often leads to job loss and altered interpersonal relationships. While the cognitive decline is not often as severe as that in SDAT, it is devastating to the MS patient's place in their linked environment.

Factors close in impact on function are fatigue and loss of sexuality. I suspect that these factors are intimately dependent on the cognitive decline.

The lesson to be learned from this compelling data is that the early treatment of MS will reduce the likelihood of this progression.

Data Presented by: Stephen M. Rao, PhD, Professor of Neurology, Section of Neuropsychology, Medical College of Wisconsin, Milwaukee

Contrary to past assumptions, researchers now know that cognitive dysfunction is common in MS, occurring in 43-65 percent of patients. Even though these cognitive deficits can be viewed as mild in many cases, they nevertheless interfere with employment, socializing, and general functioning.

The types of cognitive dysfunction that occur in MS are not uniform, explained Stephen M. Rao, PhD. Declines are commonly observed on measures of sustained attention, recent memory, executive functions, and information processing speed, with language and intellectual skills being relatively spared. Studies at Dr. Rao's institution show that more than 20 percent of MS patients have deficits in information processing and memory, eight to nine percent have language deficits, and 12-19 percent have compromised visuospatial skills.

"Cognitively impaired MS patients are less likely to work and socialize, and they need more personal assistance than cognitively intact persons, even with the same EDSS," he told attendees.

Tests such as the Wisconsin Card Sort, the 12-Word List, and the PASAT (Paced Auditory Serial Addition Test) are used to detect cognitive impairment. The Wisconsin Card Sort Test requires patients to shift from one organizing concept (i.e., color) to another (shape). Many patients who take this test have trouble shifting to a new organizing principle (perseveration), which has negative implications for work performance. The 12-Word Sort List selectively reminds subjects to recall words, and the test identifies problems in learning and memory. "Patients with MS usually have no trouble . . . getting the information in; it's the retrieval of information that is faulty," explained Dr. Rao. PASAT is a sensitive test for information processing, and many MS patients have trouble performing the serial addition required by the test.

Results of neuropsychological tests (i.e., cognitive dysfunction) are highly correlated with total cerebral lesion load (T2-weighted MRI), but the correlations between MRI lesion load and EDSS have been somewhat disappointing, observed Dr. Rao. Correlates of cognitive dysfunction in MS patients include emotional factors, medications, severity of physical disability, duration of illness, and extent of brain involvement.

A natural history study of 77 community-based MS patients, conducted by Dr. Rao and colleagues, showed that over a three-year period, 62 patients had no change in cognitive function but 15 got worse (Rao et al. Neurology, 1991 May; 41(5): 685-91; Rao et al. Neurology, 1989 Feb; 39(2 Pt 1): 161-6). In the group that worsened, a greater total T2 lesion load was seen on MRI: an increase of nearly 15 cmІ compared to less than a 5 cmІ increase in the cognitively stable group (p < 0.003). The increase in EDSS in the two groups was roughly equivalent.

"This suggests that preventing new lesions with immunomodulatory treatment can prevent cognitive deterioration, whereas untreated groups with increased lesion burden and brain atrophy should demonstrate a worsening of cognitive function," he stated.

This report is supported by an unrestricted educational grant from Biogen, Inc. and published by Millennium Medical Communications, Inc. © 2001 Millennium Medical Communications, Inc.

Multiple Sclerosis Express Report™ is a product of Millennium Medical Communications, Inc. ("MMC, Inc."), an independent, third-party organization providing educational information concerning current medical data and opinions presented at worldwide medical meetings. The Multiple Sclerosis Express Report™ is published in accordance with the Guidance for Industry: Industry Supported Scientific and Educational Activities, 62 Fed. Reg. 64,093, 64,096-99 (1997) adopted by the U.S. Department of Health and Human Services Food and Drug Administration. Pursuant to the foregoing standards, MMC, Inc. is solely responsible for selecting the topics discussed herein. This Multiple Sclerosis Express Report™ may contain data on products, product uses, indications, and dosages which are not approved for use in the USA, Canada, and the European Union and no endorsement is hereby made or intended by coverage of any unapproved use. The content of this report is intended for educational purposes only, and merely conveys scientific data presented at medical meetings. Approved product labeling should always be consulted for prescribing information. The Multiple Sclerosis Express Report™ is an independent and non- promotional report intended to provide accurate scientific and medical information for educational purposes. MMC, Inc. is not responsible for errors or omissions in reports. The production of this report was supported by a wholly unrestricted educational grant from Biogen, Inc. Biogen, Inc. maintains no control, direct or indirect, over the content, substance, or distribution of this report.