All About Multiple Sclerosis

More MS news articles for August 2003

MS News

The following brief reports summarize research news recently published in the peer review literature.

International Journal of MS Care
page 1, Volume 5, Issue 2
Summer 2003

Health Impact of MS and Parkinson’s Disease

Researchers in the United Kingdom found that measures of health status, such as the 36-item short form health survey (SF-36), can be useful in detecting areas of disease impact that may not be obvious from clinical investigation. Their report, published in the June Journal of Neurology, Neurosurgery and Psychiatry, compared 638 patients representing the full spectrum of multiple sclerosis (MS) and 227 patients with Parkinson’s disease to 2,056 controls. Scores for the eight health domains of the SF-36 were compared between groups after controlling for age, sex, disease duration, mobility, social class, ethnicity, education, marital status, and employment status.

The investigators found that patients with MS and those with Parkinson’s disease had significantly worse health than the controls on all eight domains of the SF-36. While the relative impact of MS and Parkinson’s disease was similar, MS resulted in poorer scores on physical functioning and better scores on mental health than Parkinson’s disease. The researchers added that patients with mild MS who walked without an aid also had significantly worse scores in all dimensions than did controls.

The results highlight both the utility of the SF-36 as a measure of disease impact and the need for further research into the aspects of health measured by the SF-36. While the information generated through such measures, when supplemented by additional investigations (such as assessment of health care needs) is capable of guiding subsequent disease intervention, it is important to remember that generic measures may fail to address clinically important aspects of the impact of a specific disease, they concluded.

Riazi A, Hobart JC, Lamping DL, et al. Using the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson’s disease with normal population health profiles. J Neurol Neurosurg Psychiatry. 2003;74:710-714.

New T2 Lesions Enable Earlier Diagnosis of MS

In clinically isolated syndromes, the new McDonald criteria for the diagnosis of MS require new gadolinium- enhancing lesions for dissemination in time at a three-month follow-up MRI scan. According to a report published in the May Annals of Neurology, the addition of new T2 lesions as an alternative for dissemination in time would increase the sensitivity while maintaining the diagnostic specificity for clinically definite MS at three years.

Researchers in the United Kingdom examined 56 patients (30 female) between ages 16 and 50 with clinically isolated syndromes suggestive of MS who had been followed clinically for three years after having an MRI at baseline. Patients underwent T2-weighted and gadolinium-enhanced T1-weighted brain MRI at baseline, three months, one year, and three years. During the course of the study, 20 patients developed new T2 lesions at three months; only 14 had new gadolinium-enhancing lesions, the researchers reported. The specificity of the McDonald criteria for clinically definite MS at three months was 95%, but sensitivity was only 58%. Eight patients who did not fulfill the McDonald criteria at three months developed clinically definite MS at three years.

The addition of new T2 lesions to the criteria of MRI dissemination in time at three months also had high specificity (92%) and better sensitivity (74%) than the McDonald criteria. Only five patients who failed T2-MRI criteria at three months developed clinically definite MS after three years. Regardless of the number of lesions on the baseline scan, a new T2 lesion was sensitive (84%) and specific (89%) for clinically definite MS, the researchers added. They proposed that, based on their findings, the McDonald MRI criteria for dissemination in time be expanded to include T2 lesions seen on three-month follow-up scans.

Dalton CM, Brex PA, Miszkiel KA. New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes. Ann Neurol. 2003;53:673-676.

Epstein-Barr Antibodies Elevated Prior to MS Onset

There is a relationship between Epstein-Barr virus and the development of MS, suggests a study in the March 26 JAMA. While previous research has associated the virus with an increased risk of MS, the temporal relationship between the two has remained unclear.

Researchers assessed the blood samples of more than three million military personnel whose blood was collected upon entry into the military and every two years thereafter since 1988 for various Epstein-Barr virus antibodies. For each of the 83 cases of personnel granted disability due to MS, the investigators identified the earliest available serum sample, plus two samples collected before MS onset and the first sample collected after onset. Each case was matched to two controls with the same sex and ethnicity, and similar ages and dates of blood collection.

All of the cases and 96% of the controls showed evidence of Epstein-Barr virus infection at baseline, and the mean time between initial blood collection and the MS onset was four years. The researchers found that “the baseline mean serum antibody titers to Epstein-Barr virus were consistently higher among individuals who later developed MS than among their matched controls.” They noted that the lack of variation in antibody concentrations between blood samples collected six to 11 years prior to onset and those taken later suggests that “the increased antibody response to Epstein-Barr virus occurs early in relation to the pathological process that leads to demyelination and clinical disease.”

Levin LI, Munger KL, Rubertone MV, et al. Multiple sclerosis and Epstein-Barr virus. JAMA. 2003;289:1533-1536.

Cost-Effective Management of MS

The cost of treating MS is high, but it decreases with prolonged treatment, according to research in the March 8 BMJ. Researchers evaluated the cost-effectiveness of four drugs currently licensed for the treatment of relapsing-remitting and secondary progressive MS in the United Kingdom (three interferon bs and glatiramer acetate). Using a model to simulate the clinical course of the disease, they assessed the effect of each drug against conventional management during a 20-year period, measuring cost per quality-adjusted life year gained. The investigators calculated that the cost of each year of life saved or prolonged by using any of the four treatments ranged from approximately $66,469 to $156,800. Cost-effectiveness varied markedly between the four interventions, and price was the key modifiable determinant of the cost-effectiveness for each drug. For any intervention, the cost per quality- adjusted life year gained is unlikely to be less than $64,000, they reported. The researchers emphasized, however, that uncertainty surrounding these estimates is substantial, largely due to the unpredictability of the disease and the difficulty in capturing all aspects of its impact on patients. Experience after stopping treatment (which usually occurred after 10 years) is a key factor in calculating long-term cost effectiveness, they noted.

Chilcott J, McCabe C, Tappenden P, et al. Modeling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. BMJ. 2003;326:522-525.

Validation of Diagnostic MRI Criteria for MS and Response to Interferon b1a

The modified Barkhof imaging criteria supported by the McDonald diagnostic criteria for MS were tested for their predictive value for the progression to clinically definite MS by the Early Treatment of Multiple Sclerosis Study Group. Additionally, the researchers attempted to determine whether the Barkhof criteria were predictive of a response to weekly treatment with subcutaneous interferon b1a. The study results were published in the June issue of the Annals of Neurology.

MRI was performed on 309 patients enrolled in the randomized, double-blind, placebo-controlled Early Treatment of MS study as part of the prestudy screening and at the end of months 12 and 24. At baseline, all patients had supratentorial T2 lesions and 64% had infratentorial T2 lesions. Enhancing lesions were present in 59% of patients, and enhancing or nine or more T2 lesions in 94%. Most patients had either three (36%) or four (50%) modified Barkhof criteria present at baseline.

Overall, conversion to clinically definite MS within two years of follow-up occurred in 39.3% of patients. Conversion was more likely to occur in the presence of gadolinium enhancement or nine T2 lesions, with nine T2 lesions seeming to have a slightly more prognostic value, the researchers reported. In patients with multifocal presentation, the baseline MRI findings had no significant additional predictive value, whereas in patients with unifocal presentation, the baseline MRI findings did convey predictive value. Additionally, when the individual Barkhof criteria were fulfilled, the odds ratio for treatment effect was statistically significant. The effect of interferon b1a seems stronger in patients with a high number of positive MRI criteria, the researchers noted. However, the study was not of sufficient statistical power to render this significant, and further assessment is required.

Barkhof F, Rocca M, Francis G, et al. Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon b1a. Ann Neurol. 2003;53:718-724.

Two Perspectives of MS Disability

MS patients’ perception of change in disability differs not only quantitatively but also qualitatively from that of a physician, according to a longitudinal study published in the April Journal of Neurology, Neurosurgery and Psychiatry. Investigators aimed to characterize the relationship between one-year changes in neurologist ratings of exam abnormalities, measured by the Expanded Disability Status Scale (EDSS), and changes in the patient’s perceived disability, measured by the Guy’s Neurological Disability Scale (GNDS).

Two hundred fifty patients with MS were recruited from an outpatient clinic. The investigators found that the correlation between one-year changes in EDSS versus GNDS was significantly lower than cross-sectional correlations between the two scales at baseline and at follow-up. Interestingly, there were opposite changes in EDSS scores and GNDS scores in 8% of patients, they noted. In addition, the researchers also reported that “dependent on the criterion applied for significant change in the GNDS, 10% to 22% of the patients who have a significant worsening on the EDSS show a significant improvement in perceived disability.” Three reasons given for the discrepancies in the change in scores were “differences in the change perceived by the patient and that measured by the physician, changes in many disability subcategories not leading to changes in EDSS, and the GNDS incorporating aspects of disability (for example, fatigue) that are not at all considered by the EDSS.”

Hoogervorst ELJ, Eikelenboom MJ, Uitdehaag BMJ, Polman CH. One year changes in disability in multiple sclerosis: neurological examination compared with patient self-report. J Neurol Neurosurg Psychiatry. 2003;74:439-442.

Copyright © 2003, International Journal of MS Care