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ARTICLES: Ana-Luiza Sayao, Virginia Devonshire, and Helen Tremlett Longitudinal follow-up of "benign" multiple sclerosis at 20 years Neurology 2007; 68: 496-500 [Abstract] [Full text] [PDF]

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Longitudinal follow-up of "benign" multiple sclerosis at 20 years

Maria Pia Amato, Nicola De Stefano, Department of Neurology, University of Siena (Italy)   (24 April 2007)

Reply from the Authors

Helen L. Tremlett, Ana-Luiza Sayao and Virginia Devonshire   (24 April 2007)

Longitudinal follow-up of "benign" multiple sclerosis at 20 years 24 April 2007
Maria Pia Amato, Department of Neurology, University of Florence Viale Morgagni 85, 50134 Florence, Italy, Nicola De Stefano, Department of Neurology, University of Siena (Italy) Send Correspondence to journal: Re: Longitudinal follow-up of "benign" multiple sclerosis at 20 years mariapia.amato{at}unifi.it Maria Pia Amato, et al.	We read the article by Sayao et al who address the controversial issue of the benign form of multiple sclerosis (MS). [1] They report that, at 10 years from disease onset, neither an Expanded Disability Status Scale (EDSS) score </= 3 nor an EDSS score </= 2 adequately represented benign MS and, after 20-years, half of the population was no longer benign. The authors conclude that appropriate and reliable criteria to identify which MS patients will have mild disability over the long-term is still unclear. However, we believe that this cannot be based solely on EDSS cut-offs. We recently assessed an extensive neuropsychological battery of a clinic-based sample of 163 patients with EDSS </= 3.0 after at least 15 years from MS onset. [2] We found significant cognitive impairment in 45% of the subjects, depression in 54% and fatigue in 49%, with a negative impact on work and social activities. These results were further confirmed using a more conservative EDSS cut-off of 2.0 confirming that a simple definition of benign MS on the basis of EDSS score may be misleading as the proportion of benign subjects by be overestimated. It is very possible that a significant proportion of patients with MS may not have (and maintain over time) a mild clinical course. About 50% of the population described by Sayao and et al continued to have a mild clinical course after 20 years. This data suggests that a less aggressive form of MS does exist. In a recent MR study, we used magnetization transfer (MT) imaging and found biological evidence that patients with benign MS may be distinguished from other MS forms on the basis of their minor tissue damage. [3] We found that benign patients (disease duration >/= 15 years, EDSS score </= 3.0) were characterized by minor tissue damage even in comparison with relapsing-remitting patients in the incipient phases of MS, with disease duration </=3 years and comparable disability levels. In conclusion, we believe that while a reassessment of criteria to define benign MS is imperative and a correct definition cannot exclude cognition, patients with a benign course exist and new quantitative MR metrics including MT imaging may be helpful in the early identification and correct differentiation from other disease forms. References 1. Sayao AL, Devonshire V, Tremlett H. Longitudinal follow-up of “benign” multiple sclerosis at 20 years. Neurology 2007;68:496-500. 2. Amato MP, Zipoli V, Goretti B et al. Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 2006;253:1054-1059. 3. De Stefano N, Battaglini M, Stromillo ML et al. Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis. Brain 2006;129:2008-2016. Disclosure: The authors report no conflicts of interest.
Reply from the Authors 24 April 2007
Helen L. Tremlett, University of British Columbia, Medicine (Neurology) Rm. S178, UBC Hospital, 2211 Wesbrook Mall, University of British Columbia,Vancouver, BC. V6T 2B5, Ana-Luiza Sayao and Virginia Devonshire Send Correspondence to journal: Re: Reply from the Authors tremlett{at}interchange.ubc.ca Helen L. Tremlett, et al.	Drs. Amato and DeStefano provide a valuable update to the benign MS literature by highlighting further data that was published subsequent to our paper being submitted to Neurology. We agree that benign MS cannot be defined or described solely on the use of somewhat arbitary cut-offs on the EDSS scale. We found that reasonably high proportions of patients progressing to ‘not benign’ after 20 years despite a relatively low EDSS score at 10 years. [1] Furthermore, we were unable to find robust predictors of who would remain ‘benign’ in the risk factors available to us (onset age, gender, onset symptoms and EDSS score at 10 years). The limitations of the EDSS scale are well-known and we acknowledge that patients with low EDSS scores may have marked disability caused by symptoms not readily reflected by the scale such as fatigue, cognitive or functional impairments. [1] Few studies have previously addressed this issue and we are encouraged by the additional studies cited by Dr. Amato et al. [2,3] Despite these advances, defining and predicting benign MS remains a challenge. Patients who do remain ‘benign’ over extended time may provide insight into what is required to modulate the disease process, perhaps prompting new therapeutic strategies. Disclosure: The authors report no conflicts of interest.