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Does the Natural History of Childhood Onset MS Differ from Adult Onset?
Abstract & Commentary
By Susan Gauthier, DO, Assistant Professor of Neurology, Weill Medical College of Cornell University. Dr. Gauthier reports no financial relationships relevant to this field of study.
Synopsis: The time to secondary progression and irreversible disability in childhood-onset MS is slower as compared to adult-onset disease. However, it occurs at a younger age.
Source: Renoux C, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007;356:2603-2613.
The natural history of adult-onset multiple sclerosis (MS) has been well described in a number of large cohort studies, where in the average time for a patient to reach irreversible disability as measured on the Kurtzke Disability Status Scale (DSS) as well as time to secondary progression has been established. Short-term disease progression in adult-onset MS was recently evaluated using a Markov transitional model, which incorporates both clinical and MRI prognostic factors to create short-term predictive curves for various patient profiles.1 How our understanding of adult-onset MS can be applied to childhood-onset disease has yet to be fully established.
Renoux et al identified a cohort of 394 patients from the European Database for Multiple Sclerosis (EDMUS) with an onset of multiple sclerosis before the age of 16 and compared disability endpoints to the Lyon Natural History Multiple Sclerosis Cohort, an adult-onset MS cohort. In addition to secondary progression, endpoints of irreversible disability were studied and included a DSS score that could be easily assigned retrospectively - DSS of 4 (walking limited to 500 meters), a score of 6 (walking that requires unilateral support), and a score of 7 (the ability to walk no more than 10 meters with an aid). Information regarding the disease course was obtained retrospectively at the time of initial visit and was collected prospectively thereafter.
The mean age of MS onset within the childhood-onset cohort was 13.7 years and the patients were followed for a mean of 17 years. The female to male ratio was higher and more often had a relapsing-remitting onset (98% vs. 84%) as compared to the adult cohort. At disease onset, isolated optic neuritis or brain-stem symptoms occurred more frequently in childhood-onset MS as compared to adult-onset, whereas long-tract symptoms, although the most common initial presentation in both cohorts, occurred less frequently in children as compared to adults. In addition, encephalitic symptoms were present in 7% of childhood-onset patients and essentially absent in adult-onset disease. Secondary progression occurred in 28.6% of the childhood-onset patients after 28 years and at a median age of 41; progression in this cohort was 10 years slower than the adult cohort; however, the childhood-onset patients were 10 years younger when they reached this stage. The times to reach DSS of 4, 6 and 7 for childhood-onset MS were 34.6, 42.2, and 50.5 years, respectively, and were approximately 10 years longer as compared to adult-onset MS; however, once these patients reached an EDSS of 4, the time to an EDSS of 6 or 7 was similar to that of the adult cohort. As in secondary progression, childhood-onset patients were at least 10 years younger at these disability milestones. Prognostic factors associated with higher rates of disease progression included a progressive onset of disease or a higher relapse rate within the first 2 years.
This is the largest study to describe a cohort of childhood-onset MS patients and revealed distinct features of childhood-onset MS as compared to adult-onset MS; specifically, there is a higher female to male ratio, the initial course is more often relapsing-remitting and the development of irreversible disability follows a different course. In a separate study of the Lyon Natural History Multiple Sclerosis Cohort, disability was felt to be age dependent wherein regardless of the initial course, either relapsing-remitting or primary progressive, patients reached levels of irreversible disability at similar ages.2 However, in the Lyon cohort, as in the current study, the younger onset patients (< 19 years of age) were at risk for having irreversible disability at younger age although the time to the disability milestones was longer. Based upon the results of these studies, the age of onset of MS appears to influence the clinical phenotype of the disease.
Lastly, children with MS are typically treated with immunomodulatory drugs approved for the treatment of adult-onset disease and approximately one half of the patients had received therapy within this cohort. How phenotypic differences in MS influence the response to treatment is presently unknown. Therefore, an effort to further delineate the phenotype of childhood-onset MS and to study therapeutic options specific for this subgroup of MS is warranted.
1. Gauthier SA, et al. Prediction of short-term disability in multiple sclerosis. Neurology. 2007; 68: 2059-2065.
2. Confavreux C, Vukusic S. Age at disability milestones in multiple sclerosis. Brain. 2006 Mar; 129 (Pt 3):595-605.