Childhood-Onset MS Moves Slowly, But Disables Younger

LYON, France, June 21 -- When multiple sclerosis (MS) strikes in childhood, it develops more slowly than adult-onset disease, but still leads to irreversible disability at a younger age, researchers here found.

In a large, observational study, patients who developed MS by age 16 took approximately 10 years longer to reach progression landmarks than those with adult-onset disease, but they reached those landmarks at an age approximately 10 years younger (P<0.001 for both).

The findings are in accord with smaller studies of the natural history of childhood-onset MS, reported Christian Confavreux, M.D., of Universit Lyon 1, and colleagues in the June 21 issue of the New England Journal of Medicine.

"Efforts to improve therapy for multiple sclerosis have focused on the population with adult-onset disease," they wrote. Adding that, although childhood-onset MS represents only 0.4% to 10.5% of cases, these patients "clearly deserve similar attention."

The researchers studied the disease course of 394 MS patients with disease onset by age 16 (mean age 13.7) and a comparison group of 1,775 patients with MS onset after age 16 (mean age 32.2).

Data was collected retrospectively at patients' first visit and prospectively thereafter when the patients were seen at the 13 adult neurology departments in Belgium and France affiliated with the European Database for Multiple Sclerosis network. The data was validated with medical records.

Mean duration of disease after onset during follow-up was 17.1 years in the childhood-onset group and 11.5 years in the adult-onset group.

Among the findings comparing childhood-onset MS with adult-onset disease, the researchers reported:

• The initial course was exacerbating-remitting in 97.7% versus 84.3% (P<0.001).
• The female-to-male ratio was higher among those with childhood-onset disease (2.8 vs. 1.8, P<0.001).
• Encephalitic symptoms, such as headache, vomiting, seizures, or disorders of consciousness were present in 7.4% of the childhood-onset group but in virtually none of the adult-onset group.
• Isolated optic neuritis and isolated brain-stem dysfunction were more frequent with childhood-onset disease (23.4% versus 17.9% and 16.8% versus 8.5%, respectively, both P<0.001).
• Isolated dysfunction of long tracts-such as corticospinal and sensory tracts-was less frequent with childhood-onset MS (37.8% versus 52.9%, P<0.001).

The time from onset to the second neurologic episode was similar between groups (2.0 vs. 2.2 years, P=0.2), but, median time to secondary progression among those with childhood-onset disease was about 10 years longer (28.1 versus 18.8, P<0.001) and occurred at an earlier age (41.4 versus 52.1 (P<0.001).

The disability progression findings on the Kurtzke Disability Status Scale for the childhood-onset group in comparison with the adult-onset group were:

• A disability score of four, representing limited walking ability, took longer to reach after onset (20.0 versus 8.1 years, P<0.001) but was reached at a younger age (34.6 versus 44.6, P<0.001).
• A disability score of six, representing ability to walk only with unilateral support, likewise took longer to reach after onset ((28.9 versus 19.7 years, P<0.001) but was reached at a younger age (42.2 versus 54.8, P<0.001).
• A disability score of seven, indicating ability to walk only by using a wall or furniture for support, also took longer to reach (37.0 versus 30.1 years, P<0.001) but at a younger age (50.5 versus 63.2, P<0.001).

The only significant prognostic factor for age at development of irreversible disability-when a disability score persisted for at least six months excluding transient relapses-was whether the initial course of the disease was progressive rather than relapsing-remitting. The adjusted hazard ratios were 2.94 for a score of four, 4.48 for a score of six, and 3.13 for a score of seven.

The researchers noted that their study may have been subject to selection bias if some patients with childhood-onset multiple sclerosis were not seen in adult neurology departments because they had such severe disease that they died in childhood or such benign disease that they required no specialized care in adulthood.

However, "we think both situations are rare," Dr. Confavreux and colleagues wrote.

Noting that their findings are consistent with other studies, the researchers believe that "the present results, drawn entirely from one region of Europe, can be generalized to other populations."