Quantitative Determination of Regional Lesion Volume and Distribution in Children and Adults with Relapsing-Remitting Multiple Sclerosis

Abstract

IntroductionOnset of MS occurs during childhood in about 5% of cases. It is unclear whether very young age at MS onset, when the nervous system is still myelinating, affects MS lesion accrual or regional distribution.ObjectiveTo compare the frequency, volume and distribution of T2 and T1 lesions in children and adults with relapsing-remitting multiple sclerosis (RRMS).MethodsLesions were segmented on T2- and T1-weighted MRI images from 29 children and 29 adults with RRMS, matched for disease duration.ResultsAll subjects exhibited T2-weighted brain lesions. Children had higher whole-brain T2-weighted-lesion-volume (T2LV) compared to adults (mean (SD) in cm3: 12.76(2.7) vs. 10.03(3.4), p<0.0013). The supratentorial-T2LV was similar in children and adults (8.45(1.7) vs. 7.94(1.7), mean (SD), p = 0.2582), but adults were more likely to have supratentorial lesions (96.5% vs. 68.9%, p<0.012). Children were more likely to have infratentorial-T2-weighted lesions (75.9% vs. 43.4%, p<0.03), specifically in the brainstem (62.1% vs. 26.7%, p<0.019) and the pons (48.3% vs. 17.24%, p<0.024), had higher infratentorial-T2-weighted-lesion counts (4.1(5.6) vs. 1.45(2.3), p<0.021), a greater infratentorial-T2LV (4.31(2.7) vs. 2.08(2.4), p<0.0013), and a greater infratentorial-T1-weighted-lesion-volume (T1LV) (3.7(2.5) vs. 1.08(1.9), p<0.0007). Whole-brain-T1LV was higher in children (9.3(2.5) vs. 6.43(2.1), p>0.001). Adult MS patients had higher supratentorial-T1LV (5.5(0.92) vs. 6.41(2.1), mean (SD), p<0.034), whereas children were more likely to have infratentorial-T1-weighted lesions (58.6% vs. 23.3%, p<0.015).DiscussionOnset of MS during childhood is associated with a higher volume of brain lesions in the first few years of disease relative to adults. Children with MS are more likely than adults to have T2 and T1 lesions in the infratentorial white matter, raising the possibility of preferential immune targeting of more mature myelin. Children with MS have a lower supratentorial T1 lesion burden, possibly reflecting more effective remyelination and repair in brain regions that are still engaged in active primary myelination.

Treatment of multiple sclerosis in children and its challenges

“…As mentioned above, pediatric-onset MS patients have high relapse rates, with more than 75% of children having a second clinical attack within one year. They also have higher cerebrospinal fluid (CSF) white blood cell counts at diagnosis and a higher volume of brain lesions early in the disease with more infratentorial lesions as compared to patients with adult-onset MS [3,[11][12][13]. Despite having more attacks, pediatric patients tend to have complete and prompt recovery from their relapses and have a slow accrual of physical disability [3,14].…”

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

“…As mentioned above, pediatric patients with MS tend to have a more inflammatory course within the first 2 years of onset [11], manifesting with more frequent clinical relapses and a higher brain T2-and T1-weighted lesion volume [31][32][33][34]. Patients with pediatric-onset MS generally maintain good recovery from relapses with minimal-to-no progression in disability within the first 10 years of disease onset; however, irreversible disability and secondary progression ultimately occur at a much earlier age than in adult-onset MS [35].…”

Pediatric versus adult MS: similar or different?

“…-lesions are more frequently found in the cerebellum/ brainstem [86,87] Pathobiology and pathophysiology: common risk factors for a fairly rare disease?…”