Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure

Abstract

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

Clinical and Magnetic Resonance Imaging Outcome Predictors in Pediatric Anti–N‐Methyl‐D‐Aspartate Receptor Encephalitis

“…This suggests that the biological onset of NMDARE in children might precede the clinical presentation, resulting in brain volume loss already present on the initial MRI. Similar observations, that is, reduced brain volumes already at disease onset, have also been reported in children with multiple sclerosis 18,32 …”

“…Similar observations, that is, reduced brain volumes already at disease onset, have also been reported in children with multiple sclerosis. 18,32 Limitations of the study include the retrospective study design, the relatively small sample size, especially in some of the subgroup analyses, and the lack of neuropsychological data. As this study aimed at exploring new clinical predictors, multiple comparison was not applied.…”

Multiple Sclerosis in Children: Current and Emerging Concepts

“…One study of Canadian children and one from France reported that children with MS have reduced whole brain volumes when assessed at a single time point and lower-than-expected brain growth over multiple time points compared with matched controls. 45,46 In the Canadian study, reduced regional brain growth in the thalamus was especially marked. Inconsistent associations have been reported between gray matter involvement and white matter lesion volume.…”

Effects of Fingolimod on MRI Outcomes in Patients with Pediatric-onset Multiple Sclerosis: Results from the Phase 3 ParadigMS Study

“…11 PoMS is associated with failure of age-expected brain growth during childhood and early adolescence, and brain atrophy from disease-onset to mid-adolescence and into adulthood. [12][13][14] Findings suggest that T2 and T1 lesion volumes are comparable in patients with paediatric-onset and adult-onset MS when matched for disease duration. 15 Higher T2 lesion volumes correlate with reduced thalamic volumes in paediatric patients, and total thalamic volumes are reduced relative to age-expected values, even after correcting for reductions in head size.…”