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Correlates of long-term clinical outcomes in pediatric multiple sclerosis: A 12-year study
Monica Margoni1, Alessandro Meani2, Elisabetta Pagani2
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Insights
Advanced MRI markers and high-efficacy treatment exposure are linked to long-term outcomes in pediatric multiple sclerosis (Ped-MS) patients. These findings can help guide treatment decisions for children with MS.
Area of Science:
- Neuroimmunology
- Pediatric Neurology
- Radiology
Background:
- Understanding long-term outcomes in pediatric multiple sclerosis (Ped-MS) is crucial for effective treatment selection.
- This study investigated clinical and magnetic resonance imaging (MRI) correlates of disease progression over an extended follow-up period.
Purpose of the Study:
- To identify clinical and advanced MRI markers associated with long-term outcomes in pediatric multiple sclerosis.
- To explore the relationship between baseline imaging findings, treatment exposure, and disease course in Ped-MS patients.
Main Methods:
- Fifty-two Ped-MS patients and 23 healthy controls underwent baseline 3.0T MRI scans.
- Neurological evaluations were conducted every six months.
- MRI metrics included lesion burden, brain and choroid plexus volumes, and fractional anisotropy (FA) in normal-appearing white matter (NAWM). Multivariable regression models were used to analyze long-term outcome correlates.
Main Results:
- Long-term follow-up revealed relapse rates of 69%, 6-month confirmed disability worsening (6m-CDW) in 21%, and EDSS worsening in 35% of Ped-MS patients.
- Infratentorial and spinal cord lesion presence, along with thalamic volume, were associated with time to first relapse. High-efficacy treatment (HET) exposure was linked to a longer time to relapse.
- White matter lesion volume and HET exposure influenced overall relapse risk. Younger age and NAWM FA were associated with earlier 6m-CDW, with NAWM FA also correlating with EDSS worsening.
Conclusions:
- Advanced MRI markers, including lesion burden and white matter integrity, are significant predictors of long-term outcomes in pediatric multiple sclerosis.
- High-efficacy treatment exposure is associated with a reduced risk of relapse and disability worsening.
- These findings underscore the importance of early and aggressive treatment strategies informed by comprehensive MRI assessments in managing Ped-MS.
Background:
Identifying long-term outcome substrates in pediatric multiple sclerosis (Ped-MS) can inform treatment selection. We investigated clinical/magnetic resonance imaging (MRI) correlates over a median 12.3-year follow-up.
Methods:
Fifty-two Ped-MS patients and 23 healthy controls underwent baseline 3.0 T MRI. Neurological evaluations were performed every 6 months. MRI metrics included regional lesion burden, brain and choroid plexus (CP) volumes, diffusion tensor-derived fractional anisotropy (FA), averaged in normal-appearing white matter (NAWM). Multivariable Cox, Andersen-Gill, linear regression models identified long-term outcome correlates.
Results:
At follow-up, 69% relapsed, 21% had 6-month confirmed disability worsening (6m-CDW), and 35% showed EDSS worsening. Infratentorial lesion number (hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.02 to 1.18), spinal cord lesion presence (HR = 2.45, 95% CI = 1.18 to 5.10), and thalamic volume (HR = 0.77, 95% CI = 0.60 to 0.99) were associated with shorter time to first relapse; high-efficacy treatment (HET) exposure with longer (HR = 0.20, 95% CI = 0.06 to 0.68), and CP volume (HR = 1.58, 95% CI = 0.93 to 2.68) was associated marginally. WM lesion volume (HR = 1.04, 95% CI = 1.01 to 1.06) and HET exposure (HR = 0.21, 95% CI = 0.11 to 0.40) were associated with higher/lower overall relapse risk, respectively; baseline EDSS (HR = 1.29, 95% CI = 0.96 to 1.73), spinal cord lesion presence (HR = 1.52, 95% CI = 0.95 to 2.44), and CP volume (HR = 1.35, 95% CI = 1.00 to 1.83) contributed marginally. Younger age (HR = 0.82, 95% CI = 0.68 to 0.98) and NAWM FA (HR = 0.67, 95% CI = 0.51 to 0.88) were associated with earlier 6m-CDW; NAWM FA with EDSS worsening (β = -0.26, 95% CI = -0.50 to -0.03).
Conclusion:
Advanced MRI markers and HET exposure associate with long-term outcomes in Ped-MS.
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