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Published on: January 7, 2019
Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic
Giulia Fadda1, Alonso Cardenas de la Parra1, Julia O'Mahony1
1From the Department of Medicine (G.F), University of Ottawa, Ottawa Hospital Research Institute; Montreal Neurological Institute (A.C.P., S.N., D.L.A., D.L.C.), McGill University, Quebec; Department of Community Health Sciences (J.O.M., R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Nuffield Department of Clinical Neurosciences (P.W.), John Radcliffe Hospital, University of Oxford, United Kingdom; Department of Pediatrics (E.A.Y.), University of Toronto, Ontario, Canada; Center for Neuroinflammation and Neurotherapeutics (A.B.-O.), and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Internal Medicine (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; and Division of Child Neurology (B.B.), Department of Neurology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania.
Background And Objectives:
Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination.
Methods:
We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized z scores for brain volume using a normative dataset of 813 brain MRI scans obtained from typically developing children and used mixed-effect models to assess potential deviation from brain growth trajectories.
Results:
We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (p < 0.001) age-expected and sex-expected growth of thalamus, caudate, and globus pallidus, normalized for the whole brain volume. Divergence from expected growth was particularly pronounced in the first year postonset and was detected even in children with monophasic MOGAD. Thalamic volume abnormalities were less pronounced in children with MOGAD compared with those in children with MS.
Discussion:
The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.
Insights
Pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) negatively impacts brain growth in children, particularly deep gray matter structures. This adverse effect on brain development is evident even in monophasic MOGAD cases.
Area of Science:
- Pediatric neurology
- Neuroimmunology
- Developmental neuroscience
Background:
- Pediatric-acquired demyelination involves myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), a condition with variable clinical courses.
- The effect of MOGAD on brain growth trajectories in children remains largely unknown.
- Comparing MOGAD's impact on brain growth with multiple sclerosis (MS) and monophasic demyelination provides critical insights.
Purpose of the Study:
- To quantify the impact of pediatric MOGAD on brain growth trajectories.
- To compare brain growth in children with MOGAD to healthy children, those with MS, and those with monophasic seronegative demyelination.
- To identify specific brain regions affected by MOGAD during maturation.
Main Methods:
- Prospective longitudinal Canadian Pediatric Demyelinating Disease Study data were analyzed.
- Brain MRI scans from children with MOGAD, MS, and monophasic demyelination were assessed.
- Age- and sex-normalized brain volumes were computed and compared to normative data using mixed-effect models.
Main Results:
- Children with MOGAD showed delayed age- and sex-expected growth in thalamus, caudate, and globus pallidus.
- Growth divergence was most pronounced in the first year post-MOGAD onset and observed in monophasic cases.
- Thalamic volume abnormalities were less severe in MOGAD compared to MS.
Conclusions:
- Childhood MOGAD onset adversely affects deep gray matter growth trajectories.
- Accelerated changes in brain volume occur in the months following an acute MOGAD attack.
- Further research is needed to differentiate impacts of monophasic versus relapsing MOGAD and specific attack locations.
