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Distinguishing Transient From Persistent Brain Structural Changes in Pediatric Patients With Acute Disseminated
Jason Michael Millward1, Elias Pilgrim1, Matthias Baumann1
1From the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Ultrahigh Field Facility (B.U.F.F.); Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany; Division of Paediatric Neurology, Department of Paediatrics I, Medical University of Innsbruck, Austria; Department of Pediatric Neurology, Olgahospital/Klinikum Stuttgart; Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University and Department of Neurology, Charité - Universitätsmedizin Berlin, Germany.
Insights
Pediatric acute disseminated encephalomyelitis (ADEM) can cause ventricle volume (VV) expansion. Some patients show resolving VV expansion, while others have persistent increases linked to reduced brain volume and lasting neurological deficits.
Area of Science:
- Neuroscience
- Radiology
- Pediatric Neurology
Background:
- Pediatric acute disseminated encephalomyelitis (ADEM) poses risks for impaired brain growth and long-term neuropsychiatric issues.
- Previous studies in experimental autoimmune encephalomyelitis showed transient cerebral ventricle volume (VV) expansions that normalized.
- This study investigates VV changes in pediatric ADEM patients in relation to other brain structures and clinical outcomes.
Purpose of the Study:
- To investigate changes in ventricle volume (VV) in pediatric patients with acute disseminated encephalomyelitis (ADEM).
- To analyze VV changes in relation to other brain structures and clinical outcomes.
- To identify distinct patterns of VV changes and their long-term implications in ADEM.
Main Methods:
- A multicenter cohort of 61 pediatric ADEM patients (39 MOG antibody-positive) and 1,219 healthy controls (HCs) were analyzed.
- Brain MRI scans were processed using a machine learning tool to compute volumes of multiple brain structures.
- Mixed-effect models were used to analyze VV changes concerning clinical parameters and outcomes.
Main Results:
- ADEM patients exhibited larger VV than HCs at initial presentation, with further increases observed in most within 2 months.
- Patients with ADEM showed smaller overall brain volumes, particularly in deep gray matter structures, more pronounced in MOG-negative cases.
- Persistent VV expansion was associated with greater reductions in other brain structures and a higher likelihood of residual neurological signs.
Conclusions:
- Two distinct outcomes for VV changes in ADEM were identified: resolution or persistent expansion.
- Persistent VV expansion correlates with reduced brain volumes, especially in deep gray matter, and increased risk of permanent brain atrophy.
- Regular MRI monitoring is crucial for ADEM patients to assess VV changes and associated risks.
Background And Objectives:
Pediatric patients with acute disseminated encephalomyelitis (ADEM) are at risk of impaired brain growth, with long-term neuropsychiatric consequences. We previously reported transient expansions of cerebral ventricle volume (VV) in experimental autoimmune encephalomyelitis, which subsequently normalized. In this study, we investigated changes in VV in ADEM in relation to other brain structures and clinical outcomes.
Methods:
We investigated brain MRI scans acquired in routine clinical practice from a multicenter cohort of 61 pediatric patients with ADEM, of whom 39 were myelin oligodendrocyte glycoprotein (MOG) antibody-positive. Patients were compared with 1,219 pediatric healthy controls (HCs). Volumes of multiple brain structures were computed using a contrast-agnostic machine learning-based tool and analyzed with mixed-effect models regarding other clinical parameters.
Results:
Patients with ADEM had larger VV than HCs at initial clinical presentation, before immune therapy. Most of the patients showed further VV increases within 2 months after disease onset. Patients had smaller brain volumes than HCs, with specific reductions in deep gray matter structures. These changes were more pronounced in MOG antibody-negative patients.Of the patients with more than 2 MRI scans, 12 of 22 resolved their VV expansion back to within 15% of baseline values while 10 of 22 had persistently increased VV at the last available MRI within 1 year from onset. Patients with persistent VV expansion had greater reductions in volumes of other brain structures at the last MRI than patients whose VV resolved and were more likely to have residual neurologic signs. The VV resolving and nonresolving patients did not differ regarding age, sex, elevated CSF cell counts at baseline, or occurrence of relapses. However, patients with a larger magnitude of VV expansion-≥90% of baseline volume-were more likely to be in the nonresolving group.
Discussion:
We could distinguish between 2 outcomes of VV changes in ADEM: one in which the VV expanded but ultimately returned to normal and one in which the expansions continued after disease onset and treatment but failed to resolve. The latter was associated with reduced brain volume, particularly in deep gray matter structures. This highlights the necessity for patients with ADEM to undergo regular MRI scans to assess whether developing VV expansions indicate a greater risk of permanent brain atrophy.
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