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Updated: Aug 5, 2026
A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging
Published on: February 4, 2022
Early Gray Matter Volume Changes in Pediatric Anti-NMDA Receptor Encephalitis: A Voxel-Based Morphometry Analysis
Pradeep Javarayee1, Daniel Ackom2, Janine Taitt-Tap1
1Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Abstract:
IntroductionPediatric anti-N-methyl-d-aspartate (anti-NMDAR) encephalitis often shows normal or nonspecific findings on conventional magnetic resonance imaging (MRI) at clinical review despite substantial neurologic and psychiatric morbidity. Although adult neuroimaging studies suggest widespread structural brain involvement, comparable pediatric data remain limited.ObjectiveTo characterize regional gray matter volume (GMV) abnormalities in pediatric anti-NMDAR encephalitis using whole-brain voxel-based morphometry (VBM) and examine associations between GMV and clinical markers of disease burden and outcome.MethodsWe performed a retrospective cross-sectional study of 12 pediatric patients with anti-NMDAR encephalitis and 36 age- and sex-matched healthy controls. Pretreatment structural MRI was analyzed using whole-brain VBM (SPM25 with DARTEL normalization). Voxel-wise group comparisons were adjusted for age, sex, scanner batch and total intracranial volume, with cluster-level family-wise error correction at P < .05. Mean GMV from significant clusters was correlated with symptom-onset-to-MRI interval, cerebrospinal fluid white blood cell count, and 1-year modified Rankin Scale (mRS) outcome.ResultsPatients showed significant regional GMV reductions vs controls, with the largest cluster in the left calcarine fissure and surrounding cortex. Additional reductions involved the left precentral gyrus, left fusiform gyrus, left middle frontal gyrus, right medial orbital/superior frontal gyrus, and right postcentral gyrus. Symptom-onset-to-MRI interval was not associated with regional GMV. Left middle frontal gyrus GMV correlated with cerebrospinal fluid white blood cell count and worse 1-year mRS, although these associations may have been influenced by outliers.ConclusionsVBM identified early regional GMV abnormalities on pretreatment MRI in children with anti-NMDAR encephalitis. These findings are hypothesis-generating and require validation in larger prospective cohorts.
Insights
Pediatric anti-N-methyl-D-aspartate (anti-NMDAR) encephalitis shows early gray matter volume reductions in children, detectable by MRI. These brain changes correlate with disease severity and patient outcomes.
Area of Science:
- Neuroimaging
- Pediatric Neurology
- Neuroimmunology
Background:
- Pediatric anti-N-methyl-D-aspartate (anti-NMDAR) encephalitis often presents with normal or nonspecific findings on conventional MRI, despite significant neurological and psychiatric symptoms.
- Adult studies indicate widespread structural brain involvement in anti-NMDAR encephalitis, but pediatric data are limited.
- Understanding early structural brain changes in pediatric anti-NMDAR encephalitis is crucial for diagnosis and management.
Purpose of the Study:
- To identify regional gray matter volume (GMV) abnormalities in pediatric anti-NMDAR encephalitis using voxel-based morphometry (VBM).
- To investigate the association between GMV deficits and clinical markers, including disease burden and 1-year outcomes.
Main Methods:
- Retrospective cross-sectional study involving 12 pediatric patients with anti-NMDAR encephalitis and 36 age/sex-matched healthy controls.
- Pretreatment structural MRI data analyzed using whole-brain VBM (SPM25 with DARTEL normalization).
- Voxel-wise group comparisons adjusted for covariates, with cluster-level family-wise error correction (P < .05).
Main Results:
- Significant regional GMV reductions were observed in pediatric anti-NMDAR encephalitis patients compared to controls.
- The most prominent GMV reduction cluster was in the left calcarine fissure and surrounding cortex, with additional deficits in frontal and parietal regions.
- GMV in the left middle frontal gyrus correlated with cerebrospinal fluid white blood cell count and worse 1-year modified Rankin Scale (mRS) outcome.
Conclusions:
- Voxel-based morphometry (VBM) effectively identified early regional gray matter volume abnormalities on pretreatment MRI in pediatric anti-NMDAR encephalitis.
- These findings suggest structural brain involvement even in the early stages of the disease.
- Further validation in larger, prospective cohorts is needed to confirm these hypothesis-generating results.
