title: Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly.
abstract: In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23), this study compared clinical, neuroimaging and pathologic features to discern potential mechanisms for suboptimal post-hemispherectomy developmental outcomes and structural pathogenesis. MRI measured affected and non-affected cerebral hemisphere volumes for HME and non-HME cases, including monozygotic twins where one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and white matter cell densities and sizes in HME and autopsy cases, including the non-affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was larger and the non-affected side smaller in HME compared with non-HME children. The affected HME side showed enlarged abnormal deep grey and white matter structures and/or T2-weighted hypointensity in the subcortical white matter in 75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias. Histopathological examination of the affected HME side revealed immature-appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of cases. Compared with autopsy cases, in HME children NeuN cell densities on the affected side were increased in the molecular layer and upper cortex (+244 to +18%), decreased in lower cortical layers (-35%) and increased in the white matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted white matter hypointensity correlated with the presence of immature-appearing neurons and PMG on histopathology, decreased NeuN cell densities in lower cortical layers and a positive history of infantile spasms. Post-surgery seizure control was associated with decreased NeuN densities in the molecular layer. In young children with HME and epilepsy, these findings indicate that there are bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly is a likely explanation for poorer post-surgery seizure control and cognitive outcomes. In addition, our findings support the hypothesis that HME pathogenesis probably involves somatic mutations that affect each developing cerebral hemisphere differently with more neurons than expected on the HME side.
authors.affiliation: Division of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Salamon
authors.forename: Marissa
authors.initials: M
authors.lastname: Andres
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Chute
authors.forename: Snow T
authors.initials: ST
authors.lastname: Nguyen
authors.forename: Julia W
authors.initials: JW
authors.lastname: Chang
authors.forename: My N
authors.initials: MN
authors.lastname: Huynh
authors.forename: P Sarat
authors.initials: PS
authors.lastname: Chandra
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Andre
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.forename: Joao P
authors.initials: JP
authors.lastname: Leite
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
mesh_terms: D034961:Antigens, Nuclear / Q000032:analysis; D001921:Brain / Q000002:abnormalities* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D002452:Cell Count; D048429:Cell Size; D016009:Chi-Square Distribution; D004827:Epilepsy / Q000473:pathology* / Q000601:surgery; D005260:Female; D038421:Hemispherectomy; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D013194:Staining and Labeling
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; C506808:neuronal nuclear antigen NeuN, human