Abstract
ObjectiveMalformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition.We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age. MethodsQSM and R2* maps were calculated for 40 paediatric patients with suspected MCD (18 histologically confirmed) and 17 age-matched controls.Patients’ sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* was performed within lesions, using a surface-based approach with comparison to homologous regions, and within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates.Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters. ResultsCompared to fluid‐attenuated inversion recovery (FLAIR) or T1‐weighted imaging, QSM improved lesion conspicuity in 5% of patients.In patients with well-localised lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2–3 mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining.SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium in one patient, and decreased iron in the brain region exhibiting low χ and high R2* in both patients. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus. ConclusionQSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. These findings suggest that measurements of cortical χ could be used to characterise tissue properties non-invasively in epilepsy lesions.
Highlights
Malformations of cortical development (MCD), and in particular focal cortical dysplasia (FCD), are the most common cause of drugresistant focal epilepsy in children (Blumcke et al, 2017; Harvey et al, 2008)
According to the classification system developed by the International League Against Epilepsy, the presence of disrupted radial or tangential cortical lamination is associated with FCDI lesions, dysmorphic neurons characterise FCDIIa, and dysmorphic neurons combined with balloon cells in the cortex and white matter occur in FCDIIb (Blümcke et al, 2011)
quantitative susceptibility mapping (QSM) was evaluated in a paediatric population of forty patients with drug-resistant focal epilepsy
Summary
Malformations of cortical development (MCD), and in particular focal cortical dysplasia (FCD), are the most common cause of drugresistant focal epilepsy in children (Blumcke et al, 2017; Harvey et al, 2008). According to the classification system developed by the International League Against Epilepsy, the presence of disrupted radial or tangential cortical lamination is associated with FCDI lesions, dysmorphic neurons characterise FCDIIa, and dysmorphic neurons combined with balloon cells in the cortex and white matter occur in FCDIIb (Blümcke et al, 2011). These neuro-pathological features could be the result of a developmental abnormality involving several phases of corticogenesis (Zucca et al, 2015). Iron accumulation in deep brain regions characterises brain ageing (AcostaCabronero et al, 2016; Aquino et al, 2009; Ashraf et al, 2018; Ghassaban et al, 2019; Hallgren and Sourander, 1958; Li et al, 2014; Yao et al, 2009) and drug-resistant epilepsy could potentially hasten this process
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.