An analysis of the association between various synaptic parameters during cortical development

Abstract Background Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. Case presentation We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. Conclusion We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

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Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

Nature Neuroscience ◽

10.1038/s41593-020-00794-1 ◽

2021 ◽

Author(s):

Ugomma C. Eze ◽

Aparna Bhaduri ◽

Maximilian Haeussler ◽

Tomasz J. Nowakowski ◽

Arnold R. Kriegstein

Keyword(s):

Human Brain ◽

Brain Development ◽

Single Cell ◽

Radial Glia ◽

Cortical Development ◽

Cell Types ◽

Human Cortex ◽

Early Stages ◽

Human Brain Development ◽

Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

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Malformations of Cortical Development, Cognitive Involvementand Epilepsy: A Single Institution Experience in 19 Young Patients

Children ◽

10.3390/children8080637 ◽

2021 ◽

Vol 8 (8) ◽

pp. 637

Author(s):

Valeria Venti ◽

Maria Chiara Consentino ◽

Pierluigi Smilari ◽

Filippo Greco ◽

Claudia Francesca Oliva ◽

...

Keyword(s):

Clinical Features ◽

Cortical Development ◽

Young Patients ◽

Cortical Dysplasia ◽

Drug Resistant ◽

Malformations Of Cortical Development ◽

Group Iii ◽

Group I ◽

Cognitive Involvement ◽

Group Ii

Background. Malformations of cortical development (MCD) include a wide range of congenital disorders mostly causing severe cognitive dysfunction and epilepsy. Objective: to report on clinical features including cognitive involvement, epileptic seizures with response to antiseizure medications, comorbidities in young patients affected by MCD and followed in a single tertiary hospital. Patients and methods: A retrospective review of the medical records and magnetic resonance images (MRI) of 19 young patients with an age ranging between eight days and fifteen years affected by MCD and admitted to Pediatrics Department University of Catania, Italy from October 2009 and October 2020 were selected. Patients were distinguished in three groups following the Barcovich et al. 2012 classification for MCD: 4 (21%) in Group I; 8 (42%) in Group II; and, and 7 (37%) in Group III. Clinical features and MRI of the patients including cognitive involvement, epilepsy type and response to drugs treatment were analyzed. Results: In Group I, two patients showed cortical dysplasia and two dysembryoplastic neuroepithelial tumors plus focal cortical dysplasia; developmental delay/intellectual disability (DD/ID) was severe in one, moderate in one and absent in two; the type of seizures was in all the cases focal to bilateral tonic-clonic (FBTCs), and drug resistant was found in one case. In Group II, three patients showed neuronal hetero-topias and five had pachygyria-lissencephaly: DD/ID was severe in four, moderate in two, and absent in two; the type of seizure was focal (FS) in five, focal to bilateral tonic-clonic (FBTCs) in two, infantile spasms (IS) in one, and drug resistant was found in three. In Group III, six showed polymicrogyria and one schizencephaly: DD/ID was found severe in five, moderate in two, and the type of seizure was focal (FS) in five, FBTCS in two, and drug resistance was found in three.

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