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November 06-07, 2019 | Tokyo, Japan
STEM CELLS AND REGENERATIVE MEDICINE
PEDIATRICS AND CHILD CARE
International Conference on
2nd World Congress on
&
Stem Cells 2019 & Pediatrics Congress 2019
November 06-07, 2019
Journal of Child and Adolescent Psychiatry Volume 03
J Child Adolesc Psych, Volume 03
New concepts on developmental pathogenesis of Epileptogenic Focal Cortical
Dysplasias
Background: Focal cortical dysplasias (FCD) are the principal cause of focal epilepsy in infants and children and are successfully
treatedby surgical resection and confirmedneuropathologically.The pathogenesis of these focalmalformations of cortical development
is elucidated by recent advances in neuroembryology and genetics. FCD type II is due to disturbances in the mTOR signaling pathway
that causes dysmorphic neurons as well as abnormal brain architecture. During normal fetal brain development, keratan sulfate (KS)
proteoglycan surrounds and isolates fascicles and tracts in the brain; KS also binds to neuronal somatic membranes where it repels
excitatory but enables inhibitory axons; no KS surrounds dendritic spines, hence axodendritic synapses are excitatory.
Objective: To elucidate factors of pathogenesis of FCD and relate them to normal brain maturation.
Methods: 30 normal fetal and 12 infant and child brains, and also 10 cases of FCD were examined at autopsy or in surgical
resections for epilepsy, with immunocytochemistry applied to tissue sections.
Results: FCD type I is persistence of normal fetal micro-columnar cortical architecture before horizontal lamination is
superimposed during the second half of gestation. FCD II and hemimegalencephaly (isolated or associated with neurocutaneous
syndromes) are the same disorder, the difference in extent depending in which of the 33 mitotic cycles of neuroepithelium the
defective gene is first expressed. KS is altered in FCD and other brain malformations.
Conclusion: Neuroembryology and genetics are the bases for understanding pathogenetic mechanisms of brain malformations.
Maturational arrest is a factor in FCD I. KS repels glutamatergic (excitatory) axons and facilitates GABAergic (inhibitory)
axons, which explains why deep heterotopia often generate few or no seizures because of a KS barrier in the U-fibre layer that
prevents integration into epileptic networks, why axosomatic synapses are inhibitory, and how KS isolates axonal fascicles to
prevent exit or entry of axons along their trajectory.
Biography
Sarnat is professor of Paediatric Neurology and Neuropathology at the University of Calgary and Alberta Children’s Hospital, Canada.
He has devoted most of his career to developmental (fetal and neonatal) neuroanatomy and neuropathology, particularly in relation to
brain malformations with clinical correlates and to the developmental neuropathology of epilepsy. He is one of 8 permanent member of
the International League Against Epilepsy, Commission on Neuropathology. His 180 research publications include clinical studies that
have become classics as the Sarnat grading scale of neonatal encephalopathies (1976) and the first description of neonatal olfactory
reflexes (1978), as well as a recent long series of articles defining the sequence of synaptogenesis in the fetal brain and another series on
development of the olfactory system. He is sole or co-author or editor of several textbooks and has contributed 120 chapters to textbooks
and monographs. He serves on the editorial boards of 9 journals. He was keynote speaker at the 50th anniversary meeting of the Canadian
Association of Neuropathologists and was the prestigious Bernard Sachs Lecturer in 2016 at the congress of the Child Neurology Society
(U.S.A.). He lectures frequently throughout Europe, Latin America, Japan, Australia, U.S.A. and Canada. His wife and co-author of many
publications, Dr. Laura Flores-Sarnat, is professor of Paediatrics and Clinical Neurosciences at the University of Calgary, formerly head of
Child Neurology at the Instituto Nacional de Pediatría, a large university children’s teaching hospital in Mexico City.
Harvey B Sarnat
University of Calgary and Alberta Children’s Hospital, Canada