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Children’s Hospital Doctors Publish Book On Developing Human Brain

Floyd H. Gilles

Credit the not-so-subtle prodding by a group of enthusiastic publishers and cerebral palsy experts from the Spastics Society, a British disabilities charity, for the making of the definitive textbook, The Developing Human Brain: Growth and Adversities (Mac Keith Press), by Children’s Hospital Los Angeles physicians Floyd H. Gilles, MD, and Marvin D. Nelson Jr., FACR, MD, MBA.

“They went to work on me,” Gilles says, recalling the encounter at a London neonatal brain damage conference back in the mid 1980s. “They said quite bluntly, ‘we want this stuff written down before you die.’”

Almost 30 years later, the book is published, with terrific peer reviews no less, and Gilles, an internationally-renowned neuropathologist and one of the foremost experts on the developing human brain, is still producing plenty of stuff from his lab at Children’s Hospital Los Angeles (CHLA).

“This book was an incredible undertaking that drew on the extensive medical experience of Drs. Gilles and Nelson with documentation from one of the most significant and largest national studies ever conducted on the human brain,” says Brent Polk, MD, chair of the  CHLA department of pediatrics and VP of academic affairs, and chair of pediatrics and vice dean for child health at USC’s Keck School of Medicine. “Their penchant for detail and in-depth coverage of embryonic and fetal brain development resulted in a book that transcends what one might find in a typical text. It’s a must read for pediatric specialists, researchers and academicians with an interest in the human brain.”

The Developing Human Brain examines development and growth of the child’s brain, particularly during the last 20 weeks of pregnancy. Gilles, the Burton E. Green Professor of Neuropathology at Children’s Hospital, and Nelson, the hospital’s John L. Gwinn Professor of Radiology, explain that this is the period of greatest risk for childhood functional neurological deficits, including cerebral palsy, developmental delays and intellectual disability.

Drawing on vast personal experience, Gilles and Nelson wrote a textbook that embodies their work over five decades in the fields of pediatric pathology, neurology and neurosurgery. An earlier book co-authored by Gilles, The Developing Human Brain: Growth and Epidemiologic Neuropathology, had been out of print since 1983, Gilles explains, so an updated edition was overdue. Gilles invited Nelson to collaborate, calling on the hospital’s chairman of the Department of Radiology and his renowned work and studies in area of diagnostic imaging, and the writing project commenced in 2002.

In addition to their highly regarded work in their respective fields, the team also had another tool at their disposal—an extensive personal collection of medical texts dating back to the early 19th century. “Marvin and I collect old books, rare textbooks with a huge amount of research on the brain,” Gilles says. Those collectibles include German physiologist Paul Flechsig’s Anatomy of Human Brain and Spinal Cord,” published in 1920, and “The Anatomic Pathology of the Human Body,” written by legendary French anatomist and pathologist J. Cruveilhier in 1828.

More than 200 historical photos, drawings and lithographs of the human brain are published in their 405-page book, including one of the earliest paintings showing a child being treated for hydrocephalus dating back to the 10th century.

“Most current books have either pathology or imaging. We tried to put both together in one book,” Gilles says.

The textbook also draws from the autopsy results and clinical data from the U.S. National Collaborative Perinatal Project, one of the largest studies ever attempted on the maturing human brain.

“The mothers were followed through their pregnancy and the children, both normal and abnormally developing, were followed after they were born,” says Nelson. “What arose was a nice data set of growth parameters that we detailed in the book.”

On top of that, the authors combined the documentation with a combined 76 years of clinical experience. “It’s a very one-of-a-kind discussion about the brain’s development and the adversities that affect brain growth,” Nelson says.

Meticulously researched and annotated, Gilles and Nelson’s book has drawn raves from peer reviewers, who call it must reading for obstetricians, neonatologists, pediatric neuropathologists, developmental specialists and radiologists.

“This is an extraordinary work….generated out of their meticulously recorded observations of human brain development,” reports the Journal of Developmental Medicine & Child Neurology.

Pediatric Radiology gave the authors, both Keck School of Medicine faculty member, an “outstanding” grade, declaring it as “essential” reading for pediatric specialists.

Pediatric Neurology called Gilles and Nelson’s effort a “singular” work, a “comprehensive and sophisticated guide to in utero and perinatal brain injuries that occur from the last half of gestation into early infancy.”

“They’re biased,” Gilles says, downplaying the acclaim. “But it is the only place where you can find the details of myelination of the human brain, pre- and postnatal, in one spot,” he says, referring to the process of forming a myelin sheath around a nerve to allow nerve impulses to move more quickly. Those measurements are revealed in the sixth chapter of the text, including never before seen imaging of the myelination growth pattern. “There are tons of imaging pictures, which made the process of putting together the book a lot of fun,” Gilles says.

An authority on the human brain during the last half of gestation, Gilles has studied brains quantitatively since 1962 when he was head of Pediatric Neuropathology at Boston Children’s Hospital and a professor at Harvard University. Joined by pediatric epidemiologist Al Leviton, Gilles was the first to apply epidemiological methods to brain autopsies. The pair was at the forefront of studying autopsy populations and defining the role of biologic variability in human development, statistical and epidemiologic tools and to critical thinking applied to human disease.

Nelson says the experience of working on the book piqued his curiosity on areas that beckon more investigation, such as the role the placenta plays in children with developmental disabilities disorders. “Research is coming out now that shows the placenta produces hormones that have a major role in in brain development,” he says.

Although Gilles and Nelson write that future research on the maturing brain is restricted by the decline of autopsy rates, neuroimaging is helping fill the void. “We now are looking beyond the basic structure of the brain, and can now image how the brain responds to various tasks, like moving your fingers, looking at pictures, reading words, listening to sounds etc. “These new functional imaging techniques are giving us a new window on how the brain actually works.”


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