See 2013 article and radio piece at Voice of America
House Foreign Relations Subcommittee on Africa, Global Health, and Human Rights hearings August 2, 2011
Congressional Hearing Book with Testimony on Hydrocephalus
CSPAN Coverage of Hydrocephalus Hearings August 2, 2011
See Fall 2010 article in Engineering Penn State Magazine
I am devoting increasing effort towards addressing problems affecting children in the developing world. The following projects address hydrocephalus, epilepsy and malaria, and the intersection of the potential infectious underpinnings of these conditions, as well as new technological approaches to diagnosis and treatment.
In treating epilepsy in the industrialized countries, MRI technology is the mainstay of the structural diagnosis of the scarring and shrinking of the deep parts of the temporal lobes of the brain in such patients. Such asymmetric scarring, when consistent with the clinical signs and scalp EEG characteristics of a deep temporal lobe epilepsy focus, carries high prognostic value that a surgical resection of the deep temporal structures will have a significant benefit to reduce seizures and improve the quality of life. The risk to benefit evaluation of the medical versus surgical treatment of such illnesses, in parts of the world where drug maintenance and pharmacological laboratory monitoring are often impractical, may be different from the industrialized countries. Despite the substantial literature supporting the use of MRI for volume measurements of the deep structures of the temporal lobe, has been no previous work using CT for this diagnosis. Although MRI is generally not available in the developing world, the less expensive CT is now becoming increasingly prevalent. We recently published a 3-part companion set of papers in the Journal of Neurosurgery Pediatrics demonstrating how to use CT as a volumetric tool to extract information that helps us guide our evaluation of postinfectious hydrocephalus, as well as selection of patients for potential epilepsy surgery.
One needs to ask why the incidence of epilepsy in malarial prone regions of Africa can be upwards of 5 times the indigence in the industrialized countries. There is a known relationship between cerebral malaria, which is especially dangerous to children, and post-malarial epilepsy in the survivors have been reported between 5-10%. We have been awarded a grant from Citizen’s United for Research in Epilepsy to pursue further development of therapies capable of preventing post-malarial epilepsy in children with cerebral malaria.
Neonatal infections kill over a million newborn infants each year worldwide, with the vast majority of these deaths occurring in sub-Saharan Africa and southern Asia. A related issue for sub-Saharan Africa is postinfectious hydrocephalus in early childhood. Serious neonatal infections within the first month of life, known as sepsis, appear to account for the majority of hydrocephalus cases seen in East Africa. Maintaining shunt hardware, and managing the early postoperative complications, and the late emergent shunt obstructions in children who become shunt dependent, weakens the risk-benefit balance for shunt insertions. A growing effort to use endoscopic fluid diversions, especially third ventriculostomy, is being applied by surgical centers in sub-Saharan Africa such as the CURE Children’s Hospital of Uganda in Mbale, Uganda. Nevertheless, the question of whether these children so treated do as well as children treated with shunts remains unanswered. In addition, as our technological approaches to hydrocephalus treatment increase in sophistication, one must ask whether the organisms causing post-infectious hydrocephalus can be identified and prevented. The NIH Fogarty Internation Center, in partnership with the National Institute of Neurological Disorders and Stroke, have teamed up to fund a Phase III Randomized Controlled Clinical Trial in Uganda comparing shunt with endoscopic treatment. In this study, whose PIs are Drs Warf (Harvard), Schiff (Penn State), and Kulkarni (Toronto), volumetric analysis techniques are being used in a prospective fashion to learn how to better treat and predictively manage such patients.
We have clinical trials underway to further explore the microbial origins of postinfectious hydrocephalus in East Africa. At the Mbarara University of Science and Technology, the department head of Pediatrics, Dr Julius Kiwanuka, and I are exploring the microbial spectrum of bacteria and viruses that comprise the pathogens in neonatal sepsis – the Neonatal Septisome. At the Children's Hospital of Uganda, in Mbale, surgeons John Mugamba, Peter Ssenyonga, Benjamin Warf and I are exploring the microbial components of postinfectious hydrocephalus in young infants, several months following recovery from neonatal sepsis. Following completion of this organism discovery, we hope to use engineering feedback control strategies to both optimize treatment of neonatal sepsis and devise rational public health policies to reduce both neonatal sepsis and postinfectious hydrocephalus in such settings. I recently received the NIH Director's Pioneer Award for Control of the Neonatal Septisome and Hydrocephalus in sub-Saharan Africa that will enable me to intensively pursue these issues over the coming years.
These projects are a collaborative effort between faculty and trainees across Penn State, as well as our colleagues at other universities and at medical centers, including: Penn State University Park: Department of Biology (Andrew Read), and Veterinary and Biomedical Science (Dr. Mary Poss, Dr. Vivek Kapur), Department of Engineering Science and Mechanics (Drs. Bruce Gluckman, Corina Drapaca, and Patrick Drew, as well as Paddy Ssentongo), and Department of Aerospace Engineering (Jacob Langelaan).
Penn State Hershey Medical Center: Department of Neurosurgery (Drs. Steven Schiff, Robert Harbaugh, James McInerney, Kenneth Hill), Department of Radiology (Drs. Dan Nguyen, Kevin Moser), and the Institute for Personalized Medicine (Drs. James Broach, Lijun Zhang, Feng Yue, and Lan Nguyen, and Kathryn Sheldon).
And beyond Penn State: Dr. Benjamin Warf (Harvard University), Abhaya Kulkarni (University of Toronto), Dr. Andrew Webb (University of Leiden), Dr. Warren Boling (University of West Virginia), Dr. John Mugamba, Dr. Peter Ssenyonga, and Derek Johnson (CURE Children’s Hospital of Uganda), and Drs. Julius Kiwanuka, Juliet Mwanga, and Joel Bazira (Mbarara University of Science and Technology).