Joseph J. Volpe, MD, Neurologist-in-Chief Emeritus, Bronson Crothers Professor of Neurology, Harvard Medical School
As requested by Dr. Mohamed El-Dib, President of the Newborn Brain Society, the following consists of brief reflections on the past, present and future of neonatal neurology. The reflections are highly selective and will not include names, to avoid the inevitable, accidental omission of important contributors.
Concerning the past, the emergence of neonatal neurology grew from the fascinating, detailed clinical descriptions of the neurological behavior and development of newborns and young infants, principally recorded in Europe in the 1950’s to 1970’s.
This descriptive work developed on a foundation created by the classical early neuropathological studies of the early to mid-20th century both in Europe and North America. During this period neonatal neurological disease involved principally hypoxic-ischemic and traumatic entities. However, interestingly, a systematic, detailed clinicopathological approach to the newborn with neurological disease, i.e., application of the neurological method, did not gain particular traction until the early to mid-1970’s. Application of this approach to the broad spectrum of neurological disease and associated clinical neurological phenomena led to recognition of neonatal neurology as a distinct entity around 1980.
With the advent of cranial ultrasonography in the mid to late 1970’s, there evolved a particular focus on intraventricular hemorrhage and posthemorrhagic hydrocephalus in the premature infant. This important work was stimulated during this period by the remarkable increase in survival rates of premature infants associated with major developments in neonatal intensive care. In the early 1980’s the addition of CT to ultrasonography led to an emphasis in the post-asphyxial full-term infant of varieties of hypoxic-ischemic injury and neonatal stroke. In the 1990’s the application of MRI led to the recognition of a broad spectrum of cerebral white matter disease in premature infants and of cerebral gray matter disease in post-asphyxial term infants, and the critical roles played by these pathologies in determining neurological outcomes. In the early 2000’s, advanced MRI methods elucidated unexpected and pronounced disturbances in development of neuronal-axonal structures in the premature infant.
A series of neuropathological studies based on advanced anatomical methods for studying neonatal brain elucidated the structural correlates of many of these MRI findings. Sophisticated applications of both ultrasonography and MRI led to recognition of injuries to cerebellum, especially in premature infants, and of specific neurological sequelae previously unrecognized to be related to cerebellar disease. Moreover, numerous neurobiological studies at the molecular, cellular, and systems levels in models relevant to both premature and term infants elucidated pathogenetic mechanisms and potential means of intervention. The impact of experimental studies in leading to a major therapeutic breakthrough was illustrated vividly by the application of moderate hypothermia in treatment of hypoxic-ischemic encephalopathy in the term infant.
The current era of neonatal neurology has focused on the concept of neonatal injury leading to impaired brain development. This concept of secondary dysmaturation was introduced near the end of the first decade of 2000 and likely is important in all neonatal neuropathological states. An important pathogenetic role in neonatal neurological disease of cerebral inflammation, provoked not only by such well-recognized factors as hypoxia-ischemia, but such relatively recently recognized factors as intrauterine and postnatal systemic inflammation (caused by such obvious phenomena as systemic infection but also by some less obvious events, such as nutritional and environmental disturbances). Additionally, numerous experimental and a few clinical studies have focused on efforts to enhance the important, though moderate beneficial effects of therapeutic hypothermia in the infant with hypoxic-ischemic encephalopathy.
The future of neonatal neurology will be most fruitful when neonatologists and neonatal neurologists recognize that they need each other, and when combined programs that include not only neonatology and neonatal neurology, but also neuropathology, neuroradiology and developmental neurobiology are developed. Such truly multidisciplinary programs currently are very few among the world’s medical centers. Nevertheless, with dedicated leadership, the critical components often can be found in many centers “hiding in plain sight”. Moreover, welcoming and stimulating societies, dedicated to the development of such multidisciplinary efforts, can be major facilitators. Herein lies a particular value of the Newborn Brain Society.