Of Muscles, Merosin, and Migration

Saturday, May 16, 1998, was a landmark day in pediatric neuroradiology. The First International Pediatric Neuroradiology Symposium was held in Philadelphia in conjunction with the Symposium Neuroradiologicum XVI and the 36th annual meeting of the American Society of Neuroradiology. Organized by Jim Barkovich, a fascinating day unfolded for those interested in the imaging of the developing brain as international luminaries from both sides of the Atlantic presented stimulating discussions of many topics related to pediatric neuroradiology. The first session of the day, entitled Neuroimaging Reflections of the Developing Brain, presented excellent updates on recent advances in histology, pathology, imaging, and spectroscopy of brain development in the fetus and young child. Most intriguing for me was the lecture given by Jeff Golden, Molecular Basis of CNS Development (1). Dr. Golden opened our eyes to the “explosion of knowledge” in the field of molecular biology and the light that has been recently shed on the molecular basis of normal and abnormal brain development. For instance, we learned that a protein molecule secreted from the notochord, affectionately known as “sonic hedgehog” (Shh), induces the development of neuroectoderm, which gives rise to the floor plate and eventually the ventral neural tube. Deficiency of Shh leads to a loss of the basal forebrain in laboratory animals. Deficiency or misexpression of another gene product, Pax-2, leads to holoprosencephaly in the forebrain of chicks. The protein cyclin D1 regulates phases of neuronal cell cycle replication. Mice deficient in cyclin D1 have fewer than normal cells in the retina and in the CNS and fail to thrive. Proteins with intriguing names like notch and astrotactin are integral to the orderly migration of neurons along radial glial processes and their subsequent organization into a six-layered cortex. Dr. Golden concluded with the bold, but believable prediction that the molecular, cellular, and functional basis of the brain and its development will be elucidated within the next decade. Incredible! In this issue of the American Journal of Neuroradiology (page 1389), Barkovich makes an important contribution to our better understanding of the clinical classification of the congenital muscular dystrophies (CMD), a challenging group of relatively rare clinical diseases that affect brain, muscles, and eyes, and brings together some of the recent research on a unifying theory of the molecular basis of CMD. He reviewed the brain MR studies of 12 patients seen at the University of California, San Francisco, between 1986 and 1997, and classified the patients into one of four clinical groups: (1) “pure” CMD, (2) Fukuyama CMD, (3) muscle-eye-brain disease and (4) WalkerWarburg syndrome. This classification scheme is clinically useful since the muscle biopsy results in these