The Division of Child Neurology provides a fertile environment for scholarship. The Department of Neurology and Neurological Sciences and the many other programs of Stanford University offer investigators access to superior research assets, with technological and biological laboratory resources that are unparalleled. Clinical investigations and clinical programs collaborate upon and often lead national trials and studies. Faculty, fellows, and residents see a large volume of children, and treat complex cases that are rarely seen elsewhere, affording unique opportunities for investigator-driven research. Researchers in the Child Neurology Division thus conduct research in a broad range of neurological subspecialties.
Scientists in the division pursue research on a number of fronts in pediatric neuro-oncology. They are exploring the epidemiology, natural history, and disease patterns of brain tumors in childhood, as well as conducting multiple clinical trials for these neoplasms. Stanford is an active member of the National Cancer Institute-sponsored Pediatric Brain Tumor Consortium, as well as the Collaborative Ependymoma Research Network and Children’s Oncology Group. There is also simultaneously superb bench research. The Cho lab is focused on genomics of medulloblastoma with application of computational biology to elucidate better understanding of the tumor’s biology, origins, and behavior. In the Monje lab, researchers are pioneering models of diffuse intrinsic pontine glioma and now exploring pathway underpinnings of these tumors at the level of neural progenitor cells. Other Stanford researchers are conducting studies of various gliomas, and some of these studies have resulted in translational trials. Studies of tissue from a diffuse pontine glioma, for instance, led to the identification of an unusual cell surface marker (EGFRvIII peptide) and the development of an antibody therapy that is now in clinical trials. Researchers in the Division of Child Neurology also focus on understanding and treating the neurological deficits that frequently follow radiation therapy or chemotherapy for children with cancer.
Stanford researchers have a distinguished history of advances in epilepsy research. Currently investigators are studying the basic mechanisms of epilepsy, such as the regulation of neural excitability and the mechanisms underlying development of epilepsy. Studies from several labs, including the Porter lab, are focused on understand how neuronal injury produces changes in structure and function of neurons and neuronal networks that lead to hyperexcitability and epileptogenesis. Investigators are also delving into the neuronal mechanisms that underlie slow electrical oscillatory activity in the thalamus. These oscillatory rhythms are related to both normal sleep activities and generalized epilepsies. Stanford clinical epilepsy researchers are using novel devices and stimulation paradigms to move basic research findings into the clinic.
Stanford clinical investigators are helping identify the genetic causes of peripheral nerve and muscle disorders, and are helping define the molecular mechanisms underlying one of the most common forms of muscular dystrophy, myotonic dystrophy. Eager to improve the lives of neuromuscular patients, researchers are investigating muscle development and gene therapy approaches for Duchenne muscular dystrophy that will replace dystrophin, the protein missing in this disease, but will also then be modifiable to improve myotonic dystrophy, spinal muscular atrophy, congenital myopathies, familial neuropathies, and many other neuromuscular disorders.
Protocol ID: NCT01839656
Protocol Title: The SMA Type I Clinical Trial. “This is a phase 2 study to assess the safety, tolerability, and Pharmacokinetics of ISIS-SMNRx in infants with Spinal Muscular Atrophy Type 1.
PI: Dr. John Day
The Division of Child Neurology shares a rich collaboration with the Division of Neonatal and Developmental Medicine in efforts to understand better the causes of, and potential interventions for, brain injury in newborns. Dr. Wusthoff's projects focus on the use of brain monitoring to enhance care of newborns at risk for brain injury. Ongoing neonatal neurology research seeks to identify ways to both improve care in the Neonatal Intensive Care Unit, and to use neurodevelopmental follow-up to understand more fully how to help babies in the years after they leave the hospital.
The Stanford Pediatric Stroke Program is a new and growing entity within the Division of Child Neurology. Clinical research in this area is focusing on novel neuroimaging techniques to help establish the cause of stroke in children, and ultimately to guide therapy in multi-centered, clinical trials. Collaborative projects are also in the works in the following areas: the incidence and outcome of stroke in children with cardiac disease requiring a ventricular assistive device, the role of placental pathology in neonatal stroke, and the role of vascular inflammation in inflammatory/demyelinating brain diseases.
Stanford has a long tradition of pioneering work in the world of translational neuroimmunology. Our child and adult neuroimmunology teams work closely on a variety of clinical and translational studies. Current studies are exploring the role of immunomodulatory therapies, both traditional (interferon-beta) and novel (vitamin D, amyloid proteins, and endogenous myelin lipids), and biomarker discovery in a variety of human and animal studies. Our clinical teams in the Pediatric Neuroinflammation clinic think broadly and work in multidisciplinary teams with pediatric rheumatology, child psychiatry, and other allied services to provide optimal diagnostic, therapeutic, and psychosocial care, while promoting research. The team has a long-term clinical interest in innovating cost-effective care models that prioritize the patient’s global well-being alongside more traditional outcome measures.
White Matter Disorders
Stanford investigators participate in both clinical and translational studies of leukodystrophies. The White Matter Clinic at Stanford is currently the only dedicated leukodystrophy clinic on the West Coast, offering a unique, multi-disciplinary approach to the diagnosis and treatment of challenging inherited disorders of myelin. In the lab, Stanford scientists are exploring the interface of myelin lipids and human macrophages to better understand inflammatory demyelination at its inception. They are also exploring a novel role for vitamin D supplementation in the prevention of the cerebral demyelinating phenotype of X-linked adrenoleukodystrophy with the plan to bring this treatment into clinic trials in the near term. These investigators also collaborate with other leukodystrophy centers across the country to perform innovative cost-of-care analyses to identify new targets to improve the quality and cost-effectiveness of complex care delivery.