Convection-Enhanced Delivery in Children: Techniques and Applications

Since its first description in 1994, convection-enhanced delivery (CED) has become a reliable method of administering drugs directly into the brain parenchyma. More predictable and effective than simple diffusion, CED bypasses the challenging boundary of the blood brain barrier, which has frustrated many attempts at delivering large molecules or polymers into the brain parenchyma. Although most of the clinical work with CED has been carried out on adults with incurable neoplasms, principally glioblastoma multiforme, an increasing number of studies have recognized its potential for paediatric applications, which now include treatment of currently incurable brain tumours such as diffuse intrinsic pontine glioma (DIPG), as well as metabolic and neurotransmitter diseases. The roadmap for the development of hardware and use of pharmacological agents in CED has been well-established, and some neurosurgical centres throughout the world have successfully undertaken clinical trials, admittedly mostly early phase, on the basis of in vitro, small animal and large animal pre-clinical foundations. However, the clinical efficacy of CED, although theoretically logical, has yet to be unequivocally demonstrated in a clinical trial; this applies particularly to neuro-oncology.This review aims to provide a broad description of the current knowledge of CED as applied to children. It reviews published studies of paediatric CED in the context of its wider history and developments and underlines the challenges related to the development of hardware, the selection of pharmacological agents, and gene therapy. It also reviews the difficulties related to the development of clinical trials involving CED and looks towards its potential disease-modifying opportunities in the future.