Developmental Epilepsy: From Clinical Medicine to Neurobiological Mechanisms
06 February 2020
12 February 2020
30 March 2020 (online)
Stafstrom CE, Velisek L, eds. Developmental Epilepsy: From Clinical Medicine to Neurobiological Mechanisms. New Jersey, NJ: World Scientific Publishing; 2019: 436. ISBN: 9789813277724
Developmental Epilepsy: From Clinical Medicine to Neurobiological Mechanisms, edited by Carl Stafstrom and Libor Velíšek, is a small treasure chest of information presented in a compact textbook format. The unique contribution of this volume is the authors' ability to seamlessly bridge our current understanding of the basic science and genetics of this group of disorders to the clinical aspects of each epilepsy. The book is edited by a pair of clinician researchers who have assembled a group of experts to treat each topic. The style in which the authors present the basic science of each topic is particularly user-friendly for the clinical practitioner in the field—coverage of the neurochemistry and genetics presented seems tailored to the interests of practicing neurologists and does not go off on tangents that might only be of interest to pure researchers in the field, but perhaps outside the scope of interest of the clinician. Like a good lecture, chapters start with the basics of a topic, which the reader may or may not already be acquainted with—no matter—and patiently build on these in a logical and understandable way, bringing the audience to a sophisticated level of understanding of the neurobiology underpinning the various pediatric epilepsies. As the authors do not make assumptions about our knowledge of the various topics as they are introduced, a careful reading of each topic can lead to a solid understanding.
As an example, the introductory chapter covers the development of the nervous system, describing the details of the formation of the neural tube, neural crests, cell migration to form the cortical layers, synaptogenesis (including the early activity of electrical synapses), and myelination in well-written prose. The focus then moves on to the sequence of development of neurotransmitters and the membrane transporters that maintain the shifting of ionic gradients across the membrane at different stages of embryonic and early life. We were all surprised when some 20 years ago, it was discovered that GABA could be excitatory rather than inhibitory in the developing brain due to the reversal of the chloride equilibrium potential compared with the adult neuronal membrane. There is a description of the varying expression in the developing nervous system of the NKCC1 and KCC2 pumps which help regulate the chloride gradient across the developing neuronal membrane, but (spoiler alert!) it is not variation in the expression of these pumps that is responsible for the shifting impact of opening chloride channels. Rather, as described in the following chapter, the distribution of impermeable anions across the membrane is now felt to be responsible for this phenomenon.
Other chapters bring the reader up-to-date on various topics. These include a review of the neonatal genetic epilepsies, including a discussion of the widely varying phenotypes associated with KCNQ2 abnormalities. Another chapter gives a concise summary of the drug treatment of many different pediatric epilepsies. This summary may serve as a useful review for some, but the topic may have been overly ambitious for the space allotted, and those interested in understanding the advantages and disadvantages of different treatment options may need to seek out more comprehensive sources. The genetics of juvenile myoclonic epilepsy (JME) originally looked like it should not be a tough nut to crack, but that has not been the case. One chapter includes an entertaining historical narration of the winding trail from the late 1980s to the present day of our understanding of the genetics of JME and its relation to other genetic generalized epilepsies, and what a gene called BRD2 that codes for a histone-binding protein might have to do with it all.
Epigenetics is a relatively new field and its role in the developmental epilepsies will be of interest to many readers. Other topics include the mechanism of how prolonged febrile seizures cause temporal lobe epilepsy and problems with cognition, models and mechanisms of epileptic encephalopathies, the impact of prenatal and perinatal stress on epilepsy, immunity and inflammation in the developing brain, a nicely written review of the classification of the focal cortical dysplasias, a summary of mTORopathies, sex differences in developmental epilepsies, and the neurobiology of cognitive impairment in developmental epilepsies.
In short, those who practice in the field of epilepsy will find this text an easily accessible miniencyclopedia of reviews of our current understanding of the mechanisms that underlie the various childhood epilepsies. Readers will appreciate the digestible length and level of detail of each chapter and enjoy grabbing this book off the shelf.