Simon Platt
Simon Platt
Luisa De Risio
23 Pathophysiology and Management of Cluster Seizures
Simon Platt
24 Pathophysiology and Management of Status Epilepticus
Simon Platt
25 Novel and Adjunctive Treatments
Simon Platt
Glossary of Pharmacological Terminology
Preface
Seizures are one of the most common neurological conditions encountered in small animal practice. Epilepsy is the most common chronic neurological disease in dogs; it is often associated with dramatic clinical signs, lifelong treatment and potential effects on the animal quality of life and lifespan. The emotional and financial impact of this disease on the pet-owners can be dramatic.
Diagnosis and management of the seizure patient can be challenging. To date, information on various aspects of this topic has been covered in individual chapters in neurology, internal medicine and pharmacology textbooks and in scientific articles. Therefore consultation of numerous publications has been necessary to obtain comprehensive knowledge.
The authors have compiled this textbook in order to provide information on multiple aspects of canine and feline seizures and epilepsy such as pathophysiology, classification, aetiologies and differential diagnoses, epidemiology, diagnostic investigations and emergency and maintenance treatment. Mechanism of action, metabolism and pharmacokinetics, pharmacokinetic interactions and adverse reactions, dosing, monitoring recommendations and efficacy of old and new generation antiepileptic medications are presented in detail. A glossary on pharmacological terminology has been added at the end of the book to help understanding in this area. Extensive referencing has been provided.
Having all of this information available in one textbook should help to improve knowledge on this complex subject and subsequently help veterinarians to improve the care of dogs and cats with seizure activity.
The authors are very grateful to the invited authors, Holger Volk and Fiona James, for their invaluable contribution in their respective area of expertise, Pathophysiology of refractory seizures (Chapter 2) and Electroencephalography (Chapter 11), and to colleagues who have contributed images. We also wish to thank the publisher CABI and particularly our senior editorial assistant, Alexandra Lainsbury.
Due to production requirements the number of colour images is greater in the e-book than in the printed book. The layout of colour images in the printed book has been determined by the publisher’s production.
We hope that this textbook provides useful information for veterinary students, veterinary general practitioners, as well as veterinary interns, residents and specialists in neurology or in disciplines related to neurology (e.g. internal medicine, oncology, surgery, behavioural medicine and pharmacology). The depth of the information provided will allow those who would like a little bit more detail in certain areas hopefully to find this; however, we hope that the book also serves as a practical source for advancing the treatment of the most routine and most challenging seizure cases.
The information provided in this textbook is up to date to the best of the authors’ knowledge at the time of production. The field of veterinary science is rapidly evolving and advances in diagnosis and treatment are likely to occur in the next years. Therefore knowledge would require constant updating to provide optimal management of our patients.
Luisa De Risio
Simon Platt
October 2013
1 Pathophysiology of Seizure Activity
Simon Platt BVM&S MRCVS Dipl. ACVIM (Neurology) Dipl. ECVN Professor Neurology and Neurosurgery Service, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
Several decades have been devoted to the study of the pathophysiology of epilepsy. Increasing knowledge in the field has only contributed to a partial understanding of the underlying mechanisms. Nevertheless, insight into the pathophysiology of epilepsy and its underlying histological and neurochemical alterations has contributed to rational development strategies of new anti-epileptic medications (AEMs). Although various epileptic syndromes in people have been shown to differ pathophysiologically, they apparently share common ictogenesis-related characteristics such as increased neuronal excitability and synchronicity. Emerging insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability. Progress in the field of molecular genetics has revealed arguments in favour of this hypothesis as mutations of genes encoding ion channels were recently discovered in some forms of human epilepsy.
Epileptic seizures arise from an excessively synchronous and sustained discharge of a group of neurons. The single feature of all epileptic syndromes is a persistent increase of neuronal excitability. Abnormal cellular discharges may be associated with a variety of causative factors such as trauma, oxygen deprivation, tumours, infection and metabolic derangements. However, no specific causative factors are found in many dogs and cats suffering from epilepsy.
Underlying causes and pathophysio-logical mechanisms are (partially) understood for some forms of epilepsy, at least in people, e.g. epilepsies caused by disorders of neuronal migration and monogenic epilepsies. For several other types of epilepsy, current knowledge is only fragmentary. This chapter will review several areas that are understood to contribute to the evolution and maintenance of epilepsy. The genetics of epilepsy are discussed in Chapter 6.
The Electrical Basis of Nerve Cell Function
At the most fundamental level, the nervous system is a function of its ionic milieu, the chemical and electrical gradients that create the setting for electrical activity. Therefore, some of the most easily appreciated controls on excitability are the ways the nervous system maintains the ionic environment. An example is the electrical basis of resting membrane potential. Resting potential is set normally so that neurons are not constantly firing but are close enough to threshold so that it is still possible that they can discharge, given that action potential generation is essential