Posttraumatic Epilepsy: Basic and Clinical Aspects

By Carrie R. Jonak, Allison R. Peterson and Devin K. Binder

Posttraumatic Epilepsy: Basic and Clinical Aspects provides a synthesized resource on the recent basic and clinical science developments in the field of posttraumatic epilepsy. This book provides a clear understanding of the history of studies and epidemiology of posttraumatic epilepsy after head injury. The book also considers the neuropathology of posttraumatic epilepsy and clinical trials of antiepileptogenic agents evaluated after traumatic brain injury. The book covers the basic science of animal models of traumatic brain injury and the necessary and sufficient changes that must occur to generate epilepsy after head trauma. The authors explore potential mechanisms and novel therapeutic approaches to prevent posttraumatic epilepsy. The book is written for basic and clinical researchers in neuroscience as well as for clinicians treating patients with epilepsy.

• Reviews the history and epidemiology of posttraumatic epilepsy
• Considers the neuropathology of posttraumatic epilepsy
• Synthesizes studies demonstrating risk factors for susceptibility to epilepsy after head trauma
• Reviews animal models of traumatic brain injury
• Addresses our current understanding of mechanisms of posttraumatic epilepsy
• Explores novel therapeutic approaches to prevent posttraumatic epilepsy

• Language: English
• Publisher: Academic Press
• Release date: Oct 21, 2022
• ISBN: 9780323886345

Carrie R. Jonak

Carrie R. Jonak (research associate) is a neuroscience researcher in Dr. Binder’s laboratory, in the Division of Biomedical Sciences at the University of California, Riverside.

Book preview

Chapter 1: History of posttraumatic epilepsy

Abstract

Posttraumatic epilepsy (PTE) is a recurrent seizure disorder caused by traumatic brain injury (TBI). In this chapter, we review some historical aspects of PTE. We trace some of the early recognition that head trauma may lead to seizures. Both the conception of epilepsy and its interaction with methods of treatment of TBI evolved from antiquity through medieval and Renaissance practitioners. Key to a more modern and logical approach to diagnosis and treatment of PTE was the emerging understanding of cortical localization beginning in the 1870s. This paralleled the rise of neurology and neurosurgery as localization-based diagnosis and treatment were tested and proven. Despite these advances, however, by the 1920s, the understanding of the neuropathology and pathophysiology of PTE was still in its infancy.

Keywords

Epilepsy; Head trauma; Brain; History; Trephination; Cortical localization; Neurosurgery

Overview

Posttraumatic epilepsy (PTE) is a recurrent seizure disorder caused by traumatic brain injury (TBI). In this chapter, we review some historical aspects of PTE. We trace some of the early recognition that head trauma may lead to seizures. Both the conception of epilepsy and its interaction with methods of treatment of TBI evolved from antiquity through medieval and Renaissance practitioners. Key to a more modern and logical approach to diagnosis and treatment of PTE was the emerging understanding of cortical localization beginning in the 1870s. This paralleled the rise of neurology and neurosurgery as localization-based diagnosis and treatment were tested and proven. Despite these advances, however, by the 1920s, the understanding of the neuropathology and pathophysiology of PTE was still in its infancy.

Hippocrates

The words epilepsy and epileptic are of Greek origin from the root epilambanein, which means to seize or to attack. The earliest detailed descriptions of the phenomenology of epilepsy were by the Babylonians in the 2nd millennium BC [1]. It was the Babylonians’ perception that seizures resulted from the invasion of the body by a particular evil spirit, which presaged the Greek concept of the The Sacred Disease in which the supernatural invasion was by gods [1,2]. Hippocrates (460–370 BC) (Fig. 1.1) was born on the island of Kos, off the Doric coast of what is now Turkey, but studied in Athens and traveled extensively [3]. Hippocrates was the first to identify the brain as the organ associated with epilepsy [4]. This is recorded in the book On the Sacred Disease at about the year 400 BC:

Fig. 1.1

Fig. 1.1 Hippocrates of Kos (460–370 BC). Greek physician of the Age of Pericles (Classical Greece) sometimes termed the Father of Medicine. The Hippocratic school of medicine revolutionized ancient Greek medicine, establishing medicine as a profession.

Mankind must realize that there is but a single organ from which come our pleasures, joys, laughter and wit. From that organ also comes our sorrow, grief, anxiety and lamentation. The brain is in fact that organ; from it comes our intellect, and our vision, and our hearing. Through it we judge the ugly and the beautiful, the noble and the ignoble, the pleasant and the unpleasant…And it is from the brain that we become mad and delirious…Based on the foregoing concepts I believe that the brain is the most powerful organ in man [5,6].

On the Sacred Disease comprises the first monograph on epilepsy that we possess. Interestingly, the word sacred is ironic in the sense that the message of the book is that epilepsy is instantiated in the brain and is not therefore in that sense more divine or sacred than any other disease. This conceptualization of epilepsy as arising from the brain and the brain only has therapeutic implications that it can and must be treated not with magical incantations and sorceries but rather by diet, drugs, and (possibly) surgery [4]. According to On the Sacred Disease, seizures themselves were caused by stagnation of phlegm but are also influenced by other factors such as the winds [5]. The identity of the author of the book On the Sacred Disease is unknown; he is thought to have been one of the anonymous physicians whose writings go under the name Hippocrates as part of the corpus Hippocraticum (Hippocratic canon, a heterogeneous collection of about 60 medical treatises largely gathered during the Alexandrian era (4th century BC) reflecting the teaching of the school of the Ionic island of Kos [5]).

Writings of the corpus Hippocraticum were also the first to clearly describe the extent of experience with head injuries in classical antiquity. The treatise On Wounds of the Head is a short surgical text written as a guide to the diagnosis and treatment of head injury [5]. It begins with a detailed description of cranial anatomy, recognizing, for example, that the bone along the temples is the weakest [5,7] (modern understanding: the temporal bone is the thinnest cranial bone and most susceptible to traumatic fracture). Next, fractures of the cranium are categorized into six types: (1) fissured fractures; (2) contusion without fracture; (3) depressed fractures; (4) hedra, or dents in the skull caused by weapons; (5) cranial lesions away from the scalp wound (contrecoup fractures); and (6) wounds above cranial sutures [8]. Finally, each of these fracture types is separately discussed regarding etiology, evaluation, treatment, and prognosis. Interestingly, the treatise mentions little about injury to the brain itself but rather serves as a guide to treatment of skull injuries. However, of key importance to posttraumatic epilepsy and with a hint of early cerebral localization, it is noted that a wound of the left side of the head would cause convulsions on the right side of the body and vice versa:

And, for the most part, convulsions seize the other side of the body; for, if the wound be situated on the left side, the convulsions will seize the right side of the body; or if the wound be on the right side of the head, the convulsion attacks the left side of the body [7,9].

The Middle Ages and Renaissance

By the Middle Ages, the term sacred disease had been replaced with various versions of the falling sickness (morbus caducus) [4]. In addition, the conflation of epilepsy with mental disorders became marked during the transition from antiquity to the Middle Ages, with epilepsy now associated with possession or lunacy. The Galenic conception of humors and humors being out of balance in epilepsy was now combined with the medieval idea of demoniac possession. In Temkin’s words, the devil does not cause the epileptic attack by his own power, rather he exerts his influence when the body is off balance, the humors being stirred up and the brain affected [4].

Gradually, Renaissance conceptions of humanism led to further observations and further writings on epilepsy and on individual cases. In this context, many of the publications refer to various factors which precede the onset of epileptic attacks. Thus, attention was paid to head injury as a precipitating factor for epilepsy. Valescus de Tharanta (1523) described a head wound in a man that penetrated to the pia mater resulting in accumulation of a fetid ichor which caused multiple seizures per day until his death several days later [4,10]. Jacopo Berengario da Carpi (1460–1530) (Fig. 1.2), the son of a barber surgeon [11], published a comprehensive book dealing entirely with head injuries (De fractura calve sive cranei) in 1518 [12]. In this treatise, he described six patients who survived severe brain injuries. One case was a man who had seizures 60 days after head injury (hence posttraumatic epilepsy). He placed the man feet up and head down, opened the wound and evacuated copious fluid with the color of milk, after which the epilepsy ceased [13]. The title page of the 3rd edition of his treatise (published in 1535) shows some of the weapons associated with head injuries at the time (Fig. 1.3).

Fig. 1.2

Fig. 1.2 Jacopo Berengario da Carpi (1460–1530). Physician and surgeon. Published De fractura cranei in 1518, a landmark work on head injuries ( Fig. 1.3). Treated Lorenzo de’ Medici, Duke of Urbino, who had been shot in the head in 1517. Also described the anatomy of the meninges, cranial nerves, and ventricular system. (Reproduced with permission from Parent A. Berengario da Carpi and the renaissance of brain anatomy. Front Neuroanat 2019;13:11.)

Fig. 1.3

Fig. 1.3 Title page of De fractura cranei by Jacopo Berengario da Carpi from 3 rd edition (Venice, 1535). First published in Bologna in 1518. Considered the first modern treatise specifically devoted to head injuries. It offered Renaissance surgeons instructions for management of skull fractures and explanations of various surgical instruments and techniques. (Reproduced with permission from Parent A. Berengario da Carpi and the renaissance of brain anatomy. Front Neuroanat 2019;13:11.)

It was also realized that epilepsy may begin many years after head injury (the concept of latency to posttraumatic epilepsy after traumatic brain injury). Ludovicius Duretus (1527–86) reported that:

A bone of the skull of a 12-year-old youth had been broken and depressed by a fall and had by negligence not been restored. The brain was therefore hindered in its growth, since the injured bone itself could not grow so as to become able to hold a larger brain. Consequently, in his eighteenth year, the youth suffered from epilepsy because of the oppression of the brain. He was, however, cured by the perforation of the depressed bone, for thus the oppression of the brain was removed [4,14].

Trephination to craniotomy: Early surgical approaches to epilepsy

Trephination (making a hole in the skull) has been practiced for many centuries [3,15–18]. Trephination is extensively discussed in Hippocrates’ On Wounds in the Head[8]. One major indication for trephination followed the Galenic conception of humoral imbalance and trephination then allowed evil humors to escape in certain cases [3]. The Quattuor magistri, a 13th-century surgical text, recommended opening the skulls of melancholics, epileptics, and others so that the humors and air could be expelled [4]. Such practices persisted over many centuries. In the 17th century, Riverius in The Compleat Practice of Physick stated that:

If all means fail the last remedy is to open the fore part of the Skull with a Trepan, at distance from the Sutures, that the evil air may breathe out. By this means many times desperate Epilepsies have been cured, and it may be safely done if the Chyurgeon be skillful [19].

Gradually over time, however, the indications for trephination for epilepsy became limited to: (1) a morbid condition of the skull such as contusion or fracture; and (2) accumulation of humors directly under the skull. The older notion of giving outlet to vapors and humors gradually gave way over time to the concept of treating a localized pathological condition of the brain and its membranes [4].

In the 19th century, trephination continued to be practiced for traumatic epilepsy and diseased bone of the skull. The indication was usually based on the concept of mechanical irritation of the subjacent brain tissue [20]. One key American proponent of this operation was Benjamin Winslow Dudley (1785–1870) [21] (Fig.