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Historical documents on epilepsy: From antiquity through the 20th century
Brain & Development 39 (2017) 457–463 www.elsevier.com/locate/braindev
Review article
Historical documents on epilepsy: From antiquity through the 20th century Christos P. Panteliadis a,⇑, Photios Vassilyadi b, Julia Fehlert c, Christian Hagel c a
Division of Pediatric Neurology and Developmental Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece b Department of Internal Medicine, St. John Hospital & Medical Center, Detroit, MI, USA c Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Received 28 September 2016; received in revised form 8 February 2017; accepted 8 February 2017
Abstract Historical documents dating back almost 4500 years have alluded to the condition of epilepsy, describing signs and symptoms that are well-known today. Epilepsy was thought to be a mystical disorder by almost all Ancient cultures, including the Babylonians, Egyptians, Greeks, Indians, Iranians and Chinese. Hippocrates was the first to de-mystify the condition of epilepsy, providing a more scientific approach to the condition. As the signs and symptoms of epilepsy occurred without an obvious cause, the idea stood that it was a mystical phenomenon of divine punishment. This portrayal persisted through the early centuries of the common era, including the Middle Ages. It was not until the 16th and 17th century that Paracelsus, le Pois and Sylvius started to investigate internal causes for epilepsy. By the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. This resulted in Tissot writing the first modern book on epilepsy. Research continued in the 19th century with Jackson describing different types of seizures and many researchers showing interest in electroencephalography (EEG). The 20th century saw more detailed research being done on epilepsy and EEG, in addition to the establishment of many epilepsy-associated medical societies. The goal of this historical documentation is to provide an overview of the most important milestones in the history of epilepsy. Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Epilepsy; Seizure; Diagnostics; Electroencephalography; Antiquity; Historical
1. Introduction The history of epilepsy is intermingled with the history of human existence, dating back to antiquity. There are few diseases in the history of medicine that can be traced back over thousands of years. Numerous documents, philosophical texts, written evidence and legal references about epilepsy can be found in multiple cul⇑ Corresponding author at: Division of Pediatric Neurology and Developmental Medicine, University of Thessaloniki, Avdella 10, 55131 Thessaloniki, Greece. E-mail address: [email protected] (C.P. Panteliadis).
tures, including the ancient Babylonians (2000 years B. C), Egyptians (1700 years B.C.) and Greeks (5–4th century B.C.) [1–3]. References can also be seen in more modern medicine, including: Indian (Ayurveda) [4], Iranian (Avicenna) [5], and Chinese [6]. Over the course of history, epilepsy has been known by a variety of names, such as: sacred disease (Greek: ieqά mo´ro1), an illness sent by the gods, lunacy (Greek: rekgmiarlo´1), possession by evil spirits, falling sickness, Valentine’s disease and Herakleia (derived from Hercules, who also suffered from it according to the legend) [7,8]. There are numerous Latin synonyms, including morbus:
http://dx.doi.org/10.1016/j.braindev.2017.02.002 0387-7604/Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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herculeus, sacer, divinus, divus, coelestus, comitialis, iudaicus, mensalis and daemonicus [7]. Depending on the era and the prevailing concept of medicine and religion, there were different assumptions about the causes of epilepsy. Basic knowledge of epilepsy was outlined by Hippocrates in Ancient Greece (460–377 B.C.) [9–11]. Up until the 18th century, epilepsy was still considered an idiopathic disease derived from the brain. The work of William Cullen and Samuel A. Tissot set the basis for the modern understanding of epilepsy [12,13]. Knowledge of epilepsy increased in the 19th century, focusing on classification, etiology, pathophysiology and topographic localization. This was followed by rapid development in medical knowledge in the 20th century [14–17]. The aim of this documentation is to provide a brief, yet concise overview of the most important milestones in the history of epilepsy. In comparison to the many books written on this topic, this document references a significant number of Ancient texts from before the Common Era. This text provides the reader with a unique opportunity to appreciate the evolution of the idea of epilepsy: from a divine phenomenon to a more concise scientific explanation. 2. Before the common era The first description of epilepsy can be found in Sumerian documents from the region of Mesopotamia (2500 B.C.) [2]. The original text (written in the Akkadic language) describes the condition of anta’subbu (English: the hand of sin), which affects unclean and infectious-looking people. These patients were described as ‘‘unconscious with neck turned, arms/legs tense, eyes open and froth around the mouth”. It was believed that this person had broken social/religious rules and, as a sinner, was being punished by the goddess of the moon. At the time, known remedies included: exorcism, sacrificial offerings, atonements and religious rituals under the instruction of priests [18]. It was not until 1790 B.C. that the symptoms of epilepsy were meticulously described in The Code of Hammurabi. This was a set of laws written on a piece of stone 2.5 meters high and commissioned by the Babylonian King to regulate the social welfare of the epileptic. The law stated that if a slave were purchased, that slave can be returned within one month if he/she fell ill with bennu (English: falling sickness) [1]. Medical texts from ancient Egypt, dating back to the 18th Dynasty (1700 B.C.), were the first to presumably describe focal seizures [3,8]. The original papyrus (as described by the Egyptologist Edwin Smith) referred to a condition called nesejet, which describes five patients suffering from involuntary convulsions of the body [18]. The earliest classification of seizures can be found in Sakikku (English: All Diseases), one of the oldest Babylonian medical texts (1050 B.C.). It was writ-
ten on a stone tablet and refers to epilepsy as miqtu and anta’subba (similar to the name used by the Akkadians nearly 1500 years prior) [19]. The translated Babylonian text described nearly all types of epilepsy, such as: febrile seizures, petit and grand mal seizures, focal seizures, simple and complex partial seizures, pediatric seizures and status epilepticus [1,20]. A medical text from Ancient China (600 B.C.) entitled Zhu Bing Yuan Hou differentiates between five categories of seizures. One category was called Dian and Xian, which was characterized by post-ictal memory loss [6]. A similar concept called Caraca Samhita˜ Sutra was described by the Indian medical author Atreya (600 B.C.). He described a post-ictal paroxysmal loss of consciousness, which he thought was caused by cerebral dysfunction (and not by the Gods). Another Indian text Ayuerveda, mentions four different types of epilepsy, which were accompanied by Abasmara (loss of previously acquired skills) [21]. The word epilepsy (Greek: epikgwίa) undoubtedly has its roots in Ancient Greece (600–200 B.C.). It may be derived from the Ancient Greek verbs epikalbάmeim (English: in crisis), episίhelai (English: to attack), aq pάfx (English: to seize) and έpiare (English: to grip) [22]. In Greek Mythology, epilepsy was a mystical phenomenon called a miasma. It was seen as a punishment by the Gods, was considered contagious and cured by the sacrificial death of the affected person [11]. It was not until the time of Hippocrates (460–390 B.C.), though, that the conception of epilepsy shifted from mystical to scientific. The Hippocratic Corpus, within its 60 chapters, contains an essay entitled On the Sacred Disease [9–11]. This was the first scientific paper written that directly used the term epilepsy and very accurately described epileptic seizures. The goal of this script was to inform people about the disease, explain its natural origin, release fears, and recommend treatment. In his cardinal work, Hippocrates contrasted the natural opinion that epilepsy was a disease of the Gods, with an objective description: (1) the disease is not divine, (2) it is not a sacred disease, (3) it has the same origin as other illnesses, (4) it begins during embryogenesis and is caused by many factors such as temperature, fear, crying and heat stroke, and (5) prognosis is worse in children than in adults. He even went as far as to propose a neurosurgical procedure as treatment, referring that craniotomy should be performed at the opposite side of the brain as the seizures in order to spare patients from the phlegma that was causing the disease [23,24]. Aristotle (384–322 B.C.) was another Greek philosopher who wrote on epilepsy. In his treatise On Sleep and Walking, he described ‘‘sleep-related epilepsy”: he thought that food was able to produce vapor and that this would move through blood vessels and reach the brain during sleep [25]. The theory of vapor was later
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studied by Erasistatos (born 304–250 B.C), a Greek physician and intellectual student of Aristotle. He used camel brain, hare hearts and the blood of doves as a treatment for epilepsy [26]. In the centuries that followed, scientific efforts reached a low and epilepsy was being treated with exorcism and magical potions. 3. Common era prior to Middle Ages Roman physicians, philosophers, magistrates and historians were the first to address epilepsy at the beginning of the common era. Aulus Cornelius Celsus (25 B. C–50 A.D), who was both a physician and encyclopedist, documented many diseases and therapies in his work, De Medicina. He had a very precise and therapeutic approach to epilepsy, where he recommended bloodletting, cupping therapy and drinking wine [27]. Lucius Mestrius Plutarchus (50–120 A.D), a well-known Greek-Roman historian and magistrate, addressed the ideas and methods of epilepsy developed by Greek physicians and explained his own concept of The Sacred Disease [28]. Perhaps the most influential physician of the Roman period, Aelius Galenus (131–201 A.D), classified epilepsy according to its origin. He theorized that epilepsy was either intracranial (and therefore idiopathic) or extracranial (and therefore attributed to a primary disorder, such as irritation of the stomach or other body organs) [29]. Around the same time period, Aretaeus of Cappadocia (100 A.D) was a physician in Alexandria. In his two works, Corpus Medicorum and Corpus Graecorum, he defined epilepsy as an ‘‘illness of various shapes” and distinguished three phases of an epileptic crisis: appearance, decline and end of symptoms. He theorized that the etiology of epilepsy was a humoral disturbance caused by ‘‘something evil in the head” – he described aura and photosensitive crises experienced by patients. His recommendations for the treatment of epilepsy involved emesis, medical herbs and trepanation of the skull [30,31]. A few centuries later, Oribasius (320–400 A.D.), the personal physician to the Roman Emperor Julian the Apostate, believed that phlegma provoked epileptic convulsions. He theorized that the brain’s function was influenced by various external factors, such as the moon and climate. He noticed that patients with epilepsy experienced ‘‘mental effects” but that he could not distinguish these ‘‘mental effects” from those resulting from apoplexy [28]. 4. The Middle Ages (5th to 15th century) For most of the Middle Ages, scientific research in epilepsy experienced a deep setback, interest remained low and non-medical methods were being used as therapy. The predominating views of epilepsy involved sym-
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bolism, demonology, hyperbolical religiousness and distorted medical opinions from the Greek & Roman period. Mysticism and dogmatism prevailed among physicians practicing ancient methods from the Babylonian era, under the notion that epilepsy was a contagious or hysteric disease. Patients were considered as ‘‘possessed” or labeled as witches/warlocks. The basis for treatment fell into three main categories: conventional (diet and botanical remedies), magical (phases of the moon, trepanation of the skull) and religious (fasting, prayer, religious exorcisms and social marginalization). Religious therapies for epilepsy were documented by both Islamic and Christian medical practitioners. Ali ibn al-0 Abbas al-Majusi (10th century), a Persian Islamic physician, strongly influenced occidental medicine through his work The Complete Book of Medical Art. He explained that because there is ‘‘liquid” in the brain, epilepsy must be caused by changes in temperature. Even though he ascribed much of disease to science, he was also a Holy Man and still considered epilepsy to be a divine punishment of human sin – as such, he recommended purgation and fasting [32]. Constantine the African (11th century), a Christian monk and medical writer, recommended that parents of epileptic children should to go to church (in particular, to mass on Friday and Saturday) [33]. 5. The 16th and 17th centuries The beginning of the 16th century came with new thoughts about the origin and the clinical appearance of epilepsy. Gradually, old therapies were replaced by new ones, scientific advances were made and Hippocratic theories on epilepsy once-again became topics up for discussion. At the onset of the century, an infirmary was built at the Benedictine monastery specifically for people suffering from falling sickness. This was built in honor of Saint Valentine, a medieval saint of the Catholic Church, who was said to have treated epilepsy. His name in German originates from the phrase fall net hin (English: do not fall down). Saint Valentine was said to protect people from diseases that cause someone to ‘‘fall down and lose their senses” [34]. One of the most influential physicians of the 16th century was the Swiss-German physician Theophrastus Bombastus von Hohenheim (widely known as Paracelsus, 1493–1541). He emphasized that epilepsy was not caused by spirits or demons, but had a natural origin (either hereditary, weakness of the semen or malnutrition). He extensively investigated epilepsy, wrote three books on the topic and tried to explain its pathogenesis [35]. In the same time period, the definition of epilepsy was highly impacted by German physician Johannes Marcus Marci (1595–1667) and French physician Charles le Pois (1563–1636), who independently
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described epileptic crises with loss of consciousness [36,37]. In his text De Medicina, Charles le Pois further declared that epilepsy originated in the brain, became noticeable in different parts of the body, generalized and eventually lead to unconsciousness [37]. The etiology of epilepsy was being geared towards a chemical theory by Francois le Boe (widely known as Sylvius, 1614–1672) and Thomas Willis (1621–1675), an English physician specializing in neuroanatomy and neurology [38,39]. Sylvius introduced the idea that acid vapors irritated animal spirits in the brain and caused convulsions (a similar idea that Aristotle presented 2000 years earlier) [39]. Willis expanded on this idea in his book Pathologicae Cerebri et Nervosa Generis Specimen (1667). He came up with the idea that animal spirits released vitriolic chemical particles into the blood, which mix together, move into the cerebral cortex, ‘‘spill” into brain and spinal cord and ‘‘irritate the nerves” in order to make the muscles ‘‘explode” [38,39]. He was also the first to describe post-ictal urinary incontinence, aura originating from the brain (not the periphery) and post-ictal memory/intelligence loss. Late in the 17th century, Charles Drelincourt (1633–1694) was the first to experimentally provoke epileptic convulsions by driving a needle into the fourth ventricle of a dog’s brain [40]. 6. The 18th century In the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. In 1708, the well-known Dutch physician Herman Boerhaave (1668– 1738) was the first to define epilepsy as a serious disease that may be inherited. He described this disease as occurring in abnormally shaped skulls where foul fluid was stagnant – this resulted in excess water accumulating in the brain [41]. Gerard van Swieten (1700–1772), a student of Boerhaave, extensively described the clinical characteristics of different types of seizures and tried to explain symptoms such as screams and salivation [42]. The second half of the 18th century provided more detailed accounts of specific types of seizures. In 1770, the Swiss neurologist Samuel August Tissot (1728– 1797) wrote the first modern book on epilepsy, Traite´ de l’Epilepsie. He introduced a new and innovative view of epilepsy – his book contained clear remarks about types of seizures (grand e´tat and petit e´tat) and even mentioned syndromes associated with epilepsy. He was also the first to label absence seizures in children as ‘‘subtle stoppage in behavior” [13]. In 1789, William Cullen (1710–1790) accurately characterized a focal seizure by describing convulsions that only affected certain parts of the body and did not result in loss of consciousness [12].
7. The 19th century At the beginning of the 19th century, the scientific interest in epilepsy increased exponentially. Society became more sympathetic to these patients – ostracism lessened and progress was made toward social integration. The epileptic was seen as a patient similar to others and was perceived as a normal member of society. In 1803, the French physician Louis Maisonneuve (1745– 1826) published Recherches et Observations sur l‘Epilepsie, where he explained that patients suffering from epilepsy are better observed and treated in a hospital setting. He believed that a physician can closely study distinct patterns of the disease while observing patients for a short time in hospital compared to generally observing these patients in a less intimate setting [43]. In 1824, Calmeil (1798–1895) introduced the term epilectic absence (not to be confused with absence seizure) that referred to post-ictal, brief loss of consciousness/confusion [44]. In 1838, Jean-Etienne Dominique Esquirol (1772–1840) wrote a detailed chapter on epilepsy in his book Des Maladies Mentales. He made a clear distinction between grand mal and petit mal seizures, coining both of these terms [45]. In 1841, William James West (1794–1848), an English surgeon, described spasms that occurred to his 4-month-old son starting from birth. His colleagues from London, Charles Clarke and Charles Locock, saw similar pediatric cases in their own practice. This led West to name these episodes Salaam attacks (this condition would later be called West Syndrome or infantile spasm) [46,47]. The mid-to-late 19th century was highlighted by the establishment of medical societies and initial topographic localization of seizures. In 1857, The National Hospital for The Paralyzed and Epileptic was founded in London, with a similar institution opening in New York ten years later [48]. Between 1866 and 1899, John Hughlings-Jackson (1835–1911), the father of modern scientific neurology, published many manuscripts on psychomotor attacks and epilepsy. He distinguished that epilepsy was caused by local discharges from grey matter in the brain that are sudden, rapid and excessive. His name has been used as an eponym for simple partial seizures: Jacksonian Epilepsy, Jacksonian March and Jacksonian Paresis. Jackson was one of the founders/ editors of the journal Brain (1879), he founded the Neurological Society in London (1885) and co-founded the National Society for the Employment of Epileptics (1892). In 1897, the Hughlings-Jackson Lecture was launched at the London Hospital [49–51]. The late 19th century was also the time when electroencephalography (EEG) started to be of interest. In 1870, neurophysiologist Gustav Fritsch (1838–1927) and psychiatrist Edvard Hitzig (1838–1927) succeeded in inducing seizures in a dog by electric stimulation [52]. Five years later, in 1875, the English physician
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and physiologist Richard Caton (1842–1926) presented his findings to the British Medical Association – he used a galvanometer to register oscillations of electric potential in the cerebral hemispheres of rabbits and monkeys [53]. Some years later, similar studies were published by Vasili Yakovlevich Danilewsky (1852–1939) from Cracau in Poland [54]. In 1890, Adolf Beck (1863–1942), one of the pioneers of EEG, wrote his famous dissertation Investigations into the Physiology of the Brain. He studied electrical brain stimulation in dogs and rabbits and argued that the brain has ‘‘priority” over the body’s electrical activity. Using a galvanometer, he found constant electric activity in the brains of dogs and rabbits which was asynchronous to respiration and heartbeat. He also measured nerve conduction velocities, which were vastly overestimated up to that time [55]. About two weeks later, Ernst Fleischl von Marxow (1846– 1891), a physiologist and physician from Vienna, claimed to have conducted similar unpublished studies [56]. In the following years, Beck and his teacher Napoleon Cybulski (1854–1919) continued their work on dogs and apes, producing a cortical map of evoked potentials, coined experimental electroencephalographic studies [57]. Similar findings were published by the physiologists Francis Gotch (1853–1913) and Victor Horsley (1857– 1916) who electrically stimulated the cortices of other mammals [58–60]. 8. The 20th century The beginning of the 20th century saw more detailed research being done on epilepsy and more medical societies being established. In 1904, William Spratling (1863–1915), an American neurologist, introduced the term epileptologist in his work Epilepsy and Its Treatment, which was used to describe a physician that specialized in epilepsy [61]. In 1907, Gowers published his famous book The Borderlands of Epilepsy, focusing on fainting, vagal/vasovagal attacks, migraine, vertigo and some sleep symptoms (especially narcolepsy) [16]. The neurologist Stanley Cobb (1887–1968) published two monographs: Epilepsy from the Standpoint of Physiology and Treatment and Epilepsy and Related Disorders [62]. The International League Against Epilepsy (ILAE) was founded in 1909 in Budapest and released the world-renowned journal Epilepsia. Around the same time, the American Epilepsy Society (AES) was founded during a joint meeting by the Association for the Research in Nervous and Mental Disease (ARNMD) and the American League Against Epilepsy (ALAE). The proceedings of this meeting stimulated further research in epilepsy. The first president of AES was Charles Dair Aring (1904–1998), a renowned American neurologist and pioneer in medical education [63]. Much of the 20th century specifically focused on research to develop EEG. In 1912, Pavel Yurevich Kauf-
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man (1877–1951) and Vladimir Vladimirovich PravdichNeminsky (1879–1952) noticed electrical changes in the brain during experimentally-induced seizures. They were the first to associate epileptic attacks with abnormal electric discharges on EEG [64]. Two years later in 1914, the neurophysiologists Cybulski and JelenskaMacieszyna (1854–1919) published the first photographs of an EEG recording action potentials of dog brains during a focal seizure [57]. The same year, Vladimir Prawdicz-Neminski (1879–1952) published studies on the brain cortices of dogs, which strengthened the understanding of electrical waves in the cortex – this introduced the term electrocerebrogram [65]. Ten years later, in 1924, the German psychiatrist Hans Berger (1873–1941) succeeded in demonstrating neural oscillations in the human brain. He was actually the first to use the term electroencephalography. From 1926 to 1929, Berger managed to establish a good EEG recording of alpha waves by using a double-coil galvanometer [66]. His findings were later confirmed by the English physiologists Andrian and Matthews who conducted experimental investigations in Faraday cages [67,68]. This publication left no doubt about the rhythmic resting activity of the brain – EEG was enthusiastically added to clinical diagnostics in the AngloSaxon world. In 1932, Berger reported a number of postictal EEG’s after generalized tonic–clonic seizures, and, in 1933, he described the first patterns of inter-ictal changes in epilepsia minor [66,69]. In the same year, Alois Kornmu¨ller (1905–1968) observed distinctions in electric activity in different parts of the cortex by using direct leads from the cortex [70]. He also was the first to describe seizure-related electrical discharge in epileptics. In 1933 and 1935, Ottfried Foerster (1873–1941) and Herbert Altenburger reported placing the first intraoperative leads directly into the human cortex and in 1935, the psychologist Hubert Rohracher (1904–1972) investigated the effectiveness of this method [71,72]. Berger’s work on the EEG in epilepsy was completed by the findings of the American neurologist Frederic Andrews Gibbs (1903–1992) and his wife/technician Erna Leonhardt-Gibbs (1904–1987). In cooperation with William Lennox they established the correlation between EEG findings and epileptic convulsions [73,74]. Lennox and Gibbs published their monumental monograph Atlas of Electroencephalography, in which they included mechanical and mathematical analysis [74,75]. Starting from 1939, Wilder Penfield (1891–1976), a famous Canadian neurosurgeon, and Herbert Jasper (1906–1999), a Canadian neurologist, introduced EEG as a routine method in neurosurgery. In 1949, they studied the role of thalamic reticular structures in the genesis of metrazol-induced generalized paroxysmal EEG discharges and developed the concept of centrencephalic seizures [76]. In 1951, the French neurologist Henri Gastaut (1915–1995) coined the term photosensitive epilepsy
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(Gastaut Syndrome) when noticing that epileptic patients would seize when exposed to visual stimuli (such as flashing lights) [77]. Furthermore, Gastaut studied selfinduced epileptic seizures, startle epilepsy, hemiconvulsion hemiplegia epilepsy (HHE syndrome) and benign partial epilepsy with occipital spike-wave focus [78]. In 1981, the ILAE proposed a revised clinical and EEG classification of epileptic seizures [79]. In 1993, the ILAE defined fever seizure as those occurring in children after the age of 1 month (usually between 3 months and 6 years old), associated with a febrile illness and not caused by an infection of the central nervous system [77]. Finally, the invention of imaging modalities considerably facilitated the diagnosis of symptomatic epilepsy. This includes brain computed tomography (CT) in the 1970’s, brain magnetic resonance imaging (MRI) in the 1980’s, and PET scanning (positron emission tomography) towards the end of the 20th century [80]. 9. Discussion The intellectual evolution of epilepsy experienced a number of paradigm shifts since first being described as ‘‘a disease that affects unclean and infectiouslooking people” [2] and ‘‘being brought-on by the wrath of the Gods” [11]. The first major advancement was experienced by Hippocrates when he de-mystified the idea of epilepsy and described it as having a more organic etiology [23–24]. Like many philosophers, however, Hippocrates was ahead of his time and the idea of mysticism remained for many centuries. The first modern paradigm shift did not occur until the 16th and 17th centuries when Charles le Pois described epilepsy as originating in the brain [39], followed by Charles Drelincourt who provoked seizures in a dog by driving a needle into its brain [43]. This led to the next paradigm shift in the 18th century when Samuel August Tissot wrote the first modern book on epilepsy. The 19th century was highlighted by the contributions of John Hughlings-Jackson, known today as the father of modern scientific neurology [53–55]. The last major paradigm shift occurred in the 20th century with the advent of EEG and the contribution of a number of scientist to this field, including the well-known neurosurgeon, Wilder Penfield [76]. There are a number of drawbacks to compiling a historical review. Firstly, a certain degree of bias exists when selection manuscripts, specifically observer bias when selecting Ancient texts that subjectively describe a topic. Second, misinterpretations of text can occur when translating from another language. Lastly, the compilation of the text itself contains small portions of much larger documents and may lack important details that further illustrate a topic.
10. Conclusion The notion of epilepsy has existed since 2500 B.C. Over the past 4500 years, the view of epilepsy has evolved from a primordial idea of divine punishment to a scientific explanation involving conduction pathways in the brain. The purpose of this review was to transport the reader through an evolutionary journey of human intellect regarding the historical development of epilepsy. Highlights of this journey include: (1) Historical texts alluding to the idea of epilepsy starting 2500 B.C., (2) Hippocrates being the first scientific mind to de-mystify epilepsy as ‘‘non-divine”, (3) Modern understanding of epilepsy only beginning in the 18th century, and (4) The advent of electroencephalography in the 19th century, which expanded the current view of epilepsy. References [1] Wilson JV, Reynolds EH. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. Med Hist 1990;34:185–98. [2] Labat R. Traite´ akkadien de diagnostics et pronostics me´dicaux. Paris-Leiden: Brill; 1951. [3] Wilson JA. Medicine in ancient Egypt. Bull Hist Med 1962;36:114–28. [4] Jain S, Tandon PN. Ayurvedic medicine and Indian literature on epilepsy. Neurol Asia 2004;9:57–8. [5] Gorji A, Khaleghi Ghadiri M. History of epilepsy in Medieval Iranian medicine. Neurosci Biobehav Rev 2001;25:455–61. [6] Lai CW, Lai YH. History of epilepsy in Chinese traditional medicine. Epilepsia 1991;32:299–302. [7] Bakhtiar L, Gruner OC. The Canon of Medicine. Chicago, IL: Kazi: Avicenna; 1999. [8] Edelstein L. Ancient Medicine. Selected papers of Ludwig Edelstein. In: Temkin O, Temkin C, editors. Baltimore: The John Hopkins University Press; 1967. [9] Hippocrates. The sacred disease. In: Chadwich J, Mann WN, editors. Oxford: Blackwell; 1950. [10] The sacred disease. The genuine works of hippocrates gryphon editions. Hippocrates. Birmingham: Gryphon Editions; 1985. [11] Lipourllis D. The suffix in presocratic philosophy and in the Hippocratic corpus (in Greek). Thessaloniki: Aristotle University; 1968. [12] Cullen W. First lines of the practice of physic. Edinburgh: Bell & Bradfute and William Creech; 1791. [13] Tissot DM. Traite´ de l’epilepsie: faisant le tome troisieme du traite´ des nerfs et de leurs maladies. In: Didot PF (ed.), Paris: Didot le jeune; 1770. [14] Herpin T. Des acce`s incomplets d’e´pilepsie. Paris: JB Baillie`re; 1867. [15] Delasiauve LJF. Traite´ de l’e´pilepsie: histoire, traitement, me´decine le´gale. Paris: Victor Masson; 1854. [16] Gowers WR. Epilepsy and other chronic convulsive diseases: their causes, symptoms, and treatment. London: Churchill; 1901. [17] Gowers WR. The border-land of epilepsy. Faints, vagal attacks, vertigo, migraine, sleep symptoms, and their treatment. Philadephia: P. Blakiston’s son & Company; 1903. ¨ ber Pathologie und Therapie der Epilepsien in [18] Heller F. U Altertum. Janus 1911;16:591–5. [19] Ko¨cher F. Die babylonisch-assyrische Medizin in Texten und Untersuchungen. Berlin: Walter de Gruyter; 1980. [20] Schurlock J, Andersen B. Diagnosis in Assyrian and Babylonian medicine. Chicago: University of Illinois Press; 2005.
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Review article
Historical documents on epilepsy: From antiquity through the 20th century Christos P. Panteliadis a,⇑, Photios Vassilyadi b, Julia Fehlert c, Christian Hagel c a
Division of Pediatric Neurology and Developmental Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece b Department of Internal Medicine, St. John Hospital & Medical Center, Detroit, MI, USA c Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Received 28 September 2016; received in revised form 8 February 2017; accepted 8 February 2017
Abstract Historical documents dating back almost 4500 years have alluded to the condition of epilepsy, describing signs and symptoms that are well-known today. Epilepsy was thought to be a mystical disorder by almost all Ancient cultures, including the Babylonians, Egyptians, Greeks, Indians, Iranians and Chinese. Hippocrates was the first to de-mystify the condition of epilepsy, providing a more scientific approach to the condition. As the signs and symptoms of epilepsy occurred without an obvious cause, the idea stood that it was a mystical phenomenon of divine punishment. This portrayal persisted through the early centuries of the common era, including the Middle Ages. It was not until the 16th and 17th century that Paracelsus, le Pois and Sylvius started to investigate internal causes for epilepsy. By the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. This resulted in Tissot writing the first modern book on epilepsy. Research continued in the 19th century with Jackson describing different types of seizures and many researchers showing interest in electroencephalography (EEG). The 20th century saw more detailed research being done on epilepsy and EEG, in addition to the establishment of many epilepsy-associated medical societies. The goal of this historical documentation is to provide an overview of the most important milestones in the history of epilepsy. Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Epilepsy; Seizure; Diagnostics; Electroencephalography; Antiquity; Historical
1. Introduction The history of epilepsy is intermingled with the history of human existence, dating back to antiquity. There are few diseases in the history of medicine that can be traced back over thousands of years. Numerous documents, philosophical texts, written evidence and legal references about epilepsy can be found in multiple cul⇑ Corresponding author at: Division of Pediatric Neurology and Developmental Medicine, University of Thessaloniki, Avdella 10, 55131 Thessaloniki, Greece. E-mail address: [email protected] (C.P. Panteliadis).
tures, including the ancient Babylonians (2000 years B. C), Egyptians (1700 years B.C.) and Greeks (5–4th century B.C.) [1–3]. References can also be seen in more modern medicine, including: Indian (Ayurveda) [4], Iranian (Avicenna) [5], and Chinese [6]. Over the course of history, epilepsy has been known by a variety of names, such as: sacred disease (Greek: ieqά mo´ro1), an illness sent by the gods, lunacy (Greek: rekgmiarlo´1), possession by evil spirits, falling sickness, Valentine’s disease and Herakleia (derived from Hercules, who also suffered from it according to the legend) [7,8]. There are numerous Latin synonyms, including morbus:
http://dx.doi.org/10.1016/j.braindev.2017.02.002 0387-7604/Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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herculeus, sacer, divinus, divus, coelestus, comitialis, iudaicus, mensalis and daemonicus [7]. Depending on the era and the prevailing concept of medicine and religion, there were different assumptions about the causes of epilepsy. Basic knowledge of epilepsy was outlined by Hippocrates in Ancient Greece (460–377 B.C.) [9–11]. Up until the 18th century, epilepsy was still considered an idiopathic disease derived from the brain. The work of William Cullen and Samuel A. Tissot set the basis for the modern understanding of epilepsy [12,13]. Knowledge of epilepsy increased in the 19th century, focusing on classification, etiology, pathophysiology and topographic localization. This was followed by rapid development in medical knowledge in the 20th century [14–17]. The aim of this documentation is to provide a brief, yet concise overview of the most important milestones in the history of epilepsy. In comparison to the many books written on this topic, this document references a significant number of Ancient texts from before the Common Era. This text provides the reader with a unique opportunity to appreciate the evolution of the idea of epilepsy: from a divine phenomenon to a more concise scientific explanation. 2. Before the common era The first description of epilepsy can be found in Sumerian documents from the region of Mesopotamia (2500 B.C.) [2]. The original text (written in the Akkadic language) describes the condition of anta’subbu (English: the hand of sin), which affects unclean and infectious-looking people. These patients were described as ‘‘unconscious with neck turned, arms/legs tense, eyes open and froth around the mouth”. It was believed that this person had broken social/religious rules and, as a sinner, was being punished by the goddess of the moon. At the time, known remedies included: exorcism, sacrificial offerings, atonements and religious rituals under the instruction of priests [18]. It was not until 1790 B.C. that the symptoms of epilepsy were meticulously described in The Code of Hammurabi. This was a set of laws written on a piece of stone 2.5 meters high and commissioned by the Babylonian King to regulate the social welfare of the epileptic. The law stated that if a slave were purchased, that slave can be returned within one month if he/she fell ill with bennu (English: falling sickness) [1]. Medical texts from ancient Egypt, dating back to the 18th Dynasty (1700 B.C.), were the first to presumably describe focal seizures [3,8]. The original papyrus (as described by the Egyptologist Edwin Smith) referred to a condition called nesejet, which describes five patients suffering from involuntary convulsions of the body [18]. The earliest classification of seizures can be found in Sakikku (English: All Diseases), one of the oldest Babylonian medical texts (1050 B.C.). It was writ-
ten on a stone tablet and refers to epilepsy as miqtu and anta’subba (similar to the name used by the Akkadians nearly 1500 years prior) [19]. The translated Babylonian text described nearly all types of epilepsy, such as: febrile seizures, petit and grand mal seizures, focal seizures, simple and complex partial seizures, pediatric seizures and status epilepticus [1,20]. A medical text from Ancient China (600 B.C.) entitled Zhu Bing Yuan Hou differentiates between five categories of seizures. One category was called Dian and Xian, which was characterized by post-ictal memory loss [6]. A similar concept called Caraca Samhita˜ Sutra was described by the Indian medical author Atreya (600 B.C.). He described a post-ictal paroxysmal loss of consciousness, which he thought was caused by cerebral dysfunction (and not by the Gods). Another Indian text Ayuerveda, mentions four different types of epilepsy, which were accompanied by Abasmara (loss of previously acquired skills) [21]. The word epilepsy (Greek: epikgwίa) undoubtedly has its roots in Ancient Greece (600–200 B.C.). It may be derived from the Ancient Greek verbs epikalbάmeim (English: in crisis), episίhelai (English: to attack), aq pάfx (English: to seize) and έpiare (English: to grip) [22]. In Greek Mythology, epilepsy was a mystical phenomenon called a miasma. It was seen as a punishment by the Gods, was considered contagious and cured by the sacrificial death of the affected person [11]. It was not until the time of Hippocrates (460–390 B.C.), though, that the conception of epilepsy shifted from mystical to scientific. The Hippocratic Corpus, within its 60 chapters, contains an essay entitled On the Sacred Disease [9–11]. This was the first scientific paper written that directly used the term epilepsy and very accurately described epileptic seizures. The goal of this script was to inform people about the disease, explain its natural origin, release fears, and recommend treatment. In his cardinal work, Hippocrates contrasted the natural opinion that epilepsy was a disease of the Gods, with an objective description: (1) the disease is not divine, (2) it is not a sacred disease, (3) it has the same origin as other illnesses, (4) it begins during embryogenesis and is caused by many factors such as temperature, fear, crying and heat stroke, and (5) prognosis is worse in children than in adults. He even went as far as to propose a neurosurgical procedure as treatment, referring that craniotomy should be performed at the opposite side of the brain as the seizures in order to spare patients from the phlegma that was causing the disease [23,24]. Aristotle (384–322 B.C.) was another Greek philosopher who wrote on epilepsy. In his treatise On Sleep and Walking, he described ‘‘sleep-related epilepsy”: he thought that food was able to produce vapor and that this would move through blood vessels and reach the brain during sleep [25]. The theory of vapor was later
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studied by Erasistatos (born 304–250 B.C), a Greek physician and intellectual student of Aristotle. He used camel brain, hare hearts and the blood of doves as a treatment for epilepsy [26]. In the centuries that followed, scientific efforts reached a low and epilepsy was being treated with exorcism and magical potions. 3. Common era prior to Middle Ages Roman physicians, philosophers, magistrates and historians were the first to address epilepsy at the beginning of the common era. Aulus Cornelius Celsus (25 B. C–50 A.D), who was both a physician and encyclopedist, documented many diseases and therapies in his work, De Medicina. He had a very precise and therapeutic approach to epilepsy, where he recommended bloodletting, cupping therapy and drinking wine [27]. Lucius Mestrius Plutarchus (50–120 A.D), a well-known Greek-Roman historian and magistrate, addressed the ideas and methods of epilepsy developed by Greek physicians and explained his own concept of The Sacred Disease [28]. Perhaps the most influential physician of the Roman period, Aelius Galenus (131–201 A.D), classified epilepsy according to its origin. He theorized that epilepsy was either intracranial (and therefore idiopathic) or extracranial (and therefore attributed to a primary disorder, such as irritation of the stomach or other body organs) [29]. Around the same time period, Aretaeus of Cappadocia (100 A.D) was a physician in Alexandria. In his two works, Corpus Medicorum and Corpus Graecorum, he defined epilepsy as an ‘‘illness of various shapes” and distinguished three phases of an epileptic crisis: appearance, decline and end of symptoms. He theorized that the etiology of epilepsy was a humoral disturbance caused by ‘‘something evil in the head” – he described aura and photosensitive crises experienced by patients. His recommendations for the treatment of epilepsy involved emesis, medical herbs and trepanation of the skull [30,31]. A few centuries later, Oribasius (320–400 A.D.), the personal physician to the Roman Emperor Julian the Apostate, believed that phlegma provoked epileptic convulsions. He theorized that the brain’s function was influenced by various external factors, such as the moon and climate. He noticed that patients with epilepsy experienced ‘‘mental effects” but that he could not distinguish these ‘‘mental effects” from those resulting from apoplexy [28]. 4. The Middle Ages (5th to 15th century) For most of the Middle Ages, scientific research in epilepsy experienced a deep setback, interest remained low and non-medical methods were being used as therapy. The predominating views of epilepsy involved sym-
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bolism, demonology, hyperbolical religiousness and distorted medical opinions from the Greek & Roman period. Mysticism and dogmatism prevailed among physicians practicing ancient methods from the Babylonian era, under the notion that epilepsy was a contagious or hysteric disease. Patients were considered as ‘‘possessed” or labeled as witches/warlocks. The basis for treatment fell into three main categories: conventional (diet and botanical remedies), magical (phases of the moon, trepanation of the skull) and religious (fasting, prayer, religious exorcisms and social marginalization). Religious therapies for epilepsy were documented by both Islamic and Christian medical practitioners. Ali ibn al-0 Abbas al-Majusi (10th century), a Persian Islamic physician, strongly influenced occidental medicine through his work The Complete Book of Medical Art. He explained that because there is ‘‘liquid” in the brain, epilepsy must be caused by changes in temperature. Even though he ascribed much of disease to science, he was also a Holy Man and still considered epilepsy to be a divine punishment of human sin – as such, he recommended purgation and fasting [32]. Constantine the African (11th century), a Christian monk and medical writer, recommended that parents of epileptic children should to go to church (in particular, to mass on Friday and Saturday) [33]. 5. The 16th and 17th centuries The beginning of the 16th century came with new thoughts about the origin and the clinical appearance of epilepsy. Gradually, old therapies were replaced by new ones, scientific advances were made and Hippocratic theories on epilepsy once-again became topics up for discussion. At the onset of the century, an infirmary was built at the Benedictine monastery specifically for people suffering from falling sickness. This was built in honor of Saint Valentine, a medieval saint of the Catholic Church, who was said to have treated epilepsy. His name in German originates from the phrase fall net hin (English: do not fall down). Saint Valentine was said to protect people from diseases that cause someone to ‘‘fall down and lose their senses” [34]. One of the most influential physicians of the 16th century was the Swiss-German physician Theophrastus Bombastus von Hohenheim (widely known as Paracelsus, 1493–1541). He emphasized that epilepsy was not caused by spirits or demons, but had a natural origin (either hereditary, weakness of the semen or malnutrition). He extensively investigated epilepsy, wrote three books on the topic and tried to explain its pathogenesis [35]. In the same time period, the definition of epilepsy was highly impacted by German physician Johannes Marcus Marci (1595–1667) and French physician Charles le Pois (1563–1636), who independently
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described epileptic crises with loss of consciousness [36,37]. In his text De Medicina, Charles le Pois further declared that epilepsy originated in the brain, became noticeable in different parts of the body, generalized and eventually lead to unconsciousness [37]. The etiology of epilepsy was being geared towards a chemical theory by Francois le Boe (widely known as Sylvius, 1614–1672) and Thomas Willis (1621–1675), an English physician specializing in neuroanatomy and neurology [38,39]. Sylvius introduced the idea that acid vapors irritated animal spirits in the brain and caused convulsions (a similar idea that Aristotle presented 2000 years earlier) [39]. Willis expanded on this idea in his book Pathologicae Cerebri et Nervosa Generis Specimen (1667). He came up with the idea that animal spirits released vitriolic chemical particles into the blood, which mix together, move into the cerebral cortex, ‘‘spill” into brain and spinal cord and ‘‘irritate the nerves” in order to make the muscles ‘‘explode” [38,39]. He was also the first to describe post-ictal urinary incontinence, aura originating from the brain (not the periphery) and post-ictal memory/intelligence loss. Late in the 17th century, Charles Drelincourt (1633–1694) was the first to experimentally provoke epileptic convulsions by driving a needle into the fourth ventricle of a dog’s brain [40]. 6. The 18th century In the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. In 1708, the well-known Dutch physician Herman Boerhaave (1668– 1738) was the first to define epilepsy as a serious disease that may be inherited. He described this disease as occurring in abnormally shaped skulls where foul fluid was stagnant – this resulted in excess water accumulating in the brain [41]. Gerard van Swieten (1700–1772), a student of Boerhaave, extensively described the clinical characteristics of different types of seizures and tried to explain symptoms such as screams and salivation [42]. The second half of the 18th century provided more detailed accounts of specific types of seizures. In 1770, the Swiss neurologist Samuel August Tissot (1728– 1797) wrote the first modern book on epilepsy, Traite´ de l’Epilepsie. He introduced a new and innovative view of epilepsy – his book contained clear remarks about types of seizures (grand e´tat and petit e´tat) and even mentioned syndromes associated with epilepsy. He was also the first to label absence seizures in children as ‘‘subtle stoppage in behavior” [13]. In 1789, William Cullen (1710–1790) accurately characterized a focal seizure by describing convulsions that only affected certain parts of the body and did not result in loss of consciousness [12].
7. The 19th century At the beginning of the 19th century, the scientific interest in epilepsy increased exponentially. Society became more sympathetic to these patients – ostracism lessened and progress was made toward social integration. The epileptic was seen as a patient similar to others and was perceived as a normal member of society. In 1803, the French physician Louis Maisonneuve (1745– 1826) published Recherches et Observations sur l‘Epilepsie, where he explained that patients suffering from epilepsy are better observed and treated in a hospital setting. He believed that a physician can closely study distinct patterns of the disease while observing patients for a short time in hospital compared to generally observing these patients in a less intimate setting [43]. In 1824, Calmeil (1798–1895) introduced the term epilectic absence (not to be confused with absence seizure) that referred to post-ictal, brief loss of consciousness/confusion [44]. In 1838, Jean-Etienne Dominique Esquirol (1772–1840) wrote a detailed chapter on epilepsy in his book Des Maladies Mentales. He made a clear distinction between grand mal and petit mal seizures, coining both of these terms [45]. In 1841, William James West (1794–1848), an English surgeon, described spasms that occurred to his 4-month-old son starting from birth. His colleagues from London, Charles Clarke and Charles Locock, saw similar pediatric cases in their own practice. This led West to name these episodes Salaam attacks (this condition would later be called West Syndrome or infantile spasm) [46,47]. The mid-to-late 19th century was highlighted by the establishment of medical societies and initial topographic localization of seizures. In 1857, The National Hospital for The Paralyzed and Epileptic was founded in London, with a similar institution opening in New York ten years later [48]. Between 1866 and 1899, John Hughlings-Jackson (1835–1911), the father of modern scientific neurology, published many manuscripts on psychomotor attacks and epilepsy. He distinguished that epilepsy was caused by local discharges from grey matter in the brain that are sudden, rapid and excessive. His name has been used as an eponym for simple partial seizures: Jacksonian Epilepsy, Jacksonian March and Jacksonian Paresis. Jackson was one of the founders/ editors of the journal Brain (1879), he founded the Neurological Society in London (1885) and co-founded the National Society for the Employment of Epileptics (1892). In 1897, the Hughlings-Jackson Lecture was launched at the London Hospital [49–51]. The late 19th century was also the time when electroencephalography (EEG) started to be of interest. In 1870, neurophysiologist Gustav Fritsch (1838–1927) and psychiatrist Edvard Hitzig (1838–1927) succeeded in inducing seizures in a dog by electric stimulation [52]. Five years later, in 1875, the English physician
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and physiologist Richard Caton (1842–1926) presented his findings to the British Medical Association – he used a galvanometer to register oscillations of electric potential in the cerebral hemispheres of rabbits and monkeys [53]. Some years later, similar studies were published by Vasili Yakovlevich Danilewsky (1852–1939) from Cracau in Poland [54]. In 1890, Adolf Beck (1863–1942), one of the pioneers of EEG, wrote his famous dissertation Investigations into the Physiology of the Brain. He studied electrical brain stimulation in dogs and rabbits and argued that the brain has ‘‘priority” over the body’s electrical activity. Using a galvanometer, he found constant electric activity in the brains of dogs and rabbits which was asynchronous to respiration and heartbeat. He also measured nerve conduction velocities, which were vastly overestimated up to that time [55]. About two weeks later, Ernst Fleischl von Marxow (1846– 1891), a physiologist and physician from Vienna, claimed to have conducted similar unpublished studies [56]. In the following years, Beck and his teacher Napoleon Cybulski (1854–1919) continued their work on dogs and apes, producing a cortical map of evoked potentials, coined experimental electroencephalographic studies [57]. Similar findings were published by the physiologists Francis Gotch (1853–1913) and Victor Horsley (1857– 1916) who electrically stimulated the cortices of other mammals [58–60]. 8. The 20th century The beginning of the 20th century saw more detailed research being done on epilepsy and more medical societies being established. In 1904, William Spratling (1863–1915), an American neurologist, introduced the term epileptologist in his work Epilepsy and Its Treatment, which was used to describe a physician that specialized in epilepsy [61]. In 1907, Gowers published his famous book The Borderlands of Epilepsy, focusing on fainting, vagal/vasovagal attacks, migraine, vertigo and some sleep symptoms (especially narcolepsy) [16]. The neurologist Stanley Cobb (1887–1968) published two monographs: Epilepsy from the Standpoint of Physiology and Treatment and Epilepsy and Related Disorders [62]. The International League Against Epilepsy (ILAE) was founded in 1909 in Budapest and released the world-renowned journal Epilepsia. Around the same time, the American Epilepsy Society (AES) was founded during a joint meeting by the Association for the Research in Nervous and Mental Disease (ARNMD) and the American League Against Epilepsy (ALAE). The proceedings of this meeting stimulated further research in epilepsy. The first president of AES was Charles Dair Aring (1904–1998), a renowned American neurologist and pioneer in medical education [63]. Much of the 20th century specifically focused on research to develop EEG. In 1912, Pavel Yurevich Kauf-
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man (1877–1951) and Vladimir Vladimirovich PravdichNeminsky (1879–1952) noticed electrical changes in the brain during experimentally-induced seizures. They were the first to associate epileptic attacks with abnormal electric discharges on EEG [64]. Two years later in 1914, the neurophysiologists Cybulski and JelenskaMacieszyna (1854–1919) published the first photographs of an EEG recording action potentials of dog brains during a focal seizure [57]. The same year, Vladimir Prawdicz-Neminski (1879–1952) published studies on the brain cortices of dogs, which strengthened the understanding of electrical waves in the cortex – this introduced the term electrocerebrogram [65]. Ten years later, in 1924, the German psychiatrist Hans Berger (1873–1941) succeeded in demonstrating neural oscillations in the human brain. He was actually the first to use the term electroencephalography. From 1926 to 1929, Berger managed to establish a good EEG recording of alpha waves by using a double-coil galvanometer [66]. His findings were later confirmed by the English physiologists Andrian and Matthews who conducted experimental investigations in Faraday cages [67,68]. This publication left no doubt about the rhythmic resting activity of the brain – EEG was enthusiastically added to clinical diagnostics in the AngloSaxon world. In 1932, Berger reported a number of postictal EEG’s after generalized tonic–clonic seizures, and, in 1933, he described the first patterns of inter-ictal changes in epilepsia minor [66,69]. In the same year, Alois Kornmu¨ller (1905–1968) observed distinctions in electric activity in different parts of the cortex by using direct leads from the cortex [70]. He also was the first to describe seizure-related electrical discharge in epileptics. In 1933 and 1935, Ottfried Foerster (1873–1941) and Herbert Altenburger reported placing the first intraoperative leads directly into the human cortex and in 1935, the psychologist Hubert Rohracher (1904–1972) investigated the effectiveness of this method [71,72]. Berger’s work on the EEG in epilepsy was completed by the findings of the American neurologist Frederic Andrews Gibbs (1903–1992) and his wife/technician Erna Leonhardt-Gibbs (1904–1987). In cooperation with William Lennox they established the correlation between EEG findings and epileptic convulsions [73,74]. Lennox and Gibbs published their monumental monograph Atlas of Electroencephalography, in which they included mechanical and mathematical analysis [74,75]. Starting from 1939, Wilder Penfield (1891–1976), a famous Canadian neurosurgeon, and Herbert Jasper (1906–1999), a Canadian neurologist, introduced EEG as a routine method in neurosurgery. In 1949, they studied the role of thalamic reticular structures in the genesis of metrazol-induced generalized paroxysmal EEG discharges and developed the concept of centrencephalic seizures [76]. In 1951, the French neurologist Henri Gastaut (1915–1995) coined the term photosensitive epilepsy
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(Gastaut Syndrome) when noticing that epileptic patients would seize when exposed to visual stimuli (such as flashing lights) [77]. Furthermore, Gastaut studied selfinduced epileptic seizures, startle epilepsy, hemiconvulsion hemiplegia epilepsy (HHE syndrome) and benign partial epilepsy with occipital spike-wave focus [78]. In 1981, the ILAE proposed a revised clinical and EEG classification of epileptic seizures [79]. In 1993, the ILAE defined fever seizure as those occurring in children after the age of 1 month (usually between 3 months and 6 years old), associated with a febrile illness and not caused by an infection of the central nervous system [77]. Finally, the invention of imaging modalities considerably facilitated the diagnosis of symptomatic epilepsy. This includes brain computed tomography (CT) in the 1970’s, brain magnetic resonance imaging (MRI) in the 1980’s, and PET scanning (positron emission tomography) towards the end of the 20th century [80]. 9. Discussion The intellectual evolution of epilepsy experienced a number of paradigm shifts since first being described as ‘‘a disease that affects unclean and infectiouslooking people” [2] and ‘‘being brought-on by the wrath of the Gods” [11]. The first major advancement was experienced by Hippocrates when he de-mystified the idea of epilepsy and described it as having a more organic etiology [23–24]. Like many philosophers, however, Hippocrates was ahead of his time and the idea of mysticism remained for many centuries. The first modern paradigm shift did not occur until the 16th and 17th centuries when Charles le Pois described epilepsy as originating in the brain [39], followed by Charles Drelincourt who provoked seizures in a dog by driving a needle into its brain [43]. This led to the next paradigm shift in the 18th century when Samuel August Tissot wrote the first modern book on epilepsy. The 19th century was highlighted by the contributions of John Hughlings-Jackson, known today as the father of modern scientific neurology [53–55]. The last major paradigm shift occurred in the 20th century with the advent of EEG and the contribution of a number of scientist to this field, including the well-known neurosurgeon, Wilder Penfield [76]. There are a number of drawbacks to compiling a historical review. Firstly, a certain degree of bias exists when selection manuscripts, specifically observer bias when selecting Ancient texts that subjectively describe a topic. Second, misinterpretations of text can occur when translating from another language. Lastly, the compilation of the text itself contains small portions of much larger documents and may lack important details that further illustrate a topic.
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