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Journal of Neurological Sciences [Turkish] 33:(4)# 56; 515-525, 2016 http://www.jns.dergisi.org/text.php3?id=1021 Review

Medicine in Stamps: History of Epilepsy (The Sacred Disease) Through Philately

Emine Elif VATANOGLU-LUTZ1,Ahmet Doğan ATAMAN2,Suat BİÇER3

1Yeditepe University Medical Faculty, History of Medicine and Ethics, Istanbul, Turkey

2Vienna University Medical Faculty, History of Medicine, Vienna, Austria 3Vienna University Medical Faculty, History of Medicine, Vienna, Austria

Abstract It is not wrong to say that the history of epilepsy is intervened with the history of humanity. Indeed, the disease of epilepsy has existed for thousands of years but only in the past hundred years it has begun to be understood. Epilepsy is the most common serious brain disorder, but it is often surrounded by prejudice and myth; and was even considered a "sacred disease" for a long time in ancient times. Some historical outlines may help understand the origins of such prejudice. Only in the 19th century, the enlightenment began to change the way epilepsy was looked at, and epilepsy was once again believed to be a natural disease and this time the theory was widely accepted. Without the benefit of modern science to allow theories to develop or the ability to research the nature of the brain, epilepsy would have still been misunderstood. This paper provides an overview on the discovery and understanding of Epilepsy through philately. Keywords: Epilepsy, sacred disease, John Hughlings Jackson, Hans Berger, history, philately

Pullardaki Tıp: Filateli Aracılığıyla Kutsal Hastalık Epilepsinin Tarihi Özet Epilepsinin tarihi insanlık tarihiyle ölçülebilir demek yanlış olmaz. Binlerce yıldır insanlık tarihinde yerini alan bir hastalık olan epilepsi, ancak son yüz yılda anlaşılabilmiştir. Çoğunlukla önyargılar ve hurafelerle çevrili olarak ele alınan ve özellikle antik çağlarda uzun yıllar "kutsal hastalık" olarak adlandırılan epilepsi, aslında en sık görülen ciddi beyin hastalıklarından biridir. Hastalığı çevreleyen önyargılar ancak belli başlı tarihi dönemlerin bilinmesiyle anlaşılabilir. Epilepsi hastalığı 19.yüzyılda aydınlığa kavuşmuş, doğal bir hastalık olarak görülmüş ve bu teori kabul görmüştür. Modern bilimin gelişmesi ve beyin yapısını gösteren araştırmalar sayesinde epilepsi hastalığı yanlış tanılardan kurtulabilmiştir. Bu çalışma, filateli yoluyla epilepsi hastalığının keşif ve anlaşılma sürecine genel bir bakış sunmayı hedeflemektedir. Anahtar Kelimeler: Epilepsi, kutsal hastalık, John Hughlings Jackson, Hans Berger, tarih, filateli

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INTRODUCTION The word epilepsy derives from the Greek verb epilambanein, meaning to be seized, to be overwhelmed by surprise. People with epilepsy were regarded as "being chosen" or "being possessed," depending on the prevailing popular belief; this affected treatment and society's attitudes towards people with epilepsy. In different parts of the world and in different cultures, epilepsy was associated with many misconceptions.Indeed it is not difficult to understand why epilepsy, with its sudden and dramatic seizures, has been so mystifying(8). The fascinating history of epilepsy is connected with the history of humanity; early reports on epilepsy go back to the ancient Assyrian and Babylonian texts, spanning a period of almost 4,000 years. Major advances in the understanding of epilepsy will come much later, during the 18th and 19th century; theories on epilepsy during this period were formulated on a solid scientific basis and epileptics were for the first time treated as patients and not as lunatics or possessed people. The advent of the 20th century led to the in-depth understanding of the mechanisms of the disease, the development of effective drugs and neuro-imaging methods, important advances in the molecular biology of the disease and the connection of various genes with various forms of epilepsy(9) (Figure 1). The unfortunate but widely held view of epilepsy as being due to occult or evil influences gained adherents during ancient times even in the medical world, and the later acceptance of Christianity allowed theological interpretations of seizures as well. As a result, magical or religious treatments were more frequently prescribed, practices, which persist to this day(3). In the Renaissance, an attempt was made to view epilepsy as a manifestation of physical illness, but it was during the Enlightenment that epilepsy was viewed

along more modern lines, helped by advances in anatomy and pathology and the development of chemistry, pharmacy and physiology(12). The idea that focal irritation may cause seizures came about from clinical and experimental work, and was supported by the successful control of seizures by sedative bromides and barbiturates in the late 19th century. The introduction of phenytoin showed that non-sedative drugs could be effective in controlling seizures as well, and the development of in vivo seizure models widened the scope of pharmaceutical agents tested for their efficacy against epilepsy. Increasing knowledge of the cellular mechanisms of epilepsy will, hopefully, allow the development and introduction of drugs with increasing specificity against seizure activity and the development of epilepsy(4) (Figure 2). Description of the Sacred Disease in Ancient Times Basic concepts surrounding epilepsy in ancient Indian medicine were refined and developed during the Vedic period of 4500-1500 BC. In the Ayurvedic literature of Charaka Samhita (the oldest existing description of the complete Ayurvedic medical system), epilepsy is described as "apasmara" which means "loss of consciousness". The Charaka Samhita contains abundant references to all aspects of epilepsy including symptomatology, aetiology, diagnosis and treatment(10). The modes of administration of drugs for epilepsy recommended in Ayurveda include external applications, internal use, application in the eyes and nose. The only first-aid measure recommended in epilepsy is blood-letting (Siravedha) from the veins of the temples(8). Cauterization of both the parietal bones with needles (Soocivedha) has is also been mentioned. In Ayurvedic texts, three basic factors have beenare implicated for the etiology of epilepsy:. endogenous factors as genetic, congenital, constitutional, enzymatic disturbances and

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idiopathic; exogenous factors as intake of unwholesome and unhygienic foods, aggravation of vata dosa due to trauma, worms and other environmental factors ; and psychological factors as excessive worry, grief, fear, passion, anger, anxiety and excitement(8) (Figure 3).

Another ancient and detailed account of epilepsy is on a Babylonian tablet in the British Museum in London. This is a chapter from a Babylonian textbook of medicine comprising 40 tablets dating as far back as 1067 BC. In contrast to the Ayurvedic medicine of Charaka Samhita, the Babylonian tablet emphasizes the supernatural nature of epilepsy, with each seizure type associated with the name of a spirit or god usually evil. It accurately records many of the different seizure types we recognize today(6). Treatment was, therefore, largely a spiritual matter.

The Hammurabi code, dated 1780 B.C. in Babylon, dictated that the person with epilepsy could not marry, or testify in court, and the purchase contract of a slave was considered void if the slave suffered an epileptic seizure within the first three months of purchase(15). The Greeks also have records of epilepsy and called it the Sacred Disease. The Greeks believed that epilepsy was the result of a curse from the gods delivered for the offense of the goddess Selene. It was believed that if you spent a night in the temple of Selene, she would come to you in a dream and tell you how to remove the curse(13).

However, Hippocrates believed that epilepsy was not sacred, but a disorder of the brain; it was a revolutionary view. In 400 B.C., Hippocrates wrote, "Epilepsy is no more divine than other diseases; it is hereditary, its origin lies in the brain, the releasing factors of the seizures are cold, sun and winds which change the consistency of the brain(13).

Therefore, epilepsy can and must be treated not by magic, but by diet and

drugs"(8). According to Hippocrates, among the predispositional factors that can lead to an epileptic fit are: (a) the changes of the winds and temperature, (b) the exposition of the head to the sun, (c) crying, and (d) fear. Hippocrates described the disease accurately, including its unilateral nature and the symptoms of aura. He called epilepsy the "great disease", the originator of the term "grand mal." He described symptoms reminiscent of psychomotor epilepsy and temporal lobe fits. Hippocrates also noted that head injuries often lead to convulsions, introducing the idea of traumatic epilepsy(13) (Figure 4). Throughout the Middle Ages and the Renaissance, epilepsy took on religious connotations again as it did in Greece though there was a difference in opinion between the common people and the nobility as to the nature of the disease. The nobility and the church believed epilepsy not to be a disease at all but rather a sign of prophetic powers and great intelligence adding a sacred dimension to it. The common people found it to be a terrible illness and sought a cure for it through contact with holy relics. The popular belief that epilepsy is contagious, dates to antiquity when people used to spit at a person with the condition and refused to use the same dish. In the early Christian church, clergy and synods segregated the possessed from the faithful, because they were afraid that the possessed would desecrate the holy objects and would infect the communion plate and cup(11). The end of the Medieval times and the beginning of the European Renaissance (14th-17th century) is marked with an exceptional production of literature regarding epilepsy. Science emancipated from the restrains of the Catholic Church would undoubtedly make important progress; also in the field of epilepsy(12).

Understanding the Etiology and Genetic Background

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The beginning of the 18th century is marked by the work of doctors of the Dutch medical school founded by Herman Boerhaave and his pupil Gerard van Swieten. Herman Boerhaave (1668-1738) provided a rather strict definition of epilepsy: "Epilepsy is the sudden abolishment of all vital functions with accompanying increase of mobility and convulsions in all body muscles"(13). The French medical school of the 19th century took lead in the fields of neurology and psychiatry, and, therefore, were the main driving force on epilepsy research. John Hughlings Jackson (1835-1911), is considered the father of modern epileptology(16).

Jackson studied epilepsy on a pathological and anatomical basis. He initially believed that focal convulsions were due to a discharging lesion from damage to nerve cells. He also believed, at first, that the part of the brain involved was the region of the corpus striatum or the convolutions near to it. In 1861, Jackson published his first paper containing reports from hospitals and from the medical literature, whereas, in 1863, he observed unilateral convulsions and stated that "in very many cases of epilepsy and especially in syphilitic

epilepsy, the convulsions are limited to one side of the body; and, as autopsies of patients who have died after syphilitic epilepsy appear to show, the cause is obvious organic disease on the side of the brain, opposite to the side of the body convulsed, frequently on the surface of the hemisphere". Jackson thus offered a new explanation about epileptic seizures that differed from that of his predecessors who claimed the seat of the disease lay in the medulla oblongata(14). In the following years, Jackson’s views regarding the involvement of the corpus striatum in the genesis of seizures evolved rapidly. Jackson distinguishes four factors involved in the final cause of convulsions: the "seat of the internal lesion", the functional cause of the change, the pathological process which brought about the functional change (embolus, tumour, syphilis or other causes) and the various circumstances that trigger the paroxysm. Jackson also recognized that he could not fully explain the sensory alterations with this theory but left it for future scientists to discover new things and better define his beginning theory of epilepsy as an electrical abnormality(7) (Figure 5).

Figure 1: A stamp issued in Belgium in 1972, showing a graphic emphasising epilepsy

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Figure 2: A stamp issued in Australia, emphasising epilepsy

Figure 3: A stamp issued in Sri Lanka, showing the importance of neurology for Ayurvedic medicine

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Figure 4: A stamp issued in India in 1989 for the 18’th International Epilepsy Congress and 14’th World Congress on Neurology

Figure 5: A stamp and a cancellation issued in Italy in 1988,emphasising epilepsy

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In 1929, Hans Berger (1873-1941), a psychiatrist working in Germany, developed the human electroencephalograph (EEG) and reported human brain waves. Berger showed sequential postictal EEG changes after a generalized tonic-clonic seizure, and in 1933 he published the first example of interictal changes and a minor epileptic seizure with 3/s rhythmic waves in the EEG. The eccentric electrical patterns that occurred in the brain during an epileptic seizure proved the problem to indeed be electrical and also showed that its origins was in the brain. The EEG helped to locate the site of seizure discharges and expanded the possibilities of neurosurgical treatments. It also showed different patterns of brainwave discharges associated with different seizure types(14).

Sometimes electrographic seizures may have no clinical signs in patients and therefore these seizures are named as nonconvulsive seizures. These nonconvulsive seizures can only be detected only by continuous EEG monitoring. Noncolvulsive seizures were detected by EEG up to 34% of adults in the neurologic intensive care unit and the majority of these patients (76%) have nonconvulsive status epilepticus(7). The prevalence of nonconvulsive seizures and nonconvulsive status epilepticus were seen in critically ill children at 46% and 19%, respectively(1). During the first half of this century, the main drugs for the treatment of epilepsy

were phenobarbitone (1912) and phenytoin (1938). Since the 1960s, there has been an accelerating process of drug discovery, based in part on a much greater understanding of the electrochemical activities of the brain, especially the excitatory and inhibitory neurotransmitters(2). During the 1960s, important EEG studies were conducted in animals demonstrating the spikes and waves associated with synchronous paroxysmal depolarizing bursts occurring in cortical neurons and the spike-wave complex. In 1968, Murray Falconer recognized the importance of hippocampal sclerosis in temporal lobe epilepsy(2) (Figure 6). An important development in the field of neuroscience was that of Erwin Neher (1944-), who invented the patch-clamp method to measure the flow of current through single-ion channels. Erwin Neher and Bert Sakmann developed the patch-clamp technique for which in 1992 they received the Nobel Prize(14). (Figure 7). The first connection between heredity and epilepsy was made in 1903 by Herman Bernhard Lundborg (1868-1943), a Swedish physician, who was notorious for his views on eugenics and racial hygiene, and published his research on the genetics of progressive myoclonic epilepsy. His analysis was pioneering since he was able to trace back the disease in the family since the 18th century. In that way, Lundborg was also a pioneer in the study of human genetics(12) (Figure 8).

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Figure 6: A stamp issued in Austria in 1981 on behalf of the great memory of Hans Berger

Figure 7: A stamp issued in Grenada in 1991, on behalf of the Nobel Prize of Edwin Neher in Medicine

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Later in 1989, Mark Leppert was the first to identify the link between chromosome 20 and idiopathic human epilepsy syndrome in a family with benign familial neonatal convulsions(5). Another recent stimulus towards the understanding and treatment of epilepsy in the last few decades has been the developments in structural and functional neuroimaging, especially computer tomography (CT) scanning, magnetic resonance imaging (MRI) and MRI spectroscopy and positron emission tomography. Such techniques have revealed many of the more subtle brain lesions responsible for epilepsy. Any type of brain lesion like trauma, congenital, developmental, infection, vascular, tumour, and degenerative factors can lead to epilepsy in some patients. During the 20th century, the invention of EEG, the advance in neurosurgery, the discovery of antiepileptic drugs, and the delineation of underlying pathophysiological mechanisms, were the most significant advances in the field of research in epilepsy(12).

Recently, in 2011, Jerome Engel published the identification of reliable biomarkers which would greatly facilitate differential diagnosis, eliminate the current trial-and-error approach to pharmacotherapy, facilitate presurgical evaluation, and greatly improve the cost-effectiveness of drug discovery and clinical trials of agents designed to treat, prevent, and cure epilepsy(10).

CONNECTIONS: During the last few decades, greater attention has been paid to the psychological and social needs and quality of life issues of people with epilepsy. However, it should be stressed that although they were no longer believed to be possessed, or killed, or put through terrible treatment methods, epileptics still underwent severe prejudice. In many places in the world, epileptics were sterilized or at least prevented from having children and most companies would refuse to hire an epileptic. The 1990"s, American"s with Disabilities Acts covered epileptics and tried to prevent them from

Figure 8: A stamp issued in Greece in 1992,emphasisnig the importance of Greek medicine in neurology

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being discriminated against. The Global Campaign Against Epilepsy, launched in 1997 by the WHO (World Health Organisation), ILAE (International League Against Epilepsy) and IBE (International Bureau for Epilepsy) brought epilepsy out of the shadows improving diagnosis, treatment, prevention and social acceptability(6). However, it is seen that adults with epilepsy, children with epilepsy and their parents are often ashamed of their condition, keep it secret or withdraw from society. It is somewhat disappointing that, despite all the educational efforts and the achievement of some progress, misconceptions remain and people with epilepsy continue to suffer from prejudice and discrimination. Even in the developed world, the disorder is still shrouded in secrecy, and people prefer not to reveal or discuss their illness. Nevertheless, to improve the quality of life of people with epilepsy worldwide, considerable efforts are needed to educate the media and the general public, as well as the professionals and the people with epilepsy themselves. As individuals with epilepsy continue to experience longer lives, the need to understand their aging and associated health conditions becomes more critical. Education and proper care will improve quality of life significantly. Especially adults with epilepsy should be provided with appropriate information to better understand, and cope with the changes in their own level of ability or health with counselling. Acknowledgement: We are grateful to Helena Blackburn for the excellent English revision of this article.

Correspondence to: Emine Elif Vatanoglu-Lutz E-mail: drvatanoglu@yahoo.com

Received by: 22 September 2016 Revised by: 07 October 2016 Accepted: 16 November 2016 The Online Journal of Neurological Sciences (Turkish) 1984-2016 This e-journal is run by Ege University Faculty of Medicine, Dept. of Neurological Surgery, Bornova, Izmir-35100TR as part of the Ege Neurological Surgery World Wide Web service. Comments and feedback: E-mail: editor@jns.dergisi.org URL: http://www.jns.dergisi.org Journal of Neurological Sciences (Turkish) Abbr: J. Neurol. Sci.[Turk] ISSNe 1302-1664 REFERENCES 1. Abend NS, Gutierrez-Colina AM, Topjian AA, et al:

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