A Century of Achievements

At the Centenary Congress of the International Epilepsy Congress in Budapest 2009, the Presidential Symposium was devoted to this historical perspective. Susanne Lund (International Bureau of Epilepsy, IBE) conceived and named the symposium that she cochaired with Peter Wolf (International League Against Epilepsy, ILAE). Six prominent speakers, all earlier Presidents and leading board members of the two sister organizations, addressed the major achievements of epileptology over the centennium and attempted a view of future developments. Summaries of the six talks are presented here. Throughout most of its recorded history of 3–4 millennia, epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century BC, the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries, when the concept of nervous diseases or neuroses gradually took shape. Neuroses embraced all those diseases that were later separated into neurology and psychiatry, including epilepsy, which was commonly referred to then as “convulsions.” In the late 19th century with the triumphs of neuropathology, more and more structural lesions were found in the nervous system, leading to the development of neurology as an independent discipline. The problem with epilepsy was that sometimes it was associated with brain pathology but very often it was not. Therefore, a hundred years ago epilepsy remained partly in the neurologic camp and partly in the psychiatric camp, not least of course because there was and is a relatively high incidence of psychiatric disorders associated with epilepsy. A major advance in the 20th century was that vascular theories of epilepsy, which reached their peak with Turner in 1907, have been replaced by electromagnetic discharges, based especially on the work of Todd, Jackson, and Caton in the 19th century and Berger in the early 20th century. The year 1935 was an important year in this history—firstly, because at the second Neurological Congress in London, vascular theories of epilepsy were finally discarded and electrical theories together with electroencephalography were reinforced and developed by Lennox and the Gibbs (see Reynolds & Rodin, 2009); and secondly, because at the same Congress the ILAE was reborn with Lennox as President after its demise during the First World War. It was, therefore, only in the middle of the 20th century that the concept of “epilepsy per se” as a neurologic disorder was finally adopted in international classifications of disease, led by the World Health Organization (WHO) that separated it from epilepsy with deterioration or epilepsy with psychosis, which was now psychiatry. Therefore, at last 3,000–4,000 years of the concept of epilepsy as a mental disorder was overturned. This also opened the way to redefine the psychiatric disorders of epilepsy into preictal, ictal, postictal, and interictal. This in turn led to new models of nonepileptic psychiatric disorders, such as schizophrenia or psychoses associated with “forced normalisation” of electroencephalography (EEG) (see Reynolds & Trimble, 2009). Treatment will be discussed by others but it is a sobering thought that phenobarbitone, introduced by Hauptmann almost exactly a hundred years ago, is still the most widely used antiepileptic drug in the world. In the last decade another social milestone has been the Global Campaign against Epilepsy, which is raising awareness and addressing the needs of millions of people with epilepsy around the world through the joint collaboration of the League, the Bureau, and the WHO (Reynolds, 2009). At the beginning of the 21st century, neurology and psychiatry have been converging again, led in some respects by epilepsy. However, 21st century uncertainties about symptomatic versus idiopathic or cross-sectional (seizures) versus longitudinal (epilepsy) approaches to the concept and classification of the disorder very much reflect similar divergences of views a century ago. The search for the elusive essence, diathesis, or predisposition to epilepsy, including seizure threshold, continues. The word stigma originated in ancient times in Greece, and means to brand people considered impure, contagious, and violent, have an abnormal behavior, and are mad. The definition of stigma: a deeply discrediting attribute to someone who is seen as different from other people. There are at least three “forms” of stigma. Enacted stigma: Discrimination against the stigmatized person—in this case, people with epilepsy (PWE)—imposed by others, for instance: employment rate, legal discrimination, fertility, teaching, driving, and so on (Jacoby, 1994). Felt stigma: Fear of enacted stigma experienced by the stigmatized person. The shame associated with being “an epileptic,” and the fear of facing stigma by other people. Once diagnosed PWE operate in expectation of negative reactions. The shame of being epileptic produces anguish and unhappiness, so that PWE hide their condition (Rätsepp et al., 2000). Courtesy stigma: Stigma by association, experienced by individuals in social or physical proximity to someone who is stigmatized. In epilepsy the stigma is largely based on the public perception of tonic–clonic seizure that is frightening, violent, unpredictable, affects mental faculties, and may be transmitted to children, but even in the case of partial seizures or epilepsies with tonic–clonic seizures with good control of the seizures, the stigma associated with epilepsy can cause a lot of suffering for PWE, so in many cases the brand is worse than the condition itself. The stigma of epilepsy persists until now due to prejudice and ignorance (Bleasel, 2005). The history of epilepsy can be summarized as 4,000 years of ignorance, superstition, and 100 years of knowledge and stigma. A philosopher quoted: “The power of generalized reflect is invisible, nobody can avoid it and it is almost impossible to maintain an equanimity attitude in front of it.” But concerning stigma, what happens nowadays? About 80% of epilepsy patients live in developing countries; half of them are neither diagnosed nor treated properly (WHO, 1999). Chaplin et al. (1992) reported that 70% of PWE with newly diagnosed epilepsy expected to experience stigma and discrimination at work (similar report also from Baker et al., 2000). This risk is greater in minorities and in low income people. (Salgado et al., 2005). Which factors can contribute to maintain stigma? Tonic–clonic seizures. High seizure frequency. Long term of the epilepsy syndrome. Treatment gap. Discrimination experience. Employment status. Sociocultural bias. Living in developing countries. Misconceptions about epilepsy. Examples of the misperceptions about epilepsy are related to the media. For instance, Caspermeyer et al. (2006) found that histories related to epilepsy had a lot of stigmatizing language and medical errors, which leads to social isolation and discrimination of PWE. Besides, neurologists tend to emphasize catastrophic issues related to epilepsy instead of benign ones. A survey of medical students revealed what they consider dangerous for a child with epilepsy: to play videogames, to watch TV, to drink coke and coffee, to chew gum, to do sports, to ride a bike, to walk alone, or to travel alone by bus (unpublished observations; Carlton-Ford et al.,1997). Initiatives to fight against stigma: Public education Education to health centers, universities, teachers, patients and their families. To identify patients with high level of perceived stigma or those most vulnerable. To reduce the treatment gap. To legislate about discrimination of PWE. Comprehensive epilepsy programs. Social network and social support. Many of these initiatives are part of the global campaign “Out of the shadows” (partnership of WHO, IBE, ILAE). It is very disappointing that despite all education efforts to increase knowledge, misconceptions remain and PWE continue to suffer from ignorance and discrimination. Centuries of legislation (or the lack of it) based on false belief and inaccurate information has legitimized and reinforced stigma and discrimination against people with epilepsy in countries all over the world. At the beginning of the 20th century the scientific, medical, and social view of epilepsy was changing. But in law epilepsy was still associated with insanity and mental defectiveness. This both shaped and reflected public attitudes toward people with the condition. Thousands were consequently accommodated in general asylums or epilepsy colonies in many European countries, but most lived in the community with little or no legal protection. Eugenics gained credence and popularity in the first three decades of the 20th century. Negative eugenic theory—that socially undesirable individuals should be prevented from reproducing—was enthusiastically followed in the United States, Germany, and Scandinavia. The best way to achieve this was by sterilization and the best way to enforce involuntary sterilization was by making it legal. In 1927 the US Supreme Court ruling on Buck vs. Bell effectively legitimized eugenic sterilization laws throughout the United States. By 1963 these eugenics laws were almost wholly out of use. But by then an estimated 64,000 sterilizations had been carried out with an unknown number of these on people with epilepsy. Elsewhere eugenics was largely discredited by the mid-1930s. But in Nazi Germany, in 1934 alone 7,000 people with epilepsy were sterilized under the 1933 Law for the Prevention of Offspring with Hereditary Diseases. In the 1930s and 1940s, care based in the community rather than institutional care was increasingly seen as the way forward for most people with epilepsy. But advocates like William Lennox in the United States and Joseph Tylor Fox in the United Kingdom understood that this needed to be underpinned by supportive legislation. The 1948 United Nations Declaration on Human Rights initiated a framework for fighting inequality on a global basis. It influenced national antidiscriminatory legislation that finally began to emerge in countries like the United States (Americans with Disabilities Act, 1990), Australia (Disability Discrimination Act, 1992), and the United Kingdom (Disability Discrimination Act, 1995). Even with later refinement and extension these laws were not entirely successful and their experience shows that legislation alone is not enough to end discrimination. There also has to be a matching shift in public attitudes. The most important effort by ILAE and IBE to increase the political consciousness and influence of the epilepsy community has been the Global Campaign against Epilepsy. Their partnership with the WHO has created significant political and legislative change based on a more educated understanding of the condition. The Campaign’s regional declarations on epilepsy are political manifestos for every region of the world, and political awareness projects inspired by the Campaign have been reported in 39 countries. Most of these have been about sensitizing politicians to the facts about epilepsy and the issues faced by people with the condition. But in some countries like Algeria, India, Chile, China, and Brazil, the Campaign is attributed with directly changing inappropriate law or fundamentally influencing national health policy. The law as it affects people with epilepsy has moved a long way since 1909. Bad law still exists, but if legislation does both shape and reflect wider society then perhaps we have made some progress in the last 100 years and there is hope for the future. In many countries and under different political and legal systems legislation is now increasingly rooted in a more enlightened approach toward the condition. Laws that once repressed people with epilepsy and added to their problems are now more sympathetic, protective, and permissive. The understanding and approaches to the treatment of seizures over the ages have been well illustrated by William Lennox. Effective pharmacologic and surgical therapy was developed only in the last century. Prejudice developed over time, nurtured by the fear engendered by the patients’ unconsciousness and, as Bergson put it, by “the automatic behaviour superimposed on the living or normal.” It is well known that the first effective antiepileptic medication, bromide, was found serendipitously. Because of severe side effects it was gradually replaced by phenobarbital, associated with cognitive side effects in many individuals. Recently attempts were made to replace it by more effective and less toxic agents. The reality of cost and availability, however, has forced us to accept that in many parts of the world phenobarbital continues to have an important role in the control of epileptic attacks. Clearly, the benefit of this inexpensive and usually freely available compound continues to lead to its continued use despite of its rejection in more prosperous areas, a form of “forced hypocrisy.” The second generation of effective agents such as phenytoin, primidone, carbamazepine, ethosuximide, and others arrived when the differential effects of different agents in different forms of epilepsy were recognized. National and economic factors led to preferential utilization of different drugs in different regions and countries. Therefore, phenytoin, developed in the United States, continues to be very widely used in that country, much more so than in some other parts of the world. The effectiveness of ethosuximide for the control of absence attacks has revolutionized the treatment of that seizure type. More recently, however, valproic acid, serendipitously discovered as a solvent for bismuth, was found to be equally effective for the control of absence but also for the often associated generalized tonic–clonic seizures. After an early period of great concern regarding hepatic toxicity, adequate supervision has largely allayed this worry. Valproate has brought about a virtual revolution in the control of seizures in the majority of patients with idiopathic generalized epilepsy. In recent decades we have witnessed, after initial enthusiasm, a move away from drug monitoring in epilepsy. Whether this is based on pharmacologic facts or whether it is due to industry driven reluctance to complicate antiepileptic drug utilization, is still unclear. Certainly the ability to measure drug levels leads to valuable recognition of compliance problems and also the identification of side effects occurring at high levels, and not least to improved ability to increase the doses to a level where effectiveness may be optimized. Therefore, the move away from drug level measurements is regrettable and in this field ignorance is certainly not bliss. In recent years, we have witnessed important changes in the aims, attitudes, and policies of the pharmaceutical industry. The search for blockbusters and their financial rewards in the billions has led to neglect of therapeutic areas where comparable financial rewards were not to be expected. This has proved to be detrimental to continuing research and development of more effective and better tolerated antiepileptic medications by some of the pioneering companies in the field. We are witnessing the divesting of compounds that do not promise to produce billion dollar profits onto smaller distributing companies who often do not have the scientific staff and skill to collaborate with the physicians carrying out clinical trials in the later stages of drug development. This lack of interest in developing new drugs for the treatment of epilepsy is to be opposed by both professional and lay societies whose aim it is to promote improved control of epilepsy. The foundation for surgical treatment of focal epilepsy was the recognition of cortical localization and of the significance of cortical scars and lesions. Hughlings Jackson and Victor Horsley pioneered collaboration between the neurologic clinician and the surgeon, and later complemented by the addition of the physiologist, the neuropsychologist, and the imager. Wilder Penfield realized the potential of surgical treatment and became what was probably the first epilepsy fellow, working with Otfrid Foerster in Breslau, studying and treating patients who sustained brain injuries in the First World War followed by intractable seizures. Hans Berger, the father of EEG, saw his findings confirmed by Adrian and Matthews. Two schools of EEG then developed in North America: Herbert Jasper and his students at Brown University and then at the Montreal Neurological Hospital; and Fred and Erna Gibbs, associates of Bill Lennox, at Harvard. There followed a period of great enthusiasm for surgical treatment succeeded in turn by great disappointment. Dr. Theodore Rasmussen, then Director of the Montreal Neurological Hospital and a titan in the field of surgical treatment of epilepsy, explained, “It was the wrong surgeons operating on the wrong patients.” Murray Falconer like Rasmussen, a careful and persistent believer in the potential of surgical treatment, founded the British school at the Maudsley. The flowering of clinical neurophysiology, neuropsychology and the rise of modern imaging led the current more rational and successful wave of surgical treatment. Recognition of the most common form of focal abnormality, temporal lobe epilepsy, soon followed. The role of lesionectomy was later emphasized as a result of modern imaging. The finding of cortical dysplasia by David Taylor, a psychiatrist studying patients operated by Murray Falconer led to a veritable explosion of understanding and interest in this epileptogenic lesion, with an enormous body of literature accumulated since, with no end in sight. The improved prognosis and results of surgical treatment have led to acceptance of the role of surgical treatment and to fading of the prejudice against such an approach. Surgical treatment is now practiced more widely in many parts of the world with improved results based on the recognition of ideal surgical candidates. Consequently the established centers of excellence are now faced with the investigation and challenge of patients with more and more complex epilepsies. This highlights the need for further technological advances leading to better localization and results, and also to recognition of underlying mechanisms. The role of palliative intervention is now also being recognized with the development of a range of technological devices such as vagal stimulators and deep brain stimulation. The is for improved ability to control seizures, and reduce suffering and has an important of neurology with recognition of the for in the field. 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