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This article reviews the relationship between the psychiatry and neurology of epilepsy, especially in the last 100 years. Throughout most of its recorded history of 3 to 4 millennia epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century B.C., the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries. The discipline of neurology emerged from "nervous disorders" or neuropsychiatry in the late 19th century, when vascular theories of epilepsy predominated. By the turn of the 19th century psychiatry and neurology were diverging and epilepsy remained to some extent in both disciplines. It was only in the middle of the 20th century with the development of electromagnetic theories of epilepsy that the concept of epilepsy per se as a neurological disorder was finally adopted in international classifications of disease. This was associated with a refined definition of the ictal, pre-, post-, and interictal psychological disorders of epilepsy, which have contributed to a renaissance of neuropsychiatry. At the beginning of the 21st century and the centenary of the ILAE psychiatry and neurology have been converging again, led in some respects by epilepsy, which has provided several useful models of mental illness and a bridge between the two disciplines.

Summary: Purpose: To explore the historical origins of the modern concept of electrical discharges in the brain in epilepsy. Methods: I have examined the writings of Hughlings Jackson (1835–1911) and Robert Bentley Todd (1809–1860), especially their Lumleian Lectures on convulsive disorders to the Royal College of Physicians of 1890 and 1849, respectively; and also the influence of Herbert Spencer (1820–1903) on the former and Michael Faraday (1791–1867) on the latter. Results/Conclusions: Contrary to the widely taught view that Jackson was the first to propose electrical discharges in epilepsy it is clear that the discharges suggested by Jackson, influenced by the evolutionary philosopher, Herbert Spencer, were chemical, based on katabolism and anabolism. Jackson had no understanding or proposal based on physics or electricity. On the other hand, Todd had earlier proposed and described electrical concepts of discharges in epilepsy, influenced by his contemporary and colleague in London, Michael Faraday, who at the time was laying the foundations of our modern understanding of electricity and magnetism. Todd and Faraday saw “nervous polarity” as another polar force interchangeable with the polar forces of electricity and magnetism.

Summary: Purpose: To consider the origins of our understanding of the electrical basis of epilepsy in the light of the Lumleian lectures to the Royal College of Physicians in London for 1849, “On the pathology and treatment of convulsive diseases,” by Robert Bentley Todd (1809–1860). Methods: I have reviewed Todd's neglected Lumleian lectures and his observations and concepts of the electrical basis of epilepsy in relation to the influence of Michael Faraday (1791–1867), his contemporary in London, and in relation to later nineteenth century writings on the subject by Jackson, Ferrier, and Hitzig, all of whom overlooked Todd's lectures. Results: Todd was a clinical scientist as well as Professor of Physiology and Morbid Anatomy, with a special interest in the nervous system, at King's College, where he came into contact with Michael Faraday, the greatest electrical scientist of all time, at the nearby Royal Institution. On the basis of his own clinical and experimental studies and his cutting-edge knowledge of neuroanatomy, neurophysiology, neuropathology, and electrical science, Todd brilliantly developed his concepts of the electrical basis of brain activity and of epilepsy in particular. With his microscope, he perceived each nerve vesicle and its related fibres (neurone in later terminology) as distinct entities for the generation of nervous polarity (force) and its transmission in the white nerve fibres throughout the nervous system by unknown molecular mechanisms. In epilepsy, an increase in electrical tension, especially in the grey matter of the hemispheres, led to periodic, sudden explosive discharges, based on Faraday's concept of disruptive discharges. Conclusions: Todd was the United Kingdom's first outstanding neurologist and neuroscientist before these disciplines existed. Influenced by Faraday, he proposed and confirmed the electrical basis of nervous discharges in epilepsy more than 20 years ahead of Jackson, Ferrier, and Hitzig, who did not refer to his priority, although Ferrier also worked at King's College, and Jackson also gave his own famous Lumleian lectures on the same subject in 1890. Todd deserves the credit for laying the foundations of our modern understanding of epilepsy.

The Institute of Epileptology of King's College, London has arisen from need and from opportunity. The need is due to the relative neglect nationally and internationally of the most common serious brain disorder with important physical, psychological, and social complications. The relative neglect is reflected in services, research, charitable donations, public profile, and stigma and in a serious lack of professional education. The opportunity arose because of the existence in several medical institutions at Denmark Hill, London, of a group of medical and related colleagues with a special interest covering almost every aspect of this multidisciplinary disorder who agreed to combine their expertise in this initiative. The idea was born and developed in 1991-1992 and was supported by all the parent institutions: The Maudsley and King's College Hospitals, St. Piers Lingfield, The Institute of Psychiatry, King's College School of Medicine and Dentistry, and the School of Life, Basic Medical and Health Sciences, all under the umbrella of King's College, University of London. Further stimulus and help came from a group of dedicated supporters in private and public life. There are three strands to this initiative: (a) a charity, The Fund for Epilepsy; (b) the clinical Centre for Epilepsy, which was formally opened at the Maudsley Hospital in July 1994; and (c) the academic Institute of Epileptology for research and teaching, which was launched on November 15, 1994.

This article reviews the history of clinical concepts of epilepsy and its classification, especially in the last 100 years. Throughout its recorded history of 3 to 4 millennia, epilepsy has always been defined by its most dramatic symptoms, for example, falling, motor activity or loss of consciousness, but separation from other causes of the same paroxysmal symptoms has always proved challenging. For over a century there has been some semantic confusion whether to call the various paroxysms fits, convulsions, seizures, or epilepsies. Since the middle of the 19th century a great unresolved debate has continued about whether recurrent seizures or epilepsy should be viewed as a separable symptom of underlying brain disease or as one or more idiopathic diseases or syndromes, with an inherent age-related natural history; or indeed viewed as both a symptom and a disease. A major advance in the 20th century is 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, Berger, Lennox, and the Gibbs, culminating eventually in new ILAE classifications of seizures (1981) and epilepsy syndromes (1989). However 21st century uncertainties about symptomatic versus idiopathic or cross-sectional (seizures) versus longitudinal (epilepsy) approaches to the problem very much reflect similar divergences of view a century ago. More attention is now being directed at interseizure events and processes which may lead either to remission or intractability with associated cognitive and psychosocial consequences. The search for the elusive essence, diathesis or predisposition to epilepsy, including seizure threshold, continues.

We have previously published translations of Babylonian texts on epilepsy and stroke, which we believe to be the oldest detailed accounts of these neurological disorders from the second millennium BC. We now present a short Babylonian text, which clearly describes what are today known as interictal or schizophrenia-like psychoses of epilepsy. The text includes many of the classical symptoms of the syndrome, for example, paranoid delusions, hallucinations and mood disorders, as well as religiosity and hyposexuality, which have only been crystallized in the twentieth century. The Babylonians were remarkably good observers of human disease and behavior but had little or no understanding of pathology or brain function. Although they recognized many natural causes of disease, epilepsy and behavior disorders were attributed to supernatural, usually evil forces, the forerunner of the Greek concept of the Sacred Disease.

As a young man, Graham Greene (1904-1991) experienced several episodes of loss of consciousness, which were confidently diagnosed as epilepsy by a Harley Street specialist who saw him on two occasions during the 1920s. The diagnosis was initially concealed from him by his family and the specialist, but when it was revealed, it had a profound effect such that he contemplated suicide. He was particularly concerned about his impending marriage and the risk of having children. His anxiety was not relieved by being told that the famous author, Dostoevsky, had epilepsy. Graham Greene is the only public figure in the United Kingdom, of whom I am aware, who has admitted and discussed the impact of epilepsy, even though this was more than 40 years later when there was some doubt about the diagnosis.

Clinical experience with gamma-vinyl GABA (GVG, vigabatrin) has accumulated mainly in Europe, where the drug has been licensed in several countries since 1989. Short-term efficacy studies in adolescent and adult patients with intractable drug-resistant epilepsy have shown that approximately 50% exhibit a reduction in seizure frequency of one-half or more but rarely complete seizure control. The best results are in patients with partial seizures with or without secondarily generalization. GVG responders have been followed for periods of up to 5 years, and overall 10-20% may exhibit subsequent seizure breakthrough, as probably occurs with any drug in such chronic patients. The most common side effect is drowsiness. Reversible behavior disorders, psychoses, and depression rarely occur in predisposed individuals. No new long-term side effects have been reported but vigilance is necessary. Studies of GVG as a first-line drug in newly diagnosed epileptic patients are proceeding.

Of 31 previously untreated patients with grand mal and/or partial seizures referred to a neurological clinic and treated with phenytoin monotherapy, assisted by serum level monitoring, 26 have been followed up for a mean of 42 months. Seizures were completely controlled in 80%. Failure of optimum phenytoin monotherapy occurred in 12%. The degree of seizure control was significantly related to phenytoin serum levels. The success of monotherapy was probably related to availability of serum level monitoring and to the study of a previously untreated population with a relatively short history of epilepsy. The main reasons for failure of monotherapy were poor compliance and the presence of additional neuropsychiatric handicaps, which commonly occur together. The place for polytherapy in the event of failure of monotherapy has still to be defined.

Summary: Community-based studies and our own prospective hospital-based studies suggest that the prognosis for control of epilepsy is more favorable than previously reported. Approximately three quarters of newly diagnosed patients can enter prolonged remission on currently available medication. The first 2 years of treatment are crucial in determining the subsequent course of epilepsy. The longer seizures continue, the less likely they are to be controlled. Factors that contribute to the evolution of chronic epilepsy are the presence of brain lesions, neuropsychiatric handicaps, and poor compliance. Early effective treatment may also be important in preventing the evolution of chronic epilepsy. Recent studies have not revealed any significant differences in efficacy between the major antiepileptic drugs, and the choice of drug will therefore be influenced by costs and side effects, especially cognitive and behavioral effects. The majority of patients with a single unprovoked tonic-clonic seizure go on to develop epilepsy. Studies are required to evaluate the need for and outcome of therapy in such patients. Information about the natural history of untreated epilepsy, and also the possible influence of drug therapy on the prospects for spontaneous remission, is lacking. RESUMEN Los estudios comunitarios y nuestros propios estudios prospectivos practicados en el hospital surgieren que el pronostico del control de epilepsyia es mas favorable de lo que se ha publicado previamente. Aproximadamente tres cuartos de enfermos nuevos pueden presentar una remision prolongada con la medicacion disponible actualmente. Los dos primeros anos de tratamiento son cruciales para determinar el curso subsiguiente de la epilepsyia. A medida que los ataques se repiten las posibilidades de su control son mas escasas. Los factores que contribuyen para que se establezca una evolucion cronica de la epilepsyia son la presencia de lesiones cerebrales, los trastornos neuropsiquiatricos y la poca fiabilidad de los pacientes. Un tratamiento precoz eficaz puede tambien ser importante para evitar la evolucion cronica de la epilepsyia. Estudios recientes no han revelado nigguna diferencia significativa con respecto a la eficacia entre las drogas antiepilepticas mas importantes, por lo que la eleccion de una medicacion debera ser realizada teniendo en cuenta los costes y los efectos colaterales, especialmente en lo que respecta a la capacidad cognitiva y los efectos en el comportamiento del enfermo. La mayoria de los pacientes con un solo ataque espontaneo tonico-clonico desarrollan una epilepsyia subsiguiente. En estos casos son necesarios estudios especiales para valorar la necesidad de iniciar un tratamiento y los resul-tados de tal terapia. En el momento actual falta informacion acerca de la historia natural de la epilepsyia no tratada y tambien acerca de la posible influencia de la terapia medicamentosa sobre las posibilidades de remisiones espontaneas. ZUSAMMENFASSUNG Ambulante Untersuchungen und unsere eigene prospektive Krankenhausstudie weisen auf eine bessere Prognose der Epilepsie bezugl. Anfallsfreiheit als bisher angenommen hin. Fast dreiviertel aller neu diagnostizierten Patienten konnen einer langanhaltenden Anfallsfreiheit unter den ublichen Medikamenten zugefuhrt werden. Die ersten zwei Behandlungsjahre sind fur den weiteren Verlauf der Epilepsie entscheidend. Je langer die Anfalle anhalten, desto weniger wahrscheinlich wird Anfallsfreiheit erreicht. Faktoren, die eine chronische Epilepsie begunstigen, sind Hirnschadigung, neuropsychiatrische Storungen und schlechte Compliance. Eine fruhe, effektive Behandlung kann die Entwicklung einer chronischen Epilepsie verhindern. Jungere Studien haben keine signifikanten Unterschiede in der Effektivitat der verschiedenen Haupt-Antiepileptika gefunden, so das die Wahl des Medikaments vielmehr durch seine Kosten und Nebenwirkungen–vor allem im cognitiven und Verhaltensbereich–beeinflust wird. Die meisten Patienten mit einem einzigen, nicht provozierten Grand mal entwickeln eine Epilepsie. Weitere Untersuchungen sind erforderlich, um gerade bein diesen Patienten die Notwendigkeit und den Verlauf der Therapie zu beurteilen. Es fehlen Berichte uber den naturlichen Verlauf unbehandelter Epilepsien und den Einflus der Pharmako-Therapie auf mogliche Spontanremission. RESUME Des etudes de population et nos propres etudes prospectives effectuees en milieu hospitaller suggerent que le pronostic du controle de ľepilepsie est plus favorable que ce qui avait ete rapporte anterieurement. Environ 75% des patients nouvellement diagnostiques obtiennent une remission prolongee au moyen des medications actuellement disponibles. Les deux premieres annees du traitement sont decisives pour ľevolution ulterieure de ľepilepsie. Plus les crises persistent, moins elles ont de chances ď;etre controlees par la suite. Les facteurs qui contribuent a la chronicisation de ľepilepsie sont ľexistence de lesions cerebrales, de handicaps neuropsychiatriques, et une mauvaise compliance au traitement. Un traitement precoce efficace peut aussi jouer un ro1e important dans la prevention ď;une chronicisation de ľepilepsie. Des travaux recents n'ont pas montre de difference significative dans ľefficacite des antiepileptiques majeurs, et le choix du medicament sera influencee surtout par les considerations de prix et ď;effets secondaires, surtout cognitifs et comportementaux. La majorite des patients presentant une crise tonicoclonique spontanee unique developpent une epilepsie chronique. Des etudes sont necessaires pour evaluer la necessite et le benefice ď;un traitement chez de tels patients. Nous manquons ď;informations sur ľevolution spontanee ď;une epilepsie non traitee et sur ľinfluence possible du traitement medicamenteux sur les perspectives de remission spontanee.

Summary: Although anticonvulsant polytherapy has been widely and traditionally used in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. There are many causes of polytherapy which could be avoided by more careful monitoring and supervision of therapy. Studies in new, previously untreated referrals suggest there is considerable potential for monotherapy. In the event of failure of optimum monotherapy, the value of polytherapy is not yet clear. In chronic patients on polytherapy there may be scope for careful rationalization to two or sometimes one drug, with reduction in chronic toxicity and sometimes improved seizure control. Reduction of therapy, however, may be impossible or hazardous due to withdrawal seizures. Even after successful reduction, seizure control is much less satisfactory than in new referrals. It is easier to avoid polytherapy than to reduce it. There is a need to define more carefully the limits of effective anticonvulsant therapy. ZUSAMMENFASSUNG Obgleich die antikonvulsive Polytherapie in der Behandlung der Epilepsie eine lange Geschichte hat und weit verbreitet ist, gibt es wenig Hinweise, das sie der Monotherapie uberlegen ist. Im Gegenteil, sie fuhrt zu den Problemen der chronischen Toxicitat, den Interaktionen zwischen verschiedenen Medikamenten, den Schwierigkeiten, ein einziges Medikament beurteilen zu konnen und manchmal sogar zu einer Exacerbation der Anfalle. Es gibt viele Anlasse zur Polytherapie, die durch sorgfaltiges Beobachten und Uberwachen der Therapie vermieden werden konnen. Untersuchungen bei bisher unbehandelten neu uberwiesenen Patienten lassen vermuten, das sie ein wesentliches Potential fur die Monotherapie darstellen. Fur den Fall eines Versagens einer optimal gesteuerten Monotherapie ist der Wert der Polytherapie noch nicht klar zu ersehen. Bei chronisch kranken Patienten unter Polytherapie konnte es das Ziel sein, die Therapie sorgfaltig auf 2 oder manchmal 1 Medikament zu rationalisieren, dabei die chronische Toxizitat zu vermindern und manchmal die Anfallskontrolle zu verbessern. Eine Verminderung der Therapie kann jedoch wegen Entzugskrampfen unmoglich oder gefahrlich sein. Selbst nach erfolgreicher Reduktion ist die Anfallskontrolle bei diesen Patienten weniger befriedigend als bei neu eingestellten Patienten. Es ist leichter, eine Polytherapie zu vermeiden als zu ihr zuruckzufinden. Es besteht weiterhin die Notwendigkeit sorgfaitiger die Grenzen der effektiven antikonvulsiven Therapie zu bestimmen.

SUMMARY During treatment with folic acid, 15 mg daily for 2 years, serum vitamin B12 levels fell in 24 out of 30 epileptic patients treated with anticonvulsant drugs. The most rapid fall occurred in the first 3 months of folate therapy, from a mean of 360 pg/ml to 221 pg/ml, but it continued more slowly for up to 15 months, or longer in some. In 10 of 11 patients in whom folic acid therapy was stopped but anticonvulsant therapy continued; serum folate levels subsequently fell to subnormal values within 18 months.

SUMMARY Serum and red cell folic acid concentrations, and serum vitamin B, 2 concentrations were estimated in 33 normal controls and 67 drug-treated epileptic patients. Significant lowering of both serum and red cell folate concentrations was found in the epileptic patients. A significant correlation between serum and red cell folate values was found in both control and epileptic patients. It is concluded that previously reported drug-induced lowering of serum folate concentrations is accompanied by corresponding changes in red cell folate concentrations. RESUME On a determine les concentrations d'acide folique dans le serum et les globules rouges et de vitamine B12 dans le serum chez 33 sujets normaux et 67 patients epileptiques traites. On a trouve chez les patients epileptiques une diminution significative des concentrations d'acide folique dans le serum et les globules rouges. Chez les sujets normaux et les epileptiques, on a trouve une correlation significative entre les valeurs respectives d'acide folique dans le serum et les globules rouges. On en conclut que la diminution deja decrite des concentrations d'acide folique dans le serum, a la suite du traitement, s'accompagne de modifications correspondantes de ces concentrations dans les globules rouges.

This study compares cognitive function in new referrals with epilepsy well-controlled on single drug therapy with either phenytoin or carbamazepine with that in an untreated control group. Patients receiving phenytoin performed consistently less well on memory tasks than did those untreated or receiving carbamazepine. Although patients on phenytoin overall showed a trend towards poorer performance on a tracking task, higher blood levels of this drug were correlated with better tracking performance. The correlation between blood levels of carbamazepine and tracking performance was the opposite from that of phenytoin. Blood levels of carbamazepine were negatively correlated with measures of anxiety, depression, and fatigue. These findings have implications for the choice of drug in the management of epilepsy and also for the reported claims of a psychotropic effect of carbamazepine.

SUMMARY The effects of L-DOPA, L-tryptophan, monoamine oxidase inhibitor (MAOI), and MA01 plus L-tryptophan, each for 3 months, have been assessed in 10 severe, adult epileptics with placebo control. There was no uvrrall reduction in seizure frequency, but 2 patients with minor partial seizures improved, 1 with L-DOPA. MAOI, and MA01 plus L-tryptophan. and the other with L-tryptophan and MA01 plus L-tryptophan. We have not been able to demonstrate an increased turnover of cerebral serotonin (5-HT), as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid, after treatment with L-tryptophan for 3 months. This observation casts doubt o n the ability of L-tryptophan to alter the long-term metabolism and functional activity of brain 5-HT. The importance of further exploration of manipulation of cerebral monoamines as a possible approach to the treatment of epilepsy is emphasized. RESUME Une etude en double-aveugle a ete effectuee pendant trois mois, chez 10 adultes souffrant d'une epilepsie grave, avec la L-DOPA, le L-tryptophane, un inhibiteur ete la monoamine oxydase (IMAO) et un IMAO associe au L-tryptophane. II n'a pas ete observeete reduction dans la frequence des crises mais deux patients avec crises mineures focales ont presente une amelioration, L'un avec L-DOPA et IMAO, L'autre avec le L-tryptophane, les deux avec L'association IMAO + L-tryptophane. II n'a pas ete observe un accroissement du “turnover”ete la serotonine cerebrale (5-HT) apprecie par la mesure du taux ete L'acide 5-hydroxyindoleacetique dans le liquide cdphalo-rachidien apres traitement par le L-trypto-phane pendant 3 mois. Ces observations permettent ete douter ete la possibility pour le L.-tryptophane d'alteYer le m^tabolisme a long terme et L'activite fonctionnelle du 5-HT cerebral et doivent inciter a poursuivre les recherches sur une approche therapeu-tique ete L'epilepsie par la manipulation des monoamines cdrebrales. RESUMEN En 10 enfermos con epilepsia severa se han estudiado durante 3 meses, comparandolos con placebo, los efectos ete la administracion ete L.-DOPA, L-triptefano, inhibidor ete la monoamino oxidasa (MAOI) y la MAOI y el L.-triptefano asociados. No se observo una reduccion global ete la frecuencia ete los ataques pero mejoraron dos enfermos con ataques focales menores, mientras uno tomaba L.-DOPA, MAOI y MAOI mas L.-triptefano y el otro i-DOPA y la asociacion ete MAOI y L.-triptofano. No, hemos sido capaces ete demostrar un aumento ete la serotonina cerebral (5-HT), medida como acido 5-hidroxindolacetico en el liquido cefalorraqufdeo tras la administracion ete L.-triptofano durante 3 meses. Esta observacion pone en duda la capacidad del L-triptofano ete alterar el metabolismo a largo plazo y la actividad funcional ete la 5-HT cerebral. Se hace enfasis en la importancia ete un mayor estudio ete la manipulacion ete las monoaminas cerebrales en el tratamiento ete la epilepsia. ZUSAMMENFASSUNG Die Wirkungen von L-DOPA, L-Tryptophan, Mono-aminooxidaseinhibitor (MAOI) und MAOI plus L-Tryptophan uber drei Monate wurden mit Placebo-Kontrollen bei 10 Erwachsenen mit schwerer Epilep-sie untersucht. Es kam nicht zu einer allgemeinen Minderung der Anfallsfrequenz, aber 2 Patienten mit kleinen fokalen Anfallen zeigten eine Besserung: einer unter L-DOPA, MAOI, MAOI und L-Tryptophan und der andere mit L-Tryptophan und MAOI plus L-Tryptophan. Es war nicht moglich durch Messung der 5-Hydroxyindolessigsaure im CSF einen vermehrten Umsatz des cerebralen Serotonins (5-HT) unter drei-monatiger L-Tryptophantherapie festzustellen. Diese Beobachtung last Zweifel aufkommen an der Fahig-keit des L-Tryptophan auf lange Sicht den Stoffwechsel und die funktionelle Aktivitat der 5-HT des Gehirns zu verandern. Die Wichtigkeit weiterer Untersu-chungen uber die Veranderung cerebraler Monoamine als mogliches Prinzip fur die Epilepsietherapie wild betont.

Despite the widespread and traditional use of polytherapy in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. Among other undesirable effects, it can produce subtle cognitive and behavioral changes and sometimes even exacerbate the epilepsy. Recent studies provide evidence that in many patients seizures can be controlled by carefully monitored monotherapy: Approximately 75% of newly diagnosed, previously untreated epileptic patients will enter a 2-year remission with this form of treatment. The theory has even been advanced that early control of seizures may help prevent the evolution of drug-resistant, chronic epilepsy. In some patients with chronic epilepsy, multiple-drug therapy can be reduced to single-drug treatment, usually with an improvement in cognitive function and without increase in seizures. Trials conducted to date have shown no evidence of superiority of any one major antiepileptic drug over another in control of a particular seizure type. The choice of antiepileptic drug for monotherapy may therefore be influenced by differences in toxic effects associated with individual agents. On the basis of clinical and psychometric evidence, carbamazepine has been shown to cause fewer adverse effects than other antiepileptic drugs on cognitive function, mood, and behavior.

Summary: : Recent epidemiological and hospital-based studies of newly diagnosed epileptic patients suggest that the prognosis for epilepsy is much more favourable than had previously been reported and believed. Approximately three-quarters of such patients may expect to go into prolonged remission with currently available drugs, utilised as monotherapy. For chronic epileptic patients, however, the outlook for seizure control is poor. Factors that contribute to the development of chronic epilepsy are partial or multiple seizure types, brain pathology, neuropsychiatric or social handicaps, poor compliance, and the early response to treatment. Evidence is presented that epilepsy should be viewed as a process in which early effective treatment may be important to prevent the evolution of chronic epilepsy, which is so difficult to control.

SUMMARY Evidence of a disturbance in folic acid metabolism can be detected in the majority of epileptic patients on treatment with anticonvulsant drugs. Phenobarbitone, phenytoin and primidone all appear to be responsible for this phenomenon. It is suggested that there may be a relationship between the therapeutic and antifolate action of these drugs. The possible consequences of drug-induced folate deficiency are discussed with particular reference to mental symptoms. REASUMEA On peut mettre en eAvidence une perturbation du meAtabolisme de l'acide folique chez la plupart des eApileptiques traiteAs par des meAdicaments anticonvulsivants, qu'il s'agisse de pheAnobarbital aussi bien que de pheAnytoiUne ou de primidione. Il existe peut-eCtre une relation entre les actions theArapeutiques et antifoliques de ces meAdicaments. Les auteurs discutent les conseAquences possibles d'une deAficience folique de cet ordre sur l'eAtat mental des sujets.