Sidiropoulou Et Al. 2010_Epilepsy in Scientific Era2

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Epilepsy and Behavior xxx (2010) xxx–xxx

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Epilepsy and Behavior

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Review

Hallmarks in 18th- and 19th-century epilepsy research

K. Sidiropoulou, A. Diamantis, E. Magiorkinis ⁎Office for the Study of History of Hellenic Naval Medicine, Naval Hospital of Athens, Athens, Greece

⁎ Corresponding author. Leoforos Aianteiou 3- PB 1Fax: +30 210 7486382.

E-mail address: [email protected] (E. Magiorkini

1525-5050/$ – see front matter © 2010 Elsevier Inc. Aldoi:10.1016/j.yebeh.2010.04.004

Please cite this article as: Sidiropoulou K, etyebeh.2010.04.004

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Article history:Received 18 March 2010Received in revised form 30 March 2010Accepted 2 April 2010Available online xxxx

Keywords:EpilepsyFrench medicineDutch medicineBritish medicineJohn Hughlings JacksonConvulsionsEpileptic fits

ROOThe purpose of this study was to reveal the major views of the early scientific period (18th and 19th

centuries) on epilepsy as both a disease and a symptom. The shaping of thought about illness and medicineas a science, which began in the Renaissance and progressed into the Enlightenment, intensified during the18th and 19th centuries. During this period of increasingly methodical investigation, researchers undertook athorough study of epilepsy. Renowned doctors of this period from the Dutch and German medical schools,the “golden era” of French medicine, and British medicine, including, of course, John Hughlings Jackson, allleft their mark in this era of epilepsy research. Epidemiological studies using large patient data sets wereconducted for the first time, as was systematic research on the pathophysiological, pathological, neurological,and psychiatric aspects of the disease.

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541, Salamina, 18900, Greece.

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Contents

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1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02. The work of 18th-century physicians on epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03. The 19th century: The “golden era” of French medicine and the contribution of the English school of physicians . . . . . . . . . . . . . . . 0

3.1. The French medical school of the 19th century . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03.2. The British medical school of the 19th century . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03.3. The Dutch and German medical schools of the 19th century . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03.4. Therapies for epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

4. The age of John Hughlings Jackson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 05. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

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1. Introduction

Important advances were made in epilepsy during the 18th and19th centuries, when the science of medicine became emancipiatedfrom the restrictions of the Catholic Church and evolved from thetheories developed during the Renaissance and Enlightment periods.These advances would form a scientific basis on which medicalresearch advanced during the next centuries. Themain driving force inthe area of epilepsywas thework of famous French doctors in the 19thcentury in the fields of neurology and psychiatry; the establishment of

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large hospital facilities in France provided large patient data sets thatfacilitated their research.

2. The work of 18th-century physicians on epilepsy

The beginning of the 18th century is marked by the work of doctorsof the Dutch medical school founded by Herman Boerhaave and hispupil Gerard van Swieten. Herman Boerhaave (1668–1738) (Fig. 1),doctor, botanist, and humanist, regarded as the founder of clinicalteaching and the modern academic hospital, was the first to establish ascientific basis for epilepsy. In his Institutiones Medicinae, published in1708, for example, he provides a rather strict definition of epilepsy:“Epilepsy is the sudden abolishment of all vital functions withaccompanying increase of mobility and convulsions in all bodymuscles.” In his Praelectiones de morbis nervorum, published after his

psy research, Epilepsy Behav (2010), doi:10.1016/j.

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Fig. 1. Herman Boerhaave (1668–1738).

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death in 1761, he seems to follow the Galenic classification of epilepsy,distinguishing between epilepsia idiopathica and epilepsiae deutero-pathicae [1]. In his Aphorisms (1708), regarding the epileptic attack andits variations, he says:

But all those varieties consist only in changing the motions of themoveable parts, and therefore of the muscular; wherefore theyonly suppose various contractions of the muscles; hence variousinfluxes of the nervous liquid, and thence the various distributionof it from the common sensory organs to the nerves; and lastlybefore various causes in the medulla of the brain producing thesedistributions, etc., which are best known from the historicalaccount of them [2].

Enumerating the causes of epilepsy, Boerhaave accounts forhereditary causes and the effect of imagination of the mother whilepregnant and being shocked at the sight of a person having anepileptic fit [3], and the mother's prolonged retention of urine [4]. TheDutch–Austrian Gerard Van Swieten (1700–1772), who was Boer-haave's pupil and, from 1745, personal physician to the AustrianEmpress Maria Theresa, wrote a chapter on epilepsy in which hedescribes extensively the clinical characteristics of various forms ofthe disease and discusses epilepsy in comparison with apoplexy andhysteria. He also attempts to explain the various symptoms, such asthe initial cry, the swelling of the veins, and frothing, on the basis ofthe physiological facts known in his time, while he also refers to theancient literature of Hippocrates, Aretaeus, Galen, and CaeliusAurelianus. Van Swieten, being a student of Boerhaave, also agreeswith the view that the thoughts of the mother can affect the fetus,admitting, however, that he cannot give a reasonable explanation [5].

The first major treatise on epilepsy was written by the Swissphysician Simon August André David Tissot (1728–1787). Publishedin 1770, the Traite de l’ epilepsie is considered to be a milestone inscientific research on epilepsy. Tissot completely rejects the influenceof the moon on epileptic seizures, accepts the hereditary forms ofepilepsy, and states that it is the duty of the person with epilepsy toremain unmarried [6]. Among his extreme views about epilepsy is the

Please cite this article as: Sidiropoulou K, et al, Hallmarks in 18th- and 19yebeh.2010.04.004

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belief that masturbation could cause epileptic seizures [7] or sexualexcesses or excessive continence [8]. Tissot suggests as a therapytrephining, among others, for all cases where the symptoms point to aseat of the disease accessible to the trephine, even if there were noconspicuous previous injury [9].

During this period, the French medical school took the first stepstoward understanding the disease, especially in the growing fields ofneurology and pscyhiatry. One of the early figures of the Frenchmedical school, Jacques–Louis Doussin Dubreuil (1762–1831), in hisDe l'épilepsie en général, et particulièrement de celle qui est déterminéepar des causes morales, first published in 1797, tried to explain theinfluence of various emotional states on epilepsy. He believed thatthrough the contraction of the heart, emotions affect the flow of bloodand other humors, and can thus impede the excretion of substancesthrough sweating, impeding, thus, the excretion of substancesthrough sweating [10]. Jean Maisonneuve, a pupil of Philip Pinel(1745–1826), in his Recherches et observations sur l'épilepsie présentéesà l'école de médecine de Paris, states that “epilepsy like all chronicdiseases can be studied well only in hospital,” stressing the variety ofclinical manifestations of epilepsy [11]. He considered violentpassions as a cause of epileptic seizures. Maisonneuve accepted theinitial division of epilepsy into idiopathic and sympathetic; idiopathicepilepsy can be congenital, spontaneous, plethoric, humoral, orcaused by strong emotions, whereas the sympathetic form can beproduced by “irradiation” from external parts, the stomach, theintestines, or uterus, to which “vaporous or hypochondric epilepsy” isthe fifth category of epilepsy [12]. Maisonneuve described the so-called sensitive aura of sympathetic epilepsy and its expansion to thebrain preceding the epileptic seizure, connecting the sensitive aurawith partial epilepsy [13].

This period is alsomarked by thework of eminent British physicians.Thomas Beddoes (1760–1808), physician, scientific writer, reformingpractitioner, teacher of medicine, and associate of leading scientificfigures, in his Essay on the Nature and Prevention of Some of the Disorders,Commonly Called Nervous, states that the disposition toward epilepsy iswidespread. He pays particular attention to the changes developingbefore the onset of an attack, noting that these preepileptic states aresimilar to the manifestations of the hysteric and other nervouscomplaints. According to Temkin, his essay is one of the mostcomprehensive studies on incipient epilepsy [13]. William Cullen(1712–1790), one of the greatest physicians in Scotland and also aprofessor of medicine, wrote Of Neuroses or Nervous Disorders, in whichhe includes epilepsy as one of the spasmodic affections without fever,together with tetanus and chorea or St. Vitus dance [14]. Both theLondon practitioner William Heberden (1710–1801) and John Cooke(1756–1838), in his Treatise on Nervous Disease, make extensivereferences to epilepsy [15,16].

Finally, the first experimental provocation of convulsions wasdone in Italy. The Italian naturalist Felice Gaspar Ferdinand Fontana(1730–1803), in a series of experiments on stimulation of the cerbralcortex with electricity, demonstrated that convulsions could beproduced by pressure on the brain, but not by irritation of the dura,as commonly believed [17,18].

3. The 19th century: The “golden era” of French medicine and thecontribution of the English school of physicians

During the 19th century, neurology was elevated as a new science,separate from psychiatry, and epilepsy was widely considered as abrain disturbance. The French medical school seemed to predominatein the field of epileptology, as a result of the establishment of the firstlarge hospital facilities in France. In 1857, the first hospital for thecrippled and people with epilepsy was founded. At the same time,humanitarian approaches to address the social problems that epilepsycreates led to the foundation of centers for the care and professionalorientation for people with epilepsy. Among the countries in which

th-century epilepsy research, Epilepsy Behav (2010), doi:10.1016/j.



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Fig. 3. Jean-Étienne Dominique Esquirol (1772–1840).

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such institutions were founded were Germany, The Netherlands,England, Switzerland, Denmark, and Norway.

3.1. The French medical school of the 19th century

Marie-Jean-Pierre Flourens (1794–1867) (Fig. 2), one of themostimportant figures in physiology in French medicine, published hisRecherches physiques sur le propriétés et les fonctions du systêmenerveux dans les animaux vertébrés in 1823. In it, he established thebasic rules regarding the irritability and sensibility of the centralnervous system, noting that different functions can be attributed todifferent parts. Flourens found that the cerebral hemispheres and thecerebellum were not irritable; irritability pertained to the spinal cord,its continuation (medulla oblongata), and its end (the corporaquadrigemina). These parts had the property of immediately excitingmuscular contractions, whereas the cerebral hemispheres were theexclusive site of volition and sensation, just as coordination ofmovement was placed in the cerebellum. His contribution is decisivefor the research on epilepsy, as the loss of consciousness and thevoluntary movements in epileptic attacks would imply the involve-ment of the cerebral lobes were it not for the participation of themedulla described by Flourens [19].

In 1815, French psychiatrist Jean-Étienne Dominique Esquirol(1772–1840) distinguished severe from light epileptic seizures(grand mal and petit mal) (Fig. 3). Along with his pupils Bouchetand Cazauvieilh, he studied epilepsy and insanity in parallel,publishing a series of 385 cases of women hospitalized in the epilepticward, 46 of whom were finally diagnosed with hysteria. Four-fifths ofthe remaining 339 women were seriously affected mentally. A laterstudy by Bouchet and Cazauvieilh revealed a high frequency ofepileptic attacks among patients considered to be insane [20].Examining the postmortem data, Esquirol admits that “pathologicalanatomy has shed little light on the immediate seat of epilepsy” [21].Esquirol divides epilepsy into three kinds: (1) idiopathic, (2)

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235Fig. 2. Marie-Jean-Pierre Flourens (1794–1867).


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sympathetic, and (3) symptomatic. Idiopathic and sympatheticepilepsy can be further subdivided; idiopathic epilepsy can beproduced by an external force causing fracture of the skull; a diseaseof the skull, the meninges, or the brain; or even fright. On the otherhand, sympathetic epilepsy includes epilepsia plethorica, polyposa,humoralis, metastatica, scorbutica, syphilitica, uterina, and others[22]. Bouchet and Cazauvieilh also tried to establish a anatomicalrelationship between insanity and epilepsy by placing insanity in thegray substance of the brain and epilepsy immediately underneath[23]. The problem of epilepsy classification is also discussed by LouisJean François Delasiauve (1804–1893) in his Traité de l'épilepsie, inwhich he classifies epilepsy into three categories: essential oridiopathic, symptomatic, and sympathetic [24].

In 1827, Antoine Baron de Portal (1742-1832) published hisclassic Observations sur la nature et le traitement de l'epilepsie, in whichhe presented his clinical experience based on a large amount ofclinical data and postmortem reports. Portal admits that inmany casesof epilepsy, dissection does not reveal any lesions in either the brain orother parts of the body [25]. He also makes important notes on the so-called furor epilepticus. He noted that this clinical status occurs beforethe onset of the epileptic seizure, as well as after; a patient in thiscondition could even commit murder [26].

The same year, a less well known French physician, Louis FrançoisBravais (1801–1843), published his thesis Recherches sur les symptômeset le traitement de l'épilepsie hémiplégique, in which he defines epilepsyon a new basis, that of “hemiplegic epilepsy,” duringwhich convulsionsattack one side of the body followed by paralysis. His description isliterally the forerunner of what was later called Jacksonian convulsions:

In the majority of cases the patients know that their hands, theirforearms are initially affected, either by spasms or by a particularaura…. Many amongst them are subject to incomplete attacks inwhich the arm alone is affected; they complain to their physician




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Fig. 4. Théodore Herpin's Des accès incomplets d'épilepsie.


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of experiencing jerking, numbness, nervous twitching in theaffected limb, either during the day or at nightfall. If the attacksreturn at regular periods, or if by a happy chance the physician is awitness, these are the symptoms observed: First are convulsionsof the arm and forearm, then of the muscles of the lower limb, ofthe face, of the neck and finally of the wall of the chest of theabdomen.... Do the convulsions begin with the muscles of theshoulder and of the arm, or with those of the hand and the flexorsof the fingers? The attack is too prompt and observation toodifficult for me to have been able to solve this question. Which isthe order in which the muscles of the lower limb, of the head andthe neck of the wall of the great cavities of the trunk contract? Itseemed to me that the flexor, extensor and rotator muscles of thehead convulse before the muscles which move the mouthsidewards, the patient inclining the head towards the shouldersbefore the mouth is split to the ear on the same side [27].

An important contribution in the delineation of psychic manifesta-tions of epilepsy is the work of French physician and expert in forensicmedicine Francois-Emmanuel Foderé (1764–1835). In his Les loiséclairées par les sciences physiques, one of the most influential workson legal medicine of the 19th century, Foderé discusses what he callsperiodic delirium, which is clearly epileptic mania, as one can deducefrom his description: “These paroxysms do not come suddenly.Usually the patient feels their approach; they are preceded by a noisein the head and frightening dreams; then the patient feels somethingascending from the lower parts of the body to the uppermost, almostas in the aura epileptica. He loses conciousness; he falls down; he israised up again and is now raging” [28].

Charles-Édouard Brown-Séquard (1817–1894), a well-knownMauritius-born physiologist and neurologist, while experimenting onthe spinal cord of animals, managed to provoke epileptiformconvulsions by transverse section of the lateral half of the spinalcord [29]. He noted that epileptic attacks could be provoked in manyways, and he concluded that “it is in the cutaneous ramifications ofcertain nerves of the face and the neck where the faculty of producingconvulsions in the animals resides.” Based on those experiments,Brown-Séquard contended that epilepsy could be provoked by anypart of the nervous system, either central or peripheral, and that inany form epilepsy is a reflex phenomenon [30]. His theory alsoincluded such vasomotor manifestations of epilepsy as pallor of theface (contraction of blood vessels through the irritation of sympa-thetic fibers) and loss of consciousness (contraction of the arteries ofthe brain through the samemechanism); convulsions were connectedto a decrease in oxygen concentration in the blood and a concomitantincrease in carbon dioxide [31].

The book Des accés incomplets d'épilepsie by the French neurologistThéodore Herpin (1799–1865), published 2 years after his death, isbased on 300 cases. Herpin describes half of them as having mildsymptoms, such as cramps, visceral spasms, and vertigo. Major attacksoccurred after 5 years of follow-up [32]. According to Herpin,recognition of early symptoms of epilepsy is the key to treatment.Herpin's study therefore focused on the symptoms preceding theonset of major seizures, the initial symptoms with which majorattacks began, and the minor attacks occurring in the intervalsbetween complete attacks. He thus rejected the dualistic categoriza-tion of epilepsy into idiopathic and symptomatic and returned to theancient division of epilepsy as originating (1) from external parts; (2)from the uterus, mouth, stomach, and so on; and (3) from the head orbrain. Herpin focuses on epileptic vertigo and the description of thepsychomotor attacks, but he also deals with Jacksonian convulsions[33]. Of the 300 cases described in Herpin's book, 183 experiencedshort and frequent episodes (what Herpin calls accés), 49 of whomhad initial symptoms beginning from the sense organs. Fifty-four hadattacks or vertigo that began with mental trouble or some cerebral


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malaise, whereas in 54 cases there was complete “loss of the feeling ofexistense” at the very beginning and the patients did not recall theepisode [34]. Herpin also describes epilepsies with intellectualdisturbances and with immediate loss of consciousness. “The troubleis purely intellectual,” one of Herpin's patient says. “I am neitherdazed nor giddy; I can still read words, but I no longer grasp theirmeaning. This is a most distressing condition; it seems to me that onepart of my intellect witness the disorders of the other” [35]. Herpinalso believed that the etiology of epilepsy was in the brain and not theperipheral parts [36] (Fig. 4).

Around the same period, French psychiatrists also elaborated onpsychomotor epilepsy and the psychiatric symptoms of epileptic fits.The French–Austrian physician and influential psychiatrist BénédictAugustin Morel (1809–1879), in his Etudes cliniques, noted thatirritability and anger are the salient features of the epilepticpersonality [37]. The epileptic anger could last 1 or 2 hours andwould repeat itself during the day. Epileptic fury, according to Morel,appears in two forms: either before or after the epileptic attack orindepedently “like lightning and being condensed in terrible deeds”[38]. In 1860, Morel published the article D'une forme de délire, suited'une surexcitation nerveuse se rattachant à une variété non encoedécrite d'épilepsie (Épilepsie larvée), in which he describes an atypicalform of epilepsy diagnosed primarily by symptoms of insanity, andgives a list of symptoms constituting the epileptic character [39].

The very same year, another French psychiatrist of the same era,Jules Falret (1824–1902), in his article entitled De l’ état mental desépileptiques, divides the mental disorders found in persons with




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Fig. 5. James Cowles Prichard (1786–1848).


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epilepsy into three categories. First is the category of a passing troublebefore, during, or after a convulsive attack, in relation to which thetrouble stood as a mere epiphenomenon. This category includes manypremonitory symptoms: “The same idea, the same reminiscence orthe same hallucination arises spontaneously at the moment of theinvasion of every attack and infallibly precedes its appearance.... Thisreminiscence, this idea or this image are the reproduction of the ideaor the sensation which has provoked the first attack in this patient.”The second category is of disorders ordinarily met in perons withepilepsy during the intervals between the attack, that is, epilepticpersonality. The third mental disorder is a more or less prolongeddelirium assigned as folie épileptique (epileptic insanity) [40]. Falretwas also able to identify intellectual disturbances during the epilepticattack in cases where the patient did not lose consciousness. Duringthose attacks, patients “utter certain incomprehensible sounds orarticulate a few incoherent words which seem to indicate a painfulanxiety or deep fright.” Also, some convulsions are mouvementsautomatiques, including swallowing and chewing. After the attackssome of the patients “have retained a more or less vague memory ofthe ideas that preoccupied them while the attacks lasted” [40]. Falretdivided themental disorders of the third type into petit mal intellectueland grand mal intellectuel [40]. The types of epileptic delirium couldeither follow or precede the convulsive attacks or, less commonly,could occur during the intervals between the attacks. Falret found that

The epileptic delirium, with the psychic characteristics proper toit … occurs in patients who are not considered as presentlyaffected by epilepsy. In this case either vertigo or nightly attackswhich have passed unnoticed are demonstrated; or on thecontrary, these somatic symptoms do not exist at the time whenthe patients are observed but have taken place before or will showup later in the course of their life. Under these circumstances, theepileptic delirum substitutes somehow for the epileptic convul-sions and is, so to speak, but another manifestation of the samedisease in a different form [40].

Falret also distinguished between petit mal intellectuel and grandmal: “The calm of the movements, the partial lucidity of the ideas, inshort the semblance of reason which are observed in epilepticssuffering from petit mal intellectuel contrast in the highest degreewith the manic agitation, the extreme disorder of their actions, andthe incessant loquacity of those affected by the grand mal” [40]. Falretalso strongly believed that the seat of epilepsy was the brain and notthe medulla oblongata, though he admitted, however, the inability toexplain sensory loss and motor manifestations [41]. Falret noticedexceptionally various automatisms in epileptic attacks. During thepetit mal intellectuel, the patient could leave his home and work, beabsentminded, and have dulled thinking; he had fits of despair andunprovoked anger, with various impulses followed one another atbrief intervals; he had a desire to destroy himself and the things thatpassed through his hands; he was forgetful, with complete lapses ofmemory; and experienced headaches, giddiness, sparks in the sphereof sight, visions or frightening objects. Regarding automatisms, Falretnoticed in particular that “they strike mechanically [machinalement],without motivation, without interest, without knowing what they door, at least, with a very vague consciousness of their actions” [42]. Insome rare cases their automatic acts have a motive: “Sometimes,indeed, an attack of petit mal intelectuel suddenly arouses in the heartof an epileptic a feeling of jealousy, of vengeance, or of anger towardsa definite person and then pushes him immediately into action, whilein his normal state he had succeeded in suppressing this feeling” [42].

3.2. The British medical school of the 19th century

The British medical school seemed to have followed the Frenchclosely during this period. The physician Edward Goodman Clarke, in


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his treatise The Modern Practice of Physic, summarizes the existingknowledge on epilepsy:

The predisposing causes are a hereditary disposition, intemperanceand great mobility of the system in the early periods of life. Theoccasional or exciting causes are tumours pressing upon the brain,irregularity in the arrangement of the bones of the cranium, mal-conformation of the cranium, sharp-pointed ossifications withinthe cranium, splinters or depression of the bones of the craniumfrom fracture, serous or other effusions into the ventricles, or uponthe membranes of the brain, an abscess formed in the tuberculumannulare, or its neighbourhood, violent joy and anger, pressureupon the medulla oblongata and medula spinallis, worms, denti-tion, derrangement of the primae viae, suppression of any habitualhaemorrhage or accustomed evacuation, syphilis, over-distensionof the blood-vessels of the brain, the eruptive fever in certainexanthemata, as the variola and scarlatina, nervous sympathy,profuse haemorrhages, terror, horror, pungent odours, certainpoisons, difficult patrutition, a diseased state of the liver, the aureepileptica and external irritations. The proximate cuase is supposedto be an involuntary and irregular exertion of the energy of thebrain and nervous system [43].

The physician and ethnologist James Cowles Prichard (1786–1848)(Fig. 5), in his Treatise on Diseases of the Nervous System, notes that the“epileptic delirium” occurs when the patient revives from the comatosestate consequent to a seizure, but it can also occur without any previousfit. He describes the typical symptoms of epileptic mania:

The face is flushed, and the aspect of the patient is like that of a manunder intoxication; he attempts to start frombed and run about, andon being withheld, vociferates and endeavours to overcomeresistance. Sometimes an appearance of maniacal hallucinationdisplays itself, but more generally the disorder resembles phrenitic




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delirium. It commonly continues one, two or three days, duringwhich the patient requires confinement in a straight waistcoat, andthen gradually subsides, and the patient returns into his previousstate [44].

Prichard describes other states of mental confusion, suggestingthey are like somnambulism or epileptic ecstasy: “A more unusualcircumstance in the history of epilepsy is the appearance of a speciesof somnambulism, or of a kind of ecstasis, during which the patient isin an undisturbed reverie, and walks about, fancying himself occupiedin some of his customary amusements or avocations. This takes placeduring the waking as well as the sleeping hours” [45].

His observations are the forerunners of the concept of “psychicequivalents of epilepsy.” Prichard was also the first to establish theterm partial epilepsy in the literature, devoting to the topic an entirechapter in his treatise: “Of Local Convulsion or Partial Epilepsy” [46].

In his study of epilepsy, Richard Bright (1789–1858) (Fig. 6), oneof the most famous English physicians, attempted to combineanatomical data with clinical cases. Bright was able to show changesin the cortex of the cerebral hemispheres. In his classic treatise Reportson Medical Cases, published in 1831, he describes various cases ofepilepsy in detail. He concludes that “epilepsy generally depends uponirritation on the surface of the brain, and that it is often connectedwithunusual thickness of the skull” [47]. Bright supported the theory thatthe gray matter of the brain was the main functional part of thecerebral hemispheres, referring to the discoveries of Foville:

The cineritious is the more active part of the brain generally, withregard to all its functions; and the medullary part is moreparticularly employed in the conveyance of the motions andsensations, or whatever else may be acted upon or produced inthe cineritious part. And supposing for a moment this to be the

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Fig. 6. Richard Bright (1789–1858).


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case, we might expect that lesion of the cineritious substancewould produce disordered action in that part; and that suchaction might be transferred to the distant parts of the body,producing disordered and involuntary motions: whereas, if thegreat injury were done in the substance of the brain, the means ofcommunication with the active part being cut off, paralysis mightresult, more or less mingled with convulsion, in proportion as thecineritious substance is more or less involved [48].

The physician and physiologist Marshall Hall (1790–1857)suggested that epilepsy was due in part to anemia of the medullaand that paroxysmal discharges arose from the brain [49,50].According to Hall, “epilepsy is plainly of two kinds: the first has acentric origin in the medulla itself; the second is an affection of thereflex function, the exciting cause being eccentric, and acting chieflyupon the nerves of the stomach or intestines, which consequentlyform the first part of the reflex arc” [51]. Robert Bentley Todd (1809–1860), physician at King's College Hospital, in an experiment todetermine the seat of epilepsy, observed discrete movements on theface of a rabbit on stimulation of the cerebral hemispheres, but he didnot appreciate the significance of his experiments, for he maintainedthat movement was the concern of structures from the corporastriatum rostrally (Fig. 7). He used the term epileptiform for epilepticattacks of the following description:

One arm, or both arm and leg on one side, become seized withconvulsive movements, quite of the clonic or epileptic kind. Thesecome in paroxysms; the paroxysm lasts a variable time, and thensubsides, leaving more or less general exhaustion and dispositionto sleep; but consciousness is not impaired. Yet there can be nodoubt that such fits may pass into the true epileptic fit; for it is notderangement of sensation or motion or both.

During his experiments he noticed a “slight convulsive twitchingof the muscles of the face” when he irritated electrically thehemispheric lobes, suggesting that “a disturbed state of thehemispheric lobes ... may in some degree at least, contribute to the
T
Fig. 7. Robert Bentley Todd (1809–1860).




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Fig. 8. John Russell Reynolds (1828–1896).


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development of convulsions” [52]. To explain both uremic convul-sions and convulsions during poisoning, Todd developed a “humoraltheory of epilepsy,” which was not a novelty in medical literature. Healso used the term epileptic hemiplegia, like Bravais, for epilepticattacks combined with weakening or paralysis of the affected side,which now are known as Todd's paralysis [52].

William B. Carpenter (1813–1885), physiologist and naturalist, inhis Principles of Human Physiology, clearly establishes contemporaryknowledge regarding the function of the cerebral cortex:

It has usually been considered that the cerebrum acts directlyupon the muscles, in the virtue of a direct continuity of nerve-fibres from the grey matter of its convolutions, through thecorpora striata, the motor tract of the medulla oblongata, theanterior portion of the spinal cord, and the anterior roots of thenerves; and that in the performance of any voluntary movement,the will determines the motor force to the muscles or set ofmuscles, by whose instrumentally it may be produced [53].

Carpenter introduced the theory of the sensorimotor ganglia,according to which

The thalamus is the organ of conscious sensibility, to which allimpressions made on peripheral sensory nerve-fibres must betransmitted in order to be recognized as sensations, and thecorpus striatum, the organ or instrument of voluntary motion,—the downward starting point of volitional motor impulses, or itmight be said of all cerebral motor impulses. These two gangliaare again associated … in sensori-motor action, impressionsreaching the thalamus being passed to the corpus striatum, andgiving rise to automatic movements differing from those whichhave their centre in the cord, only in being accompanied bysensation [54].

In 1836, Astley Cooper (1768–1841), surgeon and anatomist,reported his findings on provoking epileptic seizures by temporaryanemia, without the loss of blood. He tied the carotid arteries of arabbit and then compressed with his thumbs the cerebral arteries.“Respiration almost directly stopped: convulsive struggles succeeded;the animal lost its consciousness, and appeared dead. The pressurewas removed; and it recovered with a convulsive inspiration. It laidupon its side, making violent convulsive efforts; breathed laboriously;and its heart beat rapidly. In two hours it had recovered; but itsrespiration was laborious” [55].

In1850, JohnSimon (1816–1904), a physician famous for reformingthe British health system, noted in his General Pathology that the loss ofconsciousness during epileptic seizures can be attributed to the“convoluted surface of the cerebrum” and that general clonic convul-sions implied “the excitement of some aggregative centre of motion”[56]. The physician Sir Edward Henry Sieveking (1816–1904), in 1858,raised doubts about the distinction between idiopathic and symptom-atic epilepsy. He also rejected the distinction between epilepsy,eclampsia, and children's convulsions, which he considered to be allvariationsof the samedisease [57]. JohnRussellReynolds (1828–1896)(Fig. 8), an influential physician and neurologist, president of the RoyalCollege of Physicians of London and of the British Medical Association,was the first to identify “epilepsy proper” with idiopathic epilepsy, towhich, he believed, “the name of epilepsy ought to be applied” [58]. Hiswork in epilepsy is considered to be pioneering. His first article onepilepsy was published in 1855, on the interictal abnormalities thatcharacterize patients with epilepsy [59,60], and, a year later, hepresented a series of cases illustrating what was regarded as therational treatment of epilepsy [61]. His major account on epilepsy waspublished in 1861 and is entitled Epilepsy: Its Symptoms, Treatment andRelation to Other Chronic Convulsive Diseases [62] With the exception ofSieveking'smonographOn Epilepsy and Epileptiform Seizures, referred to


TEpreviously, which appeared in 1858, it is considered to be amilestone inEnglish epileptology.

Reynolds suggested that even if “we were compelled to recognisethe existence of many, or even a few, cases distinct from any moregeneral condition or systemic or local disease, we must employ theterm epilepsy in a restricted sense, implying only those cases which,in the present state of medical science, are irreducible” [63]. [[AU: Thepreceding quote is identical to the quote a few lines down. Twodifferent sources. OK?]] He defines epilepsy as an episodic loss orimpairment of consciousness, associated or not with muscle spasmsor convulsing. As far as the seat of epilepsy, he also supported thetheory of the medulla oblongata and that the change was of afunctional and not of an anatomical nature. Idiopathic epilepsywas, tohim, a disease of unknown etiology [64]. In general, he suggests thatepilepsy has its own right as a disease, but its pathological basis is stillnot known. In his Diagnosis of Diseases of the Brain, Spinal Cord andtheir Appendages (1855), he states that:

If we can succeed in distributing all the cases hitherto known asepilepsy among the several classes of better defined diseases, weought to reject the term epilepsy from our nosology: but if wecannot accomplish this distribution, and are compelled torecognise the existence of many, or even of a few, cases distinctfrom any more general condition of systemic or local disease, thenwe must employ the term (epilepsy) in a restricted sense,implying only those cases which, in the present state of medicalscience, are irreducible [65].

Reynolds employs the terms epileptiform and epileptoid for seizuresresembling epilepsy, rejecting , in that way, the existence of renal oruterine epilepsy and epilepsy from tumor of the brain; he claims that we“find these confounded togetherwith simpleor idiopathic affection” [63],




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Fig. 9. William Richard Gowers (1845–1915).


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adopting indirectly Delasiauve's theories about idiopathic epilepsy [66]as epilepsy of cerebral origin with uknown pathology. Reynold'sclassification of epilepsy, although more rational, made his epidemio-logical data hard to interpret for his contemporaries, who employed arather more broad definition for epilepsy. Reynolds also supported thetheory of positive and negative symptoms arising from brain pathology[67], earlier than his successor, Jackson; negative effects are associatedwith direct impact on structural pathology that damaged or destroyedtissue, whereas positive symptoms aremore remote effects of pathologyarising from “altered nutrition” that the pathology produced in survivingtissue. Reynolds also refers to the epileptic aura without attempting toexplain its pathogenesis. His theory on epileptogenesis is rather amixture of Marshall Hall's [68] and Brown-Sequard's [69] concepts;Reynolds adopts Brown-Sequard's hypothesis to explain the early stagesof an epileptic seizure and Hall's neck muscle spasm–cerebral venouscongestion mechanism to account for the continuation of the seizureprocess. To that point, Reynold adds his own theory involving an increasein carbondioxide concentration in theblood that converts the initial tonicphase of the epileptic seizure into a clonic phase [70].

The physician and biographer Samuel Wilks (1824–1911) wroteabout epileptic convulsions in 1866, and states clearly:

I have no hesitation in saying that for one such case fifty might befound in which the morbid changes producing these symptomsoccupy the surface.… It appears to me that, from clinical and post-mortem observations, as well as from all analogy, we cannot butconclude that the fons et origo mali is in the cineritious substanceof the brain. I believe that in this region a commotion occureswhich would, perhaps, be analogous to a palpitation affecting theheart, and that this irritates the ganglia below, which form thesummit of the motor tracts [71].

William Richard Gowers (1845–1915) (Fig. 9), one of the mostemminent figures in British neurology and a contemporary of JohnHughlings Jackson, also contributed substantially to the understand-ing of the pathogenesis of the disease. In 1879, he was honored by theRoyal College of Physicians by delivering the college's GoulstonianLectures [72], chosing epilepsy as his topic. During those lectures,Gowers presented and reviewed the clinical features of a series of1500 cases whom he observed and treated personally. Those caseswere published in some of the most prestigious contemporarymedical journals [72], and, then, he expanded further those findingsin his monograph entitled Epilepsy and Other Chronic ConvulsiveDisorders (1881), including a series of 3000 cases of epilepsy thatcover every possible clinical feature of epilepsy [73].

3.3. The Dutch and German medical schools of the 19th century

Research into epilepsy was also advanced by the work of Germanand Dutch physicians of the era. Moritz Heinrich Romberg (1795–1873), in the section on motor diseases in his classic text A Manual ofthe Nervous Diseases of Man (1840–1846), describes at lengthmuscular spasms of various etiologies including epilepsy [74].Romberg also mentions premonitory symptoms with sensitive,motor, or psychic character [75]. Karl Friedrich Burdach (1776–1847), anatomist, physiologist, and embryologist, published a series of1911 anatomical abnormalities observed in the brain. In his book Vombaue und leben des gehirus, he describes 476 epileptic cases, amongwhich the proportion of lesions in general convulsions and epilepsy tototal brain lesions was 1:4 [76]. According to those data, the lateralventricles were most frequently affected, in 86 of 476 cases, 63 ofwhichconsisted of serous effusion.

The German anatomist and pathologist Friedrich Gustav JacobHenle (1809–1895), writing in 1853, noted that epileptic convulsionsare provoked by an increased turgor at the base of the brain, and thatthe loss of consciousness depends on either increase or decrease in


Tblood flow in the hemispheres. He distinguished between “plethoricepilepsy,”where both the convex surface and the brain are congestedwith blood, and “anemic epilepsy,”where the collapse of hemispheresis the primary phenomenon leading to a subsequent turgor at the base[77].

The same year, Adolf Kussmaul (1822–1902), a Germaninternist, along with Adolf Tenner, published the classic treatiseon epileptiform convulsions. According to them, the main cause ofconvulsions in animals is a “sudden interruption in the nutrition ofthe brain.” They assumed that nutritional alterations cause changesat the molecular level of the brain substance that can also be causedby chemical agents such as poisons. In that way they not onlyincluded alteration of blood circulation in their model, but also theeffect of various poisons [78]. In 1859, Höring, a German physician,in his dissertation entitled Über Epilepsie, described a case of ayoung man who had grand mal attacks as well as many mild attacksduring which he had complete lapses of memory [79].

In 1868, the German neurologist and psychiatrist WilhelmGriesinger (1817–1868), in an article entitled “Ueber einige epilep-toide Zustände,” used the term psycho-motor symptoms (psycho-motische symptome) in epileptoid conditions. Among those symptomshe included “mild twitchings in the hands, bulbi around the mouth,rigidity in the neck, tension in the abdominal muscles” [80].

The founder of Dutch neurology and psychiatry, Jacobus Schroe-der van der Kolk (1797–1862), in concordance with, in 1859,supported the reflex theory of epilepsy to which Brown-Séquardsubscribed. According to this theory, the seat of epilepsy is in themedulla oblongata, and especially “in the ganglionic cells of themedulla oblongata, which, as reflex ganglia, possess the peculiarproperty that when once brought into an excited condition, maymore




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Fig. 10. John Hughlings Jackson (1835–1911).


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or less suddenly discharge themselves and communicate theirinfluence to different nervous filaments” [81]. However, van derKolk further believed that that the excitability of the medullaoblondgata can cause epilepsy, agreeing with Tissot on the effect ofmasturbation as an irritant of epileptic seizures [82], a theory alsoadhered to by Fournier (1832–1914) [83] and later Gowers [84].

3.4. Therapies for epilepsy

Different types of therapy for epilepsy have been suggested byvarious authors. Théodore Herpin suggests prescribing selinumpalustre and zinc oxide [85], whereas Achille-Louis-François Foville(1799–1878) advises turpentine [86]. Armand Trousseau(1801–1867) suggests administration of indigo and belladona [87],John Russel Reynolds recommends misletoe and the inhalation ofchloroform [88]. Edward Sieveking, in 1857, introduced bromidepotassium in the treatment of epilepsy [89], a treatment furthersupported by Charles Locock (1799–1875) and especially SamuelWilks [90,91]. Locock described the anticonvulsant effect ofbromides, although the earliest studies on the effects of variousdrugs as anticonvulsants were performed by Albertoni (1882), onanimals with induced seizures [92]. Delasiauve wrote that theprocess of causing “intermittent fever” as a remedy for patients withepilepsy was condoned by Selade [93]. Surgical intervention wasanother popular intervention, especially for sympathetic epilepsy.Trephining of the skull was supported by Charles-Édouard Brown-Séquard, Benjamin W. Dudley (1785–1870), John Saw Billings(1838–1913), and Paul Broca (1824–1880), most of whom hadused surgical therapy in various cases [94–96]. Other surgicalprocedures suggested were tracheoctomy, by Marsall Hall [97] andcauterization of the larynx with nitrate of silver by Brown-Séquard[98].

4. The age of John Hughlings Jackson

John Hughlings Jackson (1835–1911) (Fig. 10) inaugurated themodern period in the scientific research of epilepsy. Working at theBritish National Hospital for the Relief and Cure of the Paralysed andEpileptic, he was able to deal with a large number of epileptic cases.Jackson was in contact with such famous neurologists as Charles-Édouard Brown-Sequard, Charles Bland Radcliffe (1822–1889), RusselReynolds, Edward Sieveking, and Sir William Richard Gowers(1845–1915), who was his assistant [99]. His clinical work led himto disagree with the earlier theses of Marie-Jean-Pierre Flourens(1794–1867) and François Achille Longet (1811–1871). His clinicalobservations from 1861 to 1870, which came well before theexperimental reports of Eduard Hitzig (1839–1907) and David Ferrier(1843 –1928), were confirmed ultimately by Hitzig and Ferrier. Sometime after 1870, Gustav Theodor Fritsch (1837–1927) and Hitzigpublished their investigations On the Electric Excitability of theCerebrum, in which they published the discovery of the motor areaof the hemispheres in dogs [100]. In 1873 David Ferrier, in an articleentitled “Experimental Researches in Cerebral Physiology andPathology,” confirmed Jackson's clinical findings anatomically andexperimentally [101].

Jackson studied epilepsy on a pathological and anatomical basis.He initially believed that focal convulsions were due to a discharginglesion from damage to nerve cells. He also believed, at first, that thepart of the brain involvedwas the region of the corpus striatium or theconvolutions near to it. According to Temkin, we can distinguish threeperiods of observations in Jackson's life: from 1861 to 1863, when heformed the focus of his interest; 1864 to 1870, when his study onconvulsions appeared; and the period after that publication [102]. In1861, Jackson published his first article entitled “Cases of EpilepsyAssociated with Syphilis,” containing reports from hospitals and from


TEDPRthemedical literature [103]. In 1863, he observed about unilateral con-

vulsions that:

In very many cases of epilepsy and especially in syphiliticepilepsy, the convulsions are limited to one side of the body;and, as autopsies of patients who have died after syphiliticepilepsy appear to show, the cause is obvious organic disease onthe side of the brain, opposite to the side of the body convulsed,frequently on the surface of the hemisphere [104].

The same year he published a pamphlet entitled Suggestions forStudying Diseases of the Nervous System on Professor Owen's VertebralTheory, in which, based on Richard Owen's theory about thesegmental nature of the skull, he assumed that the vertebrae of theskull corresponded to a segmentation of bones, nerves, blood vessels,and muscles [105].

In 1864, Jackson published an important article entitled “EpilepticAphemia with Epileptic Seizures on the Right Side,” in which hediscusses the symptoms of aphasia [106]. In this article, Jackson refersto two cases, a patient with epileptic hemiplegia, loss of speech, and avalvular disease of the heart, and a patient with unilateral seizurescombined with temporary defects in speech. In the first case Jacksonassumed the involvment of emboli plugging the middle cerebralartery, whereas, for the second case, he suggested a spasm in themiddle cerebral artery. He specifically added: “when we furtherconsider that the left middle cerebral artery supplies: (1) the roots ofthe olfactory bulb; (2) the corpus striatum; and (3) the hemispheres,we can readily understand how the three strangely associatedsymptoms should occur together in plugging of that vessel; and Isubmit that temporary spasm of the vessels in that arterial regionwould account for the three temporary symptoms in epileptiformseizures” [107]. Jackson thus offered a new explanation of epilepticseizures that differed from that of his predecessors who claimed theseat of the disease lay in the medula oblongata.

In the following years, Jackson's views regarding the involvementof the corpus striatum in the genesis of seizures evolved rapidly. In1870, Jackson wrote:

Palsy depends on destruction of fibres, and convulsion oninstability of grey matter. As the convolutions are rich in greymatter I suppose them to be to blame, in severe convulsions at all




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events; but as the corpus striatum also contains much grey matterI cannot deny that it may be sometimes the part to blame inslighter convulsions. Indeed, if the discharge does begin inconvolutions, no doubt the grey matter of lower motor centres,even if these centres be healthy, will be discharged secondarily bythe violent impulse received from the primary discharge. Nowboth these parts—the corpus striatum and many convolutions—are supplied by one artery, the middle cerebral or Sylvian, and thisartery circumscribes the region I speak of [108].

His Study of Convulsions is the high point of his work. Jacksondistinguishes four factors involved in the final cause of convulsions. Thefirst is the “seat of the internal lesion,” the existence of a localized lesionin the cortex that is involved in the localized spasms; the functionalcause of the change is the second stage [109]. The pathological processthat brought about the functional change (embolus, tumor, syphilis, orother cause) is the third factor, and the fourth is the variouscircumstances that trigger the paroxysm (provocative or excitingcause) [110]. In 1873, Jackson gave the following definition for epilepsy:“Epilepsy is the name for occasional, sudden, excessive, rapid and localdischarges of grey matter” [111]. By adopting this definition, Jacksonaccepted many different clinical entities as “epilepsy.”

In 1866 Jackson discussed the mechanisms of various forms ofepilepsy in his article entitled “Clinical Remarks on the OccasionalOccurrence of Subjective Sensations of Smell etc.” He notes that “incases of sudden and temporary loss of conciousness in whichconvulsive movements were slight, or perhaps absent, the disorderof function was chiefly in the range of the anterior cerebral artery”[112]. For cases of loss of conciousness, he believed the disorder to belocated “in the very highest nervous centres of the cerebralhemisphere” [113]. As far as the mechanisms involved, genuineepilepsy was not different from unilateral epilepsy. He later refinedhis definition of epilepsy, suggesting a scientific and an empiricalclassification; in terms of anatomy and physiology, epileptic vertigo,petit mal, and grand mal were due to differences of a discharge“beginning and spreading from the same parts of the brain” [114].Empirically, he distinguished three classes of epilepsy proper fromwhich the epileptiform or epileptoid group, including convulsionsbeginning unilaterally, unilateral dysesthesia (migraine), and epilep-tiform amaurosis, had to be differentiated [115].

In his lecture “On Convulsive Seizures,” as part of the LumleianLectures, Jackson presented the most advanced form of his theory onepilepsy. According to Jackson, the central nervous system can bedivided into three levels: (1) the lowest level, which consists of thespinal cord, the medula oblongata, and the pons, representing themostrough and simple movements; (2) the “motor province,” consisting ofthe motor region of the cerebral cortex (rolandic region) and of theganglia of the corpus striatum representing complex movements of allparts of the body; and (3) the highest level formed by the centers of theprefrontal lobes (“the organ of mind”) [116]. Fits beginning at the lowerlevels can spread to higher ones through interconnecting fibers as wellas to neighboring cells of the same level. Jackson considered thereforemiddle-levelfits to correspond to epileptiform seizures andhighest-levelfits to epileptic seizures. Jackson was careful to clarify his use of terms,however: “I do not use the term cortical epilepsy because both epilepticand epileptiform seizures are, to my thinking, cortical fits…. I formerlyused the term epilepsy generically for all excessive discharges of thecortex and their consequences…. I now use the term epilepsy for thatneurosis which is often called “genuine” or “ordinary” epilepsy, and forthat only” [116]. Epileptiform convulsions, according to Jackson, startfrom a definite place in the brain and always begin with a signalsymptom which localizes the original discharging lession. The symp-toms can be either sensory or motor depending on the part of the brainwhere discharges take place, because according to Jackson, all levels aresensorimotor. Discharging lesions are diseased because of “morbid


F

nutrition,” and those cells that are discharged lose their function andtemporarily form a “negative lesion” [117]. Sensory or/and motorsymptoms are present in each epileptic or epileptiform seizure; inepileptic seizures paralysis is generalized, whereas in epileptiformseizures it is located in certain parts of the body.

To explain postepileptic states, Jackson suggests the four-layertheory of higher levels, though this theory was not supported by anyanatomical data, as Jackson admits. He thought that discharges afflictingthefirst layer are responsible for impaired consciousness, the second fora single loss of consciousness, as in the case of epileptic mania, and thethird for coma without affecting the vital operations [118].

Jackson also refers to the “dreamy state” some patients experiencebefore the onset of the epileptic fits. He mentions, writing in 1876, anumber of expressions used by patients to describe those symptomsof the so-called “intellectual aura,” some of which resemble statesknown in modern psychiatry and neurology as déjà vu: “Old scenesrevert, I fell in some strange place, a dreamy state, a panorama ofsomething familiary and yet strange, if I were walking alone and had afit, I should think ‘Oh, I saw that before”’ [119].

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OO5. Conclusion

The 18th and 19th centuries constitute the most important periodin the formation of scientific thought on epilepsy as a disease andsymptom. Theories on epilepsy during this period are formulated on asolid scientific basis, and people with epilepsy are, for the first time,treated as patients and not as lunatics or possessed. During thisperiod, experimental studies were conducted as well as advancesmade in the pathology of the disease and the connection of epilepsywith various psychiatric symptoms. The work of John HughlingsJackson was preceded by a plethora of studies by Dutch, German,English, and French physicians who evolved scientific thought andperformed thorough studies on epilepsy.

TEReferences

[1] Boerhaave H. Praelectiones academicae de morbis nervorum; 1761. p. 834. t. II.Leiden.

[2] Van Swieten G. The commentaries upon the aphorisms of Dr. Herman Boerhaave[English translation], vol. 10; 1754. p. 343. London.

[3] Van Swieten G. The commentaries upon the aphorisms of Dr. Herman Boerhaave[English translation], vol. 10; 1754. p. 351. London.

[4] Boerhaave H. Praelectiones academicae de morbis nervorum; 1761. p. 794. t. II.Leiden.

[5] Temkin O. Great systems and period of Enlightenment. The falling sickness: ahistory of epilepsy from the Greeks to the beginnings of modern neurology.London: John Hopkins Univ. Press; 1971. p. 218.

[6] Tissot SA. Traité de l'épilepsie, faisant le tome troisième du traité des nerfs et deleurs maladies; 1770. Paris.

[7] Tissot SA. L' onanisme: dissertation sur lesmaladies produites par lamasturbation(troisieme edition). Lausanne: Chez Marc Chapuis et Compagnie; 1764.

[8] Tissot SA. Traité de l'épilepsie, faisant le tome troisième du traité des nerfs et deleurs maladies; 1770. p. 70–3. Paris.

[9] Tissot SA. Traité de l'épilepsie, faisant le tome troisième du traité des nerfs et deleurs maladies; 1770. p. 263. Paris.

[10] Doussin-Dubreuil JL. De l' epilepsie en général, et particulièrement de cellequi'est déterminée par des causes morale; 1825. Paris.

[11] Maisonneuve JGF. Recherches et observations sur l'épilepsie, presentées a L'Écolede Médecine de Paris; 1803. p. 8. Paris.

[12] Maisonneuve JGF. Recherches et observations sur l'épilepsie, presentées a L'Écolede Médecine de Paris; 1803. p. 50. Paris.

[13] Maisonneuve J.G.F. Recherches et observations sur l'épilepsie, presentées aL'École de Médecine de Paris. Paris. p. 187.

[14] Cullen W. Of neuroses, or nervous diseases, Part II. Firs lines of the practice ofphysic. Edinburgh: William Creech; 1778–1784.

[15] Heberden W. Epilepsy, headache, palsy and apoplexy, and St. Vitus dance.Commentaries on the history and cure of diseases. London: T. Payne; 1802.

[16] Cooke J. A Treatise on nervous disease. London: Longman; 1820–1823.[17] Garrison FH. Felice Fontana, a forgotten physiologist of the Trentino. Bull NY Acad

Med 1935;2:117.[18] Marchand J.F., Hoff H.E. Felice Fontana: the laws of irritability. J Hist Med

1955;10:197, 302, 399.[19] Flourens P. Recherches expérimentales sur les propriétés et les fonctions du

système nerveux, dans les animaux vertébrés. Arch Gen Med 1823;2:321–70.




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982Q29

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ARTICLE IN PRESS

UNCO

RREC

[20] Esquirol J-ÉD. Des maladies mentales: considérées sous les rapports médical,hygiénique et médico-légal, vol. 1; 1838. p. 284. Paris.



[23] Soury J. Le système nerveux central, structure et fonctions, histoire critique desthéories et des doctrines; 1899. p. 526. Paris.

[24] Delasiauve LJF. Traité de l'épilepsie; 1854. p. 37. Paris.[25] Portal LB. Observations sur la nature et le traitement de l'épilepsie; 1827. p. 47–8.[26] Portal L.B. Observations sur la nature et le traitement de l'épilepsie; 1827. p. 11, 55[27] Bravais LF. Recherches sur les symptômes et le traitement de l'épilepsie

hémiplégique. These de Paris No. 118; 1827. p. 24–5. Paris.[28] Foderé F. Les lois éclairées par les sciences physiques ou traité demédecine légale

et d'hygiène publique; 1798. p. 93. Paris.[29] Brown-Séquard E. Experimental and clinical researches applied to physiology

and pathology. Boston Med Surg J 1857;56:216–20.[30] Brown-Séquard E. Experimental and clinical researches applied to physiology

and pathology. Boston Med Surg J 1857;56:433–7.[31] Brown-Séquard E. Experimental and clinical researches applied to physiology

and pathology. Boston Med Surg J 1857;56:473–8.[32] Herpin T. Des Accès incomplets d'épilepsie; 1867. Paris.[33] Temkin O. Jackson's forerunners. The falling sickness: a history of epilepsy from

the Greeks to the beginnings of modern neurology. London: Johns Hopkins Univ.Press; 1971. p. 324.

[34] Herpin T. Des Accès incomplets d'épilepsie; 1867. p. 105. Paris.[35] Herpin T. Des Accès incomplets d'épilepsie; 1867. p. 111. Paris.[36] Herpin T. Des acces incomplets de epilepsie; 1867. p. 36. Paris.[37] Morel BA. Etudes cliniques: traité théorique et pratique des maladies mentales

considérées dans leur nature, leur traitement et dans leur rapport avec lamédecine légale des aliénés, vol. 2. Nancy/Paris; 1852–1853. p. 322.

[38] Morel BA. Etudes cliniques: traité théorique et pratique des maladies mentalesconsidérées dans leur nature, leur traitement et dans leur rapport avec lamédecine légale des aliénés, vol. 2. Nancy/Paris; 1852–1853. p. 321.

[39] Morel B.A. D'une forme de délire, suite d'une surexcitation nerveuse serattachant à une variété non encore décrite d'épilepsie (Epilepsie larvée). GazHebd Med Chir 1860;7:773–5, 819–21, 836–41.

[40] Falret J. De l'état mental des épileptiques. Arch Gen Med 1860;Ve serie: 661–79.[41] Falret J. Theories physiologiques de l'épilepsie. Études cliniques sur les maladies

mentales et nerveuses; 1890. p. 305–37. Paris.[42] Falret J. De l'état mental des épileptiques. Arch Gen Med 1861;18:423–43.[43] Clarke EG. The modern practice of physic; 1805. p. 288. London.[44] Prichard JC. A treatise on diseases of the nervous system, part the first; 1822.

p. 99. London.[45] Prichard JC. A treatise on diseases of the nervous system, part the first; 1822.

p. 100. London.[46] Prichard JC. A treatise on diseases of the nervous System, part the first; 1828.

p. 385. London.[47] Bright R. Reports of medical cases, vol. II; 1831. p. 644. part II. London.[48] Bright R. Reports of medical cases, vol. II; 1831. p. 514. part II. London.[49] Hall M. Synopsis of cerebral and spinal seizures of inorganic origin and of

paroxysmal form as a class; and of their pathology as involved in the structuresand actions of the neck. London: J. Mallet; 1851.

[50] Hall M. Synopsis of apoplexy and epilepsy; with observations on the trachelismus,laryngismus and tracheotomy; and the proposal for a hospital for epileptics.London: J. Mallett; 1852.

[51] Hall M. On the reflex function of the medulla oblongata and medulla spinalis.Philos Trans 1833:635–65.

[52] Todd RB, Bowman W. The Lumleian lectures for 1849: "On the pathology andtreatment of convulsive diseases" [review probably by Carpenter]. Br ForeignMed-Chir Rev 1850;5:1–36.

[53] Carpenter W. Principles of human physiology; 1858. p. 508. Philadelphia.[54] Carpenter W. Principles of human physiology. Philadelphia; 1858. p. 490, 508.[55] Cooper SA. Some experiments and observations on tying the carotid and vertebral

arteries, and the pneumnogastric, phrenic and sympathetic nerves. Guys Hosp Rep1836;1:457–75.

[56] Simon J. General pathology, as conductive to the establishment of rationalprinciples for the diagnosis and treatment of disease; 1852. p. 152. Philadelphia.

[57] Sieveking EH. On epilepsy and epileptiform seizures; 1858. p. 162–3. London.[58] Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic

convulsive diseases; 1861. p. 27. London.[59] Reynolds JR. Some phenomena of the inter-paroxysmal condition of epileptics.

Lancet 1855;66(100–2):120–2.[60] Buchwald J, Devinsky OJ. Russel Reynolds and the study of interictal symptoms in

epilepsy. Arch Neurol 1988;45:802–3.[61] Reynolds JR. Cases illustrating the rational treatment of epilepsy. Lancet 1856;68:

15–7.[62] Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic

convulsive diseases; 1861. London.[63] Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic

convulsive diseases; 1861. p. 32–3. London.[64] Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic

convulsive diseases; 1861. p. 244. London.[65] Reynolds J. Diagnosis of diseases of the brain, spinal cord, nerves and their

appendages. London: Churchill; 1855.[66] Delasiauve LJF. Traité de l'épilepsie; 1854. Paris.


TEDPR

OOF

[67] Pearce JMS. Positive and negative cerbral symptoms: the roles of Russel Reynoldsand Hughlings Jackson. J Neurol Neurosurg Psychiatry 2004;75:1148.

[68] Hall M. Synopsis of apoplexy and epilepsy with observations on trachelismus,laryngismus, and tracheostomy: and a proposal for a hospital for epileptics.London: Mallett; 1852.

[69] Brown-Séquard CE. On the etiology, nature, and treatment of epilepsy, with a fewremarks on several other affections of the nervous centres. In: Brown-Séquards E,editor. Course of lectures on the physiology and pathology of the central nervoussystem. Philadelphia: Lippincott; 1860. p. 78–86.

[70] Eadie MJ. The neurological legacy of John Russell Reynolds (1828–1896). J ClinNeurosci 2007;14:309–16.

[71] Wilks S. Observations on the pathology of some of the diseases of the nervoussystem. Guys Hosp Rep Third Ser 1866;12:152–244.

[72] Gowers WR. Gulstonian Lectures on Epilepsy. Lancet 1880;1:315–8, 353–5, 391–3,433–6, 473–5, 513–7, 552–4.

[73] Gowers WR. Epilepsy and other chronic convulsive disorders: their causes,symptoms and treatment. London: Churchill; 1881.

[74] Romberg MH. Lehrbuch der Nervenkrankheietn des Menschen. Berlin: A.Duncker; 1840–1846.

[75] RombergMH. Amanual of the nervous diseases of man, vol II. London: SydenhamSociety; 1853. p. 197.

[76] Burdach KF. Vom Baue und Leben des Gehirns, vol. 3; 1826. p. 297. Leipzig.[77] Henle J. Hanbuch der rationellen Pathologie, 2. Band 2. Abtheilung. Braunsch-

weig. p. 46.[78] Kussmaul A, Tenner A. On the nature and origin of epileptiform convulsions

caused by profuse bleeding, and also those of true epilepsy, 57. London: NewSydenham Society; 1859. p. 89–90.

[79] Horing C.F.F. Uber epilepsie, eine Inaugural-Disseration unter dem Praesidiumvon Dr. W. Griesinger [Diss. Tubingen]; 1859. p. 19, 21.

[80] Griesinger W. Ueber einige epileptoide Zustande. Arch Psychiatr Nervekrankh1868–1869;1:320–33.

[81] Kolk Svd. On the minute structure and functions of the spinal cord and medullaoblongata and on the proximate cause and rational treatment of epilepsy.London: New Sydenham Society; 1859. p. 218, 283.

[82] Kolk Svd. On the minute structure and functions of the spinal cord and medullaoblongata, and on the proximate cause and rational treatment of epilepsy.London: New Sydenham Society; 1859. p. 250.

[83] Fournier H. De l' onanisme; 1885. p. 98. Paris.[84] Gowers WR. Epilepsy and other chronic convulsive diseases; 1881. p. 286.

London.[85] Herpin T. Du pronostic et du traitement curatif de l'épilepsie; 1852. p. 613. Paris.[86] Foville A. Epilepsie. Dictionnaire demédecine et de chirurgie pratiques, t. 7. Paris;

1831. p. 427.[87] Trousseau A. Clinique médicale de l'Hôtel-Dieu de Paris, t. II. Paris; 1868. p. 145.[88] Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic

convulsive diseases; 1861. p. 322. London.[89] Sieveking EH. Analysis of fifty-two cases of epilepsy. Lancet 1857;1:527–8.[90] Hunter R. Status epilepticus: history, incidence and problems, 1. Epilepsia Fourth

Ser; 1959–1960. p. 162–88.[91] Wilks S. Bromide and iodide of potassium in epilepsy. Med Times Gaz 1861;2:

635–6.[92] Albertoni P. Untersuchungen uber die Wirkung einiger Arzneimittel auf die

Erregbarkeit des Grosshirns nebst beitragen zur Therapie der Epilepsie. Arch ExpPathol Pharmacol 1882;15:248–88.

[93] Delasiauve LJF. Traité de l'épilepsie; 1854. p. 139. Paris.[94] Smith S. The surgical treatment of epilepsy, with statistical tables, comprising all

the recorded cases of ligature of the carotid artery: and also of trephining thecranium by American surgeons. NY J Med 1852;8:220–42.

[95] Billings JS. The surgical treatment of epilepsy. Cinci Lancet Obs 1861;4:334–41.[96] Broca P. Trépanation du crâne pratiquée avec succès dans un cas de fracture avec

enfoncement et enclavement. Bull Soc Chir Paris 1867;7:508–12.[97] Hall M. On the diseases and derangement of the nervous system; 1841. p. 279.

London.[98] Brown-Séquard E. Experimental researches applied to physiology and pathology.

New York; 1853. p. 80–4.[99] Temkin O. Jackson's forerunners. The falling sickness: a history of epilepsy from

the Greeks to the beginnings of modern neurology. London: Johns Hopkins Univ.Press; 1971. p. 303–4.

[100] Fritsch G, Hitzig E. Ueber die elektrische Erregbarkeit des Grosshirns. Berlin;1870.

[101] Ferrier D. Experimental researches in cerebral physiology and pathology. WestRiding Lunatic Asylum Med Rep 1873;3:30–96.

[102] Temkin O. John Hughlings Jackson. The falling sickness: a history of epilepsy fromthe Greeks to the beginnings of modern neurology. London: Johns Hopkins Univ.Press, Ltd; 1971. p. 329.

[103] Jackson J.H. Cases of epilepsy associated with syphilis. Med Times Gaz 1861;1:648–52; 2:59–60.

[104] Jackson JH. Convulsive spasms of the right hand and arm preceding epilepticseizures. Med Times Gaz 1863;1:110–1.

[105] Jackson JH. Suggestions for studying diseases of the nervous system on ProfessorOwen's vertebral theory. London: HK Lewis; 1863.

[106] Jackson JH. Epileptic aphemia with epileptic seizures on the right side. MedTimes Gaz 1864;2:167.

[107] Jackson JH. Unilateral epileptiform seizures beginning by a disagreeable smell.Med Times Gaz 1864;2:168.

[108] Jackson JH. Selected writings, vol. 1. London: Hodder & Stoughton; 1931–1932.




1085108610871088108910901091109210931094

1095109610971098109911001101110211031104

1105


ARTICLE IN PRESS

[109] Jackson JH. Selected Writings, vol. 1. London: Hodde & Stoughton; 1931–1932.p. 23.

[110] Jackson JH. Selected writings, vol. 1. London: Hodder & Stoughton; 1931–1932. p. 35.[111] Jackson JH. Selectedwritings, vol. 1. London: Hodder & Stoughton; 1931–1932. p. 100.[112] Jackson JH. Clinical remarks on the occasional occurence of subjective sensations

of smell in patients who are liable to epileptiform seizures, or who havesymptoms of mental derangement, and in others. Lancet 1866;1:659–60.

[113] Jackson JH. Selectedwritings, vol. 1. London:Hodder& Stoughton; 1931–1932. p. 121.[114] Jackson JH. Selected writings, vol. 1. London: Hodder & Stoughton; 1931–1932.

p. 193.
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[115] Jackson JH. Selected writings, vol. 1. London: Hodder & Stoughton; 1931–1932.p. 199.

[116] Jackson JH. Selected writings, vol. 1. London: Hodder & Stoughton; 1931–1932.p. 413–6.




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