**3. Views on epilepsy in renaissance and enlightment**

The end of the Medieval times and the beginning of the European Renaissance (14th-17th century) is marked with an exceptional production of literature regarding epilepsy. Science, emancipated from the restrains of the Catholic Church will undoubtly make important progress; in the field of epilepsy, almost all the prestigious and famous physicians of the era deal with the disease.

Various theories will be proposed regarding the mechanism that causes the epileptic fits as well as new classifications of the disease will come forth. For example, Petrus Forestus (1522-1597 AD), a Dutch physician, notes that the part of the body that epilepsy originates, leads to different manifestations. There is also a tedency to differentiate epilepsy and daemonism; in his *Daemonum investigatio peripatetica* (Peripatetic investigation of demons) Andreas Caesalpinus (1519-1603 AD), an Italian natural philosopher, tries to differ epileptic seizures and daemonic possesion (Caesalpinus, 1593).

One of the most famous physicians of this period, Paracelsus (1493–1541 AD), dealt with epilepsy. He agrees that epilepsy may originate from the brain or the liver, the heart, the intensines and the limbs. Paracelsus views about the human nature and the construction of the human body from mercury, sulfur and salt led him to a different model for the causes of epilepsy (Paracelsus, 1922-1933a). However, in his essay he clearly sets God above all, and stresses that the physician should ask for divine help in the treatment (Paracelsus, 1922- 1933b). Ioannes Marcus Marci (1595-1667 AD), a Bohemian physician and scientist, broadened the definition of epilepsy 'to any affection of the body where the victims are disordered in their minds, while the members [of the body], be it all, or some, or only one, are moved against their will.' Thus, he tied cases of epileptic convulsions with mental manifestations (Marci a Kronland, 1678). Levinus Lemnius (1505-1568 AD), famous Dutch physician and student of Vesalius, all stressed the natural origin of the disease and rejected any theological superstitions (Lemnius, 1658).

Other physicians who also dealth with epilepsy include Charles Le Pois (1563-1636 AD), consultant physician to Charles III of France, who rejected previous theories such as those postulated by Petrus Forestus suggesting that peripheral organs led to epilepsy (Le Pois, 1733), Joannes Ambianus Fernelius (Jean François Fernel) (1497-1558), a French astrologist and physiologist, who supported the theory that poisonous vapors affected the brain and led to epileptic fits, and rejected the medieval belief about the contagious nature of epilepsy (Fernelius, 1577).

An important treatise of the period is that of Jean Taxil's *Traicté de l'épilepsie,* that summarize the knowledge around epilepsy, including its causes and various remedies; he was the first Renaissance doctor who seriously doubted demonic possession (Taxil, 1602).

William Harvey (1585-1657 AD) will be the first who will make important advances for the establishment of neurology as clinical speciality with his descriptions of various neurological disorders including epilepsy (Brain, 1959; R. Hunter & MacAlpine, 1957). An interesting theory on epileptic convulsions is that of Thomas Willis Thomas Willis (1621 – 1675) who assumed the existence of a '*spasmodic explosive copula'*. For Willis 'The convulsive disease for the most part, takes its origin from the head (Willis, 1684). In his *De morbus* 

Hallmarks in the History of Epilepsy: From Antiquity Till the Twentieth Century 139

Physicians of the British medical school also dealth with epilepsy such as Thomas Beddoes (1760–1808), who described accurately the premonitionary symptoms developing before the onset of an attack, (Maisonneuve, 1804) William Cullen (1712–1790), who included epilepsy as one of the spasmodic affections without fever, together with tetanus and chorea or St. Vitus dance (Cullen, 1778-1784). Finally, the first experimental provocation of convulsions was done in Italy. The Italian naturalist Felice Gaspar Ferdinand Fontana (1730–1803), in a series of experiments on stimulation of the cerbral cortex with electricity, demonstrated that convulsions could be produced by pressure on the brain, but not by irritation of the dura, as

**4.2 The 19th century: The "golden era" of French medicine and the contribution of the** 

The progress of the French medical school is marked by a peak during the 19th century. Marie-Jean-Pierre Flourens (1794–1867) established the basic rules regarding the irritability and sensibility of the central nervous system, noting that different functions can be attributed to different parts. His contribution is decisive for the research on epilepsy, since the loss of consciousness and the voluntary movements in epileptic attacks would imply the involvement of the cerebral lobes, were it not for the participation of the medulla that Flourens found (Flourens, 1823). The French psychiatrist Jean-Étienne Dominique Esquirol (1772–1840), distinguished severe from light epileptic seizures (grand mal and petit mal) and worked withh his pupils Bouchet and Cazauvieilh, on epilepsy and insanity. A later study by his students Bouchet and Cazauvieilh revealed a high frequency of epileptic attacks among patients considered to be insane (Esquirol, 1838). In 1827, Antoine Baron de Portal (1742-1832) published his clinical experience based on a large amount of clinical data and post-mortem reports, admitting that in many cases of epilepsy, dissection did not reveal any lesions either in the brain or other parts of the body (Portal, 1827b). He also makes important notes on the so-called *furor epilepticus*. He noticed this clinical status appeared before the onset of the epileptic seizure, as well as after; a patient in this condition could even commit murder (Portal, 1827a). Louis François Bravais (1801–1843) in his thesis defines epilepsy from a new basis, that of 'hemiplegic epilepsy', during which convulsions attack one side of the body followed by paralysis, whereas he is considered to be the first to describe of what was later called Jacksonian convulsions (Bravais, 1827). Francois-Emmanuel Foderé (1764–1835), denowed French physician and expert in forensic medicine, will discuss what he calls 'periodic delirium', which is clearly epileptic mania (Foderé, 1798). Charles-Édouard Brown-Séquard (1817–1894) managed to provoke epileptiform convulsions by transverse section of the lateral half of the spinal cord in animals (Brown-Séquard, 1857). Théodore Herpin (1799–1865) will publish 300 cases on epilepsy, providing insights on the symptoms preceding the onset of major seizures, the initial symptoms with which major attacks began and the minor attacks appearing in the intervals between complete attacks. Herpin also describes epilepsies with intellectual disturbances and with

One should also note the important contibution of the French psychiatrists on the psychomotor symptoms of epilepsy. Bénédict Augustin Morel (1809–1879) noted that irritability and anger are the salient features of the epileptic personality (Morel, 1852-1853). Epileptic fury, according to Morel, appears in two forms: either before or after the epileptic

commonly believed (Garrison, 1935; Marchand & Hoff, 1955).

immediate loss of consciousness. (Herpin, 1867).

**English school of physicians 4.2.1 The French medical school** 

*convulsivis* (Morbid convulsions) Willis places the cause of epilepsy in the brain, but differed with his predecessors who pointed to the middle of the brain itself or the meninges. His hypothesis suggested that since the brain is of a weak constitution, a strong *spasmodi copula* distills from the blood to the brain leading the animal spirits that lie in the middle of the brain to explode. The explosion of anial spirits cause all the mental symptoms of the epileptic attack, and a series of similar explosions occurr along the rest of the nervous system to bring about the convulsions of the body (Willis, 1682).

Interesting cases of epileptic patients appear during this period too. For example, Martinus Rulandus (1532-1602), German physician and alchemist, describes the case of a 40-year-old man suffering from epilepsy and mania. A woman considered to be a witch was accused of causing evil to this man, but during her confession she claimed that she could not cure him. So, Ruland was called and he managed to cure him by bloodletting, sternutatory and a strong cathartic (Rulandus, 1580). Thomas Erastus (1524-1583), a Swiss theologian, documents the case of a girl with characteristic psychomotor symptoms of epileptic convulsions. After convulsing, she wandered around the room for almost half an hour and the people who were around could not stop her. After the event should could not remember anything that happened (Erastus, 1581).Felix Plater (1536-1617), as referred by Tissot, describes a young man whose malady started with a headache, stubborn insomnia and deterioration of his faculties and ended with frequent convulsive attacks and emaciation. The post-mortem dissection revealed tumor in the anterior part of the brain (Tissot, 1770a).

Charles Drélincourt (1633-1694), finally, was the first to provoke epileptic convulsions experimentally by driving a needle into the fourth ventricle of a dog's brain (Drelincurtius, 1682).

#### **4. Epilepsy during the 18th and 19th century**

#### **4.1 The work of 18th century physicians on epilepsy**

The beginning of the 18th century is marked by the work of doctors of the Dutch medical school founded by Herman Boerhaave and his pupil Gerard van Swieten. Herman Boerhaave (1668–1738) provided a rather strict definition of epilepsy: 'Epilepsy is the sudden abolishment of all vital functions with accompanying increase of mobility and convulsions in all body muscles', whereas he adopts the Galenic classification of epilepsy (Boerhaave, 1761). The Dutch-Austrian Gerard Van Swieten (1700–1772) wrote a chapter on epilepsy in which he describes extensively the clinical characteristics of various forms of the disease and discusses epilepsy in comparison with apoplexy and hysteria. (Temkin, 1971b).

The first major treatise on epilepsy was written by the Swiss physician Simon August André David Tissot (1728–1787). Published in 1770, the *Traite de l' epilepsie* is considered to be a milestone in the scientific research on epilepsy. Tissot completely rejects the influence of the moon on epileptic seizures, accepts the hereditary forms of epilepsy, and states that it is the duty of the epileptic to remain unmarried (S. Tissot, 1770b). Among his extreme views about epilepsy is the belief that masturbation could cause epileptic seizures (S. Tissot, 1770b).

The French medical school of the 19th century took lead in the fields of neurology and psychiatry, and, therefore, were the main driving force on epilepsy research. Jacques–Louis Doussin Dubreuil (1762–1831) tried to explain the influence of various emotional states on epilepsy (Doussin-Dubreuil, 1825), whereas Louis Maisonneuve, a pupil of Philip Pinel (1745 - 1826), stated that 'epilepsy like all chronic diseases can be studied well only in hospital', stressing the variety of clinical manifestations of epilepsy (Maisonneuve, 1803).

Physicians of the British medical school also dealth with epilepsy such as Thomas Beddoes (1760–1808), who described accurately the premonitionary symptoms developing before the onset of an attack, (Maisonneuve, 1804) William Cullen (1712–1790), who included epilepsy as one of the spasmodic affections without fever, together with tetanus and chorea or St. Vitus dance (Cullen, 1778-1784). Finally, the first experimental provocation of convulsions was done in Italy. The Italian naturalist Felice Gaspar Ferdinand Fontana (1730–1803), in a series of experiments on stimulation of the cerbral cortex with electricity, demonstrated that convulsions could be produced by pressure on the brain, but not by irritation of the dura, as commonly believed (Garrison, 1935; Marchand & Hoff, 1955).

#### **4.2 The 19th century: The "golden era" of French medicine and the contribution of the English school of physicians**

#### **4.2.1 The French medical school**

138 Novel Aspects on Epilepsy

*convulsivis* (Morbid convulsions) Willis places the cause of epilepsy in the brain, but differed with his predecessors who pointed to the middle of the brain itself or the meninges. His hypothesis suggested that since the brain is of a weak constitution, a strong *spasmodi copula* distills from the blood to the brain leading the animal spirits that lie in the middle of the brain to explode. The explosion of anial spirits cause all the mental symptoms of the epileptic attack, and a series of similar explosions occurr along the rest of the nervous

Interesting cases of epileptic patients appear during this period too. For example, Martinus Rulandus (1532-1602), German physician and alchemist, describes the case of a 40-year-old man suffering from epilepsy and mania. A woman considered to be a witch was accused of causing evil to this man, but during her confession she claimed that she could not cure him. So, Ruland was called and he managed to cure him by bloodletting, sternutatory and a strong cathartic (Rulandus, 1580). Thomas Erastus (1524-1583), a Swiss theologian, documents the case of a girl with characteristic psychomotor symptoms of epileptic convulsions. After convulsing, she wandered around the room for almost half an hour and the people who were around could not stop her. After the event should could not remember anything that happened (Erastus, 1581).Felix Plater (1536-1617), as referred by Tissot, describes a young man whose malady started with a headache, stubborn insomnia and deterioration of his faculties and ended with frequent convulsive attacks and emaciation. The post-mortem dissection revealed tumor in the anterior part of the brain (Tissot, 1770a). Charles Drélincourt (1633-1694), finally, was the first to provoke epileptic convulsions experimentally by driving a needle into the fourth ventricle of a dog's brain (Drelincurtius,

The beginning of the 18th century is marked by the work of doctors of the Dutch medical school founded by Herman Boerhaave and his pupil Gerard van Swieten. Herman Boerhaave (1668–1738) provided a rather strict definition of epilepsy: 'Epilepsy is the sudden abolishment of all vital functions with accompanying increase of mobility and convulsions in all body muscles', whereas he adopts the Galenic classification of epilepsy (Boerhaave, 1761). The Dutch-Austrian Gerard Van Swieten (1700–1772) wrote a chapter on epilepsy in which he describes extensively the clinical characteristics of various forms of the disease and discusses epilepsy in comparison with apoplexy and hysteria. (Temkin, 1971b). The first major treatise on epilepsy was written by the Swiss physician Simon August André David Tissot (1728–1787). Published in 1770, the *Traite de l' epilepsie* is considered to be a milestone in the scientific research on epilepsy. Tissot completely rejects the influence of the moon on epileptic seizures, accepts the hereditary forms of epilepsy, and states that it is the duty of the epileptic to remain unmarried (S. Tissot, 1770b). Among his extreme views about epilepsy is the belief that masturbation could cause epileptic seizures (S. Tissot, 1770b). The French medical school of the 19th century took lead in the fields of neurology and psychiatry, and, therefore, were the main driving force on epilepsy research. Jacques–Louis Doussin Dubreuil (1762–1831) tried to explain the influence of various emotional states on epilepsy (Doussin-Dubreuil, 1825), whereas Louis Maisonneuve, a pupil of Philip Pinel (1745 - 1826), stated that 'epilepsy like all chronic diseases can be studied well only in hospital', stressing the variety of clinical manifestations of epilepsy (Maisonneuve, 1803).

system to bring about the convulsions of the body (Willis, 1682).

**4. Epilepsy during the 18th and 19th century 4.1 The work of 18th century physicians on epilepsy** 

1682).

The progress of the French medical school is marked by a peak during the 19th century. Marie-Jean-Pierre Flourens (1794–1867) established the basic rules regarding the irritability and sensibility of the central nervous system, noting that different functions can be attributed to different parts. His contribution is decisive for the research on epilepsy, since the loss of consciousness and the voluntary movements in epileptic attacks would imply the involvement of the cerebral lobes, were it not for the participation of the medulla that Flourens found (Flourens, 1823). The French psychiatrist Jean-Étienne Dominique Esquirol (1772–1840), distinguished severe from light epileptic seizures (grand mal and petit mal) and worked withh his pupils Bouchet and Cazauvieilh, on epilepsy and insanity. A later study by his students Bouchet and Cazauvieilh revealed a high frequency of epileptic attacks among patients considered to be insane (Esquirol, 1838). In 1827, Antoine Baron de Portal (1742-1832) published his clinical experience based on a large amount of clinical data and post-mortem reports, admitting that in many cases of epilepsy, dissection did not reveal any lesions either in the brain or other parts of the body (Portal, 1827b). He also makes important notes on the so-called *furor epilepticus*. He noticed this clinical status appeared before the onset of the epileptic seizure, as well as after; a patient in this condition could even commit murder (Portal, 1827a). Louis François Bravais (1801–1843) in his thesis defines epilepsy from a new basis, that of 'hemiplegic epilepsy', during which convulsions attack one side of the body followed by paralysis, whereas he is considered to be the first to describe of what was later called Jacksonian convulsions (Bravais, 1827). Francois-Emmanuel Foderé (1764–1835), denowed French physician and expert in forensic medicine, will discuss what he calls 'periodic delirium', which is clearly epileptic mania (Foderé, 1798). Charles-Édouard Brown-Séquard (1817–1894) managed to provoke epileptiform convulsions by transverse section of the lateral half of the spinal cord in animals (Brown-Séquard, 1857). Théodore Herpin (1799–1865) will publish 300 cases on epilepsy, providing insights on the symptoms preceding the onset of major seizures, the initial symptoms with which major attacks began and the minor attacks appearing in the intervals between complete attacks. Herpin also describes epilepsies with intellectual disturbances and with immediate loss of consciousness. (Herpin, 1867).

One should also note the important contibution of the French psychiatrists on the psychomotor symptoms of epilepsy. Bénédict Augustin Morel (1809–1879) noted that irritability and anger are the salient features of the epileptic personality (Morel, 1852-1853). Epileptic fury, according to Morel, appears in two forms: either before or after the epileptic

Hallmarks in the History of Epilepsy: From Antiquity Till the Twentieth Century 141

that damaged or destroyed tissue, whereas positive symptoms are more remote effects of pathology arising from 'altered nutrition' that the pathology produced in surviving tissue. Reynolds also referrs to the epileptic aura without attempting to explain its pathogenesis. William Richard Gowers (1845-1915), also contributed substantially into the understanding of the pathogenesis of the disease. During those lectures, Gowers presented and reviewed the clinical features of a series of 1,500 cases who observed and treated them in person. Those cases were published in some of the most prestigious contemporary medical journals (Gowers, 1880), and, then, he expanded further those findings in his monograph entitled *Epilepsy and other chronic convulsive disorders* (1881), including a series of 3,000 cases of

Research into epilepsy was also advanced by the work of German and Dutch physicians of the era. Karl Friedrich Burdach (1776–1847), anatomist, physiologist and embryologist, published a series of 1,911 anatomical abnormalities observed in the brain. According to his data, the lateral ventricles were most frequently affected, with 86 out of 476 cases, of which

Friedrich Gustav Jacob Henle (1809–1895), writing in 1853, noted that epileptic convulsions are provoked by an increased turgor at the base of the brain, and that the loss of consciousness depends either on increase or decrease of blood flow in the hemispheres. (Henle, 1846). The same year, Adolf Kussmaul (1822–1902) along with Adolf Tenner published the classic treatise on epileptiform convulsions (Kussmaul & Tenner, 1859), whereas in 1859, Höring, a German physician, in his dissertation entitled *Über Epilepsie*, described a case of a young man who had grand mal attacks as well as many mild attacks during which he had complete lapses of memory (Horing, 1859). Wilhelm Griesinger (1817– 1868), in 1868, will employ for the first time the term 'psycho-motor symptoms' in epileptoid

The most important advance in anti-epileptic therapy of this period is the introduction of bromide potassium in the treatment of epilepsy by Edward Sieveking, in 1857 (Sieveking, 1857), a treatment further supported by Charles Locock (1799–1875) and especially Samuel Wilks (Richard Hunter, 1959-1960; Wilks, 1861). Locock described the anticonvulsant effect of bromides, although the earliest studies on the effects of various drugs as anticonvulsants were performed by Albertoni (1882), on animals with induced seizures (Albertoni, 1882). Extreme methods of therapy are still perpetuated such as 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 had applied surgical therapy in various cases (Billings, 1861; Broca, 1867; Smith, 1852). Other surgical procedures suggested have been tracheoctomy, by Marsall Hall (M. Hall, 1841), and cauterization of the

John Hughlings Jackson (1835-1911), is beyond any doubt the father of modern epileptology. His clinical observations from 1861 to 1870, which came well before the experimental reports of Eduard Hitzig (1839–1907) and David Ferrier (1843 –1928), were confirmed ultimately by

larynx with nitrate of silver, by Brown-Séquard (Brown-Séquard, 1853).

**5. The age of John Hughlings Jackson** 

Hitzig and Ferrier (Fritsch & Hitzig, 1870).

epilepsy which covers every possible clinical feature of epilepsy (Gowers, 1881).

**4.2.3 The Dutch and German medical school of the 19th century** 

63 consisted of serous effusion (Burdach, 1826).

conditions. (Griesinger, 1868-1869).

**4.3 Therapies on epilepsy** 

attack or indepedently "like lightning and being condensed in terrible deeds" (Morel, 1852- 1853). Jules Falret (1824–1902) will divide the mental disorders found in epileptics in three categories: premonitory symptoms, symptoms of the epileptic personality and epileptic insanity. Falret was also able to identify intellectual disturbances during the epileptic attack in cases where the patient did not lose consciousness, whereas he divided the mental disorders of the third type into *petit mal intellectuel* and *grand mal intellectuel*. (Falret, 1860).

### **4.2.2 The British medical school of the 19th century**

The contribution of the British Medical school is equally important. James Cowles Prichard (1786–1848), notes that the 'epileptic delirium' appears when the patient revives from the comatose state consequent of a seizure, but it can also appear without any previous fit, whereas he describes the typical symptoms of epileptic mania (J. C. Prichard, 1822a). Prichard describes other states of mental confusion, suggesting they are like somnambulism or epileptic ecstasy:

*'A more unusual circumstance in the history of epilepsy is the appearance of a species of somnambulism, or of a kind of ecstasis, during which the patient is in an undisturbed reverie, and walks about, fancying himself occupied in some of his customary amusements or avocations. This takes place during the waking as well as the sleeping hours'.* 

His observations are the forerunners of the concept of 'psychic equivalents of epilepsy' (James Cowles Prichard, 1822b). Prichard was also the first to establish the term 'partial epilepsy' in the literature, devoting to the topic an entire chapter in his treatise, called 'Of local convulsion or partial epilepsy'.

Richard Bright (1789–1858 attempted to combine anatomical data with clinical cases, and was able to show changes in the cortex of the cerebral hemispheres (R. Bright, 1831a). Bright supported the theory that the gray matter of the brain was the main functional part of the cerebral hemispheres, referring to the discoveries of Foville (Richard Bright, 1831b). Marshall Hall (1790–1857), on the other hand, suggested that epilepsy was due in part to anemia of the medulla and that paroxysmal discharges arose from the brain (M. Hall, 1851; Marshall Hall, 1852). Robert Bentley Todd (1809–1860), physician in King's College Hospital, in an experiment to determine the seat of epilepsy, observed discrete movements on the face of a rabbit upon stimulation of the cerebral hemispheres, but he did not appreciate the significance of his experiments, for he maintained that movement was the concern of structures from the corpora striatum rostrally. In 1836, Astley Cooper (1768–1841) reported his findings on provoking epileptic seizures by temporary anaemia, without the loss of blood.(Cooper, 1836).

John Russell Reynolds (1828–1896), was the first to identify 'epilepsy proper' with idiopathic epilepsy, to which, he believed, 'the name of epilepsy ought to be applied' (Reynolds, 1861b). His major account on epilepsy was published in 1861 entitled *Epilepsy: Its Symptoms, Treatment and Relation to Other Chronic Convulsive Diseases* (Reynolds, 1861a), which is considered to be a milestone in the English epileptology. Reynolds employs the terms 'epileptiform' or 'epileptoid' for seizures resembling epilepsy, rejecting, in that way, the existence of renal or uterine epilepsy and epilepsy from tumor of the brain; he claims that we 'find these confounded together with simple or idiopathic affection' (Reynolds, 1861a), adopting indirectly Delasiauve's theories about idiopathic epilepsy (Delasiauve, 1854) as epilepsy of cerebral origin with uknown pathology. Reynolds support also the theory about positive and negative symptoms arising from brain pathology (Pearce, 2004), earlier than his successor, Jackson; negative effects are associated with direct impact on structural pathology that damaged or destroyed tissue, whereas positive symptoms are more remote effects of pathology arising from 'altered nutrition' that the pathology produced in surviving tissue. Reynolds also referrs to the epileptic aura without attempting to explain its pathogenesis.

William Richard Gowers (1845-1915), also contributed substantially into the understanding of the pathogenesis of the disease. During those lectures, Gowers presented and reviewed the clinical features of a series of 1,500 cases who observed and treated them in person. Those cases were published in some of the most prestigious contemporary medical journals (Gowers, 1880), and, then, he expanded further those findings in his monograph entitled *Epilepsy and other chronic convulsive disorders* (1881), including a series of 3,000 cases of epilepsy which covers every possible clinical feature of epilepsy (Gowers, 1881).

#### **4.2.3 The Dutch and German medical school of the 19th century**

Research into epilepsy was also advanced by the work of German and Dutch physicians of the era. Karl Friedrich Burdach (1776–1847), anatomist, physiologist and embryologist, published a series of 1,911 anatomical abnormalities observed in the brain. According to his data, the lateral ventricles were most frequently affected, with 86 out of 476 cases, of which 63 consisted of serous effusion (Burdach, 1826).

Friedrich Gustav Jacob Henle (1809–1895), writing in 1853, noted that epileptic convulsions are provoked by an increased turgor at the base of the brain, and that the loss of consciousness depends either on increase or decrease of blood flow in the hemispheres. (Henle, 1846). The same year, Adolf Kussmaul (1822–1902) along with Adolf Tenner published the classic treatise on epileptiform convulsions (Kussmaul & Tenner, 1859), whereas in 1859, Höring, a German physician, in his dissertation entitled *Über Epilepsie*, described a case of a young man who had grand mal attacks as well as many mild attacks during which he had complete lapses of memory (Horing, 1859). Wilhelm Griesinger (1817– 1868), in 1868, will employ for the first time the term 'psycho-motor symptoms' in epileptoid conditions. (Griesinger, 1868-1869).

#### **4.3 Therapies on epilepsy**

140 Novel Aspects on Epilepsy

attack or indepedently "like lightning and being condensed in terrible deeds" (Morel, 1852- 1853). Jules Falret (1824–1902) will divide the mental disorders found in epileptics in three categories: premonitory symptoms, symptoms of the epileptic personality and epileptic insanity. Falret was also able to identify intellectual disturbances during the epileptic attack in cases where the patient did not lose consciousness, whereas he divided the mental disorders of the third type into *petit mal intellectuel* and *grand mal intellectuel*. (Falret, 1860).

The contribution of the British Medical school is equally important. James Cowles Prichard (1786–1848), notes that the 'epileptic delirium' appears when the patient revives from the comatose state consequent of a seizure, but it can also appear without any previous fit, whereas he describes the typical symptoms of epileptic mania (J. C. Prichard, 1822a). Prichard describes other states of mental confusion, suggesting they are like somnambulism

*'A more unusual circumstance in the history of epilepsy is the appearance of a species of somnambulism, or of a kind of ecstasis, during which the patient is in an undisturbed reverie, and walks about, fancying himself occupied in some of his customary amusements or avocations. This* 

His observations are the forerunners of the concept of 'psychic equivalents of epilepsy' (James Cowles Prichard, 1822b). Prichard was also the first to establish the term 'partial epilepsy' in the literature, devoting to the topic an entire chapter in his treatise, called 'Of

Richard Bright (1789–1858 attempted to combine anatomical data with clinical cases, and was able to show changes in the cortex of the cerebral hemispheres (R. Bright, 1831a). Bright supported the theory that the gray matter of the brain was the main functional part of the cerebral hemispheres, referring to the discoveries of Foville (Richard Bright, 1831b). Marshall Hall (1790–1857), on the other hand, suggested that epilepsy was due in part to anemia of the medulla and that paroxysmal discharges arose from the brain (M. Hall, 1851; Marshall Hall, 1852). Robert Bentley Todd (1809–1860), physician in King's College Hospital, in an experiment to determine the seat of epilepsy, observed discrete movements on the face of a rabbit upon stimulation of the cerebral hemispheres, but he did not appreciate the significance of his experiments, for he maintained that movement was the concern of structures from the corpora striatum rostrally. In 1836, Astley Cooper (1768–1841) reported his findings on provoking epileptic seizures by temporary anaemia, without the loss of blood.(Cooper, 1836). John Russell Reynolds (1828–1896), was the first to identify 'epilepsy proper' with idiopathic epilepsy, to which, he believed, 'the name of epilepsy ought to be applied' (Reynolds, 1861b). His major account on epilepsy was published in 1861 entitled *Epilepsy: Its Symptoms, Treatment and Relation to Other Chronic Convulsive Diseases* (Reynolds, 1861a), which is considered to be a milestone in the English epileptology. Reynolds employs the terms 'epileptiform' or 'epileptoid' for seizures resembling epilepsy, rejecting, in that way, the existence of renal or uterine epilepsy and epilepsy from tumor of the brain; he claims that we 'find these confounded together with simple or idiopathic affection' (Reynolds, 1861a), adopting indirectly Delasiauve's theories about idiopathic epilepsy (Delasiauve, 1854) as epilepsy of cerebral origin with uknown pathology. Reynolds support also the theory about positive and negative symptoms arising from brain pathology (Pearce, 2004), earlier than his successor, Jackson; negative effects are associated with direct impact on structural pathology

**4.2.2 The British medical school of the 19th century** 

*takes place during the waking as well as the sleeping hours'.* 

local convulsion or partial epilepsy'.

or epileptic ecstasy:

The most important advance in anti-epileptic therapy of this period is the introduction of bromide potassium in the treatment of epilepsy by Edward Sieveking, in 1857 (Sieveking, 1857), a treatment further supported by Charles Locock (1799–1875) and especially Samuel Wilks (Richard Hunter, 1959-1960; Wilks, 1861). Locock described the anticonvulsant effect of bromides, although the earliest studies on the effects of various drugs as anticonvulsants were performed by Albertoni (1882), on animals with induced seizures (Albertoni, 1882). Extreme methods of therapy are still perpetuated such as 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 had applied surgical therapy in various cases (Billings, 1861; Broca, 1867; Smith, 1852). Other surgical procedures suggested have been tracheoctomy, by Marsall Hall (M. Hall, 1841), and cauterization of the larynx with nitrate of silver, by Brown-Séquard (Brown-Séquard, 1853).

#### **5. The age of John Hughlings Jackson**

John Hughlings Jackson (1835-1911), is beyond any doubt the father of modern epileptology. His clinical observations from 1861 to 1870, which came well before the experimental reports of Eduard Hitzig (1839–1907) and David Ferrier (1843 –1928), were confirmed ultimately by Hitzig and Ferrier (Fritsch & Hitzig, 1870).

Hallmarks in the History of Epilepsy: From Antiquity Till the Twentieth Century 143

same parts of the brain' (Jackson, 1931-1932b). Empirically, he distinguished three classes of epilepsy proper from which the epileptiform or epileptoid group, including convulsions beginning unilaterally, unilateral dysaesthesia (migraine) and epileptiform amaurosis, had

In his lecture *On Convulsive Seizures* Jackson presented the most advanced form of his theory on epilepsy. According to Jackson, the central nervous system can be divided into three levels: (a) the lowest level, which consists of the spinal cord, the medula oblongata and the pons, representing the most rough and simple movements; (b) the 'motor province' consisting of the 'motor region of the cerebral cortex (Rolandic region) and of the ganglia of the corpus striatum representing complex movements of all parts of the body; and (c) the highest level formed by the centers of the prefrontal lobes ('the organ of mind') (Jackson, 1931-1932b). Fits beginning at the lower levels can spread to higher ones through interconnecting fibers as well as to neighboring cells of the same level. Jackson considered therefore middle level fits to correspond to *epileptiform* seizures and highest level fits to *epileptic* seizures. Jackson was careful to clarify his use of terms, however: 'I do not use the term cortical epilepsy because both epileptic and epileptiform seizures are, to my thinking, cortical fits… I formerly used the term epilepsy generically for all excessive discharges of the cortex and their consequences… I now use the term epilepsy for that neurosis which is often called "genuine" or "ordinary" epilepsy, and for that only' (Jackson, 1931-1932b). Epileptiform convulsions, according to Jackson, start from a definite place in the brain and always begin with a signal symptom which localizes the original discharging lession. The symptoms can be either be sensory or motor depending on the part of the brain where discharges take place, since according to Jackson all levels are sensorimotor. Discharging lesions are diseased because of 'morbid nutrition', and those cells who are discharged, lose their function and temporarily form a 'negative lession' (Jackson, 1931-1932b). Sensory or/and motor symptoms are present in each epileptic or epileptiform seizure; in epileptic seizures paralysis is generalized, whereas in epileptiform seizures it is located in certain

To explain post-epileptic states, Jackson suggests the four-layer theory of higher levels, though this theory was not supported by any anatomical data, as Jackson admits. He thought that discharges afflicting the first layer are responsible for impaired consciousness, the second for a single loss of consciousness, as in the case of epileptic mania, and the third

Jackson also refers to the 'dreamy state' some patients experience before the onset of the epileptic fits. He mentions, writing in 1876, a number of expressions used by patients to describe those symptoms of the so-called 'intellectual aura', some of which resemble states known in modern psychiatry and neurology as 'déjà vu': 'Old scenes revert, I fell in some strange place, a dreamy state, a panorama of something familiary and yet strange, if I were walking alone and had a fit, I should think "Oh, I saw that before" (Jackson, 1931-1932b).

Before the end of the 19th century, in 1898, William Letchworth (1823-1910) and Frederick Peterson (1859-1938) will organize the National Association for the Study of Epilepsy and the Care and Treatment of Epileptics in the US (Letchworth, 1901). At the beginning of the 20th century, William Spartling will be the first to use the term 'epileptologist' for a

for coma without affecting the vital operations (Jackson, 1931-1932b).

**6. Epilepsy in the twentieth century** 

to be differentiated (Jackson, 1931-1932b).

parts of the body.

Fig. 3. John Hughlings Jackson (1835-1911), father of modern epileptology

Jackson studied epilepsy on a pathological and anatomical basis. He initially believed that focal convulsions were due to a discharging lesion from damage to nerve cells. He also believed, at first, that the part of the brain involved was the region of the corpus striatium or the convolutions near to it. In 1861, Jackson published his first paper containing reports from hospitals and from the medical literature (Jackson, 1861), whereas, in 1863, he observed about unilateral convulsions that 'in very many cases of epilepsy and especially in syphilitic epilepsy, the convulsions are limited to one side of the body; and, as autopsies of patients who have died after syphilitic epilepsy appear to show, the cause is obvious organic disease on the side of the brain, opposite to the side of the body convulsed, frequently on the surface of the hemisphere' (Jackson, 1863).

In 1864, Jackson published his an important in which he discusses the symptoms of aphasia (Jackson, 1864). Jackson thus offered an new explanation about epileptic seizures that differed that of his predecessors who claimed the seat of the disease lay in the medula oblongata.

In the following years, Jackson's views regarding the involvement of the corpus striatum in the genesis of seizures evolved rapidly. Jackson distinguishes four factors involved in the final cause of convulsions: the 'seat of the internal lesion', the functional cause of the change, the pathological process which brought about the functional change (embolus, tumor, syphilis or other cause) and the various circumstances that trigger the paroxysm (Jackson, 1931-1932a, 1931-1932b).

In 1866 Jackson discussed the mechanisms of various forms of epilepsy noting that 'in cases of sudden and temporary loss of conciousness in which convulsive movements were slight, or perhaps absent, the disorder of function was chiefly in the range of the anterior cerebral artery' (Jackson, 1866). For cases of loss of conciousness, he believed the disorder to be located 'in the very highest nervous centres of the cerebral hemisphere' (Jackson, 1931- 1932b). As far as the mechanisms involved, genuine epilepsy was not different from unilateral epilepsy. He later refined his definition of epilepsy, suggesting an scientific and an empirical classification; 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

Fig. 3. John Hughlings Jackson (1835-1911), father of modern epileptology

of the hemisphere' (Jackson, 1863).

1931-1932a, 1931-1932b).

Jackson studied epilepsy on a pathological and anatomical basis. He initially believed that focal convulsions were due to a discharging lesion from damage to nerve cells. He also believed, at first, that the part of the brain involved was the region of the corpus striatium or the convolutions near to it. In 1861, Jackson published his first paper containing reports from hospitals and from the medical literature (Jackson, 1861), whereas, in 1863, he observed about unilateral convulsions that 'in very many cases of epilepsy and especially in syphilitic epilepsy, the convulsions are limited to one side of the body; and, as autopsies of patients who have died after syphilitic epilepsy appear to show, the cause is obvious organic disease on the side of the brain, opposite to the side of the body convulsed, frequently on the surface

In 1864, Jackson published his an important in which he discusses the symptoms of aphasia (Jackson, 1864). Jackson thus offered an new explanation about epileptic seizures that differed that of his predecessors who claimed the seat of the disease lay in the medula oblongata. In the following years, Jackson's views regarding the involvement of the corpus striatum in the genesis of seizures evolved rapidly. Jackson distinguishes four factors involved in the final cause of convulsions: the 'seat of the internal lesion', the functional cause of the change, the pathological process which brought about the functional change (embolus, tumor, syphilis or other cause) and the various circumstances that trigger the paroxysm (Jackson,

In 1866 Jackson discussed the mechanisms of various forms of epilepsy noting that 'in cases of sudden and temporary loss of conciousness in which convulsive movements were slight, or perhaps absent, the disorder of function was chiefly in the range of the anterior cerebral artery' (Jackson, 1866). For cases of loss of conciousness, he believed the disorder to be located 'in the very highest nervous centres of the cerebral hemisphere' (Jackson, 1931- 1932b). As far as the mechanisms involved, genuine epilepsy was not different from unilateral epilepsy. He later refined his definition of epilepsy, suggesting an scientific and an empirical classification; 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' (Jackson, 1931-1932b). Empirically, he distinguished three classes of epilepsy proper from which the epileptiform or epileptoid group, including convulsions beginning unilaterally, unilateral dysaesthesia (migraine) and epileptiform amaurosis, had to be differentiated (Jackson, 1931-1932b).

In his lecture *On Convulsive Seizures* Jackson presented the most advanced form of his theory on epilepsy. According to Jackson, the central nervous system can be divided into three levels: (a) the lowest level, which consists of the spinal cord, the medula oblongata and the pons, representing the most rough and simple movements; (b) the 'motor province' consisting of the 'motor region of the cerebral cortex (Rolandic region) and of the ganglia of the corpus striatum representing complex movements of all parts of the body; and (c) the highest level formed by the centers of the prefrontal lobes ('the organ of mind') (Jackson, 1931-1932b). Fits beginning at the lower levels can spread to higher ones through interconnecting fibers as well as to neighboring cells of the same level. Jackson considered therefore middle level fits to correspond to *epileptiform* seizures and highest level fits to *epileptic* seizures. Jackson was careful to clarify his use of terms, however: 'I do not use the term cortical epilepsy because both epileptic and epileptiform seizures are, to my thinking, cortical fits… I formerly used the term epilepsy generically for all excessive discharges of the cortex and their consequences… I now use the term epilepsy for that neurosis which is often called "genuine" or "ordinary" epilepsy, and for that only' (Jackson, 1931-1932b). Epileptiform convulsions, according to Jackson, start from a definite place in the brain and always begin with a signal symptom which localizes the original discharging lession. The symptoms can be either be sensory or motor depending on the part of the brain where discharges take place, since according to Jackson all levels are sensorimotor. Discharging lesions are diseased because of 'morbid nutrition', and those cells who are discharged, lose their function and temporarily form a 'negative lession' (Jackson, 1931-1932b). Sensory or/and motor symptoms are present in each epileptic or epileptiform seizure; in epileptic seizures paralysis is generalized, whereas in epileptiform seizures it is located in certain parts of the body.

To explain post-epileptic states, Jackson suggests the four-layer theory of higher levels, though this theory was not supported by any anatomical data, as Jackson admits. He thought that discharges afflicting the first layer are responsible for impaired consciousness, the second for a single loss of consciousness, as in the case of epileptic mania, and the third for coma without affecting the vital operations (Jackson, 1931-1932b).

Jackson also refers to the 'dreamy state' some patients experience before the onset of the epileptic fits. He mentions, writing in 1876, a number of expressions used by patients to describe those symptoms of the so-called 'intellectual aura', some of which resemble states known in modern psychiatry and neurology as 'déjà vu': 'Old scenes revert, I fell in some strange place, a dreamy state, a panorama of something familiary and yet strange, if I were walking alone and had a fit, I should think "Oh, I saw that before" (Jackson, 1931-1932b).
