Brief History of Epilepsy and its Surgical Treatment
Trepanation (from the Greek trupanon, which means “perforating”) is the removal of part of the cranial calvarium without
causing lesions to the vessels, meninges, or the brain tissue itself under it. Cranial
trepanation is described in manuscripts that date to before 1500 bC, and skulls from
the Neolithic period (∼ 10000 to 4000 bC) were found with signs of trepanation. The
earliest report of a successful neurosurgical procedure was obtained through a carbon-dated
skull from 5100 bC, which was found in a French archaeological site. Evidence of bone
healing at the edges of the wound shows that the skull is from the first patient who
survived the trepanation procedure.[1]
[2] Although it is not possible to know for certain. Why trepanation may have been performed
to relieve intracranial pressure? Elevate fractures with cranial sinking? To remove
bone fragments caused by penetrating trauma. It is known as a procedure that has been
performed with different purposes since prehistoric times.[3]
[4] Historically, it was performed in the Middle and Far East, among Celtic tribes,
among the Mayas, Incas, Aztecs and Brazilian Indians; it was very common in the Middle
Ages and Equatorial Africa, where it is still performed today.[5]
[6]
[7]
[8]
The first description of epilepsy as a disease can be found in the Corpus Hippocraticum, a collection composed of 60 treaties dating to 400 bC, in Ancient Greece. Then,
epilepsy was a controversial disease, often associated with possessions, genius and
divinity, being even called the “sacred disease.” It is in this book that Hippocrates,
for the first time, talks about the hypothesis that epilepsy is located in the brain,
and is not a disease of sacred origin. It would be caused by an excess of phlegm in
the brain, which, when in contact with the blood, would cause epileptic seizures.[9] But the word epilepsy would be used for the first time by Avicenna (980–1037), a Persian polymath who wrote
countless treaties on different subjects, 40 of them focused on medicine. The word
derives from the Greek verb epilambanein, which means to be taken, attacked or dominated.
The age of epileptology, stricto sensu, began in 1861, when John Hughlings Jackson (1835–1911), the founder of “modern epileptology,”
correlated convulsive crises with a cerebral dysfunction. In the following years,
new hypotheses were made, until in 1870 its concept changed: the crises would originate
in the cerebral cortex.[10]
[11]
Studying unilateral motor crises, Jackson could conclude that the motor cortex, and
not isolated muscles, as it was thought before, was responsible for limb movements.
This idea was confirmed by research with cortical stimulation in animals performed
by neurologist David Ferrier (1843–1928).
One of the first topographic maps of the somatotropic organization of the motor cortex
was idealized and published by Fedor Krause in 1911. Wilder Penfield (1891–1976) perfected
the technique, resulting in the famous homunculus of Penfield, a map with a cortical
representation of motor and sensory functions. A more modern example of cortical topographic
representations of specific functions is the work by Ojemann, which shows the cortical
variant of human speech.
The transition from cranial surgery to brain surgery occurred between the second half
of the 18th century and the first half of the 19th century, when the idea that epilepsy
could be caused by a disorder originating in the cerebral cortex was established.[12] The transition from the pre-modern era (cranial surgery) to the modern era (brain
surgery) occurred with the growing critical knowledge about trepanation, in association
with the emerging theory of the somatotropic location of the brain areas, and the
not less important evolution of asepsis and pain control during surgical procedures.
Epilepsy surgery was initially based on the visual identification of cortical lesions,
usually of traumatic origin, and trepanations or trephine were used for the surgical
access.
1886 marks the beginning of the contemporary age of epilepsy surgery, when the first
surgeries were performed, aiming at the treatment of epileptic seizures in three patients.
Sir Victor Horsley (1857–1916) was the neurosurgeon responsible for the surgeries
performed in London. Victor Horsley and William MacEwen (1848–1924), from Glasgow,
who at the same time also initiated the surgical treatment of patients with epilepsy,
are considered the founders of British neurosurgery. In the same period, neurosurgeon
Fedor Krause initiated the surgery for epilepsy in Germany. In the aforementioned
procedures, there was collaboration between neurologists and neurosurgeons – in the
United Kingdom, with Hughlings Jackson, and in Germany, with Hermann Oppenheim (1858–1919)
–, which became indispensable for the success of the proposed surgeries.[13]
[14] Such events served as the basis for the formation of multidisciplinary groups for
the treatment of epilepsy; however, in the second half of the 20th century, most of
the centers specialized in epilepsy treatment introduced the joint model, with the
collaboration of neurologists, neurosurgeons, neuroradiologists and neuropsychologists.
The scientific evolution and the increasingly concrete idea of achieving success in
the control of epileptic seizures through surgery spread quickly throughout the world
in the end of 19th century and early 20th century. With this, many countries all over
the world began to devote resources to the development and research in this area.
It is important to remember that, during this period, the surgeries performed for
epilepsy control were mostly directed to epilepsy due to trauma or tumors. Until the
1920s, the surgeries were only performed for chronic and localized epilepsy, and the
knowledge at the time allowed the physicians to program the region to be operated
based only on the semiology and detailed clinical observation of the patients seizure.
During surgery, the physicians needed to identify visually the cortical anatomical
alterations to be resected, and they often used cerebral electrical stimulation to
detect the motor area and the central sulcus, because electroencephalography (EEG)
and electrocorticography (ECoG) were not yet available.
With the discovery of X-rays, in 1895, by German physicist Wilhelm Conrad Röntgen
(1845–1923), pneumoencephalography, in 1919, by Walter Dandy (1886–1946), and cerebral
arteriography, in 1927, by Portuguese neurologist and researcher Egas Moniz (1874–1955),
there was a major breakthrough on epilepsy surgery, which enabled physicians to recognize
the etiology and topography of the causes preoperatively using images. But it was
only in 1929 that German neuropsychiatrist Berger (1873–1941) described the invention
and application of the human electroencephalogram, which enabled the recognition of
patterns associated with epilepsy and the location of areas with epileptogenic cerebral
tissue. Thus, the use of electrophysiological knowledge in epilepsy surgery began,
providing elements to aid in the diagnosis and to determine the cerebral area to be
resected prior to the surgical procedure.[15]
In 1934, the Montreal Neurological Institute, in Canada, was founded. Conceived by
Wilder Penfield in conjunction with the McGill University, it was a hybrid and unique
project for the time, with a hospital area for patients with neurological disorders,
a research center totally focused on the nervous system, and a department of neurology
and neurosurgery at the university. Penfield, who had great interest in epilepsy treatment,
conducted his studies after getting excited about the data collected by pioneer Victor
Horsley, and obtained neurosurgical training with Harvey Williams Cushing (1869–1939),
who is recognized as the father of modern neurosurgery, and who had already performed
surgeries under local anesthesia in patients with epilepsy. Cushing was the first
to report the mapping of the sensory cortex with the aid of cortical electrostimulation.
However, Cushing was mainly devoted to the study and treatment of brain tumors.[16]
[17]
In 1937, Canadian neurologist Herbert Jasper (1906–1999) joined the Montreal Neurological
Institute. With his previous experience in EEG and with the electrographic foundations
of the epilepsies already established, Jasper developed ECoG, which made it possible
to map the location of the epileptic seizures during surgery, recording directly from
the cerebral cortex and monitoring the responses of stimulation, thus delimiting the
area to be resected with greater precision. In that same year, with the aid of intraoperative
cortical stimulation and its motor findings, Penfield and Boldrey published for the
first time the illustration of what would be perfected and then recognized, 11 years
later, as the Homunculus (by Penfield and Rasmussen).
In followinf years, there was great development and many researches in the field of
epilepsy, and the surgical treatment evolved along with that. The evolutionary progress
and knowledge of the anatomopathology and the electroencephalographic parameters enabled
the performance of surgeries totally based on the interictal EEG, according to the
publication by Bailey and Gibbs,[19] in 1951, reporting the work with a series of patients with temporal lobe epilepsy
undergoing surgical resection.[18]
[19] Concomitantly, the publications of Penfield, Jasper and other collaborators of the
Montreal Institute presented their series of patients with temporal lobe epilepsy
undergoing surgical ablation, their electroencephalographic alterations, and their
results regarding crisis control.[20]
[21]
[22]
Thus, in the 1950s, there was a major worldwide spread of the surgery for epilepsy,
mainly of procedures aimed at the resection of the temporal lobe. Surgeries unrelated
to resections of lesions determined visually were initiated, but they were guided
by clinical findings and preoperative electrophysiological exams.[23]
[24]
In 1953, Murray Falconer (1910–1977) published in London the technical standards for
anterior resection of the temporal lobe, en bloc, which contributed to the research and development of the pathological bases involved
in temporal lobe epilepsy. The results showed that a large number of patients with
temporal lobe epilepsy had hippocampal sclerosis, which boosted the research and investigation
of the pathological hippocampus and the relationship between hippocampal sclerosis
and temporal lobe epilepsy.[25]
[26]
[27]
Bouchet and Cazauvieilh were the first to describe, in the early 19th century, the
presence of hippocampal sclerosis in patients with epilepsy. However, whether this
would be the cause or effect of epilepsy was still under debate until the 1960s, when
it was possible to understand that this was an epileptogenic alteration.
In Brazil, the onset of the surgical treatment for epilepsy dates to the 1950s, and
the most striking and pioneering contribution was by neurosurgeon Paulo Niemeyer Soares
(1914–2004), who worked at Santa Casa da Misericórdia do Rio de Janeiro. Paulo Niemeyer
was the first to propose and publish the amygdalohippocampectomy by transventricular
access for the treatment of temporal lobe epilepsy in 1957-1958, with expressive results
in crisis control.[28] This technique was accepted and is still used in many specialized centers. The first
program aimed at epilepsy surgery in Brazil was established in the 1970s, at Universidade
de São Paulo, by neurosurgeon Raul Marino Júnior.
Still in the 1950s, in Switzerland there was also a clear increase in the number of
surgeries for epilepsy with Hugo Krayenbühl (1902–1985), who initiated and coordinated
the department of neurosurgery at the University of Zurich.[29] At the same time, professor Krayenbühl was already performing a standardized technique
for temporal lobectomy. One of his pupils – Mahmut Gazi Yasargil –, after researching
and familiarizing himself with surgical microscopy, initiated, in 1969, the era of
neurological microsurgery, designing and reinventing materials. Subsequently, Yasargil
published a description of a microneurosurgical technique known as selective amygdalohippocampectomy,
which consisted of the removal of the temporal medial basal structures using a transsylvian
access, without the need for the removal of the anterior part of the temporal lobe.[30]
[31]
[32] This technique is used worldwide up to this days in many specialized centers for
epilepsy surgery. After the introduction of the surgical microscope, several new techniques
for epilepsy developed internationally.
The understanding and application of EEG and neurophysiology grew progressively, and,
with this, the idea of establishing a preoperative diagnosis for an increasingly precise
surgical planning caused variations and improvements to emerge in electroencephalographic
monitoring.[33]
[34]
[35] New kinds of surface electrodes for EEG were developed, and the idea of obtaining
information directly from the cerebral cortex with the subdural electrodes, already
described in the 1940s, became widely used and disseminated in the following decades
with the publications by Penfield and Jasper in Montreal.[36]
[37]
With the technological evolution and the advent of video in the EEG, prolonged electrophysiological
monitoring became possible, facilitating the semiologic investigation of seizures.[38]
[39]
[40]
Following the idea of detecting the precise cerebral site involved with the onset
of and to then proceed with surgical removal, and thus obtain the cure for epilepsy,
French neurologist Jean Bancaud (1921–1993) postulated a way to monitor different
areas and brain structures during a seizure, rather than using interictal encephalographic
findings. Bancaud and neurosurgeon Jean Talairach (1911–2007) were the first, between
the 1950s and 1960s, in Paris, to describe in detail the implantation of deep cerebral
electrodes with the aid of the device and coordinates of stereotaxy developed by Talairach,
which is recognized as the founder of modern stereotaxy. In 1962, the technique was
named stereoelectroencephalography (SEEG), and it would be the best way to correlate
the semiology of the crisis with the anatomical temporal distribution obtained, and
thus localize the ictal onset zone and the epileptiform dissemination network involved.
In addition, there would be the possibility of cerebral stimulation, and thus of creating
a three-dimensional model for investigation. The SEEG would be used in the preoperative
evaluation of patients who are candidates for epilepsy surgery in France.[41]
[42]
[43]
Neuropsychology was extensively studied in the 1950s and 1960s, and it represents
an evolution in epilepsy surgery. Brenda Milner (1918) and Juhn Wada (1924) were important
researchers in this field, and they were able to collaborate with studies relating
memory and language with mesial temporal resection in patients with temporal lobe
epilepsy. Dr. Juhn Wada introduced and demonstrated the intracarotid use of sodium
amobarbital to determine the cerebral dominance for the language function, the Wada
test, as an important part of the preoperative study. Milner developed the basis of
some neuropsychological tests that are still used today, and expanded the use of the
Wada test to evaluate the functional memory reserve of patients undergoing surgical
treatment for epilepsy. Penfield was the first to report and advocate the use of a
multiprofessional group to perform the pre- and postoperative assessments, to better
discriminate the pathological brain area with its psychological alterations and thus
predict possible memory and language deficits with surgical treatment, besides being
able to identify the presence of the cortical reorganization of cognitive functions.
This was all to better guide the type and extent of resection to be performed in patients.[44]
[45]
[46]
[47]
From the 1970s onwards, with the establishment of the anatomopathological, electrophysiological
and neuropsychological knowledge acquired, and the surgical results obtained in previous
years, associated with the invention of computed tomography (CT) and other imaging
methods, there was a grand global expansion in the surgical treatment of refractory
epilepsies. The possibility of visualizing images of the human brain in three dimensions
– and identifying structural lesions located in many patients with focal epilepsy,
until then diagnosed as cryptogenic epilepsy – marked the onset of modern neuroimaging.
The association of neuroimaging and EEG findings led us once again to surgeries based
on directly visualized lesions, but now with preoperative visualization and electrophysiological
correlation of the lesion with the crises. The CT quickly replaced the X-rays and
pneumoencephalography, because it was much more sensitive in the detection of tumors,
vascular lesions, posttraumatic alterations and infecto-inflammatory diseases.[48]
In the 1980s, magnetic resonance imaging (MRI) was introduced for the clinical practice,
causing a revolution in several fields of medicine, and quickly replaced the CT in
the diagnostic evaluation of epilepsies, as it demonstrated anatomical structures
and cerebral pathologies in more detail.
With the technological evolution, new sequences of images were being made available,
and new techniques to define the morphology and volume of deep brain structures were
developed. Currently, it is estimated that ∼ 70% of patients with focal epilepsy evaluated
in specialized centers present alterations in MRI images.[49]
[50] With the evolutionary improvement of image quality in higher magnetic field devices,
there was the possibility of identifying unrecognized lesions and to estimate anatomical
alterations in a non-invasive way.
Still during the 1980s, new exams, not only imaging but functional exams, were developed
and added to the preoperative diagnostic arsenal of epilepsies. Among them, there
is positron emission tomography (PET), which uses a radiopharmaceutical, fluorodeoxyglucose,
marked with fluoride 18 (18F-FDG), injected intravenously in the patient, to observe
its distribution in the brain, detected by tomography. In the interictal period, there
is a hypometabolism in the pathological area and a hypermetabolism in the ictal phase.
In a correlated manner, single-photon emission computed tomography (SPECT) was developed,
which uses technetium-99m as a radiopharmaceutical and presents an interictal hypometabolism
and a hypermetabolism during the ictus.[51]
[52]
With these new forms of functional metabolic investigation, patients who did not have
visible lesions in the MRI could be topographically diagnosed and, in conjunction
with the video-electrographic findings, selected for surgical treatment. The aim of
performing a high-quality and precise preoperative evaluation resulted in the development
of new techniques that improved the safety and outcome of surgeries.[53]
[54]
In the 1990s, there was the introduction of functional nuclear magnetic resonance
(fNMR). This technique explores the dependent effect on the blood oxygenation level,
and ,in brain areas activated with specific functions, the percentage of deoxyhemoglobin
is reduced compared with non-active areas, which generates an increase in the signal
in the T2-weighted images, enabling a cerebral mapping.
The use of fNMR in memory and language areas is important in the programming of patients
with refractory epilepsy selected for surgery.[55]
It is currently possible to obtain images of the interictal activity using EEG and
fNMR together. The white matter and the connectivity of the tracts became visible
with the introduction and evolution of tractography. This technology has contributed
to the precise definition of the epileptiform zone, its connections and its relationship
with eloquent areas.
Another recently available variant is subtraction ictal SPECT coregistered to MRI
(SISCOM), which enables the fusion of the ictal SPECT image with the high-resolution
images of the morphological MRI. Equally important for the non-invasive diagnosis
of ictal focus is magnetoencephalography, the three-dimensional reconstruction of
the interictal EEG tracing captured by countless surface electrodes fused with the
three-dimensional images of the morphologic MRI. These more precise diagnostic techniques
are specifically important in the so-called non-injured cases, that is, patients refractory
to medications, with no identifiable lesions in the MRI.
After the development of the MRI and its technological evolution, small congenital
cerebral alterations could be identified and correlated with the primary ictal zone.
The improvement and refinement of microsurgical techniques, and the knowledge and
development in computer graphics with the use of neuronavigation associated with intraoperative
MRI increased the success rates of the surgical procedures for epilepsy.[56]
The final decade of the 20th century was remarkable in the evolution of the surgery
for epilepsy. In the 1980s, most of the surgery groups for epilepsy used basically
one surgical technique for the approach, depending on the place where the surgeons
were trained. In 1986, the first conference on epilepsy surgery was held in California,
which managed to bring together almost all of the centers specialized in epilepsy
in the world to present and compare their techniques and their results. In the years
that followed, countless new publications and new specialized centers emerged, and
most centers innovated and adapted different techniques for the treatment of different
types of epilepsy. In the beginning of the 1990s, most of the world centers were already
conducting research with deep cerebral electrodes and encephalographic recordings
with subdural electrodes, and performing surgeries in many patients based only on
the high-quality non-invasive investigation.
At the beginning of the 21st century, the first randomized controlled scientific studies
that demonstrated the superiority of the surgical treatment in patients with temporal
lobe epilepsy without drug control were published, confirming the already established
consensus that surgery would be the best treatment for refractory epilepsies.[57]
Currently, the use of all available resources by a multidisciplinary group dedicated
specifically to the surgical treatment of epilepsy is indispensable to make an accurate
diagnosis, to precisely identify the primary ictal zone, and to perform the specific
resection of this cerebral area, to obtain the highest rate of seizure control with
the lowest risk of functional deficits.
