Sensorimotor Cortices and Early Localization

The modern era of ablative epilepsy surgery is often noted to have begun in 1886 with Horsley’s report of surgical excision of tumors in 3 cases of focal Jacksonian epilepsy. But important advancements in the understanding of brain function preceded this development. The work of John Hughlings Jackson was crucial in providing the impetus for exploring the brain in epilepsy. In promoting a physical basis for neurologic pathology and shunning the appeal to metaphysics that characterized the understanding of the brain in the early 1800s, Hughlings Jackson brought the scientific method squarely into the arena of neurology. This approach led to his characterization, in 1867, of the somatotopic procession of a seizure through the motor cortex that bears his name: the Jacksonian march.

Intrigued and influenced by his colleague’s findings, Horsley, operating in England, proceeded with craniotomies to treat epilepsy, as recorded in the aforementioned case series. In this case series, the first of its kind, Horsley documented 3 cases in which he combined analysis of clinical presentation with cortical stimulation to localize a precise region for excision. The first patient, originally a patient of Hughlings Jackson, was a 22 year old with posttraumatic epilepsy caused by a skull fracture at age 15. The patient did well, as did the 2 others reported in the series. From the success of these procedures emerged an important pattern: using clinical presentation for surgical planning. This trend crystallized distinctly in 1909, a “landmark year for epilepsy.” Among other important events in the year, such as Horsley giving a major lecture about his cases, the International League Against Epilepsy had its first meeting, and the surgical treatment of epilepsy was discussed in earnest.

Fedor Krause was one of several neurosurgeons who spoke at the inaugural International League Against Epilepsy meeting. Soon afterward, he published an article about epilepsy surgery, signifying increased awareness of neurosurgical intervention for epilepsy. Krause continued to operate on patients with epilepsy. He refined the approach pioneered by Horsley but also attempted to expand the indication for epilepsy surgery. Specifically, Krause wanted to operate not only on patients with obvious posttraumatic or tumor-based causes of epilepsy, but also on those with no discrete lesion or macroscopic pathology. His reasoning, along with his partner Schum, was that if clear seizure semiology pointed to a likely location of an epileptogenic focus, then that region should be resectable. Because the most clearly characterized semiology at the time was the aforementioned Jacksonian march, these were the patients on whom Krause operated. For those patients with Jacksonian seizures but no obvious lesion in the motor cortex, Krause used monopolar faradic stimulation along the motor cortex to induce the seizure and localize the epileptogenic focus. In doing so, he eventually mapped the motor cortex along the precentral gyrus, supporting Horsley’s (and others’) findings in monkeys. This work provided a significant advancement in neurosurgical localization and understanding of brain function. Additionally, although not all his patients improved, Krause’s work represented a significant improvement in surgical technique and held promise for advancing epilepsy surgery. Krause and Schum’s lengthy volume on epilepsy published in 1932 formally advocated for localization and surgical resection of epileptogenic foci even in the absence of discrete lesions.

Better understanding of brain function lent more confidence in the endeavor of understanding nonlesional epilepsy. Mirroring Krause’s characterization of the motor cortex, during Harvey Cushing’s brief foray into epilepsy surgery, he established the postcentral gyrus as a sensory center based on cortical stimulation of patients with focal sensorimotor seizures. With this burgeoning understanding of brain function, epilepsy surgery was poised to integrate the next big development: EEG.

The Instrumental Invention of Electroencephalography: Honing in on the Mesial Temporal Lobe

The potential role of EEG in epilepsy diagnostics began to take form with the collaboration of Herbert Jasper and Wilder Penfield in the 1930s. On hearing of Jasper’s advances in EEG recording at Brown University in Rhode Island (which were also informed by contemporaneous advances by Frederic Gibbs and William Lennox at Harvard), Penfield was sufficiently intrigued to discuss the possibility of integrating EEG with neurosurgical treatment. Having founded the Montreal Neurological Institute (MNI) in 1934 with a keen interest in epilepsy and extensively operating on non-neoplastic epilepsy based on the ideas advanced by Krause and Schum, Penfield was cautiously optimistic about the role EEG could play in advancing the field.

The collaboration between Penfield and Jasper at the MNI proved fruitful. The work of Jasper and his colleagues established and fine-tuned the diagnostic and localizing capabilities of EEG in 1941. Gibbs and Lennox, also working on EEG, went so far as to claim that nonlesional epilepsy was more common than lesional epilepsy, a bold claim at the time. Further diagnostic capability was provided by intraoperative cortical surface recordings (electrocorticography [ECoG]). By 1941, it became evident that characteristic patterns of abnormal electrical activity over mesial temporal structures along with characteristic symptomatology led to the “psychomotor” seizures; today the pathology has been termed mesial temporal lobe epilepsy, which leads to complex partial seizures. With electrophysiologic justification for temporal lobe pathology despite the absence of discrete lesions, surgical resection of this region seemed reasonable. Elucidation of mesial temporal function lagged, however, behind the identification of pathology. What sort of neurologic issues would be encountered if this region were to be resected? Through the 1940s, this question was addressed through the study of hippocampal and amygdala function and more confidence in attempting surgical exploration resulted. Electrophysiologic studies proved useful for localization in tumoral and other lesion-based epilepsy as well.

In 1949 and 1950, with the use of EEG and ECoG, Jasper, Penfield, and Flanigan reported on multiple series of patients who had been operated on in light of diagnostic EEG findings. In the first report by Jasper in 1949, 24 patients were operated on, but only 2 had had surgical resection of the uncus because of continued uncertainty about the lack of discrete structural alterations. In the 1950 report by Penfield and Flanigan, however, 68 patients were operated on, of whom 10 had resection of their uncus and 2 had hippocampectomies as well. Approximately half of these patients achieved seizure control, which provided the initial proof of principle but indicated the need for further study.

Further studies at this time led to refinements in the procedure. Histopathologic study of resected tissue by Gibbs and Percival Bailey led to better characterization of the anatomic range of microscopic pathology. Electrophysiologic studies also redefined surgical goals. In particular, early case series attempted to minimize resected surface area by taking regions with maximal abnormal ECoG activity. Because seizures persisted in these patients, however, increased region of resection was practiced until the entirety of the anterior temporal lobe began to be resected.

Refining Understanding and Surgical Approach

After the success of anteromesial resection, operative experience aimed at better understanding seizure propagation and the structures in the region. Intraoperative stimulation allowed these distinctions to be made. When ictal responses were induced, seizure propagation could be studied. When acute changes in memory and mood occurred, normal function of mesial temporal structures was better understood.

Armed with this understanding, Penfield and Baldwin defined a standardized approach to anteromesial temporal lobe resection in 1952. This seminal approach extended more mesially than what was reported in previous case series. Through the rest of the 1950s and early 1960s, this approach was used at many other centers and reported on in more case series. En bloc resection was also introduced by Falconer in 1953. Late in the 1960s, Niemeyer and Bello of Brazil developed a selective amygdalohippocampectomy (SelAH) using a transventricular approach, which allowed preservation of some anterior temporal neocortical tissue. The introduction of a selective approach was crucial for the ablative procedures of today.

With rapid innovation in surgical technique, along with improved seizure freedom outcomes in patients, surgery for epilepsy experienced a sharp rise in popularity. The 1950s saw a worldwide growth of centers practicing anterior temporal lobectomies and other procedures for epilepsy. Centers in Japan and Brazil (including that of Niemeyer) are a few international regions that practiced these surgeries with increasing frequency.

The Advent of Stereotaxis

While the neuroanatomic correlates of temporal lobe epilepsy, its treatment by open surgical resection, and potential selective approaches were being elucidated, the stereotactic approach to neurosurgery was also being developed. First used in 1906 in animal studies by Horsley and Clarke, the stereotactic frame is a rigid, head-mounted frame that allows for adjustments in the Cartesian X, Y, and Z planes. This method of coordinate-based targeting allows specific regions of the brain to be accessed in a precise manner. With continued improvement on Horsley and Clarke’s initial plaster-based fixation system, stereotactic surgery was first applied to humans in 1947. Spiegel and colleagues used a stereotactic frame to perform a medial thalamotomy for a psychiatric indication. After this initial use, they actually used stereotactic surgery for some cases of epilepsy. It was not until the 1960s, however, that further advances, including stereotactic apparatus improvement by Leksell and methodological improvements by the group of Talairach and Bancaud in France, allowed stereotaxis to be used in earnest for epilepsy surgery. The stereotactic approach remains central to today’s ablative epilepsy surgery. After the theme of localization of structures demonstrated by targeting posttraumatic scars, tumors, and mesial temporal sclerosis, stereotaxy did much to improve the precision of epilepsy surgery in 2 important domains: diagnostics and surgical approach.

Although the domains of diagnostics and surgical approach are now interdependent, they developed separately. Stereotactic surgery for epilepsy arose initially from surgical treatment of behavioral/psychiatric disturbances. In a series by Umbach and Riechert in Germany, stereotactic amygdalotomy was used in conjunction with fornicotomy, and amelioration of epileptic symptoms was an unexpected outcome. Early stereotactic epilepsy surgeries followed similar rationale, but the strict use of stereotactic surgery for epilepsy did not gain popularity until improved methods were developed. An early case series of interest was reported by Vladyka in the late 1960s, who used ventriculography and a stereotactic atlas to perform stereotactic ablative amygdalotomy (by way of a thermocoagulative lesion). Results in this series were comparable to open surgery, yet, as discussed previously, stereotactic surgery for epilepsy remained largely unpopular until much later.

The use of stereotaxis for diagnostics, however, became much more prominent in the form of stereotactic EEG (SEEG). Because the only available diagnostic modalities before SEEG were noninvasive scalp EEG and ECoG, preoperative mapping of subcortical epileptogenic foci remained limited. The work of Talairach and Bancaud was instrumental in developing and refining SEEG. Choosing a different approach from Jasper and Penfield, who relied on ECoG and cortical stimulation to define the seizure, Talairach and Bancaud used seizure semiology to formulate a reasonable hypothesis about the spatial procession of the seizure through regions of the brain. They then used a crude form of stereotaxis to place multiple flexible depth electrodes in those same regions. Recordings of electrical activity provided information about potential locations of epileptogenic foci in these patients. As discussed previously, however, the stereotactic approach was not commonly used for the surgical approach to the same patients. There are multiple reasons for this phenomenon. Even with the addition of SEEG, only an approximate location was provided and, moreover, there was a lack of definitive atlases for stereotactic navigation at this time. As a result, patients undergoing SEEG for MTLE through the 1960s and 1970s typically underwent open resection following standard approaches for anteromesial temporal lobectomies. In the 1980s, further refinement of technique occurred, including an easier approach for placing depth electrodes in the mesial temporal lobe through the foramen ovale. With better information from preoperative diagnostics, early forays into selective, microsurgical treatment of epilepsy were seen, including a 1982 report on SelAH.

SEEG continued to be refined and incorporated into surgical planning. Its technical difficulty has limited its widespread expansion out of Europe, but updated techniques have been described recently. The use of stereotactic surgery for epilepsy was similarly limited in spread, even with the publication of stereotactic atlases, and open resection continued to be favored through the 1980s and 1990s. Advances in neuroimaging in the 1990s, however, have allowed several stereotactic ablative procedures to join open resection as valuable tools for epilepsy surgery. The goal of ablative epilepsy surgery, for both lesional and nonlesional causes, is to offer minimal interruption of normal circuits (and, consequently, normal behavior) while offering maximal seizure control.

Other Forms of Epilepsy and Surgical Techniques

Until this point, primarily the history of the surgical approach for MTLE has been discussed because it is both the most commonly operated-on form of epilepsy and the form that inspired advances in ablative neurosurgery. Other forms of epilepsy, however, are also subject to surgical intervention. These approaches have developed over time as well. Surgical treatment of tumoral epilepsy has followed similar trends to MTLE, including craniotomy, better localization with EEG and imaging, and application of current minimally invasive techniques. Hypothalamic hamartoma, a less common cause of intractable secondary generalized seizures, has proved more difficult to treat given its difficult location. Reports in the late 1960s used various approaches for resection, but precise access has awaited development of neuroimaging and stereotactic techniques (described later). For epileptic disorders with less focal pathologic correlates, 2 important nonablative techniques are used: hemispherectomy and corpus callosotomy. The historical context of these procedures is discussed briefly.