Surgical Management of Low-Grade Gliomas

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Chapter 9 Surgical Management of Low-Grade Gliomas

Lorenzo Bello, Francesco Dimeco, Giuseppe Casaceli, Sergio Maria Gaini

The term “low-grade glioma” refers to a series of primary brain tumors characterized by benign histology (low proliferation, low neoangiogenesis phenomena) and aggressive behavior related to the slowly progressive tendency to invade the normal brain parenchyma.¹^–⁴ These neoplasms are classified as grade II (out of IV) by the World Health Organization classification of brain tumors and include the following entities: grade II astrocytoma (further divided in fibrillary and protoplasmic), grade II oligoastrocytoma, and grade II oligodendroglioma.⁵ Pilocytic astrocytomas, or grade I astrocytomas, are occasionally referred to as low-grade gliomas but due to their peculiar behavior, require separate considerations. In this chapter, low-grade gliomas refer only to WHO grade II tumors.

Low-grade gliomas are slow growing tumors, typically affecting younger individuals (median age 35), and mainly males (male/female ratio 1.5) who clinically present with seizures (often partial seizures).⁶ Headache, personality changes, and focal neurologic deficits represent the other most common symptoms. The neurologic symptoms include motor/sensory deficits, dysphasia/aphasia, disinhibition, apathy, and visuospatial disturbances according to tumor location and size.^1,^7,⁸ Interestingly, some authors report the tendency of low-grade gliomas to occur in eloquent areas or in their proximity.⁹

Overall, the median survival of low-grade gliomas is about 10 years and well-defined negative prognosticators include older age (>40 years), larger size (>5-cm diameter), eloquent location, and reduced Karnofsky performance status.

The optimal treatment for low-grade gliomas has yet to be determined. Watchful observation, needle biopsy, and open biopsy, as well as surgical resection have all been advocated by different authors.^2,¹⁰^–¹⁶ No evidence of class I or II exists regarding the optimal management of these patients, even if the more modern tendency is to obtain at least some type of tissue diagnosis.^17,¹⁸ The rationale behind the observational or “wait-and-see” policy was the occasionally indolent or very slowly progressive behavior of these tumors.^14,¹⁶ On the other hand, following the modern oncologic concepts, some authors proposed performing a biopsy to obtain a histopathologic confirmation of the nature of the neoplasm before deciding on further management. Surgical resection of low-grade gliomas is still matter of debate, although recent studies are increasingly supporting its role.^10,^13,^17,¹⁸^–²² Surgery can in fact achieve multiple aims: more reliable histologic diagnosis with eventual molecular profile (e.g., 1p/19q loss and MGMT status), symptom relief; beneficial effect on seizure control, and lower rate of recurrence and malignant transformation.^13,^18,²⁰ Nevertheless, surgery carries unavoidable (albeit low) risks that can potentially and permanently affect the patient’s quality of life.

Given this general information on low-grade glioma behavior and the possibility of treatment, it is clear that a modern surgical approach to these tumors has the goal of maximal resection of the mass and minimizing postoperative morbidity to preserve the patient’s functional integrity.^13,¹⁸^–²⁰ ^,23 Since the natural history of the tumor can be relatively long (with or without surgery), the conservation of simple and complex neurologic functions of patients is mandatory. To achieve the goal of a satisfactory tumor resection associated with full preservation of the patient’s abilities, a series of neuropsychological, neurophysiologic, neuroradiologic, and intraoperative investigations must be performed. In this chapter, we will describe the rationale, indications, and modality for performing a safe and rewarding surgical removal of low-grade gliomas.

Rationale and Indications

The major aims of surgical treatment are ¹ obtaining adequate specimens and representative tissue to reach a correct histologic and molecular diagnosis;² achieving cytoreduction to decrease rate of recurrence and malignant transformation, possibly prolonging survival;³ improving patient neurologic symptoms; and⁴ obtaining better seizure control. These goals can be reached by tailoring the surgical approach on location, modality of growth, and biological behavior of the tumor, as well and patient characteristics.

Histologic and Molecular Diagnosis

It is well known that astrocytomas represent a challenge for the neuropathologist, mainly in terms of grading the tumor. The size or number of needle biopsy specimens does not always permit all tests eventually required for immunohistochemical or molecular analysis. In addition, the biopsy site can significantly change the final results because gliomas are typically very heterogeneous with areas of different malignity. Recently, proton MR spectroscopy or MR perfusion has been used to partially overcome the latter problem, providing information on the presence of choline peaks (index of membrane production and malignancy) or areas of increased angiogenesis that can guide the surgeon in identifying the best location for performing the biopsy.²⁴^–²⁶ In any case, the risk of underestimating, or more rarely overestimating, the grade is a distinct possibility for needle and even open biopsies eventually resulting in significant changes in the choice of the most appropriate treatment.

Molecular markers have become a standard in determining the type of low-grade glioma. In fact, chromosome 1p/19q loss of heterozygosity plays a very important role in the distinction between oligodendrogliomas or astrocytomas. This molecular marker is relevant not only in the histotype definition but also in therapeutic implications.^18,^27,²⁸ In fact, 1p/19q loss as well as MGMT methylation (another important marker) facilitate predicting the response to certain chemotherapeutic agents. More recently, unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 77% of grade II gliomas, and it was found associated with 1p19q deletions and MGMT methylated status, and with a better outcome.²⁹ Obviously, inadequate or incorrect sampling of the tumor can dramatically impair the possibility of a molecular analysis.

Size, Location, and Growth

Most of low-grade gliomas are localized close or within the so-called eloquent areas, such as the areas of the brain that control motor, language, or visuospatial functions. In a recent series, as well as in the experience of our group, 82.6% of tumors were located within eloquent motor or language areas (27.3% of cases within the SMA, 25.0% in the insula, 18.9% in language centers, 6.0% in the primary somatosensory area, 4.5% in the primary motor area).^9,^30,³¹ As for the modality of growth, these tumors are characterized by a prevalent diffusive pattern of growth.^9,³² Groups of tumor cells or single tumor cells diffuse away from the main tumor mass along vessels or short and long white matter tracts. These features are responsible for the typical aspect of low-grade gliomas seen in MR images, which is characterized by a morphology strictly resembling that of white matter tracts along which the tumor grows and diffuses. In addition, despite their occasional apparently indolent behavior, low-grade gliomas are characterized by a continuous growth, with periods of faster and lower rates of growth during the entire time of the natural history of the tumor.³² Most of the lesions judged as stable actually did show various degrees of growth; minor changes in the diameter (e.g., 1 to 2 mm) reflect a significant cellular growth in terms of volume.³² For the sake of simplicity, the rate of growth of a tumor can be quantified by measuring the maximal diameter onto FLAIR MR images. Repetitive measurement on representative sections demonstrated that the tumor continuously grows and that the mean increase of the tumor diameter is around 4 mm/year. Furthermore, an increase in tumor diameter larger than 8 mm/year, even in the absence of contrast enhancement or modification of T2 or FLAIR images, is associated with a high tendency toward malignant transformation and aggressive biological behavior. These data stress the point that serial measurements of tumor volumes are an important tool to determine the biological behavior of the tumor. At the same time, it is clear that tumor volume is an important prognostic factor, able to determine per se the biological behavior of the tumor overtime. In fact, larger tumor volumes are more frequently associated with a higher risk of malignant transformation and shorter patient survival.¹⁸ Tumor volume is associated with the risk of developing neurologic symptoms, increase in the risk of seizures, and probability of impacting in the social and professional life of patients.

Neurologic Symptoms

The majority of patients who are diagnosed with low-grade gliomas usually come to medical attention because of sudden occurrence of seizures.^7,¹⁸ These patients are generally intact at the gross neurologic examination, but they frequently present more subtle symptoms affecting complex neurologic functions (memory, language, character, visuospatial orientation, etc.) that require a specific testing by a neuropsychologist.^31,^33,³⁴ As will be detailed below, this type of testing is mandatory when considering surgery for this type of lesion because it allows tailoring the intraoperative testing to the patient and permits finely assessing the impact of surgery on the patients’ superior neurologic functions.³⁵

Those patients who present with frank neurologic deficits (e.g., hemiparesis, ataxia, aphasia) are usually candidates for surgery because their symptoms are related to direct mass effect of the tumor on the cortex or on the subcortical white matter tracts. In this case, tumor removal can significantly relieve symptoms depending on the degree of the preoperative impairment as well as on the degree of parenchymal disruption. This category of patients carries higher surgical risks in terms of morbidity and mortality than that of neurologically intact patients. Nevertheless, in terms of surgery, the presence of a mass effect is a straightforward indication for tumor resection since a waiting policy will quickly result in further neurologic deterioration.

Seizures

Large tumors and insular locations are usually associated with a higher risk of developing seizures, which are difficult to be controlled by antiepileptic drugs, requiring the administration of multiple medications. Despite polytherapy, seizure control can still be very poor. In these latter cases, surgery becomes an appealing option to improve seizure control. It has been clearly shown that surgical resection is associated with a marked improvement in terms of seizure occurrence. In other cases, patients might be severely disabled by the side effects of multiple antiepileptic medications and again surgery can allow reduction of drug administration. It is a matter of debate whether surgical resection of low-grade gliomas for seizure control should be performed in an epilepsy surgery setting (with surface and eventually deep-electrode recordings, with resection of all the foci) or in a purely oncologic setting (with neurophysiologic monitoring, including electrocorticography, but no deep electrodes and no resection of normal brain foci).

As mentioned above, surgery for gliomas aims to maximally remove the tumor mass and at the same time to preserve the patient’s functional integrity. This policy applies to the resection of any glioma but more specifically to those located close or within eloquent areas. The concept of eloquence refers not only to areas involved in motor, language, or visuospatial functions, but also, more widely, to any area affecting the well being of the individual (e.g., memory, socioaffective behavior, specific tasks performance, etc.). In all these cases, extensive resection and maximal functional integrity can still be achieved through the intraoperative use of brain mapping techniques.^11,^18,^19,^30,³⁶^–³⁸

Intraoperative Mapping

The term “intraoperative mapping” refers to a group of techniques that allow safe and effective removal of lesions that are located in so-called eloquent or functional areas. This can be achieved by the identification and preservation at time of surgery of cortical and subcortical sites that are involved in specific functions. The concept of detecting and preserving the essential functional cortical and subcortical sites has been recently defined as surgery according to functional boundaries, and it is performed by using the so-called brain mapping technique.

Performing brain mapping requires a series of preoperative evaluations and intraoperative facilities that involve different specialists. A complete neuropsychological evaluation is generally the first step of the process permitting to select the suitable patients and to individualize the intraoperative testing. Then, sophisticated imaging techniques including fMRI and DTI-FT (diffuse tensor imaging–fiber tracking techniques) give the opportunity to attentively plan surgical strategies. In addition, these images can be loaded into the neuronavigation system becoming thus available peri- and intra-operatively for orientation. Intraoperative MR or ultrasound can be used as well, if available. Finally and most importantly, a series of neurophysiologic techniques are employed at the time of surgery to precisely guide the surgeon in the tumor removal. These include cortical and subcortical direct electrical stimulation (DES), motor-evoked potentials (MEP), multichannel EMG, EEG and ECoG recordings.

Neuropsychological Evaluation

Neuropsychological evaluation comprises a large number of tests to assess various neurologic functions such as cognitive, emotional, intelligence, and basic language functions. Such a broad-spectrum evaluation provides information on how the tumor has impacted on the social, emotional, and cognitive life of the patient. It is important that the testing be the most extensive possible because the tumor that grows along fiber tracts may alter connectivity between separate areas of the brain, resulting in impairment of functions that may not be documented in the case of a neuropsychological examination limited to testing of functions strictly related to the area of the brain in which the tumor has grown.^13,^30,^31,³⁸ When this extensive testing is administered, changes can be documented in more than 90% of patients.^13,^30,³¹ These data represent the baseline with which the effect of surgical and future treatment should be compared. Additionally, when the tumor involves language or visuospatial areas or pathways, a more extensive specific evaluation should be added.

The neuropsychological assessment also allows one to build up a series of tests composed of various items that will be used intraoperatively for the evaluation and mapping of various functions, among which memory, language in its various components, and visuospatial orientation are some of the most important. For language evaluation, a battery of preoperative tests evaluates verbal language production and comprehension, together with repetition.^30,³⁹^–⁴¹ Hemispheric language dominance is evaluated through the Edinburgh Inventory Questionnaire and fMRI. Most tests generally used have been standardized on the normal population. In addition, various tests can be adjusted according to the nationality of the patient. It is important to include in the battery both qualitative and quantitative tests, and normative data must be available for the quantitative procedure. It is also important that a speech therapist and a (neuro)psychologist manage patient assessments.

Preoperative language evaluation is also used to prepare a series of tests that will be used intraoperatively for assessing language during surgery. Among these tests, object naming is probably the most important. In the case of a tumor located in the dominant or parietal areas, number recognition and reading, as well as calculations or writing should be added to preoperative testing and considered for intraoperative evaluation.^9,^42,⁴³ When the patient is bilingual or speaks more than two languages, it is important to include evaluation of these languages in the preoperative testing.^32,⁴⁴^–⁴⁸ In any case, bi- or multi-lingual assessment is generally recommended also intraoperatively.⁴⁴ Visuospatial functions are usually evaluated for tumor located in the parietal lobe, generally on the right side.¹³ Unilateral spatial neglect is a complex and disabling syndrome that typically results from right hemisphere damage, and it is characterized by impaired awareness of the contralesional left half of space, objects, and mental images. In this case, the patient is presented with various tests such as the line bisection test or star cancellation test to evaluate spatial awareness.

Neuroradiologic Evaluation

The neuroradiologic examination consists of basic exams, such as morphologic T1, T2, and FLAIR images, as well as postcontrast T1 images. These images together with volumetric sequences provide information on the site and location of the tumor, and allows to determine its relationship with various structures, such as major vessels, and to measure tumor volume, and when performed at different time points to establish the speed of growth. Further MR studies include MR spectroscopy, which allows designing a map of areas within the tumor in which tumor metabolism is more or less pronounced (multipixel MR spectroscopy map).^25,²⁶ This is of great assistance in tissue sampling at the time of surgery for histologic and molecular purposes. Perfusion MR studies are useful for designing perfusion maps,^49,⁵⁰ which provide additional and complementary information of the biological behavior of the tumor and help in the tissue collection for histologic and molecular purposes at the time of surgery.²⁴ Metabolic information may be also obtained by performing SPECT or PET, and these data may be incorporated into the navigation system for surgical guidance as well.^51,⁵²

The neuroradiologic investigations include functional studies, such as fMRI, and anatomic studies such as DTI-FT. The former provides functional information on the location of cortical sites, which activates in response to motor or various language tasks. Motor fMRI is generally used to design a map of the cortical motor sites and to establish their relationship with the tumor.⁵³ fMRI for language provides a map of the cortical sites that activate during language tasks, such as denomination (object naming), famous face naming, verb generation, and verbal fluency.^48,⁵⁴ All these data form a complex map of how the various components of language are organized at the cortical level and allow establishment of spatial relationship between these cortical areas and the tumor mass. It is usually recommended that language fMRI be performed with the same tests that are used for language evaluation to increase its reliability.

DTI-FT techniques allow depicting the connectivity around and inside a tumor, by reconstructing and visualizing the fiber tracts, which run around or inside the tumor mass ⁵⁵ (Fig. 9-1). DTI-FT provides anatomic information on the location of motor tracts, mainly the corticospinal tract (CST), and various language tracts, involved either in the phonologic or semantic components of language.⁵⁶^–⁵⁹ For a better visualization of tracts in low-grade gliomas, an FA (fraction of anisotropy) of 0.1 should be used, and additional regions of interest (ROIs) for a particular tract such as the anterior part of the superior longitudinalis or the SMA portion of the CST can be added.^56,^60,⁶¹ The basic DTI-FT map includes the CST for the motor part, and the superior longitudinalis (SLF), which includes the fasciculus arcuatus, and the inferior fronto-occipital (IFO) tract for the language part.^38,^39,⁵⁶ The SLF is the basic tract involved in the phonologic component of language; the IFO is the basic tract involved in the semantic component of language. Additional tracts that can be reconstructed are the uncinatus (UNC) and the inferior longitudinalis (ILF) tracts, which provide information on the semantic and phonologic component of language in the frontal and temporal lobe, or the subcallosum fasciculus, involved in the phonologic component of language, sited in the lateral border of the lateral ventricle.^56,^60,⁶² Preoperative neuroimaging produces an impressive amount of information concerning the anatomic and functional boundaries of the lesion to be resected. Together with the volumetric morphologic images, the DTI-FT images are usually loaded into the neuronavigation system and help in the perioperative period in performing the resection. However, the imaging gives information based on probabilistic measurements, and although they may have a relatively high sensitivity or specificity, they still carry a certain amount of mistake, which cannot, at least nowadays, be considered as sufficient for performing a safe and effective resection.

FIGURE 9-1 (A) FLAIR MR images showing a rolandic diffuse low-grade glioma (low-grade astrocytoma). (B) DTI-FT reconstruction for CST (white) superimposed to MR T1-weighted images showing that the CST is strictly intermingled with the tumor.

Anesthesiologic Evaluation

Besides the standard anesthesiologic work-up, the patient should be examined for his or her ability to experience intraoperative awake monitoring when needed. Preparation and selection of patients by anesthesiologists with expertise in awake surgery is recommended.^63,⁶⁴ In our institution, the only absolute contraindications to awake surgery are the lack of cooperation, age older than 70 years, obesity, and difficult airway or airway affected by severe cardiovascular or respiratory diseases. In addition, common contraindications to any general anesthesia regimen, communication difficulties (moderate to severe aphasia), psychological imbalance (extreme anxiety), prone position, and inability to lie still for many hours are also included.

Once the preoperatory work-up is completed according to the site and the characteristics of the tumor, and the results of neuropsychological evaluation and functional and anatomic imaging obtained, each patient is offered an individualized surgical and monitoring strategy, which can be summarized as follows:

• Lesions in the nondominant hemisphere, away from eloquent areas and without relationship with areas of activation according to fMRI: motor monitoring (optional)

• Lesions in the nondominant hemisphere, in central or precentral area or in relationship with the CST (e.g., insular, temporomesial tumors) and small central lesions in the dominant hemisphere: motor mapping and monitoring

• Lesions in the nondominant hemisphere, in postcentral region: motor mapping and monitoring, visuospatial mapping

• Lesions in the dominant hemisphere: motor mapping and monitoring, language mapping more or less visuospatial mapping for parietal lesions

Intraoperative Protocol

The intraoperative protocol includes anesthesia modalities, neurophysiology, neuropsychology, and intraoperative imaging.

Anesthesia

Total intravenous anesthesia with propofol and remifentanil is used in our institution for performing these procedures. Newer drugs, such as dexmedetomidine, are emerging as effective and safe in producing sedation without inducing respiratory depression and without affecting electrophysiologic monitoring. In patients requiring only motor mapping, the patient is intubated through the nose and a light surgical anesthesia is maintained throughout the procedure. No muscle relaxants are employed during surgery to allow neurophysiologic assessment. When language or the visuospatial functions have to be tested during surgery, the patient can be maintained either awake during the entire surgery, or awakened for the phase of the surgery during which the mapping is performed.^18,^30,^36,^39,^44,^56,⁶³^–⁶⁵ In our institution, patients receive a laryngeal mask that is maintained until after the craniotomy and dural opening. At this point, the patient is awakened, while adequate analgesia is maintained to allow function monitoring. Time for awakening varies between 20 to 50 minutes, depending on the ability of the patient to metabolize the anesthetics. The anesthesiologist should be able to keep the patient awake for the entire time of subcortical mapping, which may be required particularly during long-lasting operations to alternate rest periods with those awake and responsive periods. Fatigue is observed in most of the patients, and its appearance correlates with duration of mapping, and the test difficulties (extensive language and visuospatial mapping).^25,⁴⁴ Five percent of patients require suspension of mapping for a period longer than 20 minutes. The occurrence of seizures is the most important complication during the awake time of surgery, and can be controlled either by cold saline irrigation or by the infusion of a small bolus (1 ml) of propofol. Partial seizures occurred in our series in 4% of patients during surgery, and were related to mapping. Generalized seizures occurred in two patients at the end of the craniotomy. These two patients required reintubation. Vomiting is a rare complication, and can be controlled by the administration of antiemetics at the beginning of the mapping phase.

Neurophysiology

The major components of the neurophysiologic protocol are monitoring (EEG, ECoG, EMG, MEP) and mapping (DES) procedures ^11,^31,^60,⁶⁶^–⁶⁸ (Table 9-1).

TABLE 9-1 Summary of Clinical Experience for 503 Patients with Low-Grade Gliomas Treated at University of Milan

EEG activity is recorded bilaterally by four subdermal needle electrodes, providing four bipolar leads. EEG is registered to monitor brain activity when EcoG is not available, that is, at the beginning and the end of surgery, when titrating the level of anesthesia is particularly useful. It also allows assessing brain activity at a distance from the operating field, such as in the contralateral hemisphere.

The EcoG activity is recorded from a cortical region adjacent to the area being stimulated, by means of subdural strip electrodes with four to eight contacts in a monopolar array, referred to a midfrontal electrode. Cerebral activity is recorded with a bandpass of 1.6 to 320 Hz, and displayed with a sensitivity of 50 to 100 microns per centimeter for EEG and 200 to 400 microns per centimeter for EcoG. Continuous electrocorticographic recordings (Comet, Grass) are used during the entire duration of the procedure to monitor the brain basal electrical activity and the level of anesthesia, to define the working current, and to monitor for the occurrence of afterdischarges, electrical seizures or even clinical seizures during the resection. Because of this, EEG and ECoG recordings should be kept during the entire duration of the operation.

Continuous multichannel EMG recording (Comet, Grass, or Inomed ISIS) is used throughout the entire procedure. Several separate muscles (agonist and antagonist muscles) can be monitored, either in the contralateral or ipsilateral body. Motor responses are collected by pairs of subdermal hooked needle electrodes inserted into the contralateral muscles from face to foot. The most used setting is comprehensive of face (upper and lower face), neck, arm, forearm, hand, upper leg, and lower leg. In addition to EMG recordings, motor activity is also evaluated clinically.

MEP recording allows continuous monitoring of motor function. The “train of five technique,” which was introduced for surgery in anesthetized patients, has been described as sensitive in detecting imminent lesions of the motor cortex and the pyramidal pathways.⁶⁹ For this purpose, a strip containing four to eight electrodes is placed over the precentral gyrus. A single stimulus or a double pulse stimulus (individual pulse width 0.3–0.5 millisecond, anodal constant current stimulation, interstimulus interval 4 milliseconds, stimulation intensity close to motor threshold) is usually delivered. MEP recording is usually alternated with direct cortical and subcortical motor mapping. MEP monitoring is very useful because it provides real-time information on the integrity of the motor pathways during the resection of large parts of the tumor not closely related to the functional structures. In addition, MEP provides warnings of impending brain ischemia, due to critical vessel interruption, mostly in deep temporal or insular regions.⁵²

Direct electrical stimulation (DES) for cortical and subcortical mapping is usually performed by the use of a bipolar handheld stimulator with a 1-mm electrode-delivered stimulation, tips 5 mm apart, connected to an Ojemann Cortical Stimulator (Integra Neuroscience) or an Osiris or ISIS stimulator (Inomed, Germany), which delivers biphasic square-wave pulses, each phase lasting 1 millisecond, at 60 Hz in trains lasting 1 to 2 seconds for cortical mapping and 1 to 4 seconds for subcortical mapping. Subcortical mapping is alternated with the resection in a back-and-forth fashion. Subcortical mapping is performed by using the same current threshold applied for cortical mapping. Alternatively, monopolar stimulation can be used, either cortically or subcortically, by delivering a single- or double-pulse stimulus, according to the train-of-five technique.

To start the mapping procedure, the working current is established. As movement is easy to observe, it is advisable to start the procedure with motor function mapping. Once the intensity of the current for stimulation is determined, the same is used in most cases throughout the procedure. Initially, a low current intensity (2 mA) is used, which is then progressively increased until a movement is induced. A stimulus duration of 1 or 2 seconds is usually enough to generate a motor response. At this point, it is good practice to stimulate the areas close to that in which the current induced the movement, map them, and check whether the current is able to evoke motor responses in these zones as well. If not, the current intensity may be increased and adjusted to evoke appreciable motor responses. It is also recommended to check with the ECoG if the applied current may induce afterdischarges in nearby brain areas. Only the current immediately below those inducing afterdischarges have to be used for mapping. If afterdischarges are seen, the current should be set up at least 0.5 mA under the previous one. In any case, ECoG recording is used to detect the appearance of afterdischarges during mapping in order to keep the test reliable. In fact, only the responses evoked in the absence of afterdischarges are considered trustworthy.

For language mapping, the initial test used is counting. The current is usually applied to the premotor cortex related to the face, and the test is aimed at determining whether the current stops the patient from counting. This has to be repeated several times and counting stopped at least three times in order to be reliable.⁴¹ If not, the current intensity is increased until these results are produced. When the current is established, DES is applied to the entire exposed surface of the brain, and the occurrence of afterdischarges checked in the ECoG. The stimulus duration is between 1 to 4 seconds. Only the current that is not inducing afterdischarges in the entire stimulated cortex is used for mapping. In case of afterdischarges, the current intensity is decreased by at least 0.5 mA.

For subcortical mapping, either the same current used for cortical mapping or a current raised to 2 mA is applied, and the stimulus is continuously alternated with the resection. When a response was induced at a subcortical level, performing an intensity–response curve is recommended to assess maintenance of the response either at very low current-intensity levels. This can help in estimating the distance between the point of stimulation and the functional tract (Fig. 9-2

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