**3. Intraoperative setting**

300 Advances in the Biology, Imaging and Therapies for Glioblastoma

supports the concept that resection should ideally go beyond the gross tumor margin apparent on preoperative imaging. Therefore, it is not only patients with tumors located within the frontal operculum who may benefit from intraoperative language mapping, but also those with lesions in proximity to this region because of the significant variability in this region's anatomical and functional organization (Edeling et al., 1989; Quiñones-

Possible causes of damage are: trajectory in subcortical tumors; abnormal anatomy in recurrent tumors; distorted anatomy due to the tumor; tumor infiltrating the functioning brain in LGGs; irregular tumors; and tumor periphery in HGGs. All are known to be crucial factors for surgical outcome, and knowledge of the structural characteristics of eloquent areas may help the surgeon to avoid clinical consequences. Aims may be categorized as linked to: 1) orientation, which is usually not histology-dependent (trajectory, abnormal anatomy, distorted anatomy); and 2) removal, usually used for specific gliomas (low-grade,

Considerable advances in functional imaging have been made in both technology and availability, raising the question of whether it may eventually supplant intraoperative ECS mapping. Devices such as fMRI and PET units may aid in the preoperative planning of resection strategy, but these techniques, while reliable for detecting the motor area, remain too imprecise for complex functions such as language mapping where their sensitivity (PET, 75%; fMRI, 81%) and specificity (PET, 81%; fMI, 53%) are suboptimal. (Fitgerald et al., 1997; Herolz et al., 1996, 1997). These modalities highlight language-associated areas of indeterminate significance, and they do not offer real-time information intraoperatively. To this end, MRI neuronavigational techniques can facilitate not only greater resection, but embedding of DTI can also prevent inadvertent resection of adjacent subcortical pathways (Talos et al., 2007; Wu et al., 2007). Although the use of DTI has not been shown to impact directly on patient survival, its utility resides in maximizing tumor resection while minimizing morbidity. Nevertheless, for the identification of functional language pathways and guidance of safe tumor removal, these diagnostic imaging tools remain supplements to,

In glioma surgery, the approach to subcortical diffuse gliomas and the decision to resect the infiltrated brain surrounding the tumor core are the cornerstones of modern, aggressive surgical strategy. This is the rationale for a sound command of knowledge of brain functions at the tumor margin in individual cases. Non-enhancing tumor periphery, pattern (sharp or blurred) and characteristics (edema or infiltrated brain) constitute the challenging part of the operation where most effort is concentrated. MRI, FLAIR and T2 weighted images will visualize structural properties but their priority is controversial. Spectroscopy and DTI have been advocated as promising tools for delineating the extent of tumor infiltration (Price, et al., 2003; Stadbauer, et al., 2004, 2006). In addition, anisotropy measures have attempted to differentiate edema from infiltrated brain (Lu, et al., 2003, 2004). In contrast, perfusion can help to distinguish tumor grading but has not

Hinojosa et al., 2003).

irregular margins, periphery).

**2.4.1 Functional imaging for eloquent tissue localization** 

not substitutes for, direct intraoperative stimulation mapping.

**2.4.2 Structural imaging for tumor periphery localization** 

given information about the periphery so far.

AS is a challenge for a working team, since it implies substantial modifications in the professional behavior of all physicians involved: for the surgeon working in an uncomfortable situation; the anesthesiologist monitoring the patient continuously; the neuroradiologist awaiting intraoperative confirmation of interpretation of findings; the neuropsychologist making real-time evaluation of scans. AS involves a complex scenario: integration of different types of knowledge, organization of a heterogeneous team, cooperation in different settings (operating room, ward, out-patient clinic), surgical and research protocols to be adopted, technical adjustments to make the research comparable.

### **3.1 Anesthesiology**

Awake surgery is performed as follows. Continuous sedation (Sarang, et al.,2003) was achieved with rapidly acting agents and infiltrative anaesthesia of the scalp. Airway management remains a concern due to the risk of aspiration or oversedation with oxygen saturation <90%. Patients breathe spontaneously during awake surgery. Propofol, fentanyl, remifentanyl and midazolam are commonly used agents. Volatile anaesthetics should not be given because they interfere with electroencephalographic (EEG) recording and cause a dose-dependent distortion on the EEG, with vasodilatation resulting in increased intracranial pressure (ICP) (Himmelseher, et al., 2001). While propofol can also alter the EEG (Herrick, et al., 1997), intravenous drugs are preferable because of their rapid onset and easily manageable duration of action which causes no nausea or vomiting. The sedation level is very important since oversedation results in an uncooperative patient and medical problems (i.e., respiratory depression), whereas undersedation makes the patient uncomfortable and restless. For this purpose, the Modified Observer's Assessment of Alertness/Sedation Scale (Bauerle, et al., 2004) was used.

The feasibility and efficacy of AS have been studied in comparison with general anesthesia (GA). The absolute anesthesiologic exclusion criteria for AS are obstructive sleep apnea and difficult intubation (Picht et al., 2006). Parameters for comparing GA versus AS:


Surgical Treatment of Supratentorial Glioma in Eloquent Areas 303

intraoperative mapping, and a more time-efficient neurosurgical procedure (Sanai et al.,

Essential devices for accurate surgical techniques are the intraoperative microscope and the ultrasonic aspirator. The neuronavigator has a multipurpose application: define the cortical boundaries of lesions, especially in LGGs; establish the site of corticectomy and the trajectory to subcortical lesions; provide image-assisted surgery for both fMRI (motor task) and DTI; and establish the distance to anatomical landmarks. These advantages are limited to the first part of the operation prior to brain shift. In this regard, intraoperative MRI is a promising tool for improving accuracy in subcortical mapping of fascicles and functions.

The intraoperative mapping technique involves selecting the tasks in relation to preoperative assessment, the operative tools, the neurophysiologic parameters and the consequent strategy, i.e., the way we combine them in a clinical situation. Taken together, these costly and time consuming procedures point to the importance of methods and

One substantial limitation to clinical comparative inference is that multiple cortical or subcortical sites are manipulated during an operation making it impossible to relate one event to the manipulation of one site. In other words, when forced to face a number of methodological issues, it is likely that surgical strategy will improve. Choices regarding positioning, surgical technique, tumor definition, clinical and intraoperative information, functional studies, intraoperative tools, all together will favor a good result. In contrast, consideration of only one or a few functional variables may be confounding. This is why research studies should be validated in the clinical setting, taking into account additional variables critical for this purpose (Sawaya et al., 1998). Furthermore, the challenge of AS and cognitive mapping is the working team, i.e., to what extent individual proficiency can

Yasargil lesson's may be summarized as follows: 1) glioma is an infiltrative tumor only in its advanced stages of growth; 2) its growth pattern follows functional pathways and respects compartmental boundaries (neo-archipallial, central nuclei, white matter and ventricles); and 3) tumor debulking starts from the center and proceeds in a circumferential manner till the white matter is exposed ("the deflating ball and one window" techniques) (Yasargil,

This last point is justified by the risk of damage to adjacent brain areas and forms the basic principle of resection strategy. In light of recent pathological and functional knowledge, however, this defensive strategy for treating both LGGs and HGGs, which seeks foremost to avoid brain injury without considering the infiltrated brain or the functional characteristics of adjacent brain areas, now seems largely unwarranted. Nonetheless, it is not an absolutely safe technique, since HGGs are often highly vascularized tumors and bleeding may mask vascular or parenchymal structures and result in involuntary injury. Moreover, tumor manipulation may induce tissue swelling and physical modifications, altering the typical

2008).

**3.5 Surgical instruments** 

**4. Surgical resection strategy** 

contribute to a clinical purpose when working in a group.

**4.1 The traditional approach (Yasargil's lesson)** 

1996b, 1996c; Yasargil et al., 2004).

surgical strategy.

of patients, whereas other studies have reported rates as high as 16% (Bello et al., 2007; Petrovich Brennan et al., 2007; Serletis et al., 2007; Taylor & Bernstein, 1999). Some authors advocated the use of propofol to reduce intraoperative seizures (Berkenstadt et al., 2001; Danks et al., 1998; Gignac et al., 1993; Herrick et al., 1997; Huncke et al., 1998; Sarang, & Dinsmore, 2003).

