**1. Introduction**

294 Advances in the Biology, Imaging and Therapies for Glioblastoma

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Awake surgery (AS) and cortical mapping have gained wider acceptance for a variety of reasons: new anesthetic agents, improved surgical techniques, increasing use of functional magnetic resonance (fMRI), and growing interest in brain mapping as shown by refinements and upgrading of imaging techniques, such as magnetoencephalography, evoked responses potentials, high density electroencephalography, positron emission tomography (PET), and optical imaging among others (Bookheimer et al., 1997; Nariai et al., 2005; Papanicolau et al., 1999; Pouratian et al., 2002; Ruge et al., 1999; Rutten et al., 1999; Simos et al., 1999). Information technology and image-guided surgery have prompted researchers to compare non-invasive versus invasive mapping while the patient is awake (Hill et al., 2000; Kamada et al., 2007; Rutten et al., 2002). Cortical mapping has rapidly evolved, but the technical characteristics of electrocortical stimulation (ECS) have remained essentially the same since Penfield's time and it is still considered the gold standard for mapping language (Fitzgerald et al., 1997; Pouratian et al., 2004; Weidemayer et al., 2004). During cortical stimulation, task disruption is taken to indicate that the underlying cortex is essential for task performance. What has changed is the increasing feasibility of mapping the brain in vivo in a way that is safe and acceptable for the patient, and the opportunity to use a broad variety of selective tasks in standardized conditions (Bulsara et al., 2005; Serletis & Bernstein, 2007; Sielbergeld et al., 1992). This has stimulated translational research and cooperation between neuroscientists and neurosurgeons from the basic sciences to clinical applications.

#### **1.1 Historical background**

Direct ECS has been used in Neurosurgery since 1930, first by Foerster, and then later by Penfield and colleagues (Foerster, 1931; Penfield & Boldrey, 1937; Penfield & Erickson, 1942;

Surgical Treatment of Supratentorial Glioma in Eloquent Areas 297

mapping techniques, like fMRI and DT imaging–based tractography (DTI), should be

Candidates for awake surgery face an unpredictable experience. To date, the choice depends on the patient who will have received a detailed description of the procedure and provided fully informed consent. Although awake craniotomy is generally considered to be well tolerated, complications such as emotional distress and agitation are not uncommon, with loss of control, the need for more sedation and failure of the mapping project. Failure rates due to agitation vary from 2 to 8% but are not systematically reported (Danks et al., 1998;

Together with imaging, symptoms and objective findings will guide the surgical strategy. Disturbances in language-related functions, whether transient or progressive, functional or organic, are more indicative of operative risks than the lesion location itself (Benzagmout et al., 2007; Peraud et al.,2004). The standard assessments for dominance are the Edinburgh handness test, the Wada test and/or fMRI with the verb generation task (Duffau et al.,

The second step in patient assessment is neurological examination. It can reveal motor impairment (Medical Research Council scale, John, 1984) and disturbances in speech and cognition; however, it cannot provide reliable or sufficient information about the type of dysphasia or specific classification nor recognize mild impairments. This is an important drawback, since the rate of patients with mild-moderate deficits undergoing AS for mapping is quite high (26-55%) (Bello et al., 2007; Sanai et al., 2008; Skirboll et al., 1996). While there is general consensus that mapping requires that patients present no significant disturbance at intraoperative task testing, some authors have underlined the utility of preoperative assessment, showing how sensitive tasks can maximize testing efficiency. The clinical aim is to recognize preserved functions or subprocesses in order to preserve them intraoperatively (Petrovich Brennan et al., 2007; Pouratian et al., 2003). This research can be pursued through consultation with a group of cognition experts during operative planning to develop personalized tests and tasks for a given patient. Specific functions include: spontaneous speech; language fluency; object naming; written/oral comprehension; reading; dictation; and repetition (baseline for French authors). Added to these are tasks involving writing sentences and words, oral controlled association by phonetic cue and semantic cue, famous face naming, action picture naming, transcoding tasks (Bello et al., 2007; Sanai et al., 2008). Nevertheless, evaluation was limited to the naming task before intraoperative assessment in the majority of cases (Haglund et al., 1994; Hamberger et al.,

Reviewing the literature, the role of the neuropsychologist in AS is seldom defined in relation to treatment and little attention has been paid to the impact of primary brain tumors on QoL (Buckner et al., 2001; Giovagnoli & Boiardi, 1994; Taphoorn et al., 1992, 2005; Weitzner et al., 1996; Weitzner & Meyers, 1997). Differently from other cancer patients, where the burden of the disease is assessed, in brain tumor patients a decrease in cognitive and emotional functioning may be the result of cerebral disease. Subclinical symptoms, personality changes and mood disturbances may prove to be as burdensome to patients, or

compared with ECS to determine their sensitivity and specificity.

**2.1.1 Patient cooperation and compliance in awake surgery** 

Sahjipaul, 2000; Whittle et al., 2005).

2003a).

2005; Ojemann, 1989).

**2.1.2 Preoperative clinical assessment** 

Penfield & Rasmussen, 1950). In recent years, intraoperative ECS has been adopted for the identification and preservation of language function and motor pathways. Of note is that while cortical mapping was originally applied to epilepsy surgery where resection is essentially limited to the cortex, its indications were later extended to tumor surgery which involves the white matter. Whether these differences result in different clinical and operative settings is unclear and there exist mixed situations between the two extremes. The pathology that benefits most from AS is low-grade glioma (LGG). LGGs pose a considerable challenge in that they have characteristics of both epilepsy and tumors, with a long history that could influence neurofunctional anatomy in patients presenting normal neurological findings (Duffau et al., 2005; Duffau, 2005b, 2006a, 2006b, 2007). Importantly, tumor surgery and epilepsy surgery differ as to the aims of treatment: minimizing neurological sequelae is only one aspect, which can be tailored to lesion characteristics, as determined by clinical and instrumental studies. Basically, the two pathologies differ in symptoms and impairment. Improvement of preoperative clinical impairment and radical tumor resection are the endpoints for tumor surgery, while improvement of preoperative performance is the end-point in epilepsy treatment (Buckner, 2003; Hamberger et al., 2007). In glioma surgery, the definitive clinical advantages are broader indications for tumor removal, higher rate of radical tumor resection, and lower rate of postoperative impairment (Duffau 2005a,b).

#### **1.2 Aim of brain mapping**

In surgical treatment of cerebral gliomas the goals are to obtain complete tumor removal to the extent the nature of the pathology allows and to accomplish this without injuring normal anatomic structures (Yasargil, 1996a). Although LGGs and high-grade gliomas (HGGs) are distinct in biological features, clinical behavior and outcomes, understanding the effect of surgery remains equally important for both. This is especially true for lesions in areas of eloquence, where the proximity of critical pathways can present a significant challenge to standard operative strategies. The concept of eloquent area is evolving and may be potentially extended to all measurable functions. Thanks to collaborative teamwork in neuroscience and neuro-oncology, current neurosurgical innovations aim to improve our anatomical, physiological, and functional understanding of the surgical region of interest with a view to prevent potential morbidity during resection and improve the patient's quality of life (QoL), an essential outcome measure.
