**5. Outcome assessment**

While the initial assumption was that no electrically identified areas should be removed if postsurgical language complications are to be avoided, it was later increasingly assumed that postsurgical language deficits would not occur only if cortex that did not result in language deficits with electrical stimulation was removed (Sanai et al., 2008). This indirect message is gaining strength, although most studies lack pre- and postoperative global assessment and objective determination of cognitive complications. Furthermore, the original assumption that resection of any essential language areas will result in postoperative aphasia has not yet been definitively confirmed nor has the assumption that sparing positive sites for naming task will result in sparing of other language functions (Hamberger, et al., 2005; (Peraud, et al., 2004; Petrovich Brennan, et al., 2007; Seek, et al., 2006; Whittle, et al., 2003, 2005).

Moving from intraoperative naming-assisted surgical resection to other language and cognitive tasks, before relying on new protocols we need a multi-staged system of evidence for the potential and limitations of AS for cognitive mapping, its clinical validity for a single task or battery of tasks and technical standardization (intentionally addressed in the present article). Meanwhile, patient safety must be guaranteed by accurate comparative assessment, which should be discussed and defined (Lacroix et al., 2001; Vives & Piepmeier, 1999).

#### **5.1 The value of glioma extent of resection**

Microsurgical resection remains a critical therapeutic modality for all gliomas (Black, 1998; Guthrie & Laws, 1990; Keles et al., 1999; Yasargil et al., 2004). For all gliomas, the

Surgical Treatment of Supratentorial Glioma in Eloquent Areas 311

then to 2-10% over the next months (Bello et al., 2008; Duffau 2005; Nariai et al., 2005). The degree of worsening varies substantially depending on the clinical scale used, arbitrarily classified at one level, with a high and low cut-off, which means great differences in deficits, at two levels (mild, moderate-severe) or at three levels (mild, moderate, severe) (Duffau, 2005; Hamberger, 2007; Nariai et al 2005; Seeck et al., 2006; Simos et al., 1999). A few authors used preoperative specific test categories for postoperative evaluation, site by site (Bello et al., 2008; Lucas et al., 2004; Lubrano et al., 2004). Nevertheless, when objective evaluations were adopted, as for motor mapping, the trend was very similar, with lower rates (20%), probably due more reliable testing (Talacchi et al 2010a; Reithmeier et al., 2003; Signorelli et

Postoperative changes in cognitive functioning depend partly on the patient's level of preoperative abilities, especially in impaired patients (Gupta et al., 2007; Ojemann, 1979, 1983; Ojeman G.A. & Mateer, 1979). This makes the assessment strategy crucial from the

Preoperative cognitive assessment is a neglected issue, but of great significance since about 80% of patients present with some degree of impairment (Talacchi et al., 2010b; Tucha et al., 2000). On the other hand, with pre- and intraoperative cognitive assessment, an extended postoperative assessment, including language and other cognitive functions, is required since research is based on the verification of the initial hypothesis and on unexpected results

Some authors found poor agreement when comparing neuropsychological tests with neurological examination and self-assess, especially in cognition, properly expressed only by neuropsychological testing (Pahlson, et al., 2003). Mental problems proved to have a greater impact on QoL than physical problems, which are specifically expressed by KPS, demonstrating that neuropsychology is a sensitive tool for analyzing brain performance, rather than self-assessment and neurological examination (Giovagnoli et al., 2004; Gustafsson et al., 2006; Påhlson et al., 2003; Taphoorn et al., 1992). In addition, specific cognitive domains such as verbal memory were found to be a better predictor of survival than KPS (Meyers et al., 2000). Accordingly, the main rationale for brain mapping, the preservation of QoL, is still largely biased by inadequate measures whenever they are used.

Some methodological shortcomings derive from the inappropriate transition from

 Mapping is not a uniform technique, but rather it differs as regards area, function, task, electrical parameters and responses evaluation. Consequently, it requires case-by-case

 The aim is a common methodological framework and personalized intraoperative tasks. Mapping the tumor periphery sistematically and mapping impaired patients remain

 Moving from cortical naming-assisted surgical resection to other language and cognitive tasks, poor clinical assessment still limits technical development of tasks and

beginning, since it can limit interpretations of final results (Hamberger et al., 2003).

al., 2001).

**5.2.3 Functional outcome** 

**6. Conclusions** 

validation.

as well as on safety (Vives & Piepmeier, 1999).

epilepsy surgery to tumor surgery.

unsolved and difficult tasks.

image-guided mapping .

identification of universally applicable prognostic factors and treatment options remains a great challenge. Among the many tumor- and treatment-related parameters, only patient age and tumor histological characteristics have been identified as reliable predictors of patient prognosis, although tumor location in an eloquent area and the patient's functional status can also be statistically significant. With significant advances in brain tumor imaging and intraoperative technology during the last 15 years, some reports showed that improved extent of resection has a significant effect on both tumor progression and overall survival (Bauman et al., 1999; McGirt et al., 2008; Sanai et al., 2010; Smith et al., 2008). Although LGGs and HGGs are distinct in their biology, clinical behavior and outcome, understanding the efficacy of surgery remains equally important for both.

As concerns longer overall survival, more aggressive resection for LGGs can also influence the risk of malignant transformation, raising the possibility that surgical intervention can alter the natural history of the disease (Sanai & Berger, 2008). These associations are evident not only in the patient population with hemispheric LGGs but also in those with specific LGGs limited to specific eloquent subregions such as insular LGGs (Chaichana et al., 2010; Sanai et al., 2010; Simon et al., 2009; Smith et al., 2008).

#### **5.2 Clinical outcome**

The assumption is that every attempt should be made to preserve neurological functions in order to maintain the preoperative QoL, which is the main clinical outcome. However, postoperative settings vary greatly, often including focal evaluation for the related eloquent area but rarely accounting for complications or a wider battery of cognitive evaluations. Inadequate preoperative assessment can limit postoperative assessment and may lead to overlooking some functions which, though not tested intraoperatively, may still hold prognostic importance.

Interestingly, the peri-operative period, which traditionally lasts for 30 days after surgery, was prolonged in some studies to 3-4 months or up to 12 months, a period conventionally used to define permanent deficits (Duffau et al., 2001; Duffau et al., 2003b; Seitz et al., 1995).

#### **5.2.1 Surgical outcome**

The rationale for any treatment is bring about benefit superior to the natural history of the disease and to other treatments. The primary aim is to improve neurological outcome by relieving mass effect on normal brain structures without causing damage. Here, the Glioma Outcome Project deserves mention because it classified postoperative outcome and prospectively provided data for a large number of cases, Class II data, a benchmark for future studies. In this study, the majority of the patients improved (53%), while neurological, regional and systemic complications accounted for 8.1%, 10% and 9.2%, respectively, as observed at 21 days postoperatively. Unfortunately, eloquent areas were not specifically classified (Chang et al., 2003).

#### **5.2.2 Focal outcome**

While AS is claimed to decrease postoperative morbidity in eloquent areas, immediate postoperative evaluation showed a high rate of worsening of these functions, usually above 50%, which can be explained by the surgeon's confidence when working with eloquent areas, as demonstrated by progressive improvement within a few weeks (Keles et al., 2004; Talacchi et al., 2010a). At 3 months, this percentage usually decreases to less than 20% and then to 2-10% over the next months (Bello et al., 2008; Duffau 2005; Nariai et al., 2005). The degree of worsening varies substantially depending on the clinical scale used, arbitrarily classified at one level, with a high and low cut-off, which means great differences in deficits, at two levels (mild, moderate-severe) or at three levels (mild, moderate, severe) (Duffau, 2005; Hamberger, 2007; Nariai et al 2005; Seeck et al., 2006; Simos et al., 1999). A few authors used preoperative specific test categories for postoperative evaluation, site by site (Bello et al., 2008; Lucas et al., 2004; Lubrano et al., 2004). Nevertheless, when objective evaluations were adopted, as for motor mapping, the trend was very similar, with lower rates (20%), probably due more reliable testing (Talacchi et al 2010a; Reithmeier et al., 2003; Signorelli et al., 2001).

## **5.2.3 Functional outcome**

310 Advances in the Biology, Imaging and Therapies for Glioblastoma

identification of universally applicable prognostic factors and treatment options remains a great challenge. Among the many tumor- and treatment-related parameters, only patient age and tumor histological characteristics have been identified as reliable predictors of patient prognosis, although tumor location in an eloquent area and the patient's functional status can also be statistically significant. With significant advances in brain tumor imaging and intraoperative technology during the last 15 years, some reports showed that improved extent of resection has a significant effect on both tumor progression and overall survival (Bauman et al., 1999; McGirt et al., 2008; Sanai et al., 2010; Smith et al., 2008). Although LGGs and HGGs are distinct in their biology, clinical behavior and outcome, understanding

As concerns longer overall survival, more aggressive resection for LGGs can also influence the risk of malignant transformation, raising the possibility that surgical intervention can alter the natural history of the disease (Sanai & Berger, 2008). These associations are evident not only in the patient population with hemispheric LGGs but also in those with specific LGGs limited to specific eloquent subregions such as insular LGGs (Chaichana et al., 2010;

The assumption is that every attempt should be made to preserve neurological functions in order to maintain the preoperative QoL, which is the main clinical outcome. However, postoperative settings vary greatly, often including focal evaluation for the related eloquent area but rarely accounting for complications or a wider battery of cognitive evaluations. Inadequate preoperative assessment can limit postoperative assessment and may lead to overlooking some functions which, though not tested intraoperatively, may still hold

Interestingly, the peri-operative period, which traditionally lasts for 30 days after surgery, was prolonged in some studies to 3-4 months or up to 12 months, a period conventionally used to define permanent deficits (Duffau et al., 2001; Duffau et al., 2003b; Seitz et al., 1995).

The rationale for any treatment is bring about benefit superior to the natural history of the disease and to other treatments. The primary aim is to improve neurological outcome by relieving mass effect on normal brain structures without causing damage. Here, the Glioma Outcome Project deserves mention because it classified postoperative outcome and prospectively provided data for a large number of cases, Class II data, a benchmark for future studies. In this study, the majority of the patients improved (53%), while neurological, regional and systemic complications accounted for 8.1%, 10% and 9.2%, respectively, as observed at 21 days postoperatively. Unfortunately, eloquent areas were not

While AS is claimed to decrease postoperative morbidity in eloquent areas, immediate postoperative evaluation showed a high rate of worsening of these functions, usually above 50%, which can be explained by the surgeon's confidence when working with eloquent areas, as demonstrated by progressive improvement within a few weeks (Keles et al., 2004; Talacchi et al., 2010a). At 3 months, this percentage usually decreases to less than 20% and

the efficacy of surgery remains equally important for both.

Sanai et al., 2010; Simon et al., 2009; Smith et al., 2008).

**5.2 Clinical outcome** 

prognostic importance.

**5.2.1 Surgical outcome** 

**5.2.2 Focal outcome** 

specifically classified (Chang et al., 2003).

Postoperative changes in cognitive functioning depend partly on the patient's level of preoperative abilities, especially in impaired patients (Gupta et al., 2007; Ojemann, 1979, 1983; Ojeman G.A. & Mateer, 1979). This makes the assessment strategy crucial from the beginning, since it can limit interpretations of final results (Hamberger et al., 2003).

Preoperative cognitive assessment is a neglected issue, but of great significance since about 80% of patients present with some degree of impairment (Talacchi et al., 2010b; Tucha et al., 2000). On the other hand, with pre- and intraoperative cognitive assessment, an extended postoperative assessment, including language and other cognitive functions, is required since research is based on the verification of the initial hypothesis and on unexpected results as well as on safety (Vives & Piepmeier, 1999).

Some authors found poor agreement when comparing neuropsychological tests with neurological examination and self-assess, especially in cognition, properly expressed only by neuropsychological testing (Pahlson, et al., 2003). Mental problems proved to have a greater impact on QoL than physical problems, which are specifically expressed by KPS, demonstrating that neuropsychology is a sensitive tool for analyzing brain performance, rather than self-assessment and neurological examination (Giovagnoli et al., 2004; Gustafsson et al., 2006; Påhlson et al., 2003; Taphoorn et al., 1992). In addition, specific cognitive domains such as verbal memory were found to be a better predictor of survival than KPS (Meyers et al., 2000). Accordingly, the main rationale for brain mapping, the preservation of QoL, is still largely biased by inadequate measures whenever they are used.
