To achieve optimal survival and quality of life outcomes in patients with glioma, the extent of tumor resection must be maximized without causing injury to eloquent structures. Preservation of language function is of particular importance to patients and requires careful mapping to reveal the locations of cortical language hubs and their structural and functional connections. Within this language network, accurate mapping of eloquent white matter tracts is critical, given the high risk of permanent neurological impairment if they are injured during surgery. In this review, we start by describing the clinical implications of gliomas involving white matter language tracts. Next, we highlight the advantages and limitations of methods commonly used to identify these tracts during surgery including structural imaging techniques, functional imaging, non-invasive stimulation, and finally, awake craniotomy. We provide a rationale for combining these complementary techniques as part of a multimodal mapping paradigm to optimize postoperative language outcomes. Next, we review local and long-range adaptations that take place as the language network undergoes remodeling after tumor growth and surgical resection. We discuss the probable cellular mechanisms underlying this plasticity with emphasis on the white matter, which until recently was thought to have a limited role in adults. Finally, we provide an overview of emerging developments in targeting the glioma-neuronal network interface to achieve better disease control and promote recovery after injury.

Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Background

Elderly patients with glioblastoma (GBM) have a worse prognosis than do younger patients. The present study aimed to identify the patient, treatment, and imaging features, including measures of sarcopenia, associated with worse survival and 90-day postoperative mortality for elderly patients with GBM.

Methods

A single-center retrospective study was conducted of patients aged ≥79 years at surgery who had undergone biopsy or resection of a World Health Organization grade IV GBM at the initial diagnosis. Imaging features of sarcopenia were collected, including the masseter and temporalis muscle diameters. Multivariate analyses were performed to identify factors associated with survival and 30-day complications.

Results

The cohort included 110 patients with a mean age of 82.8 years at surgery and a median preoperative Karnofsky performance scale score of 80. The majority of patients underwent a surgical resection (66.4%) while a minority underwent biopsy (33.6%). Adjuvant chemo- and/or radiation therapy were used in 72.5% of the cohort. On multivariate analysis, age (hazard ratio [HR], 7.97; 95% confidence interval [CI], 1.63-36.3), adjuvant therapy (RT or TMZ vs. none: HR, 0.12; 95% CI, 0.05-0.3; RT plus TMZ vs. none: HR, 0.05; 95% CI, 0.02-0.14), surgical resection (HR, 0.46; 95% CI, 0.24-0.9), multifocality (HR, 2.7; 95% CI, 1.14-6.4), and masseter diameter (HR, 0.12; 95% CI, 0.02-0.78) were associated with survival. Masseter diameter was the only factor associated with 90-day mortality after surgical resection (P = 0.044).

Conclusions

GBM patients over the age of 79 have acceptable outcomes after resection, followed by adjuvant chemotherapy and RT. In addition to the treatment factors that predicted for survival, a decreased masseter diameter on preoperative imaging, a marker of sarcopenia, was associated with shorter overall survival and 90-day mortality after surgical resection.

Background

A majority of patients with insular tumors present with seizures. Although a number of studies have shown that greater extent of resection improves overall patient survival, few studies have documented postoperative seizure control after insular tumor resection.

Objective

To (1) characterize seizure control rates in patients undergoing insular tumor resection, (2) identify predictors of seizure control, and (3) evaluate the association between seizure recurrence and tumor progression.

Methods

The study population included adults who had undergone resection of insular gliomas between 1997 and 2015 at our institution. Preoperative seizure characteristics, tumor characteristics, surgical factors, and postoperative seizure outcomes were reviewed.

Results

One-hundred nine patients with sufficient clinical data were included in the study. At 1 yr after surgery, 74 patients (68%) were seizure free. At final follow-up, 42 patients (39%) were seizure free. Median time to seizure recurrence was 46 mo (95% confidence interval 31-65 mo). Multivariate Cox regression analysis revealed that greater extent of resection (hazard ratio = 0.2899 [0.1129, 0.7973], P = .0127) was a significant predictor of seizure freedom. Of patients who had seizure recurrence and tumor progression, seizure usually recurred within 3 mo prior to tumor progression. Repeat resection offered additional seizure control, as 8 of the 22 patients with recurrent seizures became seizure free after reoperation.

Conclusion

Maximizing the extent of resection in insular gliomas portends greater seizure freedom after surgery. Seizure recurrence is associated with tumor progression, and repeat operation can provide additional seizure control.

Intrinsic brain tumors often occur within functional neural networks, leading to neurological impairment and disability of varying degrees. Advances in our understanding of tumor-network integration, human cognition and language processing, and multiparametric imaging, combined with refined intraoperative tumor resection techniques, have enhanced surgical management of intrinsic brain tumors within eloquent areas. However, cognitive symptoms impacting health-related quality of life, particularly processing speed, attention, concentration, working memory, and executive function, often persist after the postoperative recovery period and treatment. Multidisciplinary cognitive rehabilitation is the standard of care for addressing cognitive impairments in many neurological diseases. There is promising research to support the use of cognitive rehabilitation in adult brain tumor patients. In this review, we summarize the history and usefulness of postacute cognitive rehabilitation for adult brain tumor patients.

Language, cognition, and behavioral testing have become a fundamental component of standard clinical care for brain cancer patients. Many existing publications have identified and addressed potential ethical issues that are present in the biomedical setting mostly centering around the enrollment of vulnerable populations for therapeutic clinical trials. Well-established guides and publications have served as useful tools for clinicians; however, little has been published for researchers who share the same stage but administer tests and collect valuable data solely for non-therapeutic investigational purposes derived from voluntary patient participation. Obtaining informed consent and administering language, cognition, and behavioral tasks for the sole purpose of research involving cancer patients that exhibit motor speech difficulties and cognitive impairments has its own hardships. Researchers may encounter patients who experience emotional responses during tasks that challenge their existing impairments. Patients may have difficulty differentiating between clinical testing and research testing due to similarity of task design and their physician's dual role as a principal investigator in the study. It is important for researchers to practice the proposed methods emphasized in this article to maintain the overall well-being of patients while simultaneously fulfilling the purpose of the study in a research setting.

Gliomas are a major cause of morbidity. Direct cortical stimulation mapping offers the ability to identify functional areas within the broader neural network both cortically and subcortically. Since the World Health Organization (WHO) 2016 classification categorized gliomas into molecular subgroups with varied molecular signatures and clinical behavior, it is possible that gliomas may demonstrate rates of functional network integration. We therefore retrospectively reviewed a data registry of 181 patients with dominant hemisphere frontal, parietal, insular, or temporal gliomas. Our goal was to test the hypothesis that WHO glioma histopathology and molecular subtype influences functional language or motor sites identified within the tumor. Intratumoral function as determined by direct cortical and subcortical stimulation mapping was identified at the highest rate in isocitrate dehydrogenase mutant astrocytomas and oligodendrogliomas. Finally, we reviewed the emerging literature exploring the interface between functional neural networks and gliomas. These data shed light on glioma molecular and histological characteristics most commonly associated within intratumoral function.