Introduction: Surgical Management of Eloquent Area Tumors

Interconnecting Cognitive Neuroscience With Tumor Biology

Unlike cancers affecting other solid organs, brain tumors grow within the context of complex neural circuitry. The adult brain is comprised of nearly 1 billion neurons and over 1 trillion network connections; consequently, regardless of location, all intrinsic brain tumors interface with nervous system structures. There are several preclinical models illustrating the nervous system's influence on tumor progression and tumors’ influence on nervous system functions.^1-8 Therefore, interactions between intrinsic brain tumors such as gliomas and brain metastases with their neuron microenvironment are an important element for both tumor biology as well as cognitive, language, and sensorimotor processing.^9,10 The surgical management of brain tumors has remained a central theme in management. For example, patients with both low- and high-grade gliomas experience a survival benefit with maximal extent of tumor resection.^11-13 Even in the era of molecular subclassification, glioma patients with poor prognostic molecular markers may experience survival periods similar to molecularly favorably subgroups when maximal extent of resection is achieved.¹³ There are, however, distinct brain regions in which intrinsic brain tumors and their associated perilesional edema disrupt network dynamics with neurological consequences. In describing this process, clinicians use the term “functional neural networks,” which leads to the idea of eloquent regions of brain. Eloquent cerebral structures are defined as areas of the brain with readily identifiable neurological function, in which injury results in disability.¹⁴ Brain tumor–associated neurological dysfunction is thought to occur in the setting of three situations: (1) infiltration of tumor into cortical and subcortical network structures, (2) lesions sustained following cytoreduction surgery, and (3) through oncological therapeutic interventions such as brain irradiation and chemotherapy.^9,15 Within clinical neurosurgery, there must be a balance between the relative survival benefits associated with maximal resection against functional impairments established by tumor network integration as well as oncological therapies. This process is often called “onco-functional balance.”

In the surgical management of eloquent area intrinsic brain tumors, neurosurgeons play a central role in treatment through tumor resection. Tumor resection for eloquent area tumors must employ a nuanced understanding of both cognitive neuroscience (ie, managing neurological dysfunction associated with tumor network disruptions) and tumor biology (ie, understanding the benefits associated with extent of resection based on presumed molecular subtype). In this review series, we address topics central to surgery for eloquent area intrinsic brain tumors in 3 phases. Beginning with tumor network integration, we will review (1) differing rates of tumor-network disruption based on glioma molecular subclassification and (2) biomedical imaging tools used to interrogate tumor-network integration. Next, we will provide contemporary guides to (1) language and (2) cognitive processing. We will then review intraoperative tools and techniques used to maximize safety during removal of eloquent area brain tumors including (1) methods for intraoperative language mapping, (2) methods for intraoperative nonlanguage cognition mapping, (3) nontask-based passive brain mapping strategies, and (4) neuroanesthesia for asleep and awake functional mapping. Finally, we review outcomes and controversies in surgery for eloquent area tumors, including (1) outcomes following functional mapping vs non mapping of dominant temporal lobe gliomas, (2) the relationship between stimulation current and functional site localization during brain mapping, (3) clinical implications of central nervous system plasticity, (4) functional outcomes and health-related quality of life following glioma surgery, and (5) the role of postacute cognitive rehabilitation for adult brain tumor patients. Through this review series, we offer practical strategies to support the neurosurgical and neuro-oncology community caring for patients with intrinsic brain tumors within eloquent brain regions.

Funding

This study did not receive any funding or financial support.

Disclosures

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Dr Hervey-Jumper receives support from Robert Wood Johnson Foundation 74259, NINDS K08 110919-01, and the Loglio Collective.