Gliomas and resection surgery
Most primary brain tumors occur in the cerebral cortex, gliomas are the most common type of them, representing more than 70% of all brain tumors. According to their histopathology they can be divided into astrocytoma, oligodendroglioma and ependymoma, the last two being the most prevalent . Glioblastomas are the most frequent (65%) primary brain tumor, and the most malignant histological type. At five years after diagnosis, less than 3% of glioblastoma patients survive.
In general, the three most common brain tumor locations are: frontal lobe (26%), temporal lobe (19%) and parietal lobe (12%) . According to Rasmussen et al. in a 1930 patient population with diagnosis of glioblastomas (grade I-IV), 1246 of those patients had a frontotemporal glioma (65%), followed by the parietal lobe (17%), occipital lobe (9%), cerebellum (1%) and 9% in other sites . Symptoms vary depending on the location; seizures are common as an initial symptom for frontal lobe tumors, deficits related to the auditory processing are due to by temporal lobe involvement, speech and perception deficits are seen with parietal lobe tumors . When the tumor is localized in the parietal lobe, 80% of the patients present parietal association deficit (PAD).
Despite being located at a critical junction for motor, language, visual and sensory pathways, parietal gliomas are an underrepresented entity in the neurosurgical literature, this area represents 30% of all high-grade gliomas and 10% of low-grade gliomas. Lesions in this integrative region frequently present with subtle symptoms affecting complex neurological functions (memory, language, character, visuospatial orientation), which require specific testing performed by a neuropsychologist to be detected. This kind of lesions, despite of being localized in eloquent areas, frequently present with more subtle symptoms affecting complex neurological functions (memory, language, character, visuospatial orientation and so on), which require specific testing performed by a neuropsychologist to be detected . According to Sanai N. et al. there are four primary parietal areas that were identified based on clinical and radiological observation, with two additional modified subregions, resulting in 6 collective areas. Areas 1 to 3 of the parietal lobe are mainly visible on the superior view, where Area 1 is in the supramarginal gyrus which extends to the postcentral gyrus (Area 1+), Area 2 defines the superior lobe, which extends to the postcentral gyrus (Area 2+), Area 3 refers exclusively the angular gyrus, and Area 4 comprises the cingulum .
The rationale of surgical treatment is based on the ability to provide an adequate specimen for histological diagnosis, genetic and molecular analysis, control the frequency of seizures (if any), diminish the burden of drugs and improve neurological symptoms directly related to the mass effect of the tumor on the cortex or on the functional fiber bundles. Finally, the extent of the resection can influence the overall survival and the period to malignant transformation (when low grade gliomas are present) . In many institutions,
such as ours, resection is the first option of treatment for gliomas, aiming for maximal resection, while minimizing postoperative morbidity.
Identification of cerebral areas involved in motor, language, memory, and visuospatial functions, need to be preserved during surgery through the intraoperative use of brain mapping techniques.
Thorough patient evaluation and selection is required to customize surgical planning and intraoperative mapping based on anatomofunctional characteristics of the patient and the lesion. Mild deficits are usually related to direct mass effect or infiltration of the tumor on the cortex or subcortical white matter tracts reference?.
A neuropsychological evaluation is mandatory when considering surgery for regions such as the parietal lobe, to detect subtle neurological alteration and adequately implement intraoperative testing. Neuroradiological examination is composed of the usual MR imaging (T1-weighted, T2 weighted, FLAIR, and Gd-enhanced T1 weighted), and volumetric sequences, which are useful to measure tumor volume and determine its relationship with various structures, such as major vessels. Further studies would include MR spectroscopy, which provides information on the metabolic profile of the tumor, and perfusion MR imaging studies, which may reveal areas of hyperperfusion, related to malignant transformation.
Functional studies such as the fMR imaging, and anatomical studies, such as Diffusion Tensor Imaging (DTI) fiber tracking, are useful to assess motor and language tasks and are utilized to evaluate the hemispheric dominance. DTI fiber tracking maps provide a reconstruction of the subcortical fiber bundles involved in motor (CST), language (SLF, IFO, ILF, and UNC), visuospatial function, and the visual tracts, which run around or inside the tumor mass. Data can be loaded into the neuronavigation system and help the surgeon in planning the resection [25, 4]. Visual acuity should be evaluated, as well as an assessment or the Humphrey automated perimetry in order to register campimetric defects or homonymous hemianopia .
Types of Craniotomy
Modern awake craniotomy originated as a means of excising epileptogenic foci and more recently, resecting tumors in functional cortical regions. One of its main advantages include defining tumor margins in order to maximize resections while preserving cortical or subcortical function. It has been associated with decreased postoperative morbidity, decreased intensive care admissions, and overall length of hospital stay . Also, it allows the surgical team to perform an intraoperative mapping of important functional brain regions .
In a literature review, 17 patients diagnosed with WHO grade II and III astrocytomas with no preoperative visual deficit underwent awake craniotomy, 14 surgeries resulted in quadrantanopia, 1 in hemianopia, and 2 without visual deficits, with high tolerability and patient satisfaction . Awake craniotomy has been used as it has been reported to be a safe and tolerable procedure that can effectively be used to preserve visual function during resection of tumors infiltrating the temporal, parietal, and occipital lobes. As mentioned before, typically a homonymous hemianopia due to damage to optical radiations or visual cortex is a possible consequence of tumor resection .
Surgical technique follows the same steps as mapping during craniotomy, as described by Kim, et al. . Utilizing preoperative functional tests as described before as comparison (as reference?/ to compare) during the procedure the patient was instructed to note any loss of vision or blurriness during stimulation, as well as the visual evoked potentials and the Humphrey visual field test. Previous reports described stimulation between 2 mA and 5 mA. Any area of stimulation that elicited a deficit was marked as a border for the resection .
On the other hand, asleep craniotomy with subcortical mapping can be used in virtue of new technological advances that can be employed along the procedure. According to Shahar et al. both phosphene-evoked stimulation and visual evoked potentials (VEPs) recordings are limited in their utility as warning tools to alert the surgeon of an imminent anatomical disruption of the OR . Subcortical mapping has been described previously as performed using a monopolar cathodal stimulator on the white matter corticospinal tracts .
Usually, irrigation with cold Ringer lactate solution is not required during subcortical stimulation because stimulation-induced activity does not occur in this setting .
Intraoperative monitoring in parietal glioma surgery
As a result, alternative techniques to intraoperative monitoring have emerged with the purpose of preventing and avoiding postoperative complications. MRI tractography, electrophysiological monitoring, and intraoperative ultrasound are some of the alternatives that have been proposed.
Direct electrical stimulation
Despite the emergence of various techniques for transoperative brain monitoring, nowadays the technique of choice for the reduction of post-surgical neurological damage is brain mapping guided by direct electrical stimulation (DES) . This procedure is performed in open craniotomies with the patient being awake and has been fundamental for procedures such as the resection of brain tumors and the localization of epileptogenic foci .
Intraoperative ultrasonography (US) has shown to be an excellent alternative for glioma patient intraoperative monitoring. As Hammoud, et al described it has been effective in localizing, defining margins, and making a differential diagnosis between the tumor from a cyst or necrosis, it also helps guide the surgeon in detecting residual tumor. It is easily accessible, affordable, and can locate and support the tumor mass during resection. In addition, to the possibility of having the image in real time .
Several studies have shown that 3-dimensional ultrasound, in combination with Doppler, can be used to identify vascular structures in the affected region of the brain and visualize the ventricles. These methods are an excellent alternative in resource-limited areas where other monitoring resources, such as intraoperative magnetic resonance, are unavailable [18, 34].
Diffusion Tensor Magnetic Resonance Imaging-Based Tractography
Diffusion Tensor Magnetic Resonance Imaging-Based Tractography (DTI) is a noninvasive magnetic resonance technique that can delineate the brain’s white matter. It works by measuring the diffusion of water molecules. Highly cellular tissues, or those with cellular swelling, exhibit lower diffusion coefficient. The measured quantity is the diffusivity or diffusion coefficient, a proportionality constant that relates diffusive flux to a concentration gradient .
Some of the many uses that DTI has is during neurosurgical planning and intraoperative neuronavigation. The latter has been shown to increase tumor resection, survival and to decrease neurologic morbidity . MRI based tractography has been used to differentiate OR of neighboring tracts in healthy patients and evaluate lesions that could potentially affect the visual pathway . Mohamadreza et al. performed a prospective study were 25 patients with progressive visual impairment due to suprasellar mass lesions, evaluated with the use of MRI based tractography preoperatively, intraoperatively and immediately after tumor resection (1 week and 3 months after surgery). They reported that 24 out of the 25 patients with visual impairment had visual recovery, concluding that it was a tool that could help to predict visual outcome in suprasellar lesions .
Tractography has demonstrated its use during glioma resections near the pyramidal tract (PT) allowing, with help of cortical and subcortical motor-evoked potentials (MEPs), maximal preservation of motor function. As Shiro et al. reported, MRI-based tractography allows establishing preoperatively the relation of the tumor with certain tract, in this case the PT, and the threshold intensity of the subcortical MEPs has a direct and significant correlation with the distance between the resection border and the tract on postoperative DT imaging .
Functional magnetic source imaging
Functional magnetic source imaging (fMRI) is currently the mainstay of neuroimaging, it is used to pinpoint active brain areas. Changes in neural activity regulate the amount of local blood oxygenation, and the related variation of the magnetic field homogeneity can be identified. As a result, blood oxygenation level-dependent (BOLD) fMRI assesses neural activity indirectly [17, 27].
Signal specificity, as well as spatial and temporal resolution, are essential aspects in evaluating the efficacy of fMRI for deriving conclusions in brain research. Signal specificity guarantees that the resulting maps reflect actual neural changes, whilst spatial and temporal resolution define our capacity to distinguish the fundamental units of active networks, and the time course of different neural events, respectively. Spatial specificity increases with a magnetic field intensity and can be adjusted for a given magnetic field by employing pulse sequences that are less sensitive to signals from around and within large vessels 
VR-based brain mapping procedures
Surgical procedures are being adapted to new technology, which is growing faster than some years ago. The knowledge of neuroanatomy, white matter, and the correlation of structures and function during surgery is very important in order to get better results for patients with complex lesions. But technology knowledge is adapted to the learning curve, and the development technology curve.
It is very important to preserve the functional structures, and in this case the OR. There is a setup where participants can virtually dissect white matter and interact with all the structures at a VR laboratory. These tools are useful now for academic purposes, training, and simulating surgeries , but soon they will be used routinely in the operating room . The use of virtual reality headsets (VRH) during awake craniotomy and brain mapping by direct electrical stimulation has been proven safe before by Delion, et al. in a 30 patients tolerance and safety study where resection of tumors near language areas was performed .
According to Casanova et al. the main reason of the omission in regularly mapping other cognitive functions during tumor resections other than language and motor areas, is the lack of tasks that are fully compatible with the restrictive environment of an operating room and awake brain surgery procedures, but VRH technology offers a unique opportunity to develop innovative tasks for preoperative mapping of complex cognitive functions, and a controlled environment to evaluate visual pathway damage during parietal glioma resection involving, or close to the OR . Cassanova et al. demonstrated that the use of VRH equipped with eye-tracking was useful to evaluate patients' visual fields of the virtual reality headset directly, thus giving an area of opportunity to use this kind of device in parietal glioma resections where protecting the OR is the main goal .
Surgery is the gold standard for treating parietal gliomas, nevertheless, the parietal lobe has somatosensory structures and language areas, which make surgeries a great challenge . The complications that may develop are basically determined by three specific factors: the tumor’s exact location, diameter, and volume. The location must be identified, as well as whether it is in the dominant or not-dominant hemisphere, the involvement of the superior or inferior parietal lobe or both, involvement of the postcentral gyrus, and the depth . The aggressive resection of the tumor volume renders the tumor’s remnant fragments more sensitive to subsequent therapeutic alternatives, such as radiotherapy and chemotherapy . There is multiple evidence that extensive glioma resection increases survival and decreases tumor progression [35, 20, 29].
The parietal lobe is a convergence area of multiple stimulus integration, among which we find verbal, linguistic and even visual stimuli. A parietal association deficit could be defined as a lack of integration of these stimuli. The most frequent PAD is apraxia with 47% prevalence, followed by anomic ataxia with 39.5% and clinical manifestations of Gerstmann Syndrome 34.2%. One of the most important alterations was visual pathway alterations (15.8%) . Glioma resection surgery has been associated with several complications in the postoperative period. These complications can be classified into three main groups: neurological, regional, and systemic. (Table 1.)
Amongst neurological complications, the most frequent alterations found in the immediate postoperative period are loss of the visual field, agraphesthesia, hemiparesis, acalculia, and astereognosis . According to Russell SM et al. after resection of parietal lobe gliomas, neurological deterioration and improvement occur. The deficits of the parietal lobe association, primarily the components of Gerstmann syndrome, are mostly related to large tumors that include the superior and inferior parietal lobules. Following resection of lesions in the nondominant hemisphere, no patient developed new hemineglect or sensory extinction. Regardless of the hemispheric dominance, patients experienced main primary parietal lobe deficit, such as cortical sensory syndrome and visual field loss . Giuseppe et al. with the use of direct electrical stimulation during glioma resection surgery in a case series of 7 patients, described that the posterior superior parietal lobe (Brodmann's area 7) is involved in the orientation of spatial attention (corresponding to the first branch of the superior longitudinal fascicle), thus its involvement in gliomas, or its damage during surgery may present with a visuospatial neglect .