White and Gray Matter

A knowledge of brain anatomy is critical in neurosurgery. The risk of postoperative neurologic deficits is influenced by tumor location and neighboring anatomy, including white matter, gray matter, and vessel architecture. Gliomas are heterotopically diverse and can arise anywhere in the brain, although there is a predilection for the frontal lobe. LGGs are also geographically diverse but may be more commonly identified in “secondary functional areas,” or directly adjacent to eloquent brain, especially near the supplementary motor area (SMA) and insula. Some tumors are compact and appear to displace functional brain. Other tumors are more diffuse and may contain critically important functioning brain tissue. Consistent with diffusion tensor magnetic resonance imaging (MRI) fiber tractography studies, the highly invasive nature of high-grade gliomas allows these tumors to easily disrupt surrounding tissue.

Language is complex and can manifest as difficulty with expression, comprehension, prosody, pitch, volume, and intonation. Invasion of gliomas into the language centers or damage of these areas during surgery can lead to linguistic deficits in the perisylvian regions of the dominant lobe, or impairment in the emotional or rhythm elements of speech in the nondominant lobe. Essential language-related white matter tracts include the superior longitudinal fasciculus, the arcuate fasciculus, and the inferior fronto-occipital fasciculus ( Fig. 21.1 ). The subcallosal and aslant fasciculus connect the SMA with the caudate nucleus and inferior frontal gyrus, respectively. Disruption of these pathways can result in difficulty initiating speech. In the perisylvian white matter, disruption of the anterior limb of the superior longitudinal fasciculus results in dysarthrias, whereas disruption of the more medial arcuate fasciculus results in phonologic paraphasias. The inferior fronto-occipital fasciculus is part of the inferior sagittal striatum in the temporal lobe, and passes through the temporal stem terminating in the middle frontal gyrus, inferior frontal gyrus, and orbital frontal cortex. Injury of this fasciculus results in difficulty with visual naming and semantic paraphasias. Additionally, the inferior longitudinal fasciculus connects the occipital lobe with the basal temporal lobe. Injury to this fasciculus on the language-dominant side can result in reading difficulty. With respect to gray matter structures, damage to the inferior frontal gyrus, the superior temporal gyrus, the supramarginal gyrus, the angular gyrus, and any interconnections between these regions can result in language impairment.

Tractography reconstruction of the major association pathways involved in auditory processing and language.

(Courtesy of Maffei C, Soria G, Prats-Galino A, Catani M. Imaging white-matter pathways of the auditory system with diffusion imaging tractography. Handb Clin Neurol. 2015;129:277–288.)

The optic radiation transmits visual information from the retina to the visual cortex and emanates from the lateral geniculate nucleus. The anterior bundle mediating information from the inferior retina, which forms part of the superior visual field, passes lateral to the temporal horn, doubling back to join the central and posterior bundles. The three bundles pass lateral to the atrium of the ventricle in the inferior sagittal striatum, and damage to any of these fibers may cause visual field deficits. The first branch of the superior longitudinal fasciculus connects in the superior parietal lobule with the dorsal premotor cortex. Disruption of this pathway results in optic ataxia, a condition in which visually guided movements are impaired.

The SMA is a region rostral to the primary motor cortex on the mesial hemispheric surface, and damage to this area in the language-dominant hemisphere is characterized by global akinesia of the contralateral limb with preserved muscle strength and mutism. Unlike damage in other parts of the brain, SMA deficits are generally temporary and resolve within weeks to months. The incidence of SMA-related deficits in one series of 27 patients harboring gliomas in the SMA was 26%, with resolution by 6-month follow-up examination. The main motor tract or the corticospinal tract passes from the motor cortex to the posterior limb of the internal capsule deep to the sensory face area, and damage to these areas may cause contralateral motor deficits when the injury occurs above the pyramidal decussation. Injury to the dorsolateral frontal lobe, prefrontal cortex, and orbitofrontal cortex can lead to impairments in planning and executive function, verbal memory or spatial memory, and impulse control and social behavior, respectively. Within the posterior fossa, damage to the flocculonodular lobe, the vermis, or the cerebellar hemispheres can lead to alterations in eye movement and gross balance, gait and locomotion, and coordination and precise motor control.

Cognitively, neuropsychological studies demonstrate that many glioma patients have subtle deficits before surgery. Neurocognitive worsening is common in the immediate postoperative period (specifically in language and executive function domains), and in the months after surgery, recovery to preoperative levels of cognition is variable. As expected, cognitive deficits are highly correlated with tumor location.

Vascular

Injury to arteries and veins can also lead to irreparable deficits consistent with the vascular territory supplied. The frequency of direct vascular injury is estimated in the range of 1% to 2%. Arterial injuries are frequently evident in the immediate postoperative period, whereas venous injuries typically present days later, resulting in congestive edema, hemorrhage, and seizures. In a recent report using the nationwide inpatient sample from 2002 to 2011, the incidence of iatrogenic stroke approached 10%, but it has been reported to be as high as 31% when reviewing postoperative MRI scans. Tumors located in the insula, operculum, and superior temporal lobe are at higher risk for new restricted diffusion areas on postoperative MRI.

Multiple vascular structures may be compromised during surgery. Gliomas can surround major vessels such as the anterior, middle, and posterior cerebral arteries and smaller cortical vessels. Perforating vessels, the thalamostriate vessels, branches of the anterior choroidal artery, and posterior branches of the middle cerebral artery that irrigate the motor fibers in the corona radiata and internal capsule may be engulfed by tumor. Thalamostriate vessels are frequently engulfed by tumors of the insula as the vessels pass from the sylvian fissure through the uncinate fasciculus to the basal ganglia. Branches of the anterior choroidal artery passing to the posterior perforating substance may be adherent to the uncus of the temporal lobe. Small branches of the middle cerebral artery passing through the central sulcus or the posterior portion of the superior circular sulcus around the insula provide a blood supply to the corticospinal tract in the corona radiate, and disruption of these vessels may lead to motor deficits in addition to other neurologic impairments.

Complications Resulting From Tumor Resection

Neurologic deficits are associated with worse overall outcomes and decreased longevity. However, there are a number of imaging modalities and technologies that may aid in preoperative or intraoperative planning to improve EOR, especially for complex gliomas in challenging locations. Examples include diffusion tensor imaging, which can be used to delineate white matter tracts and build a three-dimensional map for preoperative visualization. Task-based functional MRI (fMRI) can also be used to identify cortical and subcortical areas of activation corresponding to eloquent brain ( Fig. 21.2 ).

Functional magnetic resonance imaging (MRI) in operative planning. (A) Axial T1-weighted MRI with contrast showing a nonenhancing isointense mass lesion of the right frontal lobe with mass effect and midline shift. (B) Same hyperintense lesion on T2-weighted sequence. (C) Functional MRI showing displacement of different white matter tracts. (D and E) Functional MRI showing the language and eye movement area in relation to the tumor. Notice the close relation with the right eye movement area (E). (F) One-year follow-up MRI showing complete resection and no recurrence.

(Fig. 19.2 from Nader, Scott, Abdulrahman, Levy, Neurosurgery Tricks of the Trade – Cranial, Thieme 2013, pg 74.)

Modalities such as intraoperative MRI (iMRI), 5-aminolevulinic acid (5-ALA) fluorescence, and intraoperative ultrasound may also be helpful for identifying tumor margins. iMRI, although expensive and potentially time-consuming, has been shown to result in greater EOR and progression-free survival (PFS) compared with conventional neuronavigation. Although conventional neuronavigation is helpful for initial localization of tumor and optimization of the surgical approach, accuracy is affected by slice thickness of cross-sectional imaging, tracking modality, image to patient registration, and especially brain shift during surgery. Newer neuronavigation platforms will have the capacity to combine multimodal imaging including fMRI and DTI with MRI data to further improve preoperative planning.

Dyes such as 5-ALA and fluorescein have also been shown to enhance EOR. The utility of ALA was demonstrated in a randomized controlled trial of 243 patients undergoing surgery for high-grade glioma. Patients receiving ALA had a significantly higher rate of gross total resection (65% vs 36%) and a higher rate of 6-month PFS (41.7% vs 21%). Intraoperative ultrasound can be easily combined with any of the other described techniques and has been shown to increase the probability of obtaining a gross total resection, especially for lesions that are solitary and subcortical.

Awake craniotomy with intraoperative mapping has been shown to significantly reduce postoperative neurologic deficits, although stringent patient selection is a key to success. Electrical stimulation of the brain during surgery with the patient awake or asleep has become a regular part of the surgeon’s armamentarium and is used to delineate the borders of safe tumor resection. The value of intraoperative mapping in preserving neurologic function has been reported by a number of surgeons. A literature review of 90 reports published between 1990 and 2010 demonstrates a significant decrease in postoperative neurologic deficits and a significant increase in the rate of gross total resections when intraoperative stimulation was used. Awake craniotomy is well tolerated by patients but is not infallible, because persistent neurologic deficits can still occur despite negative mapping. Whether these deficits are the result of ischemia, cortical function confined in the depth of a sulcus, damaged white matter tracts, or some other mechanism is uncertain.

In addition to minimizing damage to eloquent brain, it is also important to prevent injury to the vascular structures that supply eloquent brain. Malignant gliomas are highly vascular tumors and subsist in a highly proangiogenic milieu. To prevent complications resulting from damage to vascular structures in the brain, preoperative computed tomography (CT) angiography or MR angiography to identify the location of vessels embedded within tumor tissue may be helpful for preoperative planning. For tumors encasing critical arteries of veins, tumor tissue may have to be left behind. To minimize the risk of stroke from vasospasm, papaverine-soaked Gelfoam may be placed on arteries if they appear to be in spasm after tumor dissection.

Disruption of the vascular supply around a tumor may lead to iatrogenic stroke, which has been shown to increase hospital mortality 9-fold. It should be noted that small areas of restricted diffusion are not uncommon on postoperative MRI scans. Whether this is due to disruption of blood flow or contusion is uncertain. Nonetheless, disruption of large arteries such as M ₄ branches of the middle cerebral artery can lead to areas of ischemia beyond the tumor. These branches have a propensity to lie within the sulci of the brain. As with an arteriovenous malformation, the surgeon is wise to open the sulci, coagulate the branches supplying the tumor, and preserve the main trunks that go on to supply normal brain. When operating on what looks to be a compact malignant tumor, it is not uncommon to identify large vessels in the sulci surrounding the tumor. When operating on low-grade tumors in the brain surrounding the sylvian fissure, the surgeon should debulk the tumor through openings in the crest of the gyri, preserving the pial vessels passing beyond the tumor. Low-grade tumor emanating from the insula may break through the pia and engulf M2 and M3 branches within the sylvian fissure. Using a subpial dissection, large branches within the sulci can be spared.

Regional Complications

Seizures, postoperative edema, hematoma, infection, and CSF leak are examples of more frequent regional complications and occur at a rate approximately between 1% and 10%. Excess brain retraction and residual tumor can result in significant postoperative edema which may not reach its peak until several days after surgery. Local edema may manifest as a focal neurologic deficit, but severe edema can result in life-threatening trans-tentorial herniation. Postoperative edema can be minimized by limiting brain retraction during surgery. Residual tumor, especially residual high grade tumor, is a nidus for postoperative swelling and hemorrhage, and therefore as much of the tumor as possible should be resected without causing new postoperative deficits. Postoperative steroids seem to mitigate postsurgical edema, but appear to be associated with an increased risk of infection. Head elevation and osmotic agents may be necessary when postoperative edema is severe.

Postoperative hematomas causing deficits occur 1% to 5% of the time and may be influenced by coagulation status, hemostasis, age, comorbid medical conditions, and oftentimes residual tumor. Consequently, careful preoperative evaluation including analysis of coagulation status and review of the patient’s history, combined with meticulous hemostasis at the conclusion of a case, may help mitigate the risk of postoperative hematomas.

To prevent seizures, antiepileptic drugs may be administered during the pre- and postoperative period; however, the efficacy of seizure prophylaxis is controversial. In our practice, we typically add seizure prophylaxis for supratentorial tumors. To reduce perioperative infections, adherence to sterile technique is also important, including the use of clippers instead of shaving for hair removal, preoperative glycemic control, intraoperative antibiotics, careful wound closure, normothermia, and the changing of dressings when saturated. High extracellular glucose concentrations have been shown to inhibit neutrophil function; in general, the administration of insulin in the perioperative period to maintain blood glucose <180 mg/dL is recommended for the prevention of infection. CSF leaks are more common with posterior fossa tumors, and the incidence may be reduced with meticulous dural closure. Postoperative incisional pain is also very common and can be alleviated by administering pregabalin in the preoperative setting. A recent randomized controlled trial showed that administering 150 mg BID of pregabalin during the perioperative period reduced preoperative anxiety, improved sleep quality, and reduced perioperative pain scores, and we are currently using this for a vast majority of our preoperative craniotomy patients.

Systemic Complications

The risk of systemic complications such as DVT, PE, myocardial infarction, and pneumonia can also be reduced through good clinical practice behaviors. Surgical complications are associated with a significantly higher risk of general medical complications. Patients who end up with a surgical complication have a significantly higher rate of comorbidities before surgery. In a review of 20,000 glioma patients, the risk for cardiac complications was 0.7%, 0.5% for respiratory complications, 0.8% for deep wound infection, 0.6% for deep venous thromboses (DVTs), 3.1% for pulmonary embolus (PE), and 1.3% for acute renal failure (ARF). DVT prophylaxis initiated on postoperative day 1, close monitoring of respiratory status and oral intake, promotion of measures such as incentive spirometry, and judicious but appropriate use of intravenous fluids can help mitigate these risks.

There are a number of measures that may be taken to reduce the risk of postoperative systemic complications. Venous thromboembolism (VTE) rates are higher for postoperative cranial glioma patients (3.5%) than patients with other types of cancers. The risk can be reduced with the use of both mechanical and chemical prophylaxis; the combination of intermittent pneumatic compression devices with heparin prophylaxis is more effective in preventing VTE than either method alone. One retrospective review showed that there was no statistically significant increase in hemorrhagic complications but a reduction in the rate of DVTs from 16% to 9% when subcutaneous heparin was administered either 24 or 48 hours postoperatively. Blood pressure control can reduce the risk of postoperative hemorrhage; in general, systolic blood pressure in the first 24 hours after surgery is maintained at <140 mm Hg systolic. In our practice we generally maintain systolic blood pressure for all postoperative craniotomy patients less than 160 mm Hg and start chemical prophylaxis 24 hours after surgery.