Surgery guided by 5-aminolevulinic acid (ALA) fluorescence has become a valuable adjunct in the resection of malignant intracranial gliomas. Furthermore, the fluorescence intensity of biopsied areas of a resection cavity correlates with histological identification of tumor cells. However, in the case of lesions deep within a resection cavity, light penetration may be suboptimal, resulting in less excitation of 5-ALA metabolites, leading to decreased fluorescence emission. To address this obstacle, the authors report on the use of a 400-nm wavelength fiber-optic lighted suction instrument that can be used both during resection of a tumor and to provide direct light to deeper areas of a resection cavity. In the presented case, this wavelength-specific lighted suction instrument improved the fluorescence intensity of patches of malignant tissue within the resection cavity. This technique may further improve the utility of 5-ALA in identifying tumor-infiltrated tissue for deep-seated lesions. Additionally, this tool may have implications for scoring systems that correlate 5-ALA fluorescence intensity with histological identification of malignant cells.
Ramin A. Morshed, Seunggu J. Han, Darryl Lau, and Mitchel S. Berger
Darryl Lau, Mitchel S. Berger, Dhruv Khullar, and John Maa
Cigarette smoking is a common health risk behavior among the general adult population, and is the leading preventable cause of morbidity and mortality in the US. The surgical literature shows that active tobacco smoking is a major risk factor for perioperative morbidity and complications, and that preoperative smoking cessation is an effective measure to lower these risks associated with active smoking. However, few studies have examined the effects of smoking and perioperative complications following neurosurgical procedures. The goal of this review was to highlight the scientific data that do exist regarding the impact of smoking on neurosurgical outcomes, to promote awareness of the need for further work in the specific neurosurgical context, and to suggest ways that neurosurgeons can promote smoking cessation in their patients and lead efforts nationally to emphasize the importance of preoperative smoking cessation. This review indicates that there is limited but good evidence that smoking is associated with higher rates of perioperative complications following neurosurgical intervention. Specific research is needed to understand the effects of smoking and perioperative complications. Neurosurgeons should encourage preoperative smoking cessation as part of their clinical practice to mitigate perioperative morbidity associated with active smoking.
Shawn L. Hervey-Jumper, Jing Li, Joseph A. Osorio, Darryl Lau, Annette M. Molinaro, Arnau Benet, and Mitchel S. Berger
Though challenging, maximal safe resection of insular gliomas enhances overall and progression-free survival and deters malignant transformation. Previously published reports have shown that surgery can be performed with low morbidity. The authors previously described a Berger-Sanai zone classification system for insular gliomas. Using a subsequent dataset, they undertook this study to validate this zone classification system for predictability of extent of resection (EOR) in patients with insular gliomas.
The study population included adults who had undergone resection of WHO Grade II, III, or IV insular gliomas. In accordance with our prior published report, tumor location was classified according to the Berger-Sanai quadrant-style classification system into Zones I through IV. Interobserver variability was analyzed using a cohort of newly diagnosed insular gliomas and independent classification scores given by 3 neurosurgeons at various career stages. Glioma volumes were analyzed using FLAIR and T1-weighted contrast-enhanced MR images.
One hundred twenty-nine procedures involving 114 consecutive patients were identified. The study population from the authors’ previously published experience included 115 procedures involving 104 patients. Thus, the total experience included 244 procedures involving 218 patients with insular gliomas treated at the authors’ institution. The most common presenting symptoms were seizure (68.2%) and asymptomatic recurrence (17.8%). WHO Grade II glioma histology was the most common (54.3%), followed by Grades III (34.1%) and IV (11.6%). The median tumor volume was 48.5 cm3. The majority of insular gliomas were located in the anterior portion of the insula with 31.0% in Zone I, 10.9% in Zone IV, and 16.3% in Zones I+IV. The Berger-Sanai zone classification system was highly reliable, with a kappa coefficient of 0.857. The median EOR for all zones was 85%. Comparison of EOR between the current and prior series showed no change and Zone I gliomas continue to have the highest median EOR. Short- and long-term neurological complications remain low, and zone classification correlated with short-term complications, which were highest in Zone I and in Giant insular gliomas.
The previously proposed Berger-Sanai classification system is highly reliable and predictive of insular glioma EOR and morbidity.
John Futchko, Jordan Starr, Darryl Lau, Matthew R. Leach, Christopher Roark, Aditya S. Pandey, and B. Gregory Thompson
Smoking is a known risk factor for aneurysm development and aneurysmal subarachnoid hemorrhage, as well as subsequent vasospasm in both untreated individuals and patients who have undergone surgical clipping of cerebrovascular aneurysms. However, there is a lack of data in the current scientific literature about the long-term effects that smoking has on the integrity of endovascular repairs of cerebral aneurysms. This study was designed to determine if any smoking history increased the risk of poorer outcomes and/or aneurysm recurrence in patients who have had endovascular repair of cerebral aneurysms.
The authors retrospectively analyzed the medical records of patients admitted to the University of Michigan Health System from January 1999 to December 2011 with coiled aneurysms and angiography, CT angiography, or MR angiography follow-up. Patients were identified and organized based on many criteria including age, sex, smoking history, aneurysm recurrence, aneurysm location, and Hunt and Hess grade. Analysis was targeted to the patient population with a history of smoking. Bivariate chi-square tests were used to analyze the association between a positive smoking history and documented aneurysm recurrence and were adjusted for potential confounders by fitting multivariate logistic regression models of recurrence.
A total of 247 patients who had undergone endovascular treatment of 296 documented cerebral aneurysms were included in this study. The recurrence rate among all patients treated with endovascular repair was 24.3%, and the average time to the most recent follow-up imaging studies was 1.62 years. Smokers accounted for 232 aneurysms and were followed up for an average of 1.57 years, with a recurrence rate of 26.3%. Never smokers accounted for the remaining 64 aneurysms and were followed up for an average of 1.82 years, with a recurrence rate of 17.2%. Multivariate analysis revealed that, after controlling for potential confounders, a history of smoking—whether current or former—was associated with a significantly increased risk of aneurysm recurrence. The odds ratios for aneurysm recurrence for current and former smokers were 2.739 (95% CI 1.127–7.095, p = 0.0308) and 2.698 (95% CI 1.078–7.212, p = 0.0395), respectively, compared with never smokers.
A positive smoking history is associated with a significantly increased risk of aneurysm recurrence in patients who have undergone endovascular repair of a cerebral aneurysm, compared with the risk in patients who have never smoked.
Matthew B. Potts, Darryl Lau, Adib A. Abla, Helen Kim, William L. Young, and Michael T. Lawton
Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs—the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process.
A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period.
Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0–1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs).
Surgery should be regarded as the “gold standard” therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.
Shawn L. Hervey-Jumper, Jing Li, Darryl Lau, Annette M. Molinaro, David W. Perry, Lingzhong Meng, and Mitchel S. Berger
Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon's experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery.
The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986–1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997–2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases.
The median patient age was 42 years (range 13–84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90–100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer's solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation-induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%.
Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.
Darryl Lau, Shawn L. Hervey-Jumper, Susan Chang, Annette M. Molinaro, Michael W. McDermott, Joanna J. Phillips, and Mitchel S. Berger
There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.
A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.
A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.
The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.
Edward F. Chang, Jonathan D. Breshears, Kunal P. Raygor, Darryl Lau, Annette M. Molinaro, and Mitchel S. Berger
Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site.
Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a “classic” or an “atypical” location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis.
Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67–31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22–71.42, p < 0.01), than were patients with classic speech localization.
This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.
Darryl Lau, Abdulrahman M. El-Sayed, John E. Ziewacz, Priya Jayachandran, Farhan S. Huq, Grettel J. Zamora-Berridi, Matthew C. Davis, and Stephen E. Sullivan
Advances in the management of trauma-induced intracranial hematomas and hemorrhage (epidural, subdural, and intraparenchymal hemorrhage) have improved survival in these conditions over the last several decades. However, there is a paucity of research investigating the relation between patient age and outcomes of surgical treatment for these conditions. In this study, the authors examined the relation between patient age over 80 years and postoperative outcomes following closed head injury and craniotomy for intracranial hemorrhage.
A consecutive population of patients undergoing emergent craniotomy for evacuation of intracranial hematoma following closed head trauma between 2006 and 2009 was identified. Using multivariable logistic regression models, the authors assessed the relation between age (> 80 vs ≤ 80 years) and postoperative complications, intensive care unit stay, hospital stay, morbidity, and mortality.
Of 103 patients, 27 were older than 80 years and 76 patients were 80 years of age or younger. Older age was associated with longer length of hospital stay (p = 0.014), a higher rate of complications (OR 5.74, 95% CI 1.29–25.34), and a higher likelihood of requiring rehabilitation (OR 3.28, 95% CI 1.13–9.74). However, there were no statistically significant differences between the age groups in 30-day mortality or ability to recover to functional baseline status.
The findings suggest that in comparison with younger patients, patients over 80 years of age may be similarly able to return to preinjury functional baselines but may require increased postoperative medical attention in the forms of rehabilitation and longer hospital stays. Prospective studies concerned with the relation between older age, perioperative parameters, and postoperative outcomes following craniotomy for intracranial hemorrhage are needed. Nonetheless, the findings of this study may allow for more informed decisions with respect to the care of elderly patients with intracranial hemorrhage.
Daniel Orringer, Darryl Lau, Sameer Khatri, Grettel J. Zamora-Berridi, Kathy Zhang, Chris Wu, Neeraj Chaudhary, and Oren Sagher
The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR.
The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves.
The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005).
The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.