Neurosurgery Blog

J Neurosurg 116:1002–1006, 2012. (http://thejns.org/doi/abs/10.3171/2012.1.JNS111746)

Frameless stereotactic brain biopsy has become an established procedure in many neurosurgical centers worldwide. Robotic modifications of image-guided frameless stereotaxy hold promise for making these procedures safer, more effective, and more efficient. The authors hypothesized that robotic brain biopsy is a safe, accurate procedure, with a high diagnostic yield and a safety profile comparable to other stereotactic biopsy methods.

Methods. This retrospective study included 41 patients undergoing frameless stereotactic brain biopsy of lesions (mean size 2.9 cm) for diagnostic purposes. All patients underwent image-guided, robotic biopsy in which the Surgi-Scope system was used in conjunction with scalp fiducial markers and a preoperatively selected target and trajectory. Forty-five procedures, with 50 supratentorial targets selected, were performed.

Results. The mean operative time was 44.6 minutes for the robotic biopsy procedures. This decreased over the second half of the study by 37%, from 54.7 to 34.5 minutes (p < 0.025). The diagnostic yield was 97.8% per procedure, with a second procedure being diagnostic in the single nondiagnostic case. Complications included one transient worsening of a preexisting deficit (2%) and another deficit that was permanent (2%). There were no infections.

Conclusions. Robotic biopsy involving a preselected target and trajectory is safe, accurate, efficient, and comparable to other procedures employing either frame-based stereotaxy or frameless, nonrobotic stereotaxy. It permits biopsy in all patients, including those with small target lesions. Robotic biopsy planning facilitates careful preoperative study and optimization of needle trajectory to avoid sulcal vessels, bridging veins, and ventricular penetration.

J Neurosurg 116:697–702, 2012. http://thejns.org/doi/abs/10.3171/2011.12.JNS111404

Facial nerve paresis can be a devastating complication following resection of large (> 2.5 cm) cerebellopontine angle (CPA) tumors. The authors have developed and used a new high-density diffusion tensor imaging (HD-DT imaging) method, aimed at preoperatively identifying the location and course of the facial nerve in relation to large CPA tumors. Their study objective was to preoperatively identify the facial nerve in patients with large CPA tumors and compare their HD-DT imaging method with a traditional standard DT imaging method and correlate with intraoperative findings.

Methods. The authors prospectively studied 5 patients with large (> 2.5 cm) CPA tumors. All patients underwent preoperative traditional standard- and HD-DT imaging. Imaging results were correlated with intraoperative findings.

Results. Utilizing their HD-DT imaging method, the authors positively identified the location and course of the facial nerve in all patients. In contrast, using a standard DT imaging method, the authors were unable to identify the facial nerve in 4 of the 5 patients.

Conclusions. The HD-DT imaging method that the authors describe and use has proven to be a powerful, accurate, and rapid method for preoperatively identifying the facial nerve in relation to large CPA tumors. Routine integration of HD-DT imaging in preoperative planning for CPA tumor resection could lead to improved facial nerve preservation.

J Neurosurg Spine 16:308–314, 2012. DOI: 10.3171/2011.11.SPINE11536

Intramedullary spinal cord cavernous malformations (CMs), once thought to be extremely rare, have been diagnosed more frequently since the advent of MR imaging. In the literature, however, only a few studies include more than 10 cases. The aim of this study was to discuss the clinical presentation of intramedullary spinal cord CMs and the outcome of microsurgery for these histologically benign but clinically progressive lesions.

Methods. The authors retrospectively reviewed the records of 20 patients who underwent microsurgery for intramedullary spinal cord CMs. All patients had undergone pre- and postoperative MR imaging, and they were all treated using microsurgical resection. The diagnosis of spinal cord CMs was based on pathological criteria. The pre- and postoperative neurological states of the patients were classified according to the McCormick scale and Frankel scale. The microsurgical outcomes are presented and discussed.

Results. In most cases, CMs can be diagnosed on the basis of MR imaging findings, since these lesions have certain characteristic imaging patterns. Patients with intramedullary spinal cord CMs may present with either a rapid, acute onset of symptoms or slow, progressive neurological decline. The CMs in 19 of 20 patients in this series were totally resected, and most patients neurologically improved postoperatively. As previously reported, the authors confirm that the treatment of choice for symptomatic intramedullary CMs is total removal of the lesion to avoid recurrence and the possibility of further hemorrhage.

Conclusions. This study has defined the clinical features of symptomatic intramedullary spinal cord CMs. Surgery is the mainstay treatment. Surgical outcome is associated with low mortality with a high probability of functional recovery, especially when symptoms are not severe and are of relatively recent onset.

J Neurosurg 116:365–372, 2012. DOI: 10.3171/2011.9.JNS111068

Low-grade gliomas (LGGs) are rarely diagnosed as an incidental, asymptomatic finding, and it is not known how the early surgical management of these tumors might affect outcome. The purpose of this study was to compare the outcomes of patients with incidental and symptomatic LGGs and determine any prognostic factors associated with those outcomes.

Methods. All patients treated by the lead author for an LGG incidentally discovered between 1999 and 2010 were retrospectively reviewed. “Incidental” was defined as a finding on imaging that was obtained for a reason not attributable to the glioma, such as trauma or headache. Primary outcomes included overall survival, progression-free survival (PFS), and malignant PFS. Patients with incidental LGGs were compared with a previously reported cohort of patients with symptomatic gliomas.

Results. Thirty-five patients with incidental LGGs were identified. The most common reasons for head imaging were headache not associated with mass effect (31.4%) and trauma (20%). Patients with incidental lesions had significantly lower preoperative tumor volumes than those with symptomatic lesions (20.2 vs 53.9 cm3, p < 0.001), were less likely to have tumors in eloquent locations (14.3% vs 61.9%, p < 0.001), and had a higher prevalence of females (57.1% vs 36%, p = 0.02). In addition, patients with incidental lesions were also more likely to undergo gross-total resection (60% vs 31.5%, p = 0.001) and had improved overall survival on Kaplan-Meier analysis (p = 0.039, Mantel-Cox test). Progression and malignant progression rates did not differ between the 2 groups. Univariate analysis identified pre- and postoperative volumes as well as the use of motor or language mapping as significant prognostic factors for PFS.

Conclusions. In this retrospective cohort of surgically managed LGGs, incidentally discovered lesions were associated with improved patient survival as compared with symptomatic LGGs, with acceptable surgical risks.

J Neurosurg 116:373–384, 2012. DOI: 10.3171/2011.6.JNS081451

The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature.

Methods. A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months.

Results. Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors’ former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%– 66.7% vs 2.6%–50.0%) but were less frequent after transsphenoidal approaches (5.2%–19.2% vs 2.9%–45.7%).

Conclusions. Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients’ condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.

J Neurosurg 116:357–364, 2012. DOI: 10.3171/2011.8.JNS102114

The objective of this study was to analyze whether age influences the outcome of patients with glioblastoma and whether elderly patients with glioblastoma can tolerate the same aggressive treatment as younger patients.

Methods. Data from 361 consecutive patients with newly diagnosed cerebral glioblastoma (2000–2006) who underwent regular follow-up evaluation from initial diagnosis until death were prospectively entered into a database. Patients underwent resection (complete, subtotal, or partial) or biopsy, depending on tumor size, location, and Karnofsky Performance Scale score. Following surgery, all patients underwent adjuvant treatment consisting of radiotherapy, chemotherapy, or combined treatment. Patients older than 65 years of age were defined as elderly (146 total).

Results. Two hundred thirty-four patients underwent tumor resection (complete 26%, subtotal 29%, and partial 45%). One hundred twenty-seven underwent biopsy. Mean patient age was 61 years, and overall survival was 11.6 ± 12.1 months. The overall survival of elderly patients (9.1 ± 11.6 months) was significantly lower than that of younger patients (14.9 ± 16.7 months; p = 0.0001). Stratifying between resection or biopsy, age was a negative prognostic factor in patients undergoing biopsy (4.0 ± 7.1 vs 7.9 ± 8.7 months; p = 0.007), but not in patients undergoing tumor resection (13.0 ± 8.5 vs 13.3 ± 14.5 months; p = 0.86). Survival of elderly patients undergoing complete tumor resection was 17.7 ± 8.1 months.

Conclusions. In this series of patients with glioblastoma, age was a prognostic factor in patients undergoing biopsy, but not in patients undergoing resection. Tumor location and patient clinical status may prohibit extensive resection, but resection should not be withheld from patients only on the basis of age. In elderly patients with glioblastoma, undergoing resection to the extent feasible, followed by adjuvant therapies, is warranted.

J Neurosurg 116:390–398, 2012.DOI: 10.3171/2011.10.JNS11783

The cavernous sinus and surrounding regions—specifically the Meckel cave, posterior sector of the cavernous sinus itself, and the upper part of the petroclival region—are the location of a large variety of lesions that require individual consideration regarding treatment strategy. These regions may be reached for biopsy by a percutaneous needle inserted through the foramen ovale. The aim of this retrospective study was to evaluate the diagnostic accuracy of percutaneous biopsy in a consecutive series of 50 patients referred for surgery between 1991 and 2010.

Methods. Seven biopsies (14%) were unproductive and 43 (86%) were productive, among which 28 lesions subsequently underwent histopathological examination during a second (open) surgery. To evaluate the diagnostic accuracy of the procedure, results from surgery were compared with those from the biopsy.

Results. Sensitivity of the percutaneous biopsy was 0.83 (95% CI 0.52–0.98), specificity was 1 (95% CI 0.79–1), and k coefficient was 0.81.

Conclusions. Because of its valuable diagnostic accuracy, percutaneous biopsy of the cavernous sinus and surrounding regions should be performed in patients with parasellar masses when neuroimaging does not provide sufficient information of a histopathological nature. This procedure would enable patients to obtain the most appropriate therapy, such as resective surgery, corticosteroids, chemotherapy, radiotherapy, or radiosurgery.

J Neurosurg 116:341–345, 2012.DOI: 10.3171/2011.9.JNS11656

The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM.

Methods. From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involvedfield radiation therapy and concomitant temozolomide (75 mg/m2 daily for 42 days) along with bevacizumab (10 mg/ kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m2 on Days 1–7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle.

Results. The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients.

Conclusions. The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.

J Neurosurg 115:1115–1125, 2011. DOI: 10.3171/2011.8.JNS11488

Insular gliomas can be resected with acceptable rates of neurological morbidity, but little is known with regard to impairment of higher-order neurocognitive functions. The frequency and functional impact of neurocognitive deficits in patients with gliomas has until recently been underappreciated. The authors therefore examined neurocognitive function in patients with insular gliomas and compared the findings in this group to those in a matched control group of patients with gliomas in nearby brain regions.

Methods. Thirty-three patients with WHO Grade II or III insular gliomas participated in neuropsychological evaluations before and after resection. To establish whether the pattern of neurocognitive performance was different from that of other patients with tumors in neighboring areas, patients with insular tumors were matched with control patients for age, educational level, preoperative Karnofsky Performance Scale score, tumor side, grade, and volume. The control group comprised patients in whom gliomas had been resected from frontal, temporal, and parietal areas near the insula. Baseline pre- and postoperative neurocognitive test results were compared between and within groups.

Results. Preoperative neurocognitive impairment was common in both insular and control groups. Patients with insular tumors had significantly worse preoperative performance on naming tests. In both groups, postoperative decline occurred in most neurocognitive domains. There were no statistically significant differences between patients in the insular and control groups with regard to rates of postoperative decline on any test. However, there were trends suggesting differential cognitive performance postoperatively, because patients with insular tumors were more likely to experience greater decline in learning and memory. Neurological morbidity was similar to prior rates reported in the literature.

Conclusions. Few statistically significant differences in cognitive function were observed between patients in the insular and control groups at either the pre- or postoperative evaluation, although there was a trend for patients with insular tumors to exhibit greater postoperative decline in learning and memory. Although technically more challenging, surgery for insular region glioma appears feasible without profound neurological or cognitive morbidity for many patients.

J Neurosurg 115:906–914, 2011. DOI: 10.3171/2011.6.JNS11131

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin.

Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development.

Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment.

In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1.

A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma.

Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation.

With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

J Neurosurg 115:802–810, 2011.DOI: 10.3171/2011.5.JNS101812

Various surgical approaches, such as uni- and bifrontal, frontolateral, and pterional approaches, havebeen advocated for tuberculum sellae meningiomas. The authors retrospectively reviewed the effectiveness of a bilateralsubfrontal approach for tuberculum sellae meningiomas with special attention to ophthalmological outcomesand complications.

Methods. Between 1993 and 2009, 34 patients underwent surgery for removal of tuberculum sellae meningiomasat Osaka City University. Tumor size ranged from 14 to 45 mm. Thirty-two of 34 patients presented with visualdisturbances before the surgery. The visual functions in all patients were assessed using a visual impairment score(VIS) before and after surgery. Postoperative visual examination was performed 2 weeks after surgery. Long-termfollow-up examinations were conducted 1 year after surgery.

Results. Radical resection (Simpson Grades I and II) was accomplished in 27 patients, and subtotal or partialresection (Simpson Grades III and IV) was achieved in 7. There was no deterioration in postoperative visual outcome.Twenty-nine (90.6%) of 32 patients showed improved VIS compared with preoperative VIS. The average VIS was38.1 preoperatively, 23.5 in the short-term postoperative period, and 21.8 in the long-term postoperative period. Inthe short-term postoperative period, the visual function in 6 patients normalized, and visual problems persisted in theremaining 26. Six (23%) of 26 patients showed further improvement in VIS during the long-term follow-up period,and no patient exhibited a worsened VIS during this time. One patient complained of hyposmia after surgery, butthere was no indication of related complications such as CSF leakage or frontal brain contusion.

Conclusions. The bilateral subfrontal approach was previously avoided because of the relatively high rate ofcomplications in earlier surgical series of tuberculum sellae meningiomas. However, after developments in microsurgicaltechniques in recent years, the bilateral subfrontal approach can now provide satisfactory visual outcomes withminimal postoperative complications. Careful preservation of the blood supply to optic apparatus and early unroofingof the optic canal using a bilateral subfrontal approach led to further improvement in long-term postoperative visual outcome.

J Neurosurg 115:740–748, 2011. DOI: 10.3171/2011.6.JNS11252

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5- ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.

Methods. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.

Results. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.

Conclusions. Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors’ institution.

J Neurosurg 115:491–498, 2011. DOI: 10.3171/2011.4.JNS101922

Convexity meningiomas are expected to have a low recurrence rate given their classically “easy resectability.” Nonetheless, recurrence can occur. Factors playing a role in their recurrence are analyzed here, including the extent of resection and tumor histological type, among others, with a special emphasis on the cleavage plane.

Methods. The authors reviewed 100 cases of convexity meningiomas surgically treated between 1987 and 2001 with a median follow-up of 86 months (range 2–16 years). Preoperative and postoperative functional status, Simpson resection grade, histological type, and intraoperative surgical plane with pial vessel invasion were studied and cor- related with the recurrence rate.

Results. The average tumor size was 3.6 ± 0.4 cm. The pre- and postoperative Karnofsky Performance Scale scores were 92.6 ± 4.6 and 97.9 ± 2.2, respectively. Ninety-five lesions were benign (WHO Grade I) and 5 were atypical (WHO Grade II). Ninety-one and 9 tumors were subjected to Simpson Grade 1 and 3 resections (three Grade 3a and six Grade 3b), respectively. Surgical deaths did not occur. After a mean follow-up of 7.2 years, 4 meningiomas recurred; 2 (2.2%) after Simpson Grade 1 resections and 2 after Simpson Grade 3 (3a and 3b) resections (22.2%; p = 0.0034). When just the subgroup of Simpson Grade 1/WHO Grade I was studied, the recurrence rate decreased to 1.2% (1 of 86 cases). The recurrence of WHO Grade I tumors was higher in the subpial group than in the extrapial group (p = 0.025). No difference in recurrence according to the cleavage plane was seen in the WHO Grade II sub- group (p = 0.361). As for the subpial group, no difference in recurrence was noted between the WHO Grade I and II subgroups (p = 0.608). Importantly, however, the extrapial subgroup of WHO Grade II lesions had a higher recurrence rate compared with its counterpart in the WHO Grade I subgroup (p = 0.005).

Conclusions. Pial and vascular invasion affect the recurrence rate in convexity meningioma surgery. The recurrence rate of WHO Grade I tumors was higher among those with a subpial plane of dissection than among those with an extrapial one. Histological type did not determine the degree of pial invasion in WHO Grade I and II lesions.

J Neurosurg 115:232–239, 2011. DOI: 10.3171/2011.3.JNS101333

It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR imaging–defined abnormalities—a “supratotal” resection—might improve the outcome of LGG. However, because of the frequent location of LGG within “eloquent” brain areas, it is often difficult to achieve such a supratotal resection. This could nevertheless be possible when LGGs involve “noneloquent” areas, even in the left dominant hemisphere.

The authors report on their use of awake electrical mapping to tailor the resection according to functional boundaries, that is, to pursue the resection beyond MR imaging–defined abnormalities, until corticosubcortical eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while preserving brain function.

Methods. Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifestation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language, as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIRweighted MR images.

Results. Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a normal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume of the postoperative cavity (36.8 cm3) was significantly larger than the mean preoperative tumor volume (26.6 cm3) (p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean duration of postoperative follow-up was 35.7 months (range 6–135 months). Only 4 of 15 patients experienced recurrence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was compared with a control group of 29 patients who had “only” complete resection: anaplastic transformation was observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared with 1 patient who underwent supracomplete resection (p = 0.043).

Conclusions. These findings support the usefulness of awake surgery with intraoperative functional (language) mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemisphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the anaplastic transformation, even if it does not (yet) enable a cure.

J Neurosurg 115:3–8, 2011. DOI: 10.3171/2011.2.JNS10998

The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.

Methods. The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging–based volumetric tumor analysis.

Results. The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm3, equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%–100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.

Conclusions. For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.

J Neurosurg 115:11–17, 2011. DOI: 10.3171/2011.2.JNS101451

Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following d-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies.

Methods. The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo.

Results. A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon’s visual perception were classified correctly in an analysis of all tumors.

Conclusions. These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.