Neurosurgery Blog

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.

Acta Neurochir (2012) 154:223–228. DOI 10.1007/s00701-011-1200-5

Microsurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence.

Objective We were interested in the potential impact of 5- aminolevulinic acid (5-ALA)-induced-fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases.

Methods A retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens.

Results A total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%).

Conclusions The majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue.

J Neurosurg 116:135–144, 2012.DOI: 10.3171/2011.8.JNS101767

The purpose of this ongoing study is to compare the safety and efficacy of microsurgical clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes. The authors examined the null hypothesis that no difference exists between the 2 treatment modalities in the setting of subarachnoid hemorrhage (SAH). The current report is limited to the clinical results at 1 year after treatment.

Methods. The authors screened 725 patients with SAH, resulting in 500 eligible patients who were enrolled prospectively in the study after giving their informed consent. Patients were assigned in an alternating fashion to surgical aneurysm clipping or endovascular coil therapy. Intake evaluations and outcome measurements were collected by nurse practitioners independent of the treating surgeons. Ultimately, 238 patients were assigned to aneurysm clipping and 233 to coil embolization. The 2 treatment groups were well matched. There were no anatomical exclusions. Crossing over was allowed, but primary outcome analysis was based on the initial treatment modality assignment. Posttreatment care was standardized for both groups. Patient outcomes at 1 year were independently assessed using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score > 2 at 1 year. The primary outcome was based on the assigned group; that is, by intent to treat.

Results. One year after treatment, 403 patients were available for evaluation. Of these, 358 patients had actually undergone treatment. The remainder either died before treatment or had no identifiable source of SAH. A poor outcome (mRS score > 2) was observed in 33.7% of the patients assigned to aneurysm clipping and in 23.2% of the patients assigned to coil embolization (OR 1.68, 95% CI 1.08–2.61; p = 0.02). Of treated patients assigned to the coil group, 124 (62.3%) of the 199 who were eligible for any treatment actually received endovascular coil embolization. Patients who crossed over from coil to clip treatment fared worse than patients assigned to coil embolization, but no worse than patients assigned to clip occlusion. No patient treated by coil embolization suffered a recurrent hemorrhage.

Conclusions. One year after treatment, a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes than clip occlusion. Although most aneurysms assigned to the coil treatment group were treated by coil embolization, a substantial number crossed over to surgical clipping. Although a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes at 1 year, it remains important that high-quality surgical clipping be available as an alternative treatment modality.

Neurosurgery 69:1272–1280, 2011 DOI: 10.1227/NEU.0b013e3182233e24

Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs.

OBJECTIVE: To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival.

METHODS: We performed a prospective, dose-escalation phase Ib study of the topoisomerase- I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas.

RESULTS: Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies.

CONCLUSION: Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials

Neurosurgery 69:1015–1029, 2011 DOI: 10.1227/NEU.0b013e318229cfcd

A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated.

OBJECTIVE: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study.

METHODS: Twelve patients were recruited in this randomized, single-blind, shamcontrolled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest.

RESULTS: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P . .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS , 10) at some point during the study.

CONCLUSION: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment- refractory major depressive disorder.

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.

Journal of Neurosurgery: Spine Oct 2011 / Vol. 15 / No. 4 / Pages 348-358. DOI: 10.3171/2011.5.SPINE10769.

Cervical total disc replacement (CTDR) represents a relatively novel procedure intended to address some of the shortcomings associated with anterior cervical discectomy and fusion (ACDF) by preserving motion at the treated level. This prospective, randomized, multicenter study evaluates the safety and efficacy of a new metal-on-metal CTDR implant (Kineflex|C) by comparing it with ACDF in the treatment of single-level spondylosis with radiculopathy.

METHODS

The study was a prospective, randomized US FDA Investigational Device Exemption (IDE) pivotal trial conducted at 21 centers across the US. The primary clinical outcome measures included the Neck Disability Index (NDI), visual analog scale (VAS) scores, and a composite measure of clinical success. Patients were randomized to CTDR using the Kineflex|C (SpinalMotion, Inc.) cervical artificial disc or ACDF using structural allograft and an anterior plate.

RESULTS

A total of 269 patients were enrolled and randomly assigned to either CTDR (136 patients) or to ACDF (133 patients). There were no significant differences between the CTDR and ACDF groups when comparing operative time, blood loss, length of hospital stay, or the reoperation rate at the index level. The overall success rate was significantly greater in the CTDR group (85%) compared with the ACDF group (71%) (p = 0.05). In both groups, the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 24-month follow-up (p < 0.0001). Similarly, the VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 24-month follow-up (p < 0.0001). The range of motion (ROM) in the CTDR group decreased at 3 months but was significantly greater than the preoperative mean at 12- and 24-month follow-up. The ROM in the ACDF group was significantly reduced by 3 months and remained so throughout the follow-up. Adjacent-level degeneration was also evaluated in both groups from preoperatively to 2-year follow-up and was classified as none, mild, moderate, or severe. Preoperatively, there were no significant differences between groups when evaluating the different levels of adjacent-level degeneration. At the 2-year follow-up, there were significantly more patients in the ACDF group with severe adjacent-level radiographic changes (p < 0.0001). However, there were no significant differences between groups in adjacent-level reoperation rate (7.6% for the Kineflex|C group and 6.1% for the ACDF group).

CONCLUSIONS

Cervical total disc replacement allows for neural decompression and clinical results comparable to ACDF. Kineflex|C was associated with a significantly greater overall success rate than fusion while maintaining motion at the index level. Furthermore, there were significantly fewer Kineflex|C patients showing severe adjacent-level radiographic changes at the 2-year follow-up. These results from a prospective, randomized study support that Kineflex|C CTDR is a viable alternative to ACDF in select patients with cervical radiculopathy

J Neurosurg Spine 15:216–227, 2011. DOI: 10.3171/2011.4.SPINE10404

The study aimed to verify the safety and feasibility of applying acidic fibroblast growth factor (aFGF) with fibrin glue in combination with surgical neurolysis for nonacute spinal cord injury.

Methods. This open-label, prospective, uncontrolled human clinical trial recruited 60 patients with spinal cord injuries (30 cervical and 30 thoracolumbar). The mean patient age was 36.5 ± 15.33 (mean ± SD) years, and the male/ female ratio was 3:1. The mean time from injury to treatment was 25.7 ± 26.58 months, and the cause of injury included motor vehicle accident (26 patients [43.3%]), fall from a height (17 patients [28.3%]), sports (4 patients [6.7%]), and other (13 patients [21.7%]). Application of aFGF with fibrin glue and duraplasty was performed via laminectomy, and an adjuvant booster of combined aFGF and fibrin glue (2 ml) was given at 3 and 6 months postsurgery via lumbar puncture. Outcome measurements included the American Spinal Injury Association (ASIA) motor scores, sensory scores, impairment scales, and neurological levels. Examination of functional independence measures, visual analog scale, MR imaging, electrophysiological and urodynamic studies, hematology and biochemistry tests, tumor markers, and serum inflammatory cytokines were all conducted. All adverse events were monitored and reported. Exclusions were based on refusal, unrelated adverse events, or failure to participate in the planned rehabilitation.

Results. Forty-nine patients (26 with cervical and 23 with thoracolumbar injuries) completed the 24-month trial. Compared with preoperative conditions, the 24-month postoperative ASIA motor scores improved significantly in the cervical group (from 27.6 ± 15.55 to 37.0 ± 19.93, p < 0.001) and thoracolumbar group (from 56.8 ± 9.21 to 60.7 ± 10.10, p < 0.001). The ASIA sensory scores also demonstrated significant improvement in light touch and pinprick in both groups: from 55.8 ± 24.89 to 59.8 ± 26.47 (p = 0.049) and 56.3 ± 23.36 to 62.3 ± 24.87 (p = 0.003), respectively, in the cervical group and from 75.7 ± 15.65 to 79.2 ± 15.81 (p < 0.001) and 78.2 ± 14.72 to 82.7 ± 16.60 (p < 0.001), respectively, in the thoracolumbar group. At 24-month follow-up, the ASIA impairment scale improved significantly in both groups (30% cervical [p = 0.011] and 30% thoracolumbar [p = 0.003]). There was also significant improvement in neurological level in the cervical (from 5.17 ± 1.60 to 6.27 ± 3.27, p = 0.022) and thoracolumbar (from 18.03 ± 4.19 to 18.67 ± 3.96, p = 0.001) groups. The average sum of motor items in functional independence measure also had significant improvement in both groups (p < 0.05). The walking/wheelchair locomotion subscale showed increased percentages of patients who were ambulatory (from 3.4% to 13.8% and from 17.9% to 35.7% in the cervical and thoracolumbar groups, respectively). There were no related adverse events.

Conclusions. The use of aFGF for spinal cord injury was safe and feasible in the present trial. There were significant improvements in ASIA motor and sensory scale scores, ASIA impairment scales, neurological levels, and functional independence measure at 24 months after treatment. Further large-scale, randomized, and controlled investigations are warranted to evaluate the efficacy and long-term results.