Category: Oncology

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Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series

J Neurosurg 114:1350–1359, 2011.DOI: 10.3171/2010.11.JNS10670

Craniopharyngioma accounts for 2%–5% of all primary intracranial neoplasms. The optimal management of craniopharyngioma remains controversial. The authors evaluated the early results of surgery and the longterm risk of tumor recurrence in a large series of patients undergoing resection of craniopharyngiomas.

Methods. Between 1990 and 2008, 112 consecutive patients (57 male and 55 female patients with a mean [± SEM] age of 33.3 ± 1.8 years) underwent resection of craniopharyngiomas at the authors’ hospital. Recurrence or growth of residual tumor tissue during follow-up was assessed using MR imaging.

Results. There were 3 perioperative deaths (2.7%). Severe adverse events were more frequent in patients who underwent operations via the transcranial route (37%) than the transsphenoidal approach (5.6%; p < 0.001). Magnetic resonance imaging showed radical resection of the tumor in 78 (71.6%) of the remaining 109 patients. Previous surgery and maximum tumor diameter were associated with persistence of disease after surgery. Craniopharyngioma recurred in 26 (24.5%) of 106 patients. Presence of residual tumor on the first postoperative MR imaging, male sex, and no postoperative radiation therapy were associated with a risk of tumor recurrence. Quality-of-life data were assessed in the 91 patients who attended the authors’ institution for follow-up visits. Among them, 8.8% patients were partially or completely dependent on others for daily living activities before surgery. This percentage increased to 14.3% at the last follow-up visit. The 5- and 10-year overall survival rates were 94.4% (95% CI 90.0%–98.8%) and 90.3% (95% CI 83.4%–97.3%), respectively.

Conclusions. Complete surgical removal of craniopharyngioma can be achieved with reasonable safety in more than 70% of patients. Recurrence of craniopharyngioma may occur even after apparent radical excision. Prompt management of residual or recurring disease by radiotherapy, repeat surgery, or a combination of both is usually successful in controlling further tumor growth.

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The natural history of intracranial meningiomas

J Neurosurg 114:1250–1256, 2011. DOI: 10.3171/2010.12.JNS101623

Despite the increased detection of incidental or small meningiomas, the lesion’s natural history is largely unknown.

Methods. One year or longer of follow-up was conducted in 244 patients with 273 meningiomas managed conservatively by a single surgeon between 2003 and 2008. Data were stratified according to age, sex, tumor location, symptoms, initial tumor diameter, calcification, MR imaging intensity, and edema. Linear tumor growth was defined as a 2-mm or larger increase in the maximum diameter in any direction of the tumor. Volumetric analysis (ImageJ version 1.43) was also conducted in 154 of 273 meningiomas for which complete radiological data were available in the form of DICOM files throughout the follow-up period. A volume increase greater than 8.2% was regarded as significant because the preliminary volumetry based on 20 randomly selected meningiomas showed that the average SD was 4.1%.

Results. Linear growth was observed in 120 tumors (44.0%) with a mean follow-up of 3.8 years. Factors related to tumor growth were age of 60 or younger (p = 0.0004), absence of calcification (p = 0.027), MR imaging T2 signal hyperintensity (p = 0.021), and edema (p = 0.018). Kaplan-Meier analysis and Cox proportional hazards regression analysis revealed that age 60 or younger (hazard ratio [HR] 1.54, 95% CI 1.05–2.30, p = 0.026), initial tumor diameter greater than 25 mm (HR 2.23, 95% CI 1.44–3.38, p = 0.0004), and the absence of calcification (HR 4.57, 95% CI 2.69–8.20, p < 0.0001) were factors associated with a short time to progression. Volumetric growth was seen in 74.0% of the cases. Factors associated with a higher annual growth rate were male sex (p = 0.0002), initial tumor diameter greater than 25 mm (p < 0.0001), MR imaging T2 signal hyperintensity (p = 0.0001), presence of symptoms (p = 0.037), and edema (p < 0.0001).

Conclusions. Although the authors could obtain variable results depending on the measurement method, the data demonstrate patients younger than 60 years of age and those with meningiomas characterized by hyperintensity on T2-weighted MR imaging, no calcification, diameter greater than 25 mm, and edema need to be observed more closely. Volumetry was more sensitive to detecting tumor growth than measuring the linear diameter.

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Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission

J Neurosurg 114:1399–1409, 2011. DOI: 10.3171/2010.11.JNS101193

Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression.

Methods. A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12–82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results. Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2–16 years). The mean preradiosurgical tumor volume was 5.7 cm3 (range 0.3–33 cm3), and mean postradiosurgical tumor volume was 4.9 cm3 (range 0.1–33 cm3). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12–9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60–0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72–100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1–13.7; p = 0.03).

Conclusions. Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.

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Surgical management and outcome of schwannomas in the craniocervical region

J Neurosurg 114:1257–1267, 2011. DOI: 10.3171/2010.5.JNS0966

Schwannomas occupying the craniocervical junction (CCJ) are rare and usually originate from the jugular foramen, hypoglossal nerves, and C-1 and C-2 nerves. Although they may have different origins, they may share the same symptoms, surgical approaches, and complications. An extension of these lesions along the posterior fossa cisterns, foramina, and spinal canal—usually involving various cranial nerves (CNs) and the vertebral and cerebellar arteries—poses a surgical challenge. The primary goals of both surgical and radiosurgical management of schwannomas in the CCJ are the preservation and restoration of function of the lower CNs, and of hearing and facial nerve function. The origins of schwannomas in the CCJ and their clinical presentation, surgical management, adjuvant stereotactic radiosurgery, and outcomes in 36 patients treated at Barrow Neurological Institute (BNI) are presented.

Methods. Between 1989 and 2009, 36 patients (mean age 43.6 years, range 17–68 years) with craniocervical schwannomas underwent surgical resection at BNI. The records were reviewed retrospectively regarding clinical presentation, radiographic assessment, surgical approaches, adjuvant therapies, and follow-up outcomes.

Results. Headache or neck pain was present in 72.2% of patients. Cranial nerve impairments, mainly involving the vagus nerve, were present in 14 patients (38.9%). Motor deficits were found in 27.8% of the patients. Sixteen tumors were intra- and extradural, 15 were intradural, and 5 were extradural. Gross-total resection was achieved in 25 patients (69.4%). Adjunctive radiosurgery was used in the management of residual tumor in 8 patients; tumor control was ultimately obtained in all cases.

Conclusions. Surgical removal, which is the treatment of choice, is curative when schwannomas in the CCJ are excised completely. The far-lateral approach and its variations are our preferred approaches for managing these lesions. Most common complications involve deficits of the lower CNs, and their early recognition and rehabilitation are needed. Stereotactic radiosurgery, an important tool for the management of these tumors as adjuvant therapy, can help decrease morbidity rates.

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Sphenoorbital meningioma: surgical technique and outcome

J Neurosurg 114:1241–1249, 2011.DOI: 10.3171/2010.10.JNS101128

The aim of this study was to describe the surgical technique used for removal of sphenoorbital meningiomas in the authors’ practice and to review the operative outcome.

Methods. Review of the senior author’s practice between 1994 and 2009 revealed 39 patients (mean age 48 years) eligible for this study. Clinical presentation, surgical technique, postoperative outcome, and follow-up data are presented. Surgical technique is detailed, with an emphasis on aggressive removal consisting of drilling of the hypertrophied sphenoid bone, orbital wall, and anterior clinoid process, followed by tumor removal and a wide resection of the involved dura. A simple dural closure without reconstruction of the orbital roof or the lateral wall of the orbit is also described.

Results. Gross-total resection was achieved in 15 cases (38.5%), near-total resection with small residual in the cavernous sinus or periorbita in 20 cases (51.3%), and subtotal resection in 4 cases (10.3%). Postoperative complications included trigeminal hypesthesia in 9 patients, oculomotor palsy in 3 patients, and seizure in 2 patients. Seven patients had recurrence within the mean follow-up period of 40.7 months. Preoperative visual deficits were present in 21 patients (53.8%). Of these, 14 (66.7%) experienced visual recovery to normal levels postoperatively. Statistical analyses revealed preoperative severe visual deficit and sphenoid bone hypertrophy as an independent risk factor and an independent favorable factor, respectively, for a favorable visual outcome. Proptosis was resolved (≤ 2 mm) in 73.5% of the authors’ patients. No patient had postoperative enophthalmos.

Conclusions. In the authors’ practice, surgery for sphenoorbital meningiomas consists of resection of the orbital/ sphenoid intraosseous, intraorbital, and intradural tumor components. The authors believe that aggressive removal of the orbital/sphenoid intraosseous tumor is critical for a favorable visual outcome and tumor control. Furthermore, satisfactory cosmetic results can be achieved with simple reconstruction techniques as described.

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Hydrocephalus associated with vestibular schwannomas: management options and factors predicting the outcome

J Neurosurg 114:1209–1215, 2011. DOI: 10.3171/2010.10.JNS1029

The current, generally accepted optimal management for hydrocephalus related to vestibular schwannomas (VSs) is primary tumor removal, with further treatment reserved only for patients who remain symptomatic. Previous studies have shown, however, that this management can lead to an increase in surgery-related complications. In this study, the authors evaluated their experience with the treatment of such patients, with the aim of identifying the following: 1) the parameters correlating to the need for specific hydrocephalus treatment following VS surgery; and 2) patients at risk for developing hydrocephalus-related complications.

Methods. This was a retrospective study of a 400-patient series. The complication rates and outcomes following primary hydrocephalus treatment versus primary VS removal were compared. Patients undergoing primary tumor removal were further subdivided on the basis of the need for subsequent hydrocephalus treatment. The 3 categories of parameters tested for correlation with the need for such subsequent treatment as well as with heightened risk for developing complications were patient-, tumor-, and hydrocephalus-related.

Results. Of the entire series, 53 patients presented with hydrocephalus. Forty-eight of 53 patients underwent primary VS surgery, of whom 42 (87.5%) did not require additional hydrocephalus treatment. Of the 6 patients who did require additional hydrocephalus treatment, only 3 ultimately required a VP shunt. Factors correlating to the need of hydrocephalus treatment after VS removal were large tumor size, irregular tumor surface, and severe preoperative hydrocephalus. Patients with a longer symptom duration prior to surgery, those with polycyclic tumors, or with inhomogeneous VS, were at heightened risk for the development of CSF leaks. The general and functional outcome of surgery showed no correlation to the presence of preoperative hydrocephalus.

Conclusions. Primary tumor removal is the optimum management of disease in patients with VS with associated hydrocephalus; it leads to resolution of the hydrocephalus in the majority of cases, and the outcome is similar to that of patients without hydrocephalus. Certain factors may aid in identifying patients at risk for developing persistent hydrocephalus as well as those at risk for CSF leaks

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Are stereotactic sample biopsies still of value in the modern management of pineal region tumours? Lessons from a single-department, retrospective series

Acta Neurochir (2011) 153:1111–1122. DOI 10.1007/s00701-010-0936-7

Recent improvements in imaging-based diagnosis, the broader application of neuroendoscopic techniques and advances in open surgery techniques mean that the need for stereotactic biopsies in the management of pineal region tumours must be reevaluated. The primary aim of this retrospective study was to establish whether stereotactic biopsy is still of value in the modern management of pineal region tumours.

Methods From 1985 to 2009, 88 consecutive patients underwent a stereotactic biopsy in our institution (51 males and 37 females; median age at presentation 30; range 2–74).

Results Accurate tissue diagnoses were obtained in all but one case (i.e. 99%). In one case (1%), three distinct stereotactic procedures were necessary to obtain a tissue diagnosis. There was no mortality or permanent morbidity associated with stereotactic biopsy. One patient (1%) presented an intra-parenchymal hematoma but no related clinical symptoms. Five patients (6%) presented transient morbidity, which lasted for between 2 days and 3 weeks after the biopsy.

Conclusions To guide subsequent treatment, we believe that histological diagnosis is paramount. Stereotactic biopsies are currently the safest and the most efficient way of obtaining this essential information. Recent improvements in stereotactic technology (particularly robotic techniques) appear to be very valuable, with almost no permanent morbidity or mortality risk and no decrease in the accuracy rate. In our opinion, other available neurosurgical techniques (such as endoscopic neurosurgery, stereotactic neurosurgery and open microsurgery) are complementary and not competitive.

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Navigated Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging: Advanced Adjuncts in Preoperative Planning for Central Region Tumors

Neurosurgery 68:1317–1325, 2011 DOI: 10.1227/NEU.0b013e31820b528c

Tumor resection in the vicinity of the motor cortex poses a challenge to all neurosurgeons. For preoperative assessment of eloquent cortical areas, functional magnetic resonance imaging (fMRI) is used, whereas intraoperatively, direct cortical stimulation (DCS) is performed. Navigated transcranial magnetic stimulation (nTMS) is comparable to DCS in activating cortical pyramidal neurons.

OBJECTIVE: To evaluate the reliability of nTMS compared with fMRI and DCS for preoperative resection planning of centrally located tumors.

METHODS: In a prospective series, 11 patients (ages, 20-63 years; mean, 41.9 ± 14.9 years, 2 women) with tumors located in or adjacent to the motor cortex were evaluated for surgery. fMRI and nTMS were applied for preoperative assessment of the extent of tumor resection. A 3-dimensional anatomic data set with superimposed fMRI data was integrated in the eXimia Navigated Brain Stimulation station for ensuing motor cortex mapping by nTMS. Responses from nTMS were evaluated by electromyographic response. During surgery, the coordinates of each DCS site were unambiguously defined and integrated into neuronavigation. A post hoc comparison of the coordinates of nTMS, fMRI, and DCS was performed.

RESULTS: Distances from nTMS to DCS (10.5 ± 5.67 mm) were significantly smaller than those from fMRI to DCS (15.0 ± 7.6 mm).

CONCLUSION: nTMS anticipates information usually only enabled by DCS and therefore allows surgical planning in eloquent cortex surgery.

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Pineal region tumors: an optimal approach for simultaneous endoscopic third ventriculostomy and biopsy

Neurosurg Focus 30 (4):E3, 2011. DOI: 10.3171/2011.2.FOCUS10301

Simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is a widely accepted therapeutic and diagnostic procedure for patients with noncommunicating hydrocephalus secondary to a pineal region tumor. Multiple approaches have been advocated, including the use of a steerable fiberoptic or rigid lens endoscope via 1 or 2 trajectories. However, the optimal approach has not been established based on the individual anatomical characteristics of the patient.

 Methods. A retrospective review of patients undergoing simultaneous ETV and tumor biopsy was undertaken. Preoperative MR images were examined to measure the width of the anterior third ventricle and maximal diameters of the tumor, Monro foramen (right), and massa intermedia. The distances between the tumor and massa intermedia, tumor and anterior commissure, midbrain and massa intermedia, and the dorsum sella and anterior commissure were also recorded. Single and dual trajectory approaches were compared using paired t-tests for each parameter.

Results. Over an 8-year interval, 15 patients underwent simultaneous ETV and tumor management. These patients ranged from 6 to 71 years of age (mean 36.7 years); 5 were younger than 18 years of age. Seven were treated using a dual trajectory approach, and 8 were treated using a single trajectory approach. All cases were completed without complications or the need for an additional CSF diversionary procedure within 6 months. The diagnostic yield at biopsy was 86.7%. There were no statistically significant differences between the single and dual trajectory groups for the measured parameters. However, the dual trajectory group demonstrated a larger anterior third ventricular diameter (1.43 vs 1.21 cm, p = 0.29). The single trajectory group trended toward a smaller tumor– anterior commissure interval (2.23 vs 2.51 cm, p = 0.24) and a larger dorsum sella–anterior commissure distance (1.67 vs 1.49 cm, p = 0.28).

Conclusions. These data confirm the safety and diagnostic efficacy of simultaneous ETV and biopsy for tumors of the pineal region. Although no statistically significant differences were seen in the authors’ recorded measurements, several trends suggest a role for a tailored approach to selecting a single or dual trajectory approach when using a rigid endoscope

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Neuroendoscopic biopsy of ventricular tumors: a multicentric experience

Neurosurg Focus 30 (4):E2, 2011. DOI: 10.3171/2011.1.FOCUS10326

Although neuroendoscopic biopsy is routinely performed, the safety and validity of this procedure has been studied only in small numbers of patients in single-center reports. The Section of Neuroendoscopy of the Italian Neurosurgical Society invited some of its members to review their own experience, gathering a sufficient number of cases for a wide analysis.

Methods. Retrospective data were collected by 7 centers routinely performing neuroendoscopic biopsies over a period of 10 years. Sixty patients with newly diagnosed intraventricular and paraventricular tumors were included. No patient harboring a colloid cyst was included. Data regarding clinical presentation, neuroimaging findings, operative techniques, pathological diagnosis, postoperative complications, and subsequent therapy were analyzed.

Results. In all patients, a neuroendoscopic tumor biopsy was performed. In 38 patients (64%), obstructive hydrocephalus was present. In addition to the tumor biopsy, 32 patients (53%) underwent endoscopic third ventriculostomy (ETV), and 7 (12%) underwent septum pellucidotomy. Only 2 patients required a ventriculoperitoneal shunt shortly after the endoscopy procedure because ETV was not feasible. The major complication due to the endoscopy procedure was ventricular hemorrhage noted on the postoperative images in 8 cases (13%). Only 2 patients were symptomatic and required medical therapy. Infection occurred in only 1 case, and the other complications were all reversible. In no case did clinically significant sequelae affect the patient’s outcome. Tumor types ranged across the spectrum and included glioma (low- and high-grade [27%]), pure germinoma (15%), pineal parenchymal tumor (12%), primary neuroectodermal tumor (4%), lymphoma (9%), metastasis (4%), craniopharyngioma (6%), and other tumor types (13%). In 10% of patients, the pathological findings were inconclusive. According to diagnosis, specific therapy was performed in 35% of patients: 17% underwent microsurgical removal, and 18% underwent chemotherapy or radiotherapy.

Conclusions. This is one of the largest series confirming the safety and validity of the neuroendoscopic biopsy procedure. Complications were relatively low (about 13%), and they were all reversible. Neuroendoscopic biopsy provided meaningful pathological data in 90% of patients, making subsequent tumor therapy feasible. Cerebrospinal fluid pathways can be restored by ETV or septum pellucidotomy (65%) to control intracranial hypertension. In light of the results obtained, a neuroendoscopic biopsy should be considered a possible alternative to the stereotactic biopsy in the diagnosis and treatment of ventricular or paraventricular tumors. Furthermore, it could be the only surgical procedure necessary for the treatment of selected tumors.

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Trigeminal schwannomas: experience with 57 cases and a review of the literature

Neurosurg Rev (2011) 34:159–171. DOI 10.1007/s10143-010-0289-y

Trigeminal schwannoma is a mostly benign tumor that can be cured by complete resection. Over the last few decades, several pioneers have developed surgical approaches enabling the total removal of such tumors.

We analyzed 57 patients who underwent radical surgery, including 45 patients who underwent skull base surgery as their initial treatment, for removal of trigeminal schwannomas. Here, we report the surgical management of these cases. Since 1990, all such patients have been treated using three main types of middle fossa skull base approaches, which minimize the exposure of the brain: the anterior transpetrosal approach, subtemporal interdural approach (Dolenc), or a combination of these approaches.

Before 1990, total tumor removal was achieved in only three of eight patients (38%). After 1990, the tumors were totally removed in 43 patients (90%) and were nearly completely removed in an additional three patients (6%). Among the patients who underwent skull base surgery as their initial treatment, a complete resection was achieved in 93% (42/45 patients) of the cases. However, total surgical removal after surgery and Gamma knife surgery was very difficult because of dense adhesions to the brain stem and cranial nerves. No surgery-related mortalities occurred in this series, and the individual KPS scores were more than 90% among the patients who underwent skull base surgery. No recurrences requiring additional surgery have occurred after an average follow-up period of 4.9 years.

Most of the trigeminal schwannomas could be removed totally and safely during a single operation after the introduction of skull base surgery. Therefore, radiosurgery should not be applied as the treatment of first choice for younger patients. A correct anatomical knowledge is critical for minimizing brain exposure and avoiding surgical complications.

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Intraventricular craniopharyngioma: morphological analysis and outcome evaluation of 17 cases

Acta Neurochir (2011) 153:773–784. DOI 10.1007/s00701-010-0938-5

There is still some confusion with regard to the tumor–third ventricle floor (3rd VF) relationship of craniopharyngiomas located exclusively within the third ventricle. This study aims to provide some evidence to clarify the growth pattern of intraventricular craniopharyngiomas (IVC), and to summarize the surgical strategy and outcome.

Methods Seventeen cases of IVC were reviewed retrospectively in relation to preoperative imaging, clinical presentation, intraoperative findings, tumor pathology, and surgical outcome. The tumor–3rd VF relationship and the tumor’s stratification were analyzed based on intraoperative inspection and histology.

Findings: Variable adherence patterns of IVC to the 3rd VF were found, which were classified as (a) purely IVC with pedicle attachment to 3rd VF (two cases), (b) intra-3rd VF tumors with wide-based attachment but a dissectible tumor boundary (seven cases), and (c) intra-3rd VF tumors with an undissectible wide, tight attachment (eight cases). Histological analysis revealed that both of the two cases with growth pattern “a” intruded into the third ventricular cavity without a covering layer of neural tissue (which only exists in the squamous-papillary subtype). Tumors with growth pattern “b” and “c,” in contrast, were noted to have a thin layer of neural tissue. This occurred in both subtypes (11 adamantinomatous, 4 papillary). Total removal was accomplished in all tumors demonstrating growth pattern “a” and “b.” There was also better preservation of the 3rd VF and consequently a better outcome. On the other hand, total removal was only achieved in 50% of tumors showing growth pattern “c” including one mortality. No recurrence has been encountered in patients whose tumors were totally removed.

Conclusion Variable adherence patterns and tumor subtypes were observed in IVCs, which were correlated to the tumor pathology, resectability, and subsequent prognosis.

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Functional mapping–guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival

J Neurosurg 114:566–573, 2011. DOI: 10.3171/2010.6.JNS091246

Low-grade gliomas (LGGs) frequently infiltrate highly functional or “eloquent” brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown.

Methods. We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not.

Results. One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6–14.1; PFS, HR 1.9, 95% CI 1.2–2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6–25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0–8.5).

Conclusions. Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

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Diffusion tensor imaging in the cervical spinal cord

Eur Spine J (2011) 20:422–428. DOI 10.1007/s00586-010-1587-3

There are discrepancy between MR findings and clinical presentations. The compressed cervical cord in patients of the spondylotic myelopathy may be normal on conventional MRI when it is at the earlier stage or even if patients had severe symptoms. Therefore, it is necessary to take a developed MR technique—diffusion tensor imaging (DTI)—to detect the intramedullary lesions.

Prospective MR and DTI were performed in 53 patients with cervical compressive myelopathy and twenty healthy volunteers. DTI was performed along six non-collinear directions with single-shot spin echo echo-planar imaging (EPI) sequence. Intramedullary apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in four segments (C2/3, C3/4, C4/5, C5/6) for volunteers, in lesions (or the compressed cord) and normal cord for patients. DTI original images were processed to produce color DTI maps.

In the volunteers’ group, cervical cord exhibited blue on the color DTI map. FA values between four segments had a significant difference (P<0.01), with the highest FA value (0.85 ±  0.03) at C2/3 level. However, ADC value between them had no significant difference (P> 0.05). For patients, only 24 cases showed hyperintense on T2-weighted image, while 39 cases shown patchy green signal on color DTI maps. ADC and FA values between lesions or the compressed cord and normal spinal cord of patients had a significant difference (both P< 0.01). FA value at C2/3 cord is the highest of other segments and it gradually decreases towards the caudal direction. Using single-shot spin echo EPI sequence and six non-collinear diffusion directions with b  value of 400 s mm-2 ,

DTI can clearly show the intramedullary microstructure and more lesions than conventional MRI.

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Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid–induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters

J Neurosurg 114:595–603,2011.DOI: 10.3171/2010.2.JNS091322.

The aim of this study was to investigate the relationships between intraoperative fluorescence, features on MR imaging, and neuropathological parameters in 11 cases of newly diagnosed glioblastoma multiforme (GBM) treated using protoporphyrin IX (PpIX) fluorescence-guided resection.

Methods. In 11 patients with a newly diagnosed GBM, δ-aminolevulinic acid (ALA) was administered to enhance endogenous synthesis of the fluorophore PpIX. The patients then underwent fluorescence-guided resection, coregistered with conventional neuronavigational image guidance. Biopsy specimens were collected at different times during surgery and assigned a fluorescence level of 0–3 (0, no fluorescence; 1, low fluorescence; 2, moderate fluorescence; or 3, high fluorescence). Contrast enhancement on MR imaging was quantified using two image metrics: 1) Gd-enhanced signal intensity (GdE) on T1-weighted subtraction MR image volumes, and 2) normalized contrast ratios (nCRs) in T1-weighted, postGd-injection MR image volumes for each biopsy specimen, using the biopsy-specific image-space coordinate transformation provided by the navigation system. Subsequently, each GdE and nCR value was grouped into one of two fluorescence categories, defined by its corresponding biopsy specimen fluorescence assessment as negative fluorescence (fluorescence level 0) or positive fluorescence (fluorescence level 1, 2, or 3). A single neuropathologist analyzed the H & E–stained tissue slides of each biopsy specimen and measured three neuropathological parameters: 1) histopathological score (0–IV); 2) tumor burden score (0–III); and 3) necrotic burden score (0–III).

Results. Mixed-model analyses with random effects for individuals show a highly statistically significant difference between fluorescing and nonfluorescing tissue in GdE (mean difference 8.33, p = 0.018) and nCRs (mean difference 5.15, p < 0.001). An analysis of association demonstrated a significant relationship between the levels of intraoperative fluorescence and histopathological score (χ2 = 58.8, p < 0.001), between fluorescence levels and tumor burden (χ2 = 42.7, p < 0.001), and between fluorescence levels and necrotic burden (χ2 = 30.9, p < 0.001). The corresponding Spearman rank correlation coefficients were 0.51 (p < 0.001) for fluorescence and histopathological score, and 0.49 (p < 0.001) for fluorescence and tumor burden, suggesting a strongly positive relationship for each of these variables.

Conclusions. These results demonstrate a significant relationship between contrast enhancement on preoperative MR imaging and observable intraoperative PpIX fluorescence. The finding that preoperative MR image signatures are predictive of intraoperative PpIX fluorescence is of practical importance for identifying candidates for the procedure. Furthermore, this study provides evidence that a strong relationship exists between tumor aggressiveness and the degree of tissue fluorescence that is observable intraoperatively, and that observable fluorescence has an excellent positive predictive value but a low negative predictive value.

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Gamma Knife radiosurgery for larger-volume vestibular schwannomas

J Neurosurg 114:801–807, 2011.DOI: 10.3171/2010.8.JNS10674

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium- sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods. Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results. The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions. Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

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Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

J Neurosurg 114:613–623, 2011. DOI: 10.3171/2010.3.JNS097

Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA–induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery.

Methods. Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function.

Results. More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm3, p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036).

Conclusions. Extended resections performed using a tool such as 5-ALA–derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

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Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

J Neurooncol (2011) 102:105–113.DOI 10.1007/s11060-010-0296-4

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM).

Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin–eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging.

Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin–eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%.

The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.

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Identification of diagnostic serum protein profiles of glioblastoma patients

J Neurooncol (2011) 102:71–80.DOI 10.1007/s11060-010-0284-8

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients.

Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Datamining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles.

Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p< 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p< 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient.

This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate  single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size.

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Stereotactic versus endoscopic surgery in periventricular lesions

Acta Neurochir (2011) 153:517–526.DOI 10.1007/s00701-010-0933-x

Endoscopic and stereotactic surgery have gained widespread acceptance as minimally invasive tools for the diagnosis of intracerebral pathologies. We investigated the specific advantages and disadvantages of each technique in the assessment of periventricular lesions.

Method This study included a retrospective series of 70 patients with periventricular lesions. Endoscopic surgery was performed in 17 patients (mean age, 37 years; range, 4 months–78 years) and stereotactic biopsy in 55 patients (mean age, 63 years; range, 23–80 years), including two patients who underwent both procedures.

Results Hydrocephalus was present in 13/17 patients in the endoscopic group (77%) and in 11/55 patients in the stereotactic group (20%). Diagnosis was achieved in all patients in the endoscopic group and in all but one patient in the stereotactic group, in whom histological diagnosis was obtained by endoscopic biopsy during a second operation. In the endoscopic group, additional procedures performed included ventriculostomy (2/17), cyst fenestration (3/17), endoscopic shunt revision (3/17) and placement of Rickham reservoirs or external cerebrospinal fluid drains (6/17). Adverse events occurred in one patient after endoscopy (chronic subdural hematoma) and in two patients after stereotactic surgery (one mild hemiparesis and one transitory paresis of the contralateral leg).

Conclusions Endoscopic and stereotactic surgery have distinct advantages and disadvantages in approaching periventricular lesions. The advantages of endoscopy encompass the possibility to perform additional surgical procedures during the same session (e.g. tumour reduction, third ventriculostomy, fenestration of a cyst). The visual control reduces the hazard of injury to anatomical structures and allows for a better control of bleeding although there is a considerable blind-out in such situations. The advantages of stereotactic surgery include a smaller approach and precise planning of the trajectory. It is usually performed under local anaesthesia. Both methods provide a safe and efficient therapeutic option in periventricular lesions with low surgical-related morbidity.

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