Tag: Oncology

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Craniotomy for perisellar meningiomas: comparison of simple (appropriate for endoscopic approach) versus complex anatomy and surgical outcomes

J Neurosurg 126:1191–1200, 2017

Microsurgical resection of perisellar meningiomas has remained the gold standard for treatment, with extended endoscopic endonasal surgery emerging as a viable alternative. Historical microsurgical series do not distinguish based on tumor anatomy, but are being used as a comparison against endonasal surgery. In this study, the authors retrospectively reviewed and compared the anatomy of perisellar meningiomas seen at their institution. The tumors were separated into 2 groups based on whether they would be appropriate for endoscopic resection, and the authors compared the surgical outcomes.

METHODS Between 2001 and 2013, 53 patients (73.6% women) with perisellar meningiomas underwent open microsurgical resection at Vancouver General Hospital performed by the senior author (R.A.). These tumors were separated into 2 groups based on their anatomy, and the authors analyzed the resection rates, surgical results, patient quality of life, and complications.

RESULTS Among the 53 patients who presented with perisellar meningiomas, the authors were able to identify 18 lesions with “simple” anatomy suitable for endoscopic resection and 35 lesions with “complex” anatomy suitable for craniotomy resection. The mean age of patients in the study cohort was 57.4 years (range 33–91 years), and most patients presented with visual loss (68.0%) and visual field restriction (64.2%). There were no major differences in patient demographic data between the 2 groups. Patients with simple anatomy had smaller lesions (2.1 vs 3.5 cm; p = 0.004), no optic canal invasion (89% vs 26%; p < 0.0001), minimal vascular encasement (cortical cuff 83% vs 9%; p < 0.0001), and a rounded tumor shape (100% vs 31.8%; p = 0.0001) when compared with those with complex anatomy. The majority of lesions originated from the tuberculum sellae and planum sphenoidale. A greater degree of resection was achieved in the favorable anatomy group (99% vs 87.1%; p < 0.0001). Vision was improved or normalized in 96.6% of patients. Patients in the cohort with complex anatomy had more transient complications; there were no incidents of surgical-site infection, meningitis, or death in this series. One patient who underwent removal of a recurrent lesion experienced a CSF leak that required endoscopic repair. The overall persisting complications rate was higher in the group with complex anatomy (11.1% vs 37.1%; p = 0.0498); overall, 28.3% of patients experienced disabling complications. Patient-perceived quality of life improved in the simple anatomy group following surgery (DSF-36 +16.6 vs -8.4; p = 0.0045).

CONCLUSIONS Extended endoscopic surgery is emerging as a viable alternative to microsurgical resection of perisellar meningiomas. The authors identified 2 patient groups based on tumor anatomy, with distinctly separate surgical outcomes. In the future, patients considered for endoscopic resection should be compared against the surgical group with simple anatomy that includes smaller tumors, no vascular encasement, and limited optic canal invasion.

 

 

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Surgical treatment of brain metastases in the central region

J Neurosurg 126:698–707, 2017

Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not in ltrating intra- parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region.

METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors’ institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up.

RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery.

CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological de cits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

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Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification

J Neurosurg 126:661–676, 2017

This study aimed to evaluate neurological function and progression/recurrence (P/R) outcome of foramen magnum meningioma (FMM) based on a modified classification.

METHODS This study included 185 consecutive patients harboring FMMs (mean age 49.4 years; 124 females). The authors classified the FMMs into 4 types according to the previous classification of Bruneau and George as follows: Type A (n = 49, 26.5%), the dural attachment of the lesion grows below the vertebral artery (VA); Type B (n = 39, 21.1%), the dural attachment of the lesion grows above the VA; Type C1 (n = 84, 45.4%), the VA courses across the lesion with or without VA encasement or large lesions grow both above and below the bilateral VA; and Type C2 (n = 13, 7.0%), Type C1 plus partial/total encasement of the VA and extradural growth.

RESULTS The median preoperative Karnofsky Performance Scale (KPS) score was 80. Gross-total resection (GTR) was achieved in 154 patients (83.2%). Lower cranial nerve morbidity was lowest in Type A lesions (16.3%). Type C2 lesions were inherently larger (p = 0.001), had a greater percentage of ventrolateral location (p = 0.009) and VA encase-ment (p < 0.001), lower GTR rate (p < 0.001), longer surgical duration (p = 0.015), higher morbidity (38.5%), higher P/R rate (30.8%, p = 0.009), and poorer recent KPS score compared with other types. After a mean follow-up duration of 110.3 months, the most recent follow-up data were obtained in 163 patients (88.1%). P/R was observed in 13 patients (7.2%). The median follow-up KPS score was 90. Compared with preoperative status, recent neurological status was improved in 91 (49.2%), stabilized in 76 (41.1%), and worsened in 18 (9.7%) patients. The multivariate Cox proportional hazard regression model demonstrated Type C2 (HR 3.94, 95% CI 1.04–15.0, p = 0.044), nontotal resection (HR 6.30, 95% CI 1.91–20.8, p = 0.003), and pathological mitosis (HR 7.11, 95% CI 1.96–25.8, p = 0.003) as independent adverse predictors for tumor P/R. Multivariate logistic regression analysis identified nontotal resection (OR 4.06, 95% CI 1.16–14.2, p = 0.029) and pathological mitosis (OR 6.29, 95% CI 1.47–27.0, p = 0.013) as independent risks for poor outcome (KPS score < 80).

CONCLUSIONS The modified classification helped to predict surgical outcome and P/R in addition to the position of the lower cranial nerves. Preoperative imaging studies and neurological function should be reviewed carefully to establish an individualized management strategy to improve long-term outcome.

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Consensus guidelines for postoperative spine SBRT

J Neurosurg Spine 26:299–306, 2017

Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases.

METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents.

RESULTS Consensus treatment indications included: radioresistant primary, 1–2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint.

CONCLUSIONS The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1–2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

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Cushing’s disease: pathobiology, diagnosis, and management

J Neurosurg 126:404–417, 2017

Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function.
Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the current pathophysiological principles, diagnostic methods, and management of CD.
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Natural history of colloid cysts of the third ventricle

J Neurosurg 125:1420–1430, 2016

Colloid cysts are rare, histologically benign lesions that may result in obstructive hydrocephalus and death. Understanding the natural history of colloid cysts has been challenging given their low incidence and the small number of cases in most reported series. This has complicated efforts to establish reliable prognostic factors and surgical indications, particularly for asymptomatic patients with incidental lesions. Risk factors for obstructive hydrocephalus in the setting of colloid cysts remain poorly defined, and there are no grading scales on which to develop standard management strategies.

Methods The authors performed a single-center retrospective review of all cases of colloid cysts of the third ventricle treated over nearly 2 decades at Washington University. Univariate analysis was used to identify clinical, imaging, and anatomical factors associated with 2 outcome variables: symptomatic clinical status and presentation with obstructive hydrocephalus. A risk-prediction model was defined using bootstrapped logistic regression. Predictive factors were then combined into a simple 5-point clinical scale referred to as the Colloid Cyst Risk Score (CCRS), and this was evaluated with receiver-operator characteristics.

Results The study included 163 colloid cysts, more than half of which were discovered incidentally. More than half of the incidental cysts (58%) were followed with surveillance neuroimaging (mean follow-up 5.1 years). Five patients with incidental cysts (8.8%) progressed and underwent resection. No patient with an incidental, asymptomatic colloid cyst experienced acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly half (46.2%) of symptomatic patients presented with hydrocephalus. Eight patients (12.3%) presented acutely, and there were 2 deaths due to obstructive hydrocephalus and herniation. The authors identified several factors that were strongly correlated with the 2 outcome variables and defined third ventricle risk zones where colloid cysts can cause obstructive hydrocephalus. No patient with a lesion outside these risk zones presented with obstructive hydrocephalus. The CCRS had significant predictive capacity for symptomatic clinical status (area under the curve [AUC] 0.917) and obstructive hydrocephalus (AUC 0.845). A CCRS ≥ 4 was significantly associated with obstructive hydrocephalus (p < 0.0001, RR 19.4).

Conclusions Patients with incidentally discovered colloid cysts can experience both lesion enlargement and symptom progression or less commonly, contraction and symptom regression. Incidental lesions rarely cause acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly one-half of patients with symptomatic colloid cysts present with obstructive hydrocephalus, which has an associated 3.1% risk of death. The CCRS is a simple 5-point clinical tool that can be used to identify symptomatic lesions and stratify the risk of obstructive hydrocephalus. External validation of the CCRS will be necessary before objective surgical indications can be established. Surgical intervention should be considered for all patients with CCRS ≥ 4, as they represent the high-risk subgroup.

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Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas

J Neurosurg 125:1408–1419, 2016

One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue.

Methods 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas’ PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases.

Results PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases.

Conclusions The authors’ data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

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Genomic landscape of intracranial meningiomas

genomic-meningiomas

J Neurosurg 125:525–535, 2016

Meningiomas are the most common primary intracranial neoplasms in adults. Current histopathological grading schemes do not consistently predict their natural history. Classic cytogenetic studies have disclosed a progressive course of chromosomal aberrations, especially in high-grade meningiomas. Furthermore, the recent application of unbiased nextgeneration sequencing approaches has implicated several novel genes whose mutations underlie a substantial percentage of meningiomas. These insights may serve to craft a molecular taxonomy for meningiomas and highlight putative therapeutic targets in a new era of rational biology-informed precision medicine.

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Optic nerve pial circulation in tuberculum meningioma surgery

optic-nerve-pial-circulation-in-tuberculum-meningioma-surgery

J Neurosurg 125:565–569, 2016

Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery.

The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome.

The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort.

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The Simpson grading revisited

PSMeningioma

J Neurosurg 125:551–560, 2016

Recent advances in radiotherapy and neuroimaging have called into question the traditional role of aggressive resections in patients with meningiomas. In the present study the authors reviewed their institutional experience with a policy based on maximal safe resections for meningiomas, and they analyzed the impact of the degree of resection on functional outcome and progression-free survival (PFS).

Methods The authors retrospectively analyzed 901 consecutive patients with primary meningiomas (716 WHO Grade I, 174 Grade II, and 11 Grade III) who underwent resections at the University Hospital of Bonn between 1996 and 2008. Clinical and treatment parameters as well as tumor characteristics were analyzed using standard statistical methods.

Results The median follow-up was 62 months. PFS rates at 5 and 10 years were 92.6% and 86.0%, respectively. Younger age, higher preoperative Karnofsky Performance Scale (KPS) score, and convexity tumor location, but not the degree of resection, were identified as independent predictors of a good functional outcome (defined as KPS Score 90– 100). Independent predictors of PFS were degree of resection (Simpson Grade I vs II vs III vs IV), MIB-1 index (< 5% vs 5%–10% vs >10%), histological grade (WHO I vs II vs III), tumor size (≤ 6 vs > 6 cm), tumor multiplicity, and location. A Simpson Grade II rather than Grade I resection more than doubled the risk of recurrence at 10 years in the overall series (18.8% vs 8.5%). The impact of aggressive resections was much stronger in higher grade meningiomas.

Conclusions A policy of maximal safe resections for meningiomas prolongs PFS and is not associated with increased morbidity.

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Resting-state functional MRI in an intraoperative MRI setting

Resting-state functional MRI in an intraoperative MRI setting-1

J Neurosurg 125:401–409, 2016

The authors’ aim in this paper is to prove the feasibility of resting-state (RS) functional MRI (fMRI) in an intraoperative setting (iRS-fMRI) and to correlate findings with the clinical condition of patients pre- and postoperatively.

Methods: Twelve patients underwent intraoperative MRI-guided resection of lesions in or directly adjacent to the central region and/or pyramidal tract. Intraoperative RS (iRS)–fMRI was performed pre- and intraoperatively and was correlated with patients’ postoperative clinical condition, as well as with intraoperative monitoring results. Independent component analysis (ICA) was used to postprocess the RS-fMRI data concerning the sensorimotor networks, and the mean z-scores were statistically analyzed.

Results: iRS-fMRI in anesthetized patients proved to be feasible and analysis revealed no significant differences in preoperative z-scores between the sensorimotor areas ipsi- and contralateral to the tumor. A significant decrease in z-score (p < 0.01) was seen in patients with new neurological deficits postoperatively. The intraoperative z-score in the hemisphere ipsilateral to the tumor had a significant negative correlation with the degree of paresis immediately after the operation (r = -0.67, p < 0.001) and on the day of discharge from the hospital (r = -0.65, p < 0.001). Receiver operating characteristic curve analysis demonstrated moderate prognostic value of the intraoperative z-score (area under the curve 0.84) for the paresis score at patient discharge.

Conclusions: The use of iRS-fMRI with ICA-based postprocessing and functional activity mapping is feasible and the results may correlate with clinical parameters, demonstrating a significant negative correlation between the intensity of the iRS-fMRI signal and the postoperative neurological changes.

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Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors

supratentorial hemispheric ependymomas

J Neurosurg 125:410–418, 2016

Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall sur- vival (OS), and prognostic factors for hemispheric ependymomas.

Methods: The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors.

Results: Anaplastic histology/WHO Grade III tumors were identifed in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identifed on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS.

Conclusions: A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients with hemispheric ependymoma.

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Origin of craniopharyngiomas: implications for growth pattern, clinical characteristics, and outcomes of tumor recurrence

Origin of craniopharyngiomas

J Neurosurg 125:24–32, 2016

Craniopharyngiomas are associated with a high rate of recurrence. The surgical management of recurrent lesions has been among the most challenging neurosurgical procedures because of the craniopharyngioma’s complex topographical relationship with surrounding structures. The aim of this study was to define the determinative role of the site of origin on the growth pattern and clinical features of recurrent craniopharyngiomas.

Methods The authors performed a retrospective analysis of 52 patients who had undergone uniform treatment by a single surgeon. For each patient, data concerning symptoms and signs, imaging features, hypothalamic-pituitary function, and recurrence-free survival rate were collected.

Results For children, delayed puberty was more frequent in the group with Type I (infradiaphragmatic) craniopharyngioma than in the group with Type TS (tuberoinfundibular and suprasellar extraventricular) lesions (p < 0.05). For adults, blindness was more frequent in the Type I group than in the Type TS group (p < 0.05). Nausea or vomiting, delayed puberty, and growth retardation were more frequent in children than in adults (p < 0.05). Overall clinical outcome was good in 48.07% of the patients and poor in 51.92%. Patients with Type TS recurrent tumors had significantly worse functional outcomes and hypothalamic function than patients with the Type I recurrent tumors but better pituitary function especially in children.

Conclusions The origin of recurrent craniopharyngiomas significantly affected the symptoms, signs, functional outcomes, and hypothalamic-pituitary functions of patients undergoing repeated surgery. Differences in tumor growth patterns and site of origin should be considered when one is comparing outcomes and survival across treatment paradigms in patients with recurrent craniopharyngiomas.

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Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas

Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball ber tractography in patients with gliomas

J Neurosurg 125:33–45, 2016

Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection.

Methods: The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery.

Results: This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a subcohort of 35 subjects both pre- and postsurgery. The rating scales developed for fiber pathway damage were found to be highly reproducible and provided significant correlations with language performance. Preservation of the left arcuate fasciculus (AF) and the temporoparietal component of the superior longitudinal fasciculus (SLF-tp) was consistent in all patients without language deficits (p < 0.001) at the long-term follow-up. Furthermore, in patients with short-term language deficits, the AF and/or SLF-tp were affected, and damage to these 2 pathways was predictive of a long-term language deficit (p = 0.005).

Conclusions: The authors demonstrated the successful application of q-ball tracking in presurgical planning for language pathways in brain tumor patients and in assessing white matter tract integrity postoperatively to predict long-term language dysfunction. These initial results predicting long-term language deficits following tumor resection indicate that postoperative injury to dorsal language pathways may be prognostic for long-term clinical language deficits. Study results suggest the importance of dorsal stream tract preservation to reduce language deficits in patients undergoing glioma resection, as well as the potential prognostic value of assessing postoperative injury to dorsal language pathways to predict long-term clinical language deficits.

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Neuropsychological deficits of vmPFC meningiomas

The cognitive and behavioral effects of meningioma lesions involving the ventromedial prefrontal cortex

J Neurosurg 124:1568–1577, 2016

Anterior skull base meningiomas are frequently associated with changes in personality and behavior. Although such meningiomas often damage the ventromedial prefrontal cortex (vmPFC), which is important for higher cognition, the cognitive and behavioral effects of these meningiomas remain poorly understood. Using detailed neuropsychological assessments in a large series of patients, this study examined the cognitive and behavioral effects of meningioma lesions involving the vmPFC.

Methods: The authors reviewed neuropsychology and lesion mapping records of 70 patients who underwent resection of meningiomas. The patients were drawn from the Neurological Patient Registry at the University of Iowa. Patients were sorted into 2 groups: those with lesions involving the vmPFC and those with lesions that did not involve the vmPFC. Neuropsychological data pertaining to a comprehensive array of cognitive and behavioral domains were available preoperatively in 20 patients and postoperatively in all 70 patients.

Results: No change occurred in basic cognitive functions (e.g., attention, perception, memory, construction and motor performance, language, or executive functions) from the preoperative to postoperative epochs for the vmPFC and non-vmPFC groups. There was a significant decline in the behavioral domain, specifically adaptive function, for both the vmPFC and non-vmPFC groups, and this decline was more pronounced for the vmPFC group. Additionally, postoperative data indicated that the vmPFC group had a specific deficit in value-based decision making, as evidenced by poor performance on the Iowa Gambling Task, compared with the non-vmPFC group. The vmPFC and non-vmPFC groups did not differ postoperatively on other cognitive measures, including intellect, memory, language, and perception.

Conclusions: Lesions of the vmPFC resulting from meningiomas are associated with specific deficits in adaptive function and value-based decision making. Meningioma patients showed a decline in adaptive function postoperatively, and this decline was especially notable in patients with vmPFC region meningiomas. Early detection and resection of meningiomas of the anterior skull base (involving the gyrus rectus) may prevent these deficits.

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Three-dimensional MRS–guided glioma resection

Metabolic approach

J Neurosurg 124:1585–1593, 2016

The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection.

Methods: Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection.

Results: Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1HMRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up.

Conclusions: This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

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Seizures in supratentorial meningioma: a systematic review and meta-analysis

Meningiomas in Pregnancy- A Clinicopathologic Study of 17 Cases

J Neurosurg 124:1552–1561, 2016

Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life.

Methods: The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses.

Results: The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30–2.34); an absence of headache (OR 1.77, 95% CI 1.04–3.25); peritumoral edema (OR 7.48, 95% CI 6.13–9.47); and non–skull base location (OR 1.77, 95% CI 1.04–3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants.

Conclusions: Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.

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Fiber tracking for temporal tumors

Distinct displacements of the optic radiation based on tumor location revealed using preoperative diffusion tensor imaging

J Neurosurg 124:1343–1352, 2016

Visual field defects (VFDs) due to optic radiation (OR) injury are a common complication of temporal lobe surgery. The authors analyzed whether preoperative visualization of the optic tract would reduce this complication by influencing the surgeon’s decisions about surgical approaches. The authors also determined whether white matter shifts caused by temporal lobe tumors would follow predetermined patterns based on the tumor’s topography.

Methods One hundred thirteen patients with intraaxial tumors of the temporal lobe underwent preoperative diffusion tensor imaging (DTI) fiber tracking. In 54 of those patients, both pre- and postoperative VFDs were documented using computerized perimetry. Brainlab’s iPlan 2.5 navigation software was used for tumor reconstruction and fiber visualization after the fusion of DTI studies with their respective magnetization-prepared rapid gradient-echo (MP-RAGE) images. The tracking algorithm was as follows: minimum fiber length 100 mm, fractional anisotropy threshold 0.1. The lateral geniculate body and the calcarine cortex were employed as tract seeding points. Shifts of the OR caused by tumor were visualized in comparison with the fiber tracking of the patient’s healthy hemisphere.

Results Temporal tumors produced a dislocation of the OR but no apparent fiber destruction. The shift of white matter tracts followed fixed patterns dependent on tumor location: Temporolateral tumors resulted in a medial fiber shift, and thus a lateral transcortical approach is recommended. Temporopolar tumors led to a posterior shift, always including Meyer’s loop; therefore, a pterional transcortical approach is recommended. Temporomesial tumors produced a lateral and superior shift; thus, a transsylvian-transcisternal approach will result in maximum sparing of the fibers. Temporocentric tumors also induced a lateral fiber shift. For those tumors, a transsylvian-transopercular approach is recommended. Tumors of the fusiform gyrus generated a superior (and lateral) shift; consequently, a subtemporal approach is recommended to avoid white matter injury. In applying the approaches recommended above, new or worsened VFDs occurred in 4% of the patient cohort. Total neurological and surgical morbidity were less than 10%. In 90% of patients, gross-total resection was accomplished.

Conclusions Preoperative visualization of the OR may help in avoiding postoperative VFDs.

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A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery

J Neurosurg 124:1300–1309, 2016

There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.

Methods A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.

Results A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.

Conclusions The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

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Delayed contrast-enhanced MRI for brain metastases

Delayed contrast-enhanced MRI for brain metastases

J Neurosurg 124:489–495, 2016

Contrast-enhanced MRI is the preeminent diagnostic test for brain metastasis (BM). Detection of BMs for stereotactic radiosurgery (SRS) planning may improve with a time delay following administration of a high-relaxivity agent for 1.5-T and 3-T imaging systems. Metastasis detection with time-delayed MRI was evaluated in this study.

Methods Fifty-three volumetric MRI studies from 38 patients undergoing SRS for BMs were evaluated. All studies used 0.1-mmol/kg gadobenate dimeglumine (MultiHance; Bracco Diagnostics) immediately after injection, followed by 2 more axial T1-weighted sequences after 5-minute intervals (final image acquisition commenced 15 minutes after contrast injection). Two studies were motion limited and excluded. Two hundred eighty-seven BMs were identified. The studies were randomized and examined separately by 3 radiologists, who were blinded to the temporal sequence. Each radiologist recorded the number of BMs detected per scan. A Wilcoxon signed-rank test compared BM numbers between scans. One radiologist determined the scan on which BMs were best defined. All confirmed, visible tumors were contoured using iPlan RT treatment planning software on each of the 3 MRI data sets. A linear mixed model was used to analyze volume changes.

Results The interclass correlations for Scans 1, 2, and 3 were 0.7392, 0.7951, and 0.7290, respectively, demonstrating excellent interrater reliability. At least 1 new lesion was detected in the second scan as compared with the first in 35.3% of subjects (95% CI 22.4%–49.9%). The increase in BM numbers between Scans 1 and 2 ranged from 1 to 10. At least 1 new lesion was detected in the third scan as compared with the second in 21.6% of subjects (95% CI 11.3%–35.3%). The increase in BM numbers between Scans 2 and 3 ranged from 1 to 9. Between Scans 1 and 3, additional tumors were seen on 43.1% of scans (increase ranged from 1 to 14). The median increase in tumor number for all comparisons was 1. There was a significant increase in number of BMs detected from Scan 1 to Scan 2 (p < 0.0367) and from Scan 1 to Scan 3 (p < 0.0264). In 34 of the 51 subjects (66.7%), the radiologist selected the third scan as the one providing the clearest tumor definition. There was an average 25.4% increase in BM volume between Scans 1 and 2 (p < 0.0001) and a 9% increase in BM volume between Scans 2 and 3 (p = 0.0001).

Conclusions In patients who are being prepared for SRS of BMs, delayed MRI after contrast injection revealed more targets that needed treatment. In addition, apparent treatment volumes increased with a time delay. To avoid missing tumors that could be treated at the time of planned SRS and resultant “treatment failures,” the authors recommend that postcontrast MR images be acquired between 10 and 15 minutes after injection in patients undergoing SRS for treatment of BMs.

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