Neurosurgery Blog


Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

FLAIR signal increase of the fluid within the resection cavity after glioma surgery: generally valid as early recurrence marker?

J Neurosurg 127:417–425, 2017

Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients.

METHODS A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups.

RESULTS Patients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8–8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value.

CONCLUSIONS Signal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.


Complications of ventricular entry during craniotomy for brain tumor resection

J Neurosurg 127:426–432, 2017

Recent studies have demonstrated that periventricular tumor location is associated with poorer survival and that tumor location near the ventricle limits the extent of resection. This finding may relate to the perception that ventricular entry leads to further complications and thus surgeons may choose to perform less aggressive resection in these areas. However, there is little support for this view in the literature. This study seeks to determine whether ventricular entry is associated with more complications during craniotomy for brain tumor resection.

METHODS A retrospective analysis of patients who underwent craniotomy for tumor resection at Henry Ford Hospital between January 2010 and November 2012 was conducted. A total of 183 cases were reviewed with attention to operative entry into the ventricular system, postoperative use of an external ventricular drain (EVD), subdural hematoma, hydrocephalus, and symptomatic intraventricular hemorrhage (IVH).

RESULTS Patients in whom the ventricles were entered had significantly higher rates of any complication (46% vs 21%). Complications included development of subdural hygroma, subdural hematoma, intraventricular hemorrhage, subgaleal collection, wound infection, urinary tract infection/deep venous thrombosis, hydrocephalus, and ventriculoperitoneal (VP) shunt placement. Specifically, these patients had significantly higher rates of EVD placement (23% vs 1%, p < 0.001), hydrocephalus (6% vs 0%, p = 0.03), IVH (14% vs 0%, p < 0.001), infection (15% vs 5%, p = 0.04), and subgaleal collection (20% vs 4%, p < 0.001). It was also observed that VP shunt placement was only seen in cases of ventricular entry (11% vs 0%, p = 0.001) with 3 of 4 of these patients having a large ventricular entry (defined here as entry greater than a pinhole [< 3 mm] entry). Furthermore, in a subset of glioblastoma patients with and without ventricular entry, Kaplan- Meier estimates for survival demonstrated a median survival time of 329 days for ventricular entry compared with 522 days for patients with no ventricular entry (HR 1.13, 95% CI 0.65–1.96; p = 0.67).

CONCLUSIONS There are more complications associated with ventricular entry during brain tumor resection than in nonviolated ventricular systems. Better strategies for management of periventricular tumor resection should be actively sought to improve resection and survival for these patients.


Preoperative planning of hemangioblastoma using 3D imaging


J Neurosurg 127:139–147, 2017

Successful resection of hemangioblastoma depends on preoperative assessment of the precise locations of feeding arteries and draining veins. Simultaneous 3D visualization of feeding arteries, draining veins, and surrounding structures is needed.

The present study evaluated the usefulness of high-resolution 3D multifusion medical imaging (hr-3DMMI) for preoperative planning of hemangioblastoma. The hr-3DMMI combined MRI, MR angiography, thin-slice CT, and 3D rotated angiography. Surface rendering was mainly used for the creation of hr-3DMMI using multiple thresholds to create 3D models, and processing took approximately 3–5 hours. This hr-3DMMI technique was used in 5 patients for preoperative planning and the imaging findings were compared with the operative findings. Hr-3DMMI could simulate the whole 3D tumor as a unique sphere and show the precise penetration points of both feeding arteries and draining veins with the same spatial relationships as the original tumor.

All feeding arteries and draining veins were found intraoperatively at the same position as estimated preoperatively, and were occluded as planned preoperatively. This hr-3DMMI technique could demonstrate the precise locations of feeding arteries and draining veins preoperatively and estimate the appropriate route for resection of the tumor. Hr-3DMMI is expected to be a very useful support tool for surgery of hemangioblastoma.

A method for safely resecting anterior butterfly gliomas

J Neurosurg 126:1795–1811, 2017

Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas.

METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects.

RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients.

CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.


Putamen involvement and survival outcomes in patients with insular low-grade gliomas

J Neurosurg 126:1788–1794, 2017

Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system’s association with survival outcome.

METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil’s classification, was examined using multivariate analyses.

RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil’s classification.

CONCLUSIONS The current study’s findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

Variability of intraoperative electrostimulation parameters in conscious individuals: language cortex

J Neurosurg 126:1641–1652, 2017

Electrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected.

METHODS Over 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task—bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas.

RESULTS The minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5–9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca’s area), the supramarginal gyri, and the posterior temporal region.

CONCLUSIONS Intrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

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.



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.

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.

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.

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.

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.

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.

Genomic landscape of intracranial 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.

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.

The Simpson grading revisited


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.

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.

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.

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.

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.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain


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