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

Navigated transcranial magnetic stimulation for glioma removal- prognostic value in motor function recovery from postsurgical neurological deficits

J Neurosurg 127:877–891, 2017

The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits.

METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change.

RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively).

CONCLUSIONS Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.

 

Awake Craniotomy vs Craniotomy Under General Anesthesia for Perirolandic Gliomas

Neurosurgery 81:481–489, 2017

A craniotomy with direct cortical/subcortical stimulation either awake or under general anesthesia (GA) present 2 approaches for removing eloquent region tumors. With a reported higher prevalence of intraoperative seizures occurring during awake resections of perirolandic lesions, oftentimes, surgery under GA is chosen for these lesions.

OBJECTIVE: To evaluate a single-surgeon’s experience with awake craniotomies (AC) vs surgery under GA for resecting perirolandic, eloquent, motor-region gliomas.

METHODS: Between 2005 and 2015, a retrospective analysis of 27 patients with perirolandic, eloquent, motor-area gliomas that underwent an AC were case-control matched with 31 patients who underwent surgery under GA for gliomas in the same location. All patients underwent direct brain stimulation with neuromonitoring and perioperative risk factors, extent of resection, complications, and discharge status were assessed.

RESULTS: The postoperative Karnofsky Performance Score (KPS) was significantly lower for theGApatients at 81.1 compared to theACpatients at 93.3 (P=.040). The extent of resection for GA patients was 79.6% while the AC patients had an 86.3% resection (P = .136). There were significantly more 100% total resections in the AC patients 25.9% compared to the GA group (6.5%; P=.041). Patients in theGAgroup had a longer mean length of hospitalization of 7.9 days compared to the AC group at 4.2 days (P = .049).

CONCLUSION: We show that AC can be performed with more frequent total resections, better postoperative KPS, shorter hospitalizations, as well as similar perioperative complication rates compared to surgery under GA for perirolandic, eloquent motor-region glioma.

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.

 

The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors

Neurosurgery 81:307–314, 2017

Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring.

OBJECTIVE: To evaluate the cost effectiveness and clinical outcomes between AC and GA patients.

METHODS: Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, qualityadjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups.

RESULTS: Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group (P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group (P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P=.047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group (P = .049).

CONCLUSION: The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas.

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Acta Neurochir (2017) 159:151–167

Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all pre-clinically tested agents with the potential for FGS for glioma.

Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5- aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and dif cult to access brain tumors

litt

Neurosurg Focus 41 (4):E14, 2016

Laser interstitial thermal therapy (LITT), sometimes referred to as “stereotactic laser ablation,” has demonstrated utility in a subset of high-risk surgical patients with dificult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most dif cult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors.

Methoss The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, trans-sulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3.

Results The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%– 92%), the median tumor volume treated to the blue TDT line was 73% (range 60%–87%), and the median extent of resection was 93% (range 84%–100%). Two patients suffered mild postoperative neurological de cits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days.

Conclusions Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas

intraoperative_probe_based_confocal_laser

Neurosurgery 79:604–612, 2016

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection.

OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas.

METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment.

RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed.

CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study)

f1-largeNeurosurgery 79:535–540, 2016

Glioma imaging, used for diagnostics, treatment planning, and followup, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal.

OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain.

METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites.

DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment.

EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma.

Selective 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in Gliomas

selective-5-aminolevulinic-acid-induced-protoporphyrin-ix-fluorescence-in-gliomas

Acta Neurochir (2016) 158:1935–1941

Malignant gliomas are locally invasive tumors that offer a poor prognosis. Evidence shows that complete resection of the tumor at the time of surgery confers a significant improvement in overall survival.

In recent years, 5- aminolevulinic acid (ALA)-induced fluorescence has been used by neurosurgeons to good effect in increasing the rate of complete resection. Despite the considerable interest in the use of 5-ALA in fluorescence-guided neurosurgery, the mechanisms behind the accumulation of Protoporphyrin IX (PpIX) in neoplastic tissue are unclear.

In this review, we summarize the evidence in the literature on the mechanisms underlying the selective production of PpIX with a specific focus on gliomas.

Identification of language area and the pars triangularis

language-area-and-pt

Journal of Neurosurgery Vol. 125 / No. 4 : 803-811

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

Identification of language area and the pars triangularis

language-area-and-pt

J Neurosurg 125:803–811, 2016

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

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.

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.

Monopolar high-frequency language mapping: can it help in the surgical management of gliomas?

Monopolar high-frequency language mapping- can it help in the surgical management of gliomas?

J Neurosurg 124:1479–1489, 2016

Intraoperative language mapping is traditionally performed with low-frequency bipolar stimulation (LFBS). High-frequency train-of-five stimulation delivered by a monopolar probe (HFMS) is an alternative technique for motor mapping, with a lower reported seizure incidence. The application of HFMS in language mapping is still limited. Authors of this study assessed the efficacy and safety of HFMS for language mapping during awake surgery, exploring its clinical impact compared with that of LFBS.

Methods Fifty-nine patients underwent awake surgery with neuropsychological testing, and LFBS and HFMS were compared. Frequency, type, and site of evoked interference were recorded. Language was scored preoperatively and 1 week and 3 months after surgery. Extent of resection was calculated as well.

Results High-frequency monopolar stimulation induced a language disturbance when the repetition rate was set at 3 Hz. Interference with counting (p = 0.17) and naming (p = 0.228) did not vary between HFMS and LFBS. These results held true when preoperative tumor volume, lesion site, histology, and recurrent surgery were considered. Intraoperative responses (1603) in all patients were compared. The error rate for both modalities differed from baseline values (p < 0.001) but not with one another (p = 0.06). Low-frequency bipolar stimulation sensitivity (0.458) and precision (0.665) were slightly higher than the HFMS counterparts (0.367 and 0.582, respectively). The error rate across the 3 types of language errors (articulatory, anomia, paraphasia) did not differ between the 2 stimulation methods (p = 0.279).

Conclusions: With proper setting adjustments, HFMS is a safe and effective technique for language mapping.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features

Neurosurgery 78:401–411, 2016

Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade.

OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics.

METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operatingcharacteristic curves were generated for defining predictors.

RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio .1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P , .001) and Ki-67/MIB-1 index (P , .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted.

CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

Neurocognitive Changes Associated With Surgical Resection of Left and Right Temporal Lobe Glioma

Temporal lobe tumor

Neurosurgery 77:777–785, 2015

Little is known regarding the neurocognitive impact of temporal lobe tumor resection.

OBJECTIVE: To clarify subacute surgery-related changes in neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL) temporal lobe glioma.

METHODS: Patients with glioma in the LTL (n = 45) or RTL (n = 19) completed comprehensive pre- and postsurgical neuropsychological assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis of variance, with hemisphere (LTL or RTL) as an independent between-subjects factor and pre- and postoperative NCF as a within-subjects factor.

RESULTS: About 60% of patients with LTL glioma and 40% with RTL lesions exhibited significant worsening on at least 1 NCF test. Domains most commonly impacted included verbal memory and executive functioning. Patients with LTL tumor showed greater decline than patients with RTL tumor on verbal memory and confrontation naming tests. Nonetheless, over one-third of patients with RTL lesions also showed verbal memory decline.

CONCLUSION: In patients with temporal lobe glioma, NCF decline in the subacute postoperative period is common. As expected, patients with LTL tumor show more frequent and severe decline than patients with RTL tumor, particularly on verbally mediated measures. However, a considerable proportion of patients with RTL tumor also exhibit decline across various domains, even those typically associated with left hemisphere structures, such as verbal memory. While patients with RTL lesions may show even greater decline in visuospatial memory, this domain was not assessed. Nonetheless, neuropsychological assessment can identify acquired deficits and help facilitate early intervention in patients with temporal lobe glioma.

Training for brain tumour resection: a realistic model with easy accessibility

Training for brain tumour resection- a realistic model with easy accessibility

Acta Neurochir (2015) 157:1975–1981

Resection of intrinsic and extrinsic brain tumours requires an understanding of sulcal and gyral anatomy, familiarity with tissue consistency and tissue manipulation. As yet, these skills are acquired by observation and supervised manipulation during surgery, thus accepting a potential learning curve at the expense of the patient in a live surgical situation. A brain tumour model could ensure optimised manual skills and understanding of surgical anatomy acquired in an elective and relaxed teaching situation. We report and evaluate a brain tumour model, regarding availability, realistic representation of sulcal and gyral anatomy and tissue consistency.

Method Freshly prepared agar-agar solution with different concentrations was added with highlighter ink and injected into fresh sheep brains.

Results Hardened agar-agar solution formed masses comparable to malignant brain tumours. Variation of the agar-agar concentration influenced diffusion of agar-agar solution in the adjacent brain tissue. Higher concentrated agar-agar solutions formed sharply delimitated masses mimicking cerebral metastases and lower concentrated agar-agar solutions tended to diffuse into the adjacent cerebral tissue. Adding highlighter ink to the agar-agar solution produced fluorescence after blue light excitation comparable to the 5-ALA induced fluorescence of malignant glioma.

Conclusions The described in vitro sheep brain tumor model is simple and realistic, available practically everywhere and cheap. Therefore, it could be useful for young neurosurgical residents to acquire basic neuro-oncological skills, experiencing properties of the cerebral brain texture and its haptic perception and to learn handling of neurosurgical equipment.

Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas

Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas

J Neurosurg 123:1081–1092, 2015

Little attention has been given to the functional challenges of the insular approach to the resection of gliomas, despite the potential damage of essential neural networks that underlie the insula. The object of this study is to analyze the subcortical anatomy of the insular region when infiltrated by gliomas, and compare it with the normal anatomy in nontumoral hemispheres.

Methods Ten postmortem human hemispheres were dissected, with isolation of the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus. Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the subcortical anatomy of the insular region in 10 healthy volunteers and in 22 patients with insular Grade II and Grade III gliomas. The subcortical anatomy of the insular region in these 22 insular gliomas was compared with the normal anatomy in 20 nontumoral hemispheres.

Results In tumoral hemispheres, the distances between the peri-insular sulci and the lateral surface of the IFOF and uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or greater than 80% (multivariate analysis: p = 0.03).

Conclusions Insular gliomas grow in the space between the lateral surface of the IFOF and uncinate fasciculus and the insular surface, displacing and compressing the tracts medially. Moreover, these tracts may be completely infiltrated by the tumor, with a total disruption of the bundles. In the current study, the identification of the IFOF with DTI tractography was significantly associated with the extent of tumor resection. If the IFOF is not identified preoperatively, there is a high probability of achieving a resection greater than 80%.

Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period

awake craniotomy

J Neurosurg 123:325–339, 2015

Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon’s experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery.

Methods The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986–1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997–2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases.

Results The median patient age was 42 years (range 13–84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90–100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer’s solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation- induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%.

Conclusions Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.

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

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