Hemorrhagic burden in poor-grade aneurysmal subarachnoid hemorrhage

Acta Neurochirurgica (2019) 161:791–797

Volumetric assessment of aneurysmal bleeding has been evaluated in few studies and emerged as a promising outcome predictor. There is a lack of studies evaluating its impact in the poor-grade population.

Methods Retrospective review of 63 consecutive poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients, defined as grade IV and V according to theWorld Federation of Neurological Surgeons (WFNS) classifications. Global intracranial bleeding volume was calculated with its subarachnoid, intracerebral (ICH), and intraventricular (IVH) portions by means of analytical software. Univariate and multivariate analyses were performed in order to identify independent predictors of outcome. Good outcome was defined as modified Rankin Scale (mRS) 0–2 and mortality as mRS 6. The cutoff values of bleeding volumes were derived by receiver operating curve (ROC) analysis.

Results Mean follow-up was of 12.5 (± 1.5) months. Thirty (47.7%) patients achieved good outcome, whereas 19 (30.2) patients out of 63 died. Global intracranial bleeding resulted as an independent predictor of good outcome (cutoff 24 mL). Furthermore, ICH relative percentage of global volume (10% of total) and pure SAH (64% of total) emerged respectively as independent predictors of worsened and improved outcome. Global bleeding volume (cutoff 51 mL) along with global cerebral edema showed to independently predict mortality in the examined poor-grade aSAH population.

Conclusions Volumetric assessment of aneurysmal bleeding has the potential for identifying cutoff values that independently predict outcome. Further insights into the relative importance of different bleeding volumes may be implicated in better tailoring the management of this dismal aSAH population.

Prognosis of Symptoms and Complications After Microvascular Decompression for Hemifacial Spasm

World Neurosurg. (2018) 118:e557-e561

The aim of this study was to identify potential prognostic factors of hemifacial spasm (HFS) after microvascular decompression (MVD), to establish the appropriate way to tackle postprocedure symptoms and complications (PPSCs), and to find the incidence and duration of PPSCs.

METHODS: Two hundred and forty-eight patients with HFS were monitored between December 2009 and December 2014. The mean follow-up duration was 24 months (range, 6e67 months). We divided patients based on their PPSC status and investigated the following factors: age, sex, spasm side, facial nerve block before MVD (botulinum toxin treatment), acupuncture before MVD, duration of HFS, hypertension, diabetes, hepatitis B virus (HBV) infection status, herpes simplex virus infection status, smoking status and alcohol use, offending vessels, Chiari malformation, electrophysiologic monitoring results, and postoperative HFS. Univariable analysis and multivariate logistic regression were used to find potential risk factors. Kaplan-Meier analysis was used to show the duration of postprocedure facial palsy.

RESULTS: Age (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.004e1.072; P [ 0.03) and HBV status (OR, 18.256; 95% CI, 2.723e122.415; P [ 0.03) were positive predictors of PPSCs. Postoperative HFS (OR, 0.249; 95% CI, 0.084e0.0739; P [ 0.012) may be a protective factor for postprocedure facial palsy. Most PPSCs related to cranial nerves recovered spontaneously in 3 months. Infections and cerebrospinal fluid leakages were controlled by medical intervention in 1e2 weeks. The permanent complication rate was only 4.8%.

CONCLUSIONS: Although the incidence of PPSCs after MVD is very high, most PPSCs related to cranial nerves recovered spontaneously in several days. Permanent complications after MVD for HFS are rare. Age may relate to the occurrence of PPSCs, and postoperative HFS may be a protective factor for patients with facial palsy after MVD.

Intramedullary ependymoma: long-term outcome after surgery

Acta Neurochirurgica (2018) 160:439–447

Overall (OS) and progression-free survival (PFS) of patients undergoing spinal ependymoma resection has been frequently reported. Contrarily, OS and PFS of purely intramedullary ependymomas have not been clearly determined yet.

Methods The data of 37 patients undergoing resection of an intramedullary ependymoma (IE) from January 2000 to December 2016 were analysed retrospectively.

Results The mean age was 46 years. The male:female ratio was 24:13. The median duration of symptoms was 12 months. Sixtytwo per cent of ependymomas were in the cervical, 24% in the thoracic, and 14% in the conus region in our series. The median volume was 1.3 ml. A syrinx was found in 49%and a cyst in 32%. GTR was achieved in 89%, STR in three (8%), and PR in one patient (3%). Median follow-up was 114 months. PFS was 87%, 82%, and 82%at 5, 10, and 15 years, respectively. OS was 97%, 88%, and 63% at 5, 10, and 15 years, respectively. There was a significant difference in PFS depending on the extent of resection and in OS depending on the pre-operative clinical status. There was no significant difference in OS and PFS regarding the other examined influencing factors.

Conclusion GTR resection was the most important factor influencing PFS. According to our results OS of IEs is much worse than that of spinal ependymomas. Our analysis confirms that patients with good pre-operative (McCormick grade 1 and 2) clinical status have significantly better OS than patients with McCormick grade 3 and higher.

Developing an Algorithm for Optimizing Care of Elderly Patients With Glioblastoma

Neurosurgery 82:64–75, 2018

Elderly patients with glioblastoma have an especially poor prognosis; optimizing their medical and surgical care remains of paramount importance.

OBJECTIVE: To investigate patient and treatment characteristics of elderly vs nonelderly patients and develop an algorithm to predict elderly patients’ survival.

METHODS: Retrospective analysis of 554 patients (mean age=60.8; 42.0% female) undergoing first glioblastoma resection or biopsy at our institution (2005-2011).

RESULTS: Of the 554 patients, 218 (39%) were elderly (≥65 yr). Compared with nonelderly, elderly patients were more likely to receive biopsy only (26% vs 16%), have ≥1 medical comorbidity (40% vs 20%), and develop postresection morbidity (eg, seizure, delirium; 25% vs 14%), and were less likely to receive temozolomide (TMZ) (78% vs 90%) and gross total resection (31% vs 45%). To predict benefit of resection in elderly patients (n = 161), we identified 5 factors known in the preoperative period that predicted survival in a multivariate analysis. We then assigned points to each (1 point: Charlson comorbidity score >0, subtotal resection, tumor >3 cm; 2 points: preoperative weakness, Charlson comorbidity score >1, tumor >5 cm, age >75 yr; 4 points: age >85 yr). Having 3 to 5 points (n = 78, 56%) was associated with decreased survival compared to 0 to 2 points (n = 41, 29%, 8.5 vs 16.9 mo; P = .001) and increased survival compared to 6 to 9 points (n = 20, 14%, 8.5 vs 4.5 mo; P < .001). Patients with 6 to 9 points did not survive significantly longer than elderly patients receiving biopsy only (n = 57, 4.5 vs 2.7 mo; P = .58).

CONCLUSION: Further optimization of the medical and surgical care of elderly glioblastoma patients may be achieved by providing more beneficial therapies while avoiding unnecessary resection in those not likely to receive benefit from this intervention.

 

Nerve atrophy in trigeminal neuralgia due to neurovascular compression and its association with surgical outcomes after microvascular decompression

Acta Neurochir (2017) 159:1699–1705

Idiopathic trigeminal neuralgia (TN) is caused by neurovascular compression and is often related to morphological changes in the trigeminal nerve. The aim of this study was to quantitatively measure atrophic changes of trigeminal nerves in patients with TN, and to further investigate whether nerve atrophy affected the efficacy of microvascular decompression (MVD).

Methods We conducted a prospective case-control study of 60 consecutive patients with TN and 30 sex- and age-matched healthy controls. All subjects underwent high-resolution three-dimensional MRI. The volume of the cisternal segment of trigeminal nerves was measured and compared using 3D Slicer software. Patients with TN underwent primary MVD and regular follow-up for at least 2 years. Associations of nerve atrophy with patient characteristics and operative outcomes were analyzed.

Results The mean volume of the affected trigeminal nerve was significantly reduced in comparison to that of the nonaffected side (65.8 ± 21.1 versus 77.9 ± 19.3 mm3, P = 0.001) and controls (65.8 ± 21.1 versus 74.7 ± 16.5 mm3, P = 0.003). Fifty-two patients (86.7%) achieved complete pain relief without medication immediately after surgery, and 77.6% of patients were complete pain relief at the 2-year follow-up. The Spearman correlation test showed that there was a positive correlation (r=0.46, P = 0.018) between the degree of trigeminal nerve indentation and nerve atrophy. In multivariate logistic regression analysis, two factors, indentation on nerve root (OR = 2.968, P = 0.022) and degree of nerve atrophy (OR = 1.18, P = 0.035), were associated with the long-term outcome.

Conclusions TN is associated with atrophy on the affected nerve. Furthermore, greater nerve atrophy is associated with more severe trigeminal nerve indentation and better long-term outcome following MVD.

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.

Diffusion Tensor Imaging: A Possible Biomarker in Severe Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage?

diffusion-tensor-imaging-a-possible-biomarker-in-severe-traumatic-brain-injury-and-aneurysmal-subarachnoid-hemorrhage

Neurosurgery 79:786–793, 2016

A great need exists in traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH) for objective biomarkers to better characterize the disease process and to serve as early endpoints in clinical studies. Diffusion tensor imaging (DTI) has shown promise in TBI, but much less is known about aSAH.

OBJECTIVE: To explore the use of whole-brain DTI tractography in TBI and aSAH as a biomarker and early endpoint.

METHODS: Of a cohort of 43 patients with severe TBI (n = 20) or aSAH (n = 23) enrolled in a prospective, observational, multimodality monitoring study, DTI data were acquired at approximately day 12 (median, 12 days; interquartile range, 12-14 days) after injury in 22 patients (TBI, n = 12; aSAH, n = 10). Whole-brain DTI tractography was performed, and the following parameters quantified: average fractional anisotropy, mean diffusivity, tract length, and the total number of reconstructed fiber tracts. These were compared between TBI and aSAH patients and correlated with mortality and functional outcome assessed at 6 months by the Glasgow Outcome Scale Extended.

RESULTS: Significant differences were found for fractional anisotropy values (P = .01), total number of tracts (P = .03), and average tract length (P = .002) between survivors and nonsurvivors. A sensitivity analysis showed consistency of results between the TBI and aSAH patients for the various DTI measures.

CONCLUSION: DTI parameters, assessed at approximately day 12 after injury, correlated with mortality at 6 months in patients with severe TBI or aSAH. Similar patterns were found for both TBI and aSAH patients. This supports a potential role of DTI as early endpoint for clinical studies and a predictor of late mortality.

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.

Anatomic features of glioblastoma and their potential impact on survival

Anatomic features of glioblastoma and their potential impact on survival

Acta Neurochir (2015) 157:179–186

Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival.

Methods To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented.

Results Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases.

Conclusions A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

Validation of a prognostic score for early mortality in severe head injury cases

Brain_trauma_CT

J Neurosurg 121:1314–1322, 2014

Traumatic brain injury (TBI) represents a large health and economic burden. Because of the inability of previous randomized controlled trials (RCTs) on TBI to demonstrate the expected benefit of reducing unfavorable outcomes, the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) and CRASH (Corticosteroid Randomisation After Significant Head Injury) studies provided new methods for performing prognostic studies of TBI. This study aimed to develop and externally validate a prognostic model for early death (within 48 hours). The secondary aim was to identify patients who were more likely to succumb to an early death to limit their inclusion in RCTs and to improve the efficiency of RCTs.

Methods. The derivation cohort was recruited at 1 center, Hospital 12 de Octubre, Madrid (1990–2003, 925 patients). The validation cohort was recruited in 2004–2006 from 7 study centers (374 patients). The eligible patients had suffered closed severe TBIs. The study outcome was early death (within 48 hours post-TBI). The predictors were selected using logistic regression modeling with bootstrapping techniques, and a penalized reduction was used. A risk score was developed based on the regression coefficients of the variables included in the final model.

Results. In the validation set, the final model showed a predictive ability of 50% (Nagelkerke R2), with an area under the receiver operating characteristic curve of 89% and an acceptable calibration (goodness-of-fit test, p = 0.32). The final model included 7 variables, and it was used to develop a risk score with a range from 0 to 20 points. Age provided 0, 1, 2, or 3 points depending on the age group; motor score provided 0 points, 2 (untestable), or 3 (no response); pupillary reactivity, 0, 2 (1 pupil reacted), or 6 (no pupil reacted); shock, 0 (no) or 2 (yes); subarachnoid hemorrhage, 0 or 1 (severe deposit); cisternal status, 0 or 3 (compressed/absent); and epidural hematoma, 0 (yes) or 2 (no). Based on the risk of early death estimated with the model, 4 risk of early death groups were established: low risk, sum score 0–3 (< 1% predicted mortality); moderate risk, sum score 4–8 (predicted mortality between 1% and 10%); high risk, sum score 9–12 (probability of early death between 10% and 50%); and very high risk, sum score 13–20 (early mortality probability > 50%). This score could be used for selecting patients for clinical studies. For example, if patients with very high risk scores were excluded from our study sample, the patients included (eligibility score < 13) would represent 80% of the original sample and only 23% of the patients who died early.

Conclusions. The combination of Glasgow Coma Scale score, CT scanning results, and secondary insult data into a prognostic score improved the prediction of early death and the classification of TBI patients.

Management of Atypical Cranial Meningiomas, Part 1: Predictors of Recurrence and the Role of Adjuvant Radiation After Gross Total Resection

Meningioma_-_brain_invasion_-_high_mag

Neurosurgery 75:347–355, 2014

Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear.

OBJECTIVE: To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study.

METHODS: One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression.

RESULTS: Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/ EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/ EBRT (P = .8, P . .99).

CONCLUSION: Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus

The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus

J Neurosurg 120:178–184, 2014

Different neuroimaging biomarkers have been studied to find a tool for prediction of response to CSF shunting in idiopathic normal-pressure hydrocephalus (iNPH). The callosal angle (CA) has been described as useful in discriminating iNPH from ventricular dilation secondary to atrophy. However, the usefulness of the CA as a prognostic tool for the selection of shunt candidates among patients with iNPH is unclear. The aim of this study was to compare the CA in shunt responders with that in nonresponders and clarify whether the CA can serve as a predictor of the outcome.

Methods. Preoperative MRI brain scans were evaluated in 109 patients who had undergone shunt surgery for iNPH during 2006–2010. Multiplanar reconstruction was performed interactively to obtain a coronal image through the posterior commissure, perpendicular to the anterior-posterior commissure plane. The CA was measured as the angle between the lateral ventricles on the coronal image. The patients were examined clinically before surgery and at 12 months postoperatively.

Results. Shunt responders had a significantly smaller mean preoperative CA compared with nonresponders: 59° (95% CI 56°–63°) versus 68° (95% CI 61°–75°) (p < 0.05). A CA cutoff value of 63° showed the best prognostic accuracy.

Conclusions. The preoperative CA is smaller in patients whose condition improves after shunt surgery and may be a useful tool in the selection of shunt candidates among patients with iNPH.

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Surgical management and outcomes of petroclival meningiomas: a single-center case series of 259 patients

Petroclival meningioma outcomes

Acta Neurochir (2013) 155:1367–1383

Surgical management of petroclival meningiomas is challenging. Various and inconsistent outcome and prognostic factors of the lesions have been evaluated previously. In the present study, the surgical outcome, philosophy, and experience of petroclival meningiomas are detailed based on a large patient series.

Methods A series of 259 patients with petroclival meningiomas (70 males and 189 females) were surgically treated. Clinical charts and radiographs were reviewed. Follow-up results were evaluated.

Results The preoperative Karnofsky Performance Scale (KPS) score was 74.2±10.5. The mean tumor size was 4.3±1.0 cm. The gross total resection (GTR) rate was 52.5 %. During a mean follow-up period of 55.3 months, recurrence/progression (R/P) occurred in 11 patients. The recent KPS score was 78.4±22.7, it improved in 139 (57.2 %) patients and stabilized in 53 (21.8 %) patients, and 201 (82.7 %) patients lived independently. The risk factors affecting the KPS score included (but were not limited to) age≥60, preoperative KPS≤60, and brainstem edema. The adverse factors contributing to R/P-free survival included (but were not limited to) non-total resection and the absence of the subarachnoid space. The R/P-free survival rate was 94.5 % at 5 years and 91.2 % at 9 years. The overall survival rate was 94.7 % at 5 years and 94.7 % at 9 years.

Conclusions Favorable outcomes from petroclival meningiomas could be achieved by microsurgery. Neurological function and quality of life were prioritized, and GTR was attempted. Risk factors should be considered in surgical schemes, and tumor recurrence should be aggressively monitored and treated.

Prognostic Value of Residual Fluorescent Tissue in Glioblastoma Patients After Gross Total Resection in 5-Aminolevulinic Acid-Guided Surgery

Prognostic_Value_of_Residual_Fluorescent_Tissue_in

Neurosurgery 72:915–921, 2013

There is evidence in the literature supporting that fluorescent tissue signal in fluorescence-guided surgery extends farther than tissue highlighted in gadolinium in T1 sequence magnetic resonance imaging (MRI), which is the standard to quantify the extent of resection.

OBJECTIVE: To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI.

METHODS: A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated on with the use of fluorescence-guided surgery with 5-aminolevulinic acid. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale, O6-methylguanine methyltransferase methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy.

RESULTS: The median overall survival was 27.0 months (confidence interval = 22.4-31.6) in patients with nonresidual fluorescence (n = 25) and 17.5 months (confidence interval = 12.5-22.5) for the group with residual fluorescence (n = 27) (P = .015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, hazard ratio = 2.5 (P = .041). The neurological complication rate was 18.5% in patients with nonresidual fluorescence and 8% for the group with residual fluorescence (P = .267).

CONCLUSION: GBM patients with CRET in early MRI and no fluorescent residual tissue had longer overall survival than patients with CRET and residual fluorescent tissue.

Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas

GIIG

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

Prognostic factors of Grade II gliomas

neuronBig

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

Multiple resections for patients with glioblastoma: prolonging survival

Prolonged survival GBM

J Neurosurg 118:812–820, 2013

Glioblastoma is the most common and aggressive type of primary brain tumor in adults. These tumors recur regardless of intervention. This propensity to recur despite aggressive therapies has made many perceive that repeated resections have little utility. The goal of this study was to evaluate if patients who underwent repeat resections experienced improved survival as compared with patients with fewer numbers of resections, and whether the number of resections was an independent predictor of prolonged survival.

Methods. The records of adult patients who underwent surgery for an intracranial primary glioblastoma at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Multivariate proportionalhazards regression analysis was used to identify an association between glioblastoma resection number and survival after controlling for factors known to be associated with survival, such as age, functional status, periventricular location, extent of resection, and adjuvant therapy. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analysis.

Results. Five hundred seventy-eight patients with primary glioblastoma met the inclusion/exclusion criteria. At last follow-up, 354, 168, 41, and 15 patients underwent 1, 2, 3, or 4 resections, respectively. The median survival for patients who underwent 1, 2, 3, and 4 resections was 6.8, 15.5, 22.4, and 26.6 months (p < 0.05), respectively. In multivariate analysis, patients who underwent only 1 resection experienced shortened survival (relative risk [RR] 3.400, 95% CI 2.423–4.774; p < 0.0001) as compared with patients who underwent 2 (RR 0.688, 95% CI 0.525–0.898; p = 0.0006), 3 (RR 0.614, 95% CI 0.388–0.929; p = 0.02), or 4 (RR 0.600, 95% CI 0.238–0.853; p = 0.01) resections. These results were verified in a case-control evaluation, controlling for age, neurological function, periventricular tumor location, extent of resection, and adjuvant therapy. Patients who underwent 1, 2, or 3 resections had a median survival of 4.5, 16.2, and 24.4 months, respectively (p < 0.05). Additionally, the risk of infections or iatrogenic deficits did not increase with repeated resections in this patient population (p > 0.05).

Conclusions. Patients with glioblastoma will inevitably experience tumor recurrence. The present study shows that patients with recurrent glioblastoma can have improved survival with repeated resections. The findings of this study, however, may be limited by an intrinsic bias associated with patient selection. The authors attempted to minimize these biases by using strict inclusion criteria, multivariate analyses, and case-control evaluation.

Brainstem gangliogliomas: a retrospective series

Brainstem gangliogliomas- a retrospective series

J Neurosurg 118:884–888, 2013

The authors retrospectively analyzed data on brainstem gangliogliomas treated in their department and reviewed the pertinent literature to foster understanding of the preoperative characteristics, management, and clinical outcomes of this disease.

Methods. In 2006, the authors established a database of treated lesions of the posterior fossa. The epidemiology findings, clinical presentations, radiological investigations, pathological diagnoses, management, and prognosis for brainstem gangliogliomas were retrospectively analyzed.

Results. Between 2006 and 2012, 7 patients suffering from brainstem ganglioglioma were treated at the West China Hospital of Sichuan University. The mean age of the patients, mean duration of symptoms prior to diagnosis, and mean duration of follow-up were 28.6 years, 19.4 months, and 38.1 months, respectively. The main presentations were progressive cranial nerve deficits and cerebellar signs. Subtotal resection was achieved in 2 patients, and partial resection in 5. All tumors were pathologically diagnosed as WHO Grade I or II ganglioglioma. Radiotherapy and adjuvant chemotherapy were not administered. After 21–69 months of follow-up, patient symptoms were resolved or stable without aggravation, and MRI showed that the size of residual lesions was unchanged without progression or recurrence.

Conclusions. The diagnosis of brainstem ganglioglioma is of great importance given its favorable prognosis. The authors recommend the maximal safe resection followed by close observation without adjuvant therapy as the optimal treatment for this disease.

Poor Cognitive Outcome in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus

hydrocephalusNeurosurgery 72:1–8, 2013

Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce.

OBJECTIVE: To elucidate the long-term cognitive condition of shunt-responsive iNPH patients.

METHODS: The follow-up data (Kuopio University Hospital NPH Registry) of 146 patients diagnosed with iNPH by clinical and radiological examination, 24-hour intraventricular pressure monitoring, frontal cortical biopsy, and response to the shunt were analyzed for signs of dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Median follow-up was 4.8 years.

RESULTS: At the end of follow-up, 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had clinical dementia. The most common clinical diagnoses were Alzheimer disease and vascular dementia. In multivariate analysis of the 146 iNPH patients, memory deficit as a first symptom before shunt (odds ratio [OR] 18.3; 95% confidence interval [CI] 1.9–175), male sex (OR 3.29; 95% CI 1.11-9.73), age (OR 1.17 year; 95% CI 1.07-1.28), and follow-up time (OR 1.20 year; 95% CI 1.02-1.40) predicted dementia. Interestingly, 8 (5%) iNPH patients had dementia without any signs of other neurodegenerative diseases in clinical, neuroradiological, or brain biopsy evaluation. These patients initially presented a full triad of symptoms, with gait disturbance being the most frequent initial symptom followed by deterioration in cognition.

CONCLUSION: The novel findings were (a) a significant risk of dementia in iNPH initially responsive to cerebrospinal fluid shunt, (b) cognitive impairment most commonly due to iNPH-related dementia followed by concurrent degenerative brain disease, and (c) a subgroup with dementia related to iNPH without comorbidities.

Prognosis of patients with multifocal glioblastoma

J Neurosurg 117:705–711, 2012

The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival.

Methods. The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors. Each patient with a multifocal tumor was then matched with a patient with a solitary glioblastoma on the basis of age, Karnofsky Performance Scale (KPS) score, and extent of resection, using a propensity score matching methodology. Radiation and temozolomide treatments were also well matched between the 2 cohorts. Kaplan-Meier estimates and log-rank tests were used to compare patient survival.

Results. The incidence of multifocal tumors was 12.8% (47/368). The median age of patients with multifocal tumors was 61 years, 76.6% had KPS scores ≥ 70, and 87.2% underwent either a biopsy or partial resection of their tumors. The 47 patients with multifocal tumors were almost perfectly matched on the basis of age (p = 0.97), extent of resection (p = 1.0), and KPS score (p = 0.80) compared with 47 patients with a solitary glioblastoma. Age (> 65 years), partial resection or biopsy, and low KPS score (< 70) were associated with worse median survival within the multifocal group. In the multifocal group, 19 patients experienced tumor progression on postradiation therapy MRI, compared with 11 patients (26.8%) with tumor progression in the unifocal group (p = 0.08). Patients with multifocal tumors experienced a significantly shorter median overall survival of 6 months (95% CI 4–10 months), compared with the 11-month median survival (95% CI 10–19 months) of the matched solitary glioblastoma group (p = 0.02, log-rank test). Two-year survival rates were 4.3% for patients with multifocal tumors and 29.0% for the unifocal cohort. Patients with newly diagnosed multifocal tumors were found to have an almost 2-fold increase in the hazard of death compared with patients with solitary glioblastoma (hazard ratio 1.8, 95% CI 1.1–3.1; p = 0.02). Tumor samples were analyzed for expression of phosphorylated mitogen-activated protein kinase, phosphatase and tensin homolog, O6-methylguanine-DNA methyltransferase, laminin b1 and b2, as well as epidermal growth factor receptor amplification, and no significant differences in expression profile between the multifocal and solitary glioblastoma groups was found.

Conclusions. Patients with newly diagnosed multifocal glioblastoma on presentation experience significantly worse survival than patients with solitary glioblastoma. Patients with multifocal tumors continue to pose a therapeutic challenge in the temozolomide era and magnify the challenges faced while treating patients with malignant gliomas.