The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts.

Bifocal extra- and intradural melanocytoma of the spine: case report and literature review.

BACKGROUND: Spinal melanocytoma is one of the most infrequent space-occupying lesions of the central nervous system. To the best of our knowledge, this is the first report of primary bifocal intradural melanocytoma of heterogeneous pathological grade to date. CASE DESCRIPTION: We report the case of a 43-year old patient with primary bifocal melanocytoma, clinically and radiologically resembling benign schwannoma. The patient presented with myeloradiculopathy of the left C3 dermatome. Magnetic resonance imaging of the upper spine revealed two space-occupying lesions with paraspinal extension, initially diagnosed as neurofibroma. Definitive histopathological classification of both lesions was melanocytoma. Both tumours were only partially removed due to adherence to surrounding structures. The patient underwent stereotactic external beam irradiation (EBR). Follow-up at 1 year after surgery revealed no recurrence and the patient remained free of symptoms. The clinical, radiological and pathological features of this rare tumour entity are presented and the available literature is reviewed. CONCLUSIONS: Intradural melanocytoma, although exceedingly rare, requires a thorough work-up to exclude malignant melanoma. With only two previous reports of multifocal melanocytoma published in the literature, standard therapy has not yet been established and complete surgical removal remains the modality of choice. Patients should be closely monitored to detect local recurrence or malignant degeneration. EBR may be considered in cases where total excision is not achievable and reduces risk of local recurrences.

Intraoperative low-field MR-guided frameless stereotactic biopsy for intracerebral lesions.

BACKGROUND: To present our intraoperative low-field magnetic resonance imaging (ioMRI) technique for stereotactic brain biopsy in various intracerebral lesions. METHOD: Seventy-eight consecutive patients underwent stereotactic biopsies with the PoleStar N-20/N-30 ioMRI system and data were evaluated retrospectively. Biopsy technique included ioMRI before surgery, followed by insertion of the biopsy cannula in the lesion, and ioMRI before and after biopsy. Statistical analysis was performed to compare subgroups using Excel and SPSS statistic software. RESULTS: In all patients, stereotactic biopsy was possible, with a mean intraoperative surgery time of 86.2 ± 28.6 min and a mean hospital stay of 11.6 ± 4.6 days. In 97.4 % (n = 76), histology was conclusive, representing 58 brain tumors and 18 other pathologies. Five patients were biopsied previously without conclusive diagnosis, and all biopsies were conclusive this time. Mean cross-sectional lesion size in MRI T1 with contrast (n = 64) was 6.9 ± 5.7 cm(2), and in lesions without T1 contrast enhancement (n = 14), T2 mean cross-sectional lesion size was 5.5 ± 3.9 cm(2). Mean distance from the cortex surface to the lesion was 3.4 ± 1.2 cm. One patient suffered from a postoperative wound dehiscence; neither clinically or radiologically significant hemorrhage after surgery, nor intraoperative complications occurred. CONCLUSIONS: Low-field ioMR-guided frameless stereotactic biopsy accurately diagnosed different intracerebral lesions without major complications for the patients, and within an acceptable surgery time and hospital stay. In repeated non-conclusive biopsies in particular, low-field ioMRI offers a technique for arriving at a diagnosis.

Intra-operative high frequency ultrasound improves surgery of intramedullary cavernous malformations.

Intra-operative ultrasound (ioUS) is a very useful tool in surgery of spinal lesions. Here we focus on modern ioUS to analyze its use for localisation, visualisation and resection control in intramedullary cavernous malformations (IMCM). A series of 35 consecutive intradural lesions were operated in our hospital in a time period of 24 months using modern ioUS with a high frequency 7-15 MHz transducer and a true real time 3D transducer (both Phillips iU 22 ultrasound system). Six of those cases were treated with the admitting diagnosis of a deep IMCM (two cervical, four thoracic lesions). IoUS images were performed before and after the IMCM resection. Pre-operative and early postoperative MRI images were performed in all patients. In all six IMCM cases a complete removal of the lesion was achieved microsurgically resulting in an improved neurological status of all patients. High frequency ioUS emerged to be a very useful tool during surgery for localization and visualization. Excellent resection control by ultrasound was possible in three cases. Minor resolution of true real time 3D ioUS decreases the actual advantage of simultaneous reconstruction in two planes. High frequency ioUS is the best choice for intra-operative imaging in deep IMCM to localize and to visualize the lesion and to plan the perfect surgical approach. Additionally, high frequency ioUS is suitable for intra-operative resection control of the lesion in selected IMCM cases.

Clinical outcome in lumbar decompression surgery for spinal canal stenosis in the aged population: a prospective Swiss multicenter cohort study.

STUDY DESIGN: This is a prospective, multicenter cohort study including 8 medical centers in the metropolitan area of the Canton Zurich, Switzerland. OBJECTIVES: To examine whether outcome and quality of life might improve after decompression surgery for degenerative lumbar spinal stenosis (DLSS) even in patients older than 80 years and to compare data with a younger patient population from our own patient collective. SUMMARY AND BACKGROUND DATA: Lumbar decompression surgery without fusion has been shown to improve quality of life in lumbar spinal canal stenosis. In the population older than 80 years, treatment recommendations for DLSS show conflicting results. METHODS: Eight centers in the metropolitan area of Zurich, Switzerland agreed on the classification of DLSS, surgical principles, and follow-up protocols. Patients were followed from baseline, at 6 months, and 12 months. Baseline characteristics were analyzed with 5 different questionnaires "Spinal Stenosis Measure, Feeling Thermometer, Numeric Rating Scale, 5D-3L, and Roland and Morris Disability Questionnaire." In addition, our study population was compared with a younger control group. Furthermore, we calculated the minimal clinically important differences. RESULTS: Thirty-seven patients with an average age of 82.5 ± 2.5 years reached the 12-month follow-up. Spinal Stenosis Measure scores, the Feeling Thermometer, the Numeric Rating Scale, and the Roland and Morris Disability Questionnaire showed significant improvements at the 6-month and 12-month follow-ups (P < 0.001). One EQ-5D-3Lsubgroup "anxiety/depression" showed no significant improvement (P = 0.109) at 12-month follow-up. The minimal clinically important difference for the "Symptom Severity scale" in the Spinal Stenosis Measure was achieved with improvement of 70% in the older patient population. CONCLUSION: Patients 80 years or older can expect a clinically meaningful improvement after lumbar decompression for symptomatic DLSS. Our patient population showed significant positive development in quality of life in the short- and long-term follow-ups. LEVEL OF EVIDENCE: 3.

Intracranial aneurysm rupture is predicted by measures of solar activity.

OBJECTIVE: The cause precipitating intracranial aneurysm rupture remains unknown in many cases. It has been observed that aneurysm ruptures are clustered in time, but the trigger mechanism remains obscure. Because solar activity has been associated with cardiovascular mortality and morbidity, we decided to study its association to aneurysm rupture in the Swiss population. METHODS: Patient data were extracted from the Swiss SOS database, at time of analysis covering 918 consecutive patients with angiography-proven aneurysmal subarachnoid hemorrhage treated at 7 Swiss neurovascular centers between January 1, 2009, and December 31, 2011. The daily rupture frequency (RF) was correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux [F10.7 index], solar proton flux, solar flare occurrence, planetary K-index/planetary A-index, Space Environment Services Center [SESC] sunspot number and sunspot area) using Poisson regression analysis. RESULTS: During the period of interest, there were 517 days without recorded aneurysm rupture. There were 398, 139, 27, 12, 1, and 1 days with 1, 2, 3, 4, 5, and 6 ruptures per day. Poisson regression analysis demonstrated a significant correlation of F10.7 index and RF (incidence rate ratio [IRR] = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719-1.008894; P < 0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. A likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95% CI 1.001864-1.004965; P < 0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95% CI 1.000249-1.000589; P < 0.001) emerged. All other variables analyzed showed no significant correlation with RF. CONCLUSIONS: We found greater radioflux, SESC sunspot number, and sunspot area to be associated with an increased count of aneurysm rupture. The clinical meaningfulness of this statistical association must be interpreted carefully and future studies are warranted to rule out a type-1 error.

Diffusion tensor imaging for anatomical localization of cranial nerves and cranial nerve nuclei in pontine lesions: initial experiences with 3T-MRI.

With continuous refinement of neurosurgical techniques and higher resolution in neuroimaging, the management of pontine lesions is constantly improving. Among pontine structures with vital functions that are at risk of being damaged by surgical manipulation, cranial nerves (CN) and cranial nerve nuclei (CNN) such as CN V, VI, and VII are critical. Pre-operative localization of the intrapontine course of CN and CNN should be beneficial for surgical outcomes. Our objective was to accurately localize CN and CNN in patients with intra-axial lesions in the pons using diffusion tensor imaging (DTI) and estimate its input in surgical planning for avoiding unintended loss of their function during surgery. DTI of the pons obtained pre-operatively on a 3Tesla MR scanner was analyzed prospectively for the accurate localization of CN and CNN V, VI and VII in seven patients with intra-axial lesions in the pons. Anatomical sections in the pons were used to estimate abnormalities on color-coded fractional anisotropy maps. Imaging abnormalities were correlated with CN symptoms before and after surgery. The course of CN and the area of CNN were identified using DTI pre- and post-operatively. Clinical associations between post-operative improvements and the corresponding CN area of the pons were demonstrated. Our results suggest that pre- and post-operative DTI allows identification of key anatomical structures in the pons and enables estimation of their involvement by pathology. It may predict clinical outcome and help us to better understand the involvement of the intrinsic anatomy by pathological processes.

High-frequency intra-operative ultrasound-guided surgery of superficial intra-cerebral lesions via a single-burr-hole approach.

The study described here examined the feasibility of using high-frequency intra-operative ultrasound (hfioUS) guidance to resect superficial intra-cerebral lesions through a single burr hole. A cohort of 23 consecutive patients with a total of 24 intra-cerebral lesions (9 intra-cerebral metastases, 8 gliomas, 4 infections, 2 lymphomas and 1 cavernoma) were studied. All lesions could be localized and successfully resected, biopsied or aspirated, and histopathological diagnoses were obtained in all cases. The mean operating time was 59.6 ± 23.9 min. The mean cross-sectional lesion size was 6.4 ± 7.6 cm(2), and the mean cortex surface-to-lesion distance was 0.6 ± 0.8 cm. Our results illustrate the feasibility of identifying and resecting superficial intra-cerebral lesions under hfioUS guidance via a single-burr-hole approach. We were able to achieve short resection times with no post-operative complications in all patients, favorable conditions under which to start adjuvant therapy when indicated.

Hydrocephalus after resection and adjuvant radiochemotherapy in patients with glioblastoma.

OBJECTIVE: Glioblastomas are the most common primary malignant brain tumors in adults with a poor prognosis. The current study sought to identify risk factors in glioblastoma patients that are closely associated with communicating hydrocephalus. METHODS: We retrospectively analyzed data from 151 patients who were diagnosed with a glioblastoma between 2007 and 2011 and underwent complete surgical resection closely followed by adjuvant radiochemotherapy. RESULTS: We observed a significant tendency toward communicating hydrocephalus in cases of ventricular opening during surgical tumor resection (Fisher's exact test p<0.001) and a noticeable, although not statistically significant, correlation between the onset of communicating hydrocephalus and evidence of leptomeningeal tumor dissemination (Fisher's exact test p=0.067). Additionally, there was a trend toward frontal tumor location and a larger tumor volume in patients with communicating hydrocephalus. The majority of patients suffering from communicating hydrocephalus received a cerebrospinal fluid (CSF) shunt implantation after radiation therapy (63.6%, Fisher's exact test p=0.000). CONCLUSION: We identified the following risk factors associated with the onset of communicating hydrocephalus in glioblastoma patients: ventricular opening during tumor resection and leptomeningeal tumor dissemination. Shunt implantation seems to be safe and effective in these patients.

Enhanced serum creatine kinase after neurosurgery in lateral position and intraoperative neurophysiological monitoring.

OBJECTIVE: Several cases of highly elevated serum levels of creatine kinase (CK) after surgical interventions have been described in the literature. A consensus on possible risk factors is still lacking. We therefore studied CK-levels in a large population of patients undergoing neurosurgical interventions and sought to determine possible risk factors. METHODS: We retrospectively analyzed 150 elective neurosurgical interventions where pre- and postoperative CK serum levels were determined. The cases were selected such that 50 patients were operated in lateral position and 100 in prone or supine position. During the hospital stay, routine clinical diagnostics were conducted, including medical status and laboratory examinations. RESULTS: In the patient group (median age 50, 63 male) there were 129 cranial and 21 spinal interventions. In 55 cases, intraoperative neurophysiological monitoring (IONM) was performed so that in these patients muscles were not relaxed pharmacologically. In a linear regression model, the maximal postoperative CK-level increased compared to baseline (p<0.001). While age and obesity were not identified as risk factors, the CK-level was enhanced after surgery in lateral position (p<0.001) and if IONM was performed (p=0.04). CONCLUSIONS: The strong association of postoperative serum CK-level with intraoperative positioning and IONM may be related to the elevated body pressure on the operating table in the lateral position, in particular if muscles are not relaxed pharmacologically, which was the case if intraoperative monitoring was performed. In these cases special care has to be taken for the positioning and during the peri-operative management.

Excessively elevated C-reactive protein after surgery for temporal lobe epilepsy.

OBJECTIVE: We present a series of 87 patients who underwent anteromesial temporal lobe resections for therapy refractory temporal lobe epilepsy. In addition to seizure outcome, we observed excessively elevated CRP-levels in this patient population. METHODS: We followed 87 patients (m=39, f=48; mean age 33.73±12.92, range 5-67 years) who underwent surgery between July 2003 and November 2011. Seizure outcome was classified in all patients according to the ILAE-classification by Wieser et al. (mean follow-up: 38.72 months). CRP levels were measured in 59 patients of the epilepsy surgery group and in a control group of 44 consecutive patients with supratentorial tumors (22 glioblastomas, 22 meningiomas). RESULTS: Clinical benefit was seen in 96.6% of the patients (ILAE classes 1-4), 80.5% were completely seizure free (ILAE class 1). Post-OP CRP values were significantly higher in the epilepsy group (n=59; mean CRP peak value: 100.86 mg/l, range: 16-258 mg/l) compared to the control group (n=44; mean CRP peak value: 36.85 mg/l, range: 0.4-233 mg/l) (p<0.001), but the correlation of mean CRP value and mean temperature peak is weak (r=0.31). CONCLUSIONS: Seizure outcome after surgery for temporal lobe epilepsy was excellent, CRP levels were excessively elevated in these patients in the absence of clinical infection and significantly higher compared to resections of supratentorial lesions.

Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fisher's exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8-14 (8-14 versus 3-7, p = 0.016; 15 versus 3-7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8-14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3-7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8-14. To clarify and strengthen these observations, prospective, randomized trials are needed.

Impact of intraoperative MRI-guided transsphenoidal surgery on endocrine function and hormone substitution therapy in patients with pituitary adenoma.

BACKGROUND: Pituitary adenomas are rare with an incidence of 0.4-8.2 per 105 inhabitants. Symptoms range from headaches to pituitary insufficiency or excessive output of hormones with associated disease. Except for prolactinomas, surgery is recommended as the first line and most effective treatment for the majority of these tumours. One of the refinements of surgical therapy introduced was intraoperative magnetic resonance imaging (iMRI). OBJECTIVE: The aim of this study was to analyse the postoperative pituitary function and the general outcome of patients treated for non-functioning and GH-producing pituitary adenomas with a transsphenoidal iMRI-assisted approach using the PoleStar™ N20 imager. METHODS: A total of 148 consecutive iMRI-guided surgeries for GH-producing and non-functioning pituitary adenomas were retrospectively analysed. Patients' clinical data, endocrinological parameters, clinical examinations and pre-/post- and intraoperative imaging studies were evaluated. RESULTS: A total of 101 patients could be classified as being in remission at follow-up; 26 (17.6%) of them due to iMRI allowing additional tumour removal. A total of 44 patients (29.7%) had more complete tumour removal because remnants were detected by iMRI. The mean hormone levels of patients did not differ significantly between pre- and postoperative examinations. There were 62 patients with preoperative, and 43 patients with postoperative pituitary insufficiency, thus, due to surgery there were 19 (12.8%) patients with improved pituitary function. CONCLUSIONS: The results show this method to be a safe and effective treatment option increasing remission rate and keeping complication rate low. Postoperative pituitary function was preserved or improved - possibly due to more exact iMRI-assisted tumour removal.

Neurosurgical considerations on highly eloquent brainstem cavernomas during pregnancy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) and especially cavernous malformations (CMs) in highly eloquent brain areas such as brainstem CMs are rare but possible events during pregnancy. Due to the few published cases in literature clear recommendations regarding the management are rare. In this study we evaluate the proceeding decision in pregnant patients with highly eloquent brainstem CMs. METHODS: In our series 43 patients with CMs in highly eloquent brain areas, including 39 patients with brainstem CMs, were surgically treated by the senior author between July 2007 and July 2010. Out of these, 29 patients were female and three of them presented with a symptomatic brainstem CMs during pregnancy and were included in this study. According to our experiences and to the available literature we analyzed demographic and clinical variables to provide recommendations for the management of pregnant patients with highly eloquent brainstem CMs. RESULTS: Only one patient was operated during pregnancy the other two patients were surgically treated after delivery, respectively. A thorough review of the literature revealed 12 patients with brainstem cavernomas during pregnancy there of only two patients were operated during pregnancy. CONCLUSION: Surgical treatment during pregnancy is rarely required, but needs to be performed right away in life-threatening and rapidly progressive clinical situations. Pregnant women with CMs in highly eloquent brain areas such as brainstem CMs need to be treated in specialized centers to assess the best point of time for surgery. Our study offers a useful tool to support the proceeding decision in this rare but important situation.

Do iatrogenic factors bias the placement of external ventricular catheters?--a single institute experience and review of the literature.

Placement of external ventricular drainage (EVD) catheters is the gold standard for managing acute hydrocephalus, but the range of complications varies in different studies. The objective of this present single institute study is to analyze iatrogenic factors, which may influence the EVD device placement and the patient's outcome. A total of 137 EVD placements in 120 patients at the University Hospital Zurich were analyzed retrospectively. Discriminative findings between the pre- and postoperative imaging were obtained and evaluated in detail with regards to the postoperative course, ventriculostomy-related infection, and acute neurological deterioration directly related to the EVD placement. These findings were correlated to iatrogenic factors including education level of the neurosurgeon and surgical setting. Overall EVD-related complication rate was 16.1%, including infection rate of 10.2%, catheter malplacement rate of 2.2%, and hemorrhage rate of 3.6%. Although not statistically significant, catheter-associated hemorrhages and malplacements were found mostly in primary EVD surgery, with a higher complication rate associated with junior residents as the performing surgeon. In contrast, ventriculostomy-related infection was most likely present in patients with more than one EVD placement and in patients treated by more experienced physicians. Complications related to EVD are common. The rate and character of the complication depends on the education level of the surgeon.

Small supratentorial, extraaxial primitive neuroectodermal tumor causing large intracerebral hematoma.

A 16-year-old boy presented with an unusual case of a supratentorial, extraaxial small round blue cell tumor of the central nervous system, which was most likely a primitive neuroectodermal tumor (PNET). Preoperative computed tomography and magnetic resonance imaging showed a large multistage hematoma in the left central region. Intraoperatively, a small, superficial tumorous lesion was found between the sagittal sinus and a large cortical vein hidden by the hematoma. The histological diagnosis was PNET. This tumor is one of the most aggressive intracerebral tumors, not only in children, so treatment strategies must be early, profound, and interdisciplinary. This case represents an important example of atypical extraaxial appearance of this lesion, which should be considered in the differential diagnosis of cortical or subcortical hemorrhage, since complete resection of this lesion is critical for the successful treatment and outcome.