Karl Roessler

Gamma-knife radiosurgery for cranial base meningiomas : Experience of tumor control, clinical course, and morbidity in a follow-up of more than 8 years

OBJECTIVE:Surgical resection of cranial base meningiomas is often limited owing to involvement of crucial neural structures. Within the last 2 decades Gamma Knife radiosurgery (GKRS) has gained increasing importance as an adjunct treatment after incomplete resection and as an alternative treatment to open surgery. However, reports of long-term results are still sparse. We therefore performed this study to analyze the long-term results of GKRS treatment of cranial base meningiomas, following our previously published early follow-up experience. METHODS:A retrospective analysis of the medical files for Gamma Knife and surgical treatments, clinicoradiological findings, and outcome was carried out focusing on tumor control, clinical course, and morbidity. RESULTS:Between 1992 and 1995, we treated 36 patients with cranial base meningiomas using GKRS (male:female ratio, 1:5; mean age, 59 yr; range, 44–89 yr). Twenty-five patients were treated with GKRS after open surgery, and 11 patients received GKRS alone. Tumor control, neurological outcomes, and adverse effects were analyzed after a long-term follow-up period (mean, 103 mo; range, 70–133 mo) and compared with our previous results after an early follow-up period (mean, 48 mo; range, 36–76 mo). Control of tumor growth was achieved in 94% of patients. Compared with the early follow-up period, the late neuroradiological effects of GKRS on cranial base meningiomas were continuing tumor shrinkage in 11 patients (33%), stable tumor size in 20 patients (64%) and tumor progression in two meningiomas (6%). The neurological status improved in 16 patients (44%), remained stable in 19 patients (52%), and deteriorated in one patient (4%). Adverse side effects of GKRS were found only during the early follow-up period. CONCLUSION:Our data confirm that GKRS is not only a safe and effective treatment modality for cranial base meningiomas in short-term observation, but also in a mean long-term follow-up period of more than 8 years. Tumor shrinkage and clinical improvement also continued during the longer follow-up period.

Venous thromboembolism and survival in patients with high-grade glioma

Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were followed after surgery until October 2005. Objectively confirmed VTE was recorded as an event. All patients had received thrombosis prophylaxis with low-molecular-weight heparin (LMWH) during the immediate postoperative period. Subsequently, 56 patients received radiochemotherapy, 6 radiotherapy, and 1 chemotherapy only. Patients were followed over a median time period of 348 days. Fifteen patients (24%) developed VTE. Pulmonary embolism was diagnosed in nine patients (60%) and was fatal twice. The cumulative probability of VTE was 21% after three months and 26% after 12 months. The highest frequency of VTE was observed in patients with biopsy and subtotal tumor resection (n = 37; multivariate hazard ratio, 3.58; 95% CI = 0.98-13.13; P = 0.054) compared with patients with total resection. Survival did not significantly differ among patients with and without VTE and was 53% after 12 months in both groups. Patients with HGG, particularly those with biopsy and subtotal resection, are at high risk to develop VTE postoperatively. Thrombosis was not associated with a significant reduction of survival.

Progesterone-receptor index in meningiomas: correlation with clinico-pathological parameters and review of the literature

For recurrent and untreatable meningiomas alternative therapies, such as anti-progesterone treatment, have been sought. However, the few clinical studies have not determined progesterone receptor (PgR) expression in most cases, and studies correlating quantitative PgR expression (PgR index) with clinico-pathological variables are scarce. The aim of our study was to assess the PgR indices in a consecutive series of meningiomas and correlate these values with clinico-pathological parameters. We analyzed immunohistochemically 82 consecutive meningioma specimens (73 primary and nine recurrent tumors) for PgR and Ki-67 antigen (MIB-1). The male/female ratio was 1:1.7, and median age at the time of surgery was 57 years (range 29–77 years). The series comprised 55 grade I (subtyped as 36 meningothelial, seven fibrous, nine transitional, two psammomatous, and one angiomatous), 23 grade II, and one grade III meningiomas. Nuclear immunostaining for PgR was positive in 56 meningioma specimens (71%). PgR index was 21.4±2.8% (mean ± SE; range 0–79%). Significantly higher expression was found in male patients in the age group <50 years than in those ≥60 years and in grade I meningothelial meningiomas than in fibrous and transitional subtypes. There was a trend to lower PgR indices in non-benign meningiomas. Cell proliferation rate (MIB-1 index) was 4.4±0.4% (mean ± SE; range 0.3–15.4%). Significantly higher MIB-1 indices were found in male than female patients,in recurrent than primary and in grade II than grade I meningiomas. We observed a trend to higher PgR indices in meningiomas with MIB-1 index <5%. In sum, the highest PgR index in our series was observed in patients under the age of 50 years with WHO grade I meningiomas of the meningothelial subtype and low cell proliferation indices. If hormonal therapy has a direct action on the PgR, these patients should respond best to anti-progesterone treatment. We conclude that PgR index is variable in meningioma, depending on clinical parameters and histopathological features. Stratification of anti-progesterone therapy trials on the basis of PgR index should be considered.

Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography (18F-FET PET) in glioblastoma surgery

Abstract Objective: The sensitivity of 5-aminolevolinic acid (5-ALA) in detecting intraoperative glioblastoma (GBM) tissue compared to postoperative 18F-fluoroethyl-L-tyrosine and T1 contrast uptake of tumor cells in positron emission tomography (PET) and magnetic resonance imaging (MRI) scans was investigated in a retrospective image correlative study. Methods: Ten patients with histological verified GBM in eloquent brain regions underwent 11 surgeries with neuronavigation and 5-ALA assisted tumor resection. Residual 5-ALA fluorescence was labeled intraoperatively on the navigation MRI scans and images were fused with postoperative 18F-FET PET and T1 contrast MRI. Results: Intraoperatively, at the end of save resection, in all patients 2–5 faint 5-ALA positive resection planes were detected (mean 3·6), compared to 0–4 18F-FET positive resection planes (mean 1·4) and 0–2 positive T1 contrast MRI resection planes in postoperative scans. The difference between the number of 5-ALA and 18F-FET positive resection planes was statistically significant (P = 0·0002). The histological investigation of 5-ALA positive resection margins demonstrated infiltrative tumor in every case. Residual 5-ALA fluorescence on resection margins and postoperative 18F-FET uptake areas or residual contrast T1 areas were colocalized in all cases, documented by pre-/postoperative image fusion. Conclusion: Residual faint 5ALA uptake is documented in large areas at the end of GBM resection and corresponds to tumor infiltration. These 5-ALA positive resection plans exceeded the 18F-FET uptake areas in postoperative PET scans. Thus, intraoperative 5-ALA residual fluorescence seems to be a more sensitive marker than 18F-FET PET for residual tumor in malignant gliomas.

Essentials in intraoperative indocyanine green videoangiography assessment for intracranial aneurysm surgery: conclusions from 295 consecutively clipped aneurysms and review of the literature

OBJECT Indocyanine green (ICG) videoangiography (VA) in cerebral aneurysm surgery allows confirmation of blood flow in parent, branching, and perforating vessels as well as assessment of remnant aneurysm parts after clip application. A retrospective analysis and review of the literature were conducted to determine the current essential advantages of ICG-VA in aneurysm surgery. METHODS The authors retrospectively evaluated all aneurysm cases treated with the aid of intraoperative ICG-VA at a single institution between 2007 and 2013. They also analyzed the literature published since the initial description of ICG-VA in 2003. RESULTS Two hundred forty-six procedures were performed in 232 patients harboring 295 aneurysms. The patients, whose mean age was 54 years, consisted of 159 women and 73 men. One hundred twenty-four surgeries were performed after subarachnoid hemorrhage, and 122 were performed for incidental aneurysms. Single aneurysms were clipped in 185 patients, and multiple aneurysms were clipped in 47 (mean aneurysm diameter 6.9 mm, range 2-40 mm). No complications associated with ICG-VA occurred. Intraoperative microvascular Doppler ultrasonography was performed before ICG-VA in all patients, and postoperative digital subtraction angiography (DSA) studies were available in 121 patients (52.2%) for retrospective comparative analysis. In 22 (9%) of 246 procedures, the clip position was modified intraoperatively as a consequence of ICG-VA. Stenosis of the parent vessels (16 procedures) or occlusion of the perforators (6 procedures), not detected by micro-Doppler ultrasonography, were the most common problems demonstrated on ICG-VA. In another 11 procedures (4.5%), residual perfusion of the aneurysm was observed and one or more additional clips were applied. Vessel stenosis or a compromised perforating artery occurred independent of aneurysm location and was about equally common in middle cerebral artery and anterior communicating artery aneurysms. In 2 procedures (0.8%), aneurysm puncture revealed residual blood flow within the lesion, which had not been detected by the ICG-VA. In the postoperative DSA studies, unexpected small (< 2 mm) aneurysm neck remnants, which had not been detected on intraoperative ICG-VA, were found in 11 (9.1%) of 121 patients. However, these remnants remained without consequence except in 1 patient with a 6-mm residual aneurysm dome, which was subsequently embolized with coils. CONCLUSIONS In a large cohort of consecutive patients, ICG-VA proved to be a helpful intraoperative tool and led to a significant intraoperative clip modification rate of 15%. However, small, < 2-mm-wide neck remnants and a 6-mm residual aneurysm were missed by intraoperative ICG-VA in up to 10% of patients. Results in this study confirm that DSA is indispensable for postoperative quality assessment in complex aneurysm surgery.

Contour-guided brain tumor surgery using a stereotactic navigating microscope.

OBJECTIVE The benefit of intraoperative radiological data integration in approach planning and resection of brain tumors using a computer navigating microscope (MKM Zeiss) was investigated. METHODS Since February 1995, out of 86 MKM-guided surgical procedures, 53 contour-guided tumor cases (24 females, 29 males, mean age 51.6) including 16 metastasis, 14 glioblastomas, 10 low-grade gliomas, 6 anaplastic gliomas, 3 meningiomas and 4 others were performed. The preoperative planning was based on CT in 42 cases and Magnetic Resonance Tomography (MRT) in 11 cases using skin markers (4-9, mean 6). Neuroradiologically defined tumor contours were transferred into the ocular of the microscope and projected into the operating field during the procedure. RESULTS The advantages of the system were: (1) preoperative approach planning; (2) minimal, accurate skin incision and craniotomy; (3) intraoperative detection of deep seated lesions or lesion components; (4) determination of lesion boundaries; (5) minimized traumatization in/near eloquent areas. Mean registration accuracy improved from 5.3 mm for the first 10 cases up to 2 mm for the last 18 cases. In glioma surgery, the system provided exact definition of radiologically planned resection borders. In meningioma surgery, it allowed a tailored craniotomy, dura opening and resection, lowering the risk of recurrence. In metastasis surgery, it provided a safe approach to deep and eloquent located lesions. CONCLUSION Contour-guided operation planning and resection guidance using the investigated navigating microscope provides additional security to avoid some potential risks in brain tumor surgery.

Improved resection in lesional temporal lobe epilepsy surgery using neuronavigation and intraoperative MR imaging: Favourable long term surgical and seizure outcome in 88 consecutive cases

PURPOSE To investigate the value of intraoperative MR imaging (iopMRI) combined with neuronavigation to avoid intraoperative underestimation of the resection amount during surgery of lesional temporal lobe epilepsy (LTLE) patients. METHODS We retrospectively investigated 88 patients (40 female, 48 male, mean age 37.2 yrs, from 12 to 69 yrs, 41 left sided lesions) with LTLE operated at our department, including 40.9% gangliogliomas (GG), 26.1% cavernomas (CM), 10.2% dysembryoplastic neuroepithelial tumours (DNT) and 11.4% focal cortical dysplasias (FCD), excluding hippocampal sclerosis. RESULTS Complete resection was achieved in 85 of 88 patients (96.6%), as proven by postoperative MRI 6 months after surgery. In contrast, the routine first iopMR imaging before closure revealed radical resection in only 66 of these 88 patients (75%). After re-intervention, the second iopMR imaging demonstrated complete resection in 19 more patients. Thus, as a direct effect of iopMRI and neuronavigation, overall resection rate was increased by 21.6%. An excellent seizure outcome Engel Class I was found in 76.1% of patients during a mean follow-up of 26.4 months, irrespective of histological entity (74% in CM, 75% in GG, 78% in DNT and 60% in FCD). No severe postoperative complications occurred; permanent superior visual field defects were detected in 10.2% and permanent dysphasia/dyscalculia in 1.1%. CONCLUSION Refined surgery using neuronavigation combined with iopMR imaging in LTLE surgery led to radical resection in 96.6% of the patients, due to immediate correction of underestimated resection in 21.6% of patients. This protocol resulted in a favourable seizure outcome and a low complication rate.

Primary central nervous system lymphoma: a clinicopathological study of 75 cases

Aims: Pathological and clinical data in a large series of immunocompetent patients with primary lymphoma of the central nervous system (PCNSL) were analysed. Methods: We immunostained tumour specimens of 75 patients for CD3, CD4, CD5, CD8, CD10, CD20, CD30, CD79a, Bcl‐2, Bcl‐6, CD138, MUM1, TDT, PAX5, FOXP1 and Ki‐67 and performed in situ hybridisation for Epstein‐Barr virus (EBV) RNA. Eleven cases were investigated for rearrangements of BCL6, immunoglobulin heavy chain (IGH) and FOXP1 genes using fluorescent in situ hybridisation (FISH). Results: Histologically, most cases were classified as diffuse large B‐cell lymphoma (80.2%) predominantly of centroblastic type. Immunophenotypic profiling revealed that 96% and 4% of cases corresponded to non‐germinal centre and germinal centre type, respectively. FISH analysis showed t(3;14)/IGH‐BCL6 in 2/11 cases and trisomy 3 in 2/11 cases. FOXP1 rearrangements were not found. At survival analysis, Karnofsky index >80 and presence of Bcl‐6 expression showed independent significant association with favourable patient outcome. Conclusions: PCNSL represents a histologically and immunophenotypically very homogeneous lymphoma type, probably derived from germinal centre exit B cells. The frequent overexpression of FOXP1 appears not to be related to FOXP1 gene rearrangement. Survival analyses disclosed Bcl‐6 expression and high Karnofsky performance score as independent prognostic parameters associated with favourable outcome.

Image quality and artefact generation post-cerebral aneurysm clipping using a 64-row multislice computer tomography angiography (MSCTA) technology: A retrospective study and review of the literature

PURPOSE Computed tomography angiography (CTA) is a time and cost saving investigation for postoperative evaluation of clipped cerebral aneurysm patients. A retrospective study was conducted to analyse image quality and artefact generation due to implanted aneurysm clips using a new technology. METHODS MSCTA was performed pre- and postoperatively using a Philips Brilliance 64-detector-row CT scanner. Altogether, 32 clipping sites were analysed in 27 patients (11 female and 16 male, mean ages 52a, from 24 to 72 years). Clip number per aneurysm was 2.3 mean (from 1 to 4), 54 clips were made of titanium alloy and 5 of cobalt alloy. RESULTS Altogether, image quality was rated 1.8 mean, using a scale from 1 (very good) to 5 (unserviceable) and clip artefacts were rated 2.4 mean, using a 5 point rating scale (1 no artefacts, 5 unserviceable due to artefacts). A significant loss of image quality and rise of artefacts was found when using cobalt alloy clips (1.4 versus 4.2 and 2.1 versus 4.0). In 72% of all investigations, an excellent image quality was found. Excluding the cobalt clip group, 85% of scans showed excellent image quality. Artefacts were absent or minimal (grade 1 or 2) in 69% of all investigations and in 81% in the pure titanium clip group. In 64-row MSCTA of good image quality with low artefacts, it was possible to detect small aneurysm remnants of 2mm size in individual patients. CONCLUSION By using titanium alloy clips, in our study up to 85% of postoperative CTA images were of excellent quality with absent or minimal artefacts in 81% and seem adequate to detect small aneurysm remnants.

Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging

Abstract Objectives: Cure from seizures due to cavernomas might be surgically achieved dependent on both, the complete removal of the cavernoma as well as its surrounding hemosiderin rim. High field intraoperative MRI imaging (iopMRI) and neuronavigation might play a crucial role to achieve both goals. We retrospectively investigated the long-term results and impact of intraoperative 1·5T MRI (iopMRI) and neuronavigation on the completeness of surgical removal of a cavernous malformation (CM) and its perilesional hemosiderin rim as well as reduction of surgical morbidity. Methods: 26 patients (14 female, 12 male, mean age 39·1 years, range: 17–63 years) with CM related epilepsy were identified. Eighteen patients suffered from drug resistant epilepsy (69·2%). Mean duration of epilepsy was 11·9 years in subjects with drug resistant epilepsy (n  =  18) and 0·3 years in subjects presenting with first-time seizures (n  =  8). We performed 24 lesionectomies and two lesionectomies combined with extended temporal resections. Seven lesions were located extratemporally. Results: Complete CM removal was documented by postsurgical MRI in all patients. As direct consequence of iopMRI, refined surgery was necessary in 11·5% of patients to achieve complete cavernoma removal and in another 11·5% for complete resection of additional adjacent epileptogenic cortex. Removal of the hemosiderin rim was confirmed by iopMRI in 92% of patients. Two patients suffered from mild (7·7%) and one from moderate (3·8%) visual field deficits. Complete seizure control (Engel class 1A) was achieved in 80·8% of patients with a mean follow-up period of 47·7 months. Discussion: We report excellent long-term seizure control with minimal surgical morbidity after complete resection of CM using our multimodal approach.