Ibrahim Erol Sandalcioglu

Transcortical or transcallosal approach to ventricle-associated lesions: a clinical study on the prognostic role of surgical approach

Abstract Most entities in and around the anterior two-thirds of the supratentorial ventricles can be reached via transcortical or transcallosal approach. This study examined the effect of surgical approach on the postoperative neurological outcome. Thirty-eight patients with intra- and periventricular supratentorial lesions were operated on by either frontal transcortical or anterior transcallosal approach. Postoperative diencephalic damage occurred in 22% of patients in the transcortical group and in 36% in the transcallosal group; transient mutism was virtually equivalent in the two groups. Postoperative epilepsy (26%) and subdural fluid collections (30%) occurred only in the transcortical group. The incidence of postoperative hemiparesis was higher in the transcallosal group. There was a high correlation between postoperative Glasgow Outcome Score of 5 and preoperative severity of neurological disease but no correlation between postoperative Glasgow Outcome Score of 5 and location of the lesion or between postoperative clinical course and surgical approach. Surgical outcome of ventricle-associated lesions depends mainly on the severity of preoperative symptoms and not on surgical approach. Additionally, the incidence of postoperative seizures and subdural fluid collections after transcortical surgery is high.

Surgical treatment of intramedullary spinal cord metastases of systemic cancer: functional outcome and prognosis

Objective: Intramedullary spinal cord metastases (ISCM) of systemic cancer are rare. To date, patients with ISCM tend to benefit only to a limited extend from surgery and adjuvant therapy. Subject of this investigation is to assess predictive factors for surgical outcome and survival and to evaluate the value of surgical radicality in the treatment of ISCM. Patients and methods: Between 1990 and 2004, a series of 146 patients with intramedullary tumors underwent surgical treatment in our institution. Among these, 13 patients with intramedullary cancer metastases (7 adenocarcinomas, 3 poorly differentiated carcinomas, 3 sarcomas) were identified. Standard microsurgical removal of the ISCM was performed. Functional outcome was graded according to a standardized scale and factors influencing outcome and survival were statistically analyzed. Results: Median progression-free survival was 13 weeks and median overall survival was 31 weeks. In 5 patients (38) the intramedullary lesion was the initial manifestation of the malignant disease. All poorly differentiated carcinomas and all sarcomas were resected incompletely. Surgical radicality presented a negative predictive factor for functional outcome, increasing radicality leading to functional deterioration. Age, sex, tumor localization, surgical radicality and the presence of neoplastic meningeosis did not affect survival. Conclusion: Surgery of ISCM can be performed with an acceptable operative morbidity. Radicality depended on tumor histology. However, radical tumor removal did not affect survival and was correlated with a poor functional outcome. Therefore, complete surgical removal of ISCM should only be intended in patients in whom an unproblematic excision is feasible.

Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations

CCM3, a product of the cerebral cavernous malformation 3 or programmed cell death 10 gene (CCM3/PDCD10), is broadly expressed throughout development in both vertebrates and invertebrates. Increasing evidence indicates a crucial role of CCM3 in vascular development and in regulation of angiogenesis and apoptosis. Furthermore, loss of CCM3 causes inherited (familial) cerebral cavernous malformation (CCM), a common brain vascular anomaly involving aberrant angiogenesis. This study focused on signalling pathways underlying the angiogenic functions of CCM3. Silencing CCM3 by siRNA stimulated endothelial proliferation, migration and sprouting accompanied by significant downregulation of the core components of Notch signalling including DLL4, Notch4, HEY2 and HES1 and by activation of VEGF and Erk pathways. Treatment with recombinant DLL4 (rhDLL4) restored DLL4 expression and reversed CCM3‐silence‐mediated impairment of Notch signalling and reduced the ratio of VEGF‐R2 to VEGF‐R1 expression. Importantly, restoration of DLL4‐Notch signalling entirely rescued the hyper‐angiogenic phenotype induced by CCM3 silence. A concomitant loss of CCM3 and the core components of DLL4‐Notch signalling were also demonstrated in CCM3‐deficient endothelial cells derived from human CCM lesions (CCMEC) and in a CCM3 germline mutation carrier. This study defined DLL4 as a key downstream target of CCM3 in endothelial cells. CCM3/DLL4‐Notch pathway serves as an important signalling for endothelial angiogenesis and is potentially implicated in the pathomechanism of human CCMs.

Does intraoperative aneurysm rupture influence outcome? Analysis of 169 patients.

OBJECTIVES The aim of this study was to evaluate the prognostic value of intraoperative aneurysm rupture (IAR) in patients with subarachnoid hemorrhage (SAH) undergoing surgery for cerebral aneurysms. PATIENTS AND METHODS Between July 1997 and April 2000, 292 consecutive patients were admitted to our institution with SAH due to ruptured intracranial aneurysms. Of these, 169 patients were treated surgically according to standard microsurgical procedures and were included in this study. Mean age was 47 years. Initial clinical state was graded according to the classification of Hunt and Hess (HH). Outcome was classified according to the Glasgow Outcome Scale as favorable (grades IV and V) and unfavorable (grades I-III). Outcome of patients with intraoperative ruptured and non-ruptured aneurysms was analyzed in correlation to the preoperative clinical state and with respect to the time of surgery and to aneurysm localization. RESULTS Different rupture rates were observed with respect to the localization of the aneurysm: anterior circulation (n=69) 39.1%, middle cerebral artery (n=46) 34.8%, internal carotid artery (n=48) 31.2%, and posterior circulation (n=6) 16.7%. Patients with HH-grades I-III showed a favorable outcome in 72.2% (61 of 84 patients) without intraoperative rupture and in 71.7% (33 of 46 patients) with intraoperative aneurysm rupture. The corresponding values for patients with HH-grades IV/V were: favorable outcome in 34.6% (9 of 26 patients) and 23.1% (3 of 13 patients), respectively. Poor initial clinical condition (HH IV and V) as well as the initial Fisher grades III and IV were strongly associated with poor clinical outcome. CONCLUSIONS Intraoperative aneurysm rupture has no impact on the outcome, neither in patients with good initial condition nor for poor grades patients.

Caudal Image Contrast Inversion in MPRAGE at 7 Tesla: Problem and Solution

RATIONALE AND OBJECTIVES The magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence regularly shows caudal image contrast inversion at 7 T and therefore reduced clinical applicability. The investigators report the technical source of this problem and present a practical solution. MATERIALS AND METHODS A total of 71 subjects were scanned using a 7-T whole-body magnetic resonance imaging system using a 32-channel transmit/receive head coil. In 39 subjects, 45 high-resolution T1 contrast image data sets were acquired with the standard MPRAGE sequence. A modified sequence with an adiabatic wideband uniform rate smooth truncation pulse for magnetization preparation was used for 45 further scans in 39 subjects. In total, seven subjects underwent scans with both sequences. The homogeneity of T1 contrast and the occurrence of caudal image contrast inversion were evaluated in consensus reading by two neuroradiologists. RESULTS Caudal image contrast inversion was depicted in 19 acquisitions (42.2%) using the standard MPRAGE sequence. Using the adiabatic wideband uniform rate smooth truncation pulse for magnetization preparation, caudal image contrast inversion was depicted in only three acquisitions (6.7%). A χ(2) test showed a significant difference between the two preparation pulses (P < .001). CONCLUSIONS Magnetization preparation with an adiabatic wideband uniform rate smooth truncation pulse in the MPRAGE sequence at 7 T can significantly reduce the occurrence of caudal image contrast inversion and improves signal homogeneity.

Lysosomal ceramide mediates gemcitabine-induced death of glioma cells

Acid sphingomyelinase-induced ceramide release has been shown by many studies to induce apoptosis in response to various stimuli. However, the mechanisms of acid sphingomyelinase/ceramide-mediated death signaling following treatment with chemotherapeutic drugs have not been fully elucidated thus far. The present study demonstrates that treatment of glioma cells with clinically achievable doses of gemcitabine results in acid sphingomyelinase activation, lysosomal accumulation of ceramide, cathepsin D activation, Bax insertion into the mitochondria, and cell death. Pharmacological inhibition or genetic deficiency of acid sphingomyelinase prevented these events while overexpression of the enzyme sensitized cells to gemcitabine. Likewise, inhibitors of lysosomal functions also prevent gemcitabine-induced cell death. Our data indicate a critical role of the acid sphingomyelinase/ceramide system for gemcitabine-induced signaling and suggest that lysosomal ceramide accumulation mediates cell death induced by a chemotherapeutic drug.

Silent embolism after stent-assisted coiling of cerebral aneurysms: diffusion-weighted MRI study of 75 cases

Purpose New ischemic brain lesions are common findings after cerebral diagnostic angiography and endovascular therapy. Diffusion-weighted MRI (DWI) can be used for detection of these lesions. The aim of the present study was to investigate the incidence of DWI lesions after stent-assisted coiling and the evaluation of possible risk factors. Methods The study included a total of 75 consecutive patients treated with stent-assisted coiling. Post-procedural DWI of the brain was performed to detect ischemic lesions. Demographic data, aneurysm characteristics and angiographic parameters were correlated with properties of DWI lesions. Results In post-procedural DWI, 48 of the 75 patients (64%) had 163 DWI lesions in a pattern consistent with embolic events. The number of patients with DWI lesions was significantly increased in older patients (≥55 years) and longer intervention times (≥120 min). The ischemic brain volume was significantly increased in older patients (≥55 years) as well as in patients who were implanted with a shorter stent (<20 mm). Conclusions Thromboembolic events are common after stent-assisted coiling with an incidence comparable to DWI studies after coiling alone. Despite several devices and low operator experience, stent-assisted coiling for intracranial aneurysms has a very low risk of permanent neurologic disability. Further studies are necessary to improve the safety of stent-assisted coiling for patients in conditions with increased risk potential (age, procedure time, stent length).

Association of aneurysms and variation of the A1 segment

Background and purpose Previous studies have described a correlation between variants of the circle of Willis and pathological findings, such as cerebrovascular diseases. Moreover, anatomic variations of the anterior cerebral artery (ACA) seem to correspond to the prevalence of aneurysms in the anterior communicating artery (ACoA). The aim of this study was to assess the prevalence of aneurysms in patients with anatomical/morphological variations of the circle of Willis. Methods We retrospectively analyzed 223 patients who underwent cerebral angiography between January 2002 and December 2010 for aneurysm of the ACoA. Diagnostic imaging was reviewed and statistically evaluated to detect circle of Willis anomalies, aneurysm size, and rupture. 204 patients with an unrelated diagnosis served as the control group. Results Variations of the A1 segment occurred significantly more frequently in the aneurysm group than in the control group. Mean aneurysm size in patients with grades I and III hypoplasia or aplasia was 6.58 mm whereas in patients with grade II hypoplasia it was 7.76 mm. Conclusions We found that variations in the A1 segment of the ACAs are correlated with a higher prevalence of ACoA aneurysms compared with patients with a symmetric circle of Willis.

Sex-specific clinicopathological significance of novel (Frizzled-7) and established (MGMT, IDH1) biomarkers in glioblastoma

Background The Wnt receptor Frizzled-7 (FZD7) promotes tumor progression and can be currently targeted by monoclonal antibody therapy. Here, we determined the prognostic value of FZD7 for the overall survival of glioblastoma (GBM) patients, both as individual marker and taken in combination with the previously-described markers MGMT and IDH1. Additionally, we tested whether these markers (alone or in combination) exhibited sex-specific differences. Results High levels of FZD7 (FZD7high) associated with shorter survival in GBM patients; however, FZD7high was a significant predictor of poor survival only in male patients. Mutation of IDH1 significantly associated with longer survival in male but not female patients. Methylated MGMT promoter significantly associated with longer survival only in female patients. Combination of FZD7 with MGMT enhanced the prognostic accuracy and abrogated the sex differences observed upon single marker analysis. Combination of FZD7 with IDH1 was a significant predictor of survival in male GBM patients only. Materials and Methods Three independent cohorts of patients with primary GBM (n=120, n=108 and n=105, respectively) were included in this study. FZD7 and IDH1 were assessed by immunohistochemistry in tissue microarrays. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. Survival analysis was performed by Kaplan-Meier estimate, log-rank test and Cox proportional hazard regression. Conclusions Our study identifies novel individual and combination markers with prognostic and, possibly, therapeutic relevance in GBM. Furthermore, our findings substantiate the importance of sexual dimorphism in this type of cancer.

Fusion of the cerebellar hemispheres ventral to the brainstem: a rare hindbrain-related malformation

IntroductionNew variations of cerebellar malformations are being increasingly recognized using modern neuroimaging techniques. Until now only dorsal cerebellar fusion syndromes, such as the rhombencephalosynapsis and its variations have been recognized.Case reportWe report on a 17-month-old male infant presenting with an exceptional hindbrain related malformation characterized by midline fusion of the cerebellar hemispheres ventral to the brainstem and causing symptoms due to brainstem compression.Discussion and conclusionA more detailed understanding of the cerebellar embryogenesis is required to unravel the underlying mechanisms leading to this type of cerebellar malformation, which cannot easily be integrated into the common classification systems. Both the morphological features and the clinical presentation are different from those of other cerebellar structural abnormalities. If this type of congenital malformation is detected more frequently in the future, it seems reasonable that it should be added to the list of cerebellar malformations as a distinct type.