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Pascal O. Zinn, Oliver Bozinov, Jan-Karl Burkhardt, Robert Reisch, M. Gazi Yaşargil and Helmut Bertalanffy

Mechanical obstruction is a severe complication of ventricular catheter use. Its incidence was shown to be high in the 1960s and 1970s, with up to 41% of the catheters becoming obstructed within 10 years after surgery. The authors present what is to their knowledge the first reported case of a patient with failure of a Torkildsen shunt after 50 years of functioning. A 60-year-old woman presented with increasing gait ataxia, decline in cognitive functions (including short-term memory loss), and slight urinary incontinence. The diagnosis of hydrocephalus and thus malfunction of the Torkildsen shunt implanted 50 years previously was confirmed by MR images, which revealed a prominent triventricular hydrocephalus. The patient subsequently underwent endoscopic third ventriculostomy (ETV), the current surgical treatment of choice, resulting in total resolution of her neurological symptoms and amelioration of cerebral tissue distension. Decrease in ventricle dilation and success of the ETV were confirmed on postoperative follow-up MR images.

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Ulrich Sure, Sandra Freman, Oliver Bozinov, Ludwig Benes, Adrian M. Siegel and Helmut Bertalanffy

Object. Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.

Methods. The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and endoglin antibodies.

Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB-1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1α in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.

Conclusions. The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

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Carlo Serra, Jan-Karl Burkhardt, Giuseppe Esposito, Oliver Bozinov, Athina Pangalu, Antonios Valavanis, David Holzmann, Christoph Schmid and Luca Regli

OBJECTIVE

The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas.

METHODS

Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI.

RESULTS

The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5–47 mm) and 5.23 cm3 (range 0.09–22.14 cm3), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm3). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05).

CONCLUSIONS

The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

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Michel Roethlisberger, Lara Gut, Daniel Walter Zumofen, Urs Fisch, Oliver Boss, Nicolai Maldaner, Davide Marco Croci, Ethan Taub, Natascia Corti, Jan-Karl Burkhardt, Raphael Guzman, Oliver Bozinov and Luigi Mariani

OBJECTIVE

Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population.

METHODS

The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher’s exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05.

RESULTS

Of the 168 patients, 57 (age range 16–49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment.

CONCLUSIONS

The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.

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Giovanni Muscas, Christiaan Hendrik Bas van Niftrik, Jorn Fierstra, Marco Piccirelli, Martina Sebök, Jan-Karl Burkhardt, Antonios Valavanis, Athina Pangalu, Luca Regli and Oliver Bozinov

Blood oxygenation level–dependent functional MRI cerebrovascular reactivity (BOLD-CVR) is a contemporary technique to assess brain tissue hemodynamic changes after extracranial- intracranial (EC-IC) bypass flow augmentation surgery. The authors conducted a preliminary study to investigate the feasibility and safety of intraoperative 3-T MRI BOLD-CVR after EC-IC bypass flow augmentation surgery. Five consecutive patients selected for EC-IC bypass revascularization underwent an intraoperative BOLD-CVR examination to assess early hemodynamic changes after revascularization and to confirm the safety of this technique. All patients had a normal postoperative course, and none of the patients exhibited complications or radiological alterations related to prolonged anesthesia time. In addition to intraoperative flow measurements of the bypass graft, BOLD-CVR maps added information on the hemodynamic status and changes at the brain tissue level. Intraoperative BOLD-CVR is feasible and safe in patients undergoing EC-IC bypass revascularization. This technique can offer immediate hemodynamic feedback on brain tissue revascularization after bypass flow augmentation surgery.

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Jan-Karl Burkhardt, Pascal O. Zinn, Muriel Graenicher, Alejandro Santillan, Oliver Bozinov, Ekkehard M. Kasper and Niklaus Krayenbühl

Object

Some patients develop communicating hydrocephalus after meningioma surgery, and this can develop into a serious clinical condition. However, this has rarely been addressed in the literature. Therefore, the authors sought to determine predictive patient variables for the occurrence of postoperative hydrocephalus following skull base meningioma surgery.

Methods

For this purpose, the authors retrospectively analyzed all patients who underwent resection of intracranial meningiomas between 1998 and 2009 at the Department of Neurosurgery, University Hospital Zurich, Switzerland. Of 594 patients with meningioma, 227 (38%) had a lesion located at the skull base, and thus were included for analysis. The following patient variables were examined: demographic data (age and sex); tumor number (solitary vs multiple); tumor side and localization within the skull base region (anterior, medial, posterior); infiltration of the cavernous sinus; compression of the optic channel/optic nerve; tumor volume; preoperative embolization (yes/no); duration of surgery; Simpson grade of resection; histopathological features (WHO grade); number of surgeries (single vs multiple); preoperative embolization; duration of hospital stay; tumor recurrence; use of an artificial dural substitute; postoperative infection rate; and clinical outcome (Glasgow Outcome Scale score at discharge and at 3 months, and vital status at last follow-up). Hierarchical clustering, factor analysis, and stepwise regression models revealed a ranking list for the top predictive variables for the occurrence of postoperative hydrocephalus.

Results

A total of 35 patients (5.9%) of the cohort of 594 developed communicating postoperative hydrocephalus, with no patient manifesting obstructive hydrocephalus. Of these 35 patients, 18 had a meningioma located at the skull base (18 [7.9%] of 227), in contrast to 17 patients with meningiomas in other locations (17 [4.6%] of 367). The following patient variables correlated with the occurrence of hydrocephalus, as defined by factor analysis: age, duration of surgery, duration of hospital stay, tumor volume, postoperative infection, and preoperative embolization. A stepwise regression analysis of the latter variables identified 2 variables as significantly predictive: age (p = 0.0012) and duration of surgery (p = 0.0013).

Conclusions

In this study, the incidence of communicating postoperative hydrocephalus was almost twice as high in patients with skull base lesions as in patients with meningiomas in other locations. Patient age, duration of surgery, duration of hospital stay, tumor volume, postoperative infection, and preoperative embolization were associated with the occurrence of hydrocephalus. In the statistical prediction model, patient age and duration of surgery were the most significant predictors of postoperative hydrocephalus after skull base meningioma surgery.

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Jan-Karl Burkhardt, Dörthe Schmidt, Roman Schoenauer, Chad Brokopp, Irina Agarkova, Oliver Bozinov, Helmut Bertalanffy and Simon P. Hoerstrup

Object

Cerebral cavernous malformations (CCMs) are among the most prevalent cerebrovascular malformations, and endothelial cells seem to play a major role in the disease. However, the underlying mechanisms, including endothelial intercellular communication, have not yet been fully elucidated. In this article, the authors focus on the endothelial junction proteins CD31, VE-cadherin, and occludin as important factors for functional cell-cell contacts known as vascular adhesion molecules and adherence and tight junctions.

Methods

Thirteen human CCM specimens and 6 control tissue specimens were cryopreserved and examined for the presence of VE-cadherin, occludin, and CD31 by immunofluorescence staining. Protein quantification was performed by triplicate measurements using western blot analysis.

Results

Immunofluorescent analyses of the CCM sections revealed a discontinuous pattern of dilated microvessels and capillaries as well as increased expression of occludin, VE-cadherin, and CD31 in the intima and in the enclosed parenchymal tissue compared with controls. Protein quantification confirmed these findings by showing upregulation of the levels of these proteins up to 2–6 times.

Conclusions

A protocol enabling the molecular and morphological examination of the intercellular contact proteins in human CCM was validated. The abnormal and discontinuous pattern in these endothelial cell–contact proteins compared with control tissue explains the loose intercellular junctions that are considered to be one of the causes of CCM-associated bleeding or transendothelial oozing of erythrocytes. Despite the small number of specimens, this study demonstrates for the first time a quantitative analysis of endothelial junction proteins in human CCM.