Clinical Instructor, Neurosurgery
M.D. M.Sc., University of Heidelberg (2007)
Long term quality of life data of adult patients harboring intracranial ependymomas have not been reported. The role of adjuvant radiation therapy in Grade II ependymomas is unclear and differs from study to study. We therefore sought to retrospectively analyze outcome and quality of life of adult patients that were operated on intracranial ependymomas at four different surgical centers in two countries. All patients were attempted to be contacted via telephone to assess quality of life (QoL) at the time of the telephone interview. The standard EORTC QoL Questionnaire C30 (EORTC QLQ-C30) and the EORTC QLQ-Brain Cancer Module (QLQ-BN20) were used. 64 adult patients with intracranial ependymomas were included in the study. The only factor that was associated with increased survival was age <55 years (p < 0.001). Supratentorial location was correlated with shorter progression free survival than infratentorial location (PFS; p = 0.048). In WHO Grade II tumors local irradiation did not lead to increased PFS (p = 0.888) or overall survival (p = 0.801). Even for incompletely resected Grade II tumors local irradiation did not lead to a benefit in PFS (p = 0.911). In a multivariate analysis of QoL, irradiated patients had significantly worse scores in the item "fatigue" (p = 0.037) than non-irradiated patients. Here we present QoL data of adult patients with intracranial ependymomas. Our data show that local radiation therapy may have long-term effects on patients' QoL. Since in the incompletely resected Grade II tumors local irradiation did not lead to a benefit in PFS in this retrospective study, prospective randomized studies are necessary. In addition to age, supratentorial tumor location is associated with a worse prognosis in adult ependymoma patients.
View details for DOI 10.1007/s11060-013-1187-2
View details for PubMedID 23813228
Both open ulnar nerve decompression and retractor-endoscopic ulnar nerve decompression have been shown to yield good results. However, a comparative evaluation of the techniques is lacking.To compare the results of open and endoscopic surgery in cubital tunnel syndrome.One hundred fourteen patients undergoing open (n = 59) or endoscopic (n = 55) decompression of the ulnar nerve for cubital tunnel syndrome were retrospectively compared. The long- and short-term outcomes were compared with respect to the time until return to full activity and the duration of postoperative pain. Additionally, matched pairs between the 2 groups were chosen for analysis (n = 34).Long-term results in the open vs endoscopic groups were as follows: excellent results, 54.2% vs 56.4%; good results, 23.8% vs 32.7%; fair results, 20.3% vs 9.1%; and poor results, 1.7% vs 1.8%, respectively. For the matched pairs, the results had similar significance levels (P = .84). The times until return to full activity in the open vs the endoscopic groups were as follows: 2 to 7 days, 18.6% vs 76.4%; 7 to 14 days, 55.9% vs 10.9%; and > 14 days, 25.4% vs 12.7% (P < .001 between nonmatched and matched pairs). The durations of postoperative pain in the open vs the endoscopic groups were as follows: 1 to 3 days, 45.8% vs 67.3%; 3 to 10 days, 42.5% vs 25.4%; and > 10 days, 11.7% vs 7.3% (P =.04 for nonmatched and P = .05 for matched pairs).There are no significant differences in long-term outcomes after open and retractor-endoscopic in situ decompression of the ulnar nerve in cubital tunnel syndrome. The short-term results are significantly better in endoscopic surgery.
View details for DOI 10.1227/NEU.0b013e3182846dbd
View details for Web of Science ID 000316667000037
View details for PubMedID 23277372
The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm(3). Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P = 0.77) or neurological deficits (10.0 vs. 10.6%, P = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.
View details for DOI 10.1007/s11060-011-0784-1
View details for Web of Science ID 000303469400018
View details for PubMedID 22249690
The role of endovascular interventions in managing dural arteriovenous fistulas (DAVFs) is increasing. Furthermore, in patients with aggressive DAVFs, different surgical interventions are required for complete obliteration or disconnection. Our objective was to evaluate the management of patients with intracranial DAVFs treated in our institution to identify the parameters that may help guide the long-term management of these lesions.The hospital records of 53 patients with intracranial DAVFs were reviewed. We then conducted a systematic telephone interview to obtain long-term follow-up information.The main presenting symptoms were tinnitus and headache. Nineteen (35%) patients presented with intracranial bleeding, 84% of patients scored between 0 and 2 using a modified Rankin Scale at the last follow-up visit. Twenty-four patients were treated surgically. Overall postoperative complications occurred in seven (29%) surgically treated patients, but only two patients permanently worsened. For patients with Borden type II and III fistulas, the annual incidence of hemorrhage was 30%. Two patients had late recurrences of surgically and endovascularly occluded DAVFs. Long-term follow-up showed that compared with spinal DAVFs, only 50% of intracranial DAVFs showed complete remission of symptoms, 41% partial remission, 6% no remission and 4% deterioration of symptoms that led to treatment of the DAVF.In general, intracranial DAVFs can be successfully surgically managed by simple venous disconnection in many cases. However, half of the patients do not show complete remission of symptoms. Age and the occurrence of perioperative complication were the most important determinants of outcome.
View details for DOI 10.1007/s00701-011-0981-x
View details for Web of Science ID 000290795700016
View details for PubMedID 21424601
Cranial nerve palsies are regularly observed in patients with arteriovenous fistulas of the cavernous sinus. The purpose of our study was to determine the long-term clinical outcome-with a special focus on extra-ocular muscular dysfunctions-in patients who had undergone endovascular treatment of a cavernous sinus fistula with detachable coils.Sixteen patients were recalled for an ophthalmoneurologic control examination (mean interval of 4.4 years). The mRS and the EQ-5D questionnaire were used for the description of general outcome. Age, duration of symptoms, character of the fistula (direct, dural), and coil volume were tested to assess their relevance for persistent symptoms.All patients displayed complete regression of chemosis, exophthalmus, and pulsating tinnitus with no evidence of recurrences. Oculomotor disturbances persisted in 9 of 13 patients and caused permanent diplopia in 7 patients. In 15 patients a mRS score of 1 or 2 was achieved; however, 7 patients reported some limitations in life quality (EQ-5D). A significant correlation was found between coil volume and persistent diplopia (P = .032) and persistent cranial nerve VI paresis (P = .037).Coil embolization of the cavernous sinus led to durable closure of AVF and reliable regression of acute symptoms. However, long-term follow-up showed a 44% rate of persistent cranial nerve deficits with disturbances of oculomotor and visual functions. This may be explained by the underlying fistula size itself and/or the space-occupying effect of the coils. As neuro-ophthalmologic outcome is crucial for control of therapeutic success, patients should be routinely examined by ophthalmologists.
View details for DOI 10.3174/ajnr.A2040
View details for Web of Science ID 000281106700012
View details for PubMedID 20299427
Tissue factor (TF) is upregulated in several malignant diseases, including gliomas. Here, we demonstrate pronounced differences in the expression of TF and its interactors factor VII and protease-activated receptor 2 (PAR-2) in nine human glioma cell lines (U87, U251, U343, U373, MZ-18, MZ-54, MZ-256, MZ-304, Hs 683) as detected by RT-PCR and Western blot analysis. Inhibition of TF signaling by a neutralizing monoclonal antibody (mAb TF9-10H10) led to significantly reduced proliferation in high-grade astroglial (MZ-18 and MZ-304) and oligodendroglial (Hs 683) cell lines abundantly expressing TF, but not in U373 cells expressing low amounts of TF. Scratch migration assays and Boyden chamber assays indicated that mAb TF9-10H10 and lentiviral knockdown of TF significantly reduced cell migration and invasion of MZ-18, MZ-304 and Hs 683 cells, both under normoxic and hypoxic conditions. Of note, all three cell lines displayed increased cell migration and invasion under hypoxic conditions (1% O(2)), which was associated with enhanced expression of TF and increased phosphorylation of p44/42 mitogen-activated protein kinase (ERK1/2). Silencing of TF blocked activation of the ERK pathway, induction of TF expression and the potentiating effect of hypoxia on cell migration and invasion. RNA interference against PAR-2 abrogated the autocrine effects of TF on cell proliferation, migration and invasion, indicating that TF signals via PAR-2 in glioma cells. Our results suggest an important role for the TF/FVIIa/PAR-2/ERK axis in tumor growth and invasion of glioma and suggest that TF may be a suitable target for the development of novel therapies against high-grade glioma.
View details for DOI 10.1016/j.neuroscience.2009.11.049
View details for Web of Science ID 000274081500029
View details for PubMedID 19958818
The relationship between cerebral integrity, recovery of brain function, and neurologic status after mild traumatic brain injury is incompletely characterized.Prospective and randomized study in rodents.University laboratory.Male Wistar rats (290-310 g).In rats, quantitative diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2-weighted imaging (T2WI), and functional magnetic resonance imaging (fMRI) were performed up to 21 days after weight-induced, closed-head, mild traumatic brain injury (MTBI, n = 6) or sham operation (n = 6). Pixel-by-pixel analysis and region of interest analysis were used to evaluate structural (apparent diffusion coefficient [ADC] and basal cerebral blood flow [bCBF]) and functional magnetic resonance signal changes within the brain, respectively. Quantitative fMRI signal changes were correlated with behavioral measures.Despite normal appearing DWI and T2WI findings following MTBI, persistent hypoperfusion developed that was not associated with cytotoxic edema. In contrast, the ADC was significantly increased by approximately 5% at 1 and 7 days post-MTBI. Post-MTBI fMRI responses to hypercapnia and forepaw stimulation were significantly impaired and showed a differential recovery rate between and within investigated region of interests. Significant dysfunction in forepaw placement test persisted up to day 1 and correlated significantly with fMRI signal changes in the primary somatosensory and motor cortices.MTBI produced distinct changes on multimodal MRI and behavioral variables acutely and chronically. Following MTBI, fMRI and ADC-bCBF pixel-by-pixel analysis identified subtle structural and functional alterations in the brain that appeared completely normal on conventional DWI and T2WI after concussion injury. The former techniques may therefore provide great potential for understanding mild traumatic brain injury, identifying mechanisms underlying recovery, and investigating specific interventions to enhance functional outcome.
View details for DOI 10.1097/01.CCM.0000286395.79654.8D
View details for Web of Science ID 000250423500019
View details for PubMedID 17828037
The aim of the present study was to develop a model of mild traumatic brain injury in the rat that mimics human concussive brain injury suitable to study pathophysiology and potential treatments. 34 male Wistar rats received a closed head trauma (TBI) and 30 animals served as controls (CON). Immediately following trauma, animals lost their muscle tone and righting reflex response, recovering from the latter within 11.4 +/- 8.2 min. Corneal reflex and whisker responses returned within 4.5 +/- 3.0 min and 6.1 +/- 2.9 min, respectively. The impact resulted in a short transient decrease of pO2 (P < 0.001), increase in mean arterial blood pressure (P = 0.026), and a reduction of heart rate (P < 0.01). Serial MRI did not show any abnormalities across the entire cerebrum on diffusion, T1, T2, and T2*-weighted images at all investigated time points. TBI animals needed significantly longer to locate the hidden platform in a Morris water maze and spent less time in the training quadrant than controls. TBI led to a significant neuronal loss in frontal cortex (P < 0.001), as well as hippocampal CA3 (P = 0.017) and CA1 (P = 0.002) at 9 days after the trauma; however, cytoskeletal architecture was preserved as indicated by normal betaAPP- and MAP-2 staining. We present a unique, noninvasive rat model of mild closed head trauma with characteristics of human concussion injury, including brief loss of consciousness, cognitive impairment, and minor brain injury.
View details for DOI 10.1016/j.expneurol.2005.06.013
View details for Web of Science ID 000232190600019
View details for PubMedID 16084512