Search Results

You are looking at 1 - 10 of 16 items for

  • Author or Editor: Hartmut Vatter x
Clear All Modify Search
Restricted access

Hartmut Vatter, Michael Zimmermann, Veronika Tesanovic, Andreas Raabe, Lothar Schilling and Volker Seifert

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature.

Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2).

The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−).

Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Restricted access

Hartmut Vatter, Michael Zimmermann, Veronika Tesanovic, Andreas Raabe, Volker Seifert and Lothar Schilling

Object. The disturbed balance between nitric oxide and endothelin (ET)—1 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ETA receptor—dependent contractile effect, ET-1 also has ETB receptor—mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ETA receptor—selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature.

Methods. Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10−9 to 10−6 M) after a precontraction was induced by prostaglandin F. The inhibition by clazosentan was estimated by the value of the affinity constant (pA2).

The relaxation induced by sarafotoxin S6c, ET-1, and big ET-1 was inhibited in a competitive manner by clazosentan, yielding pA2 values of 7.1, 6.7, and 6.5, respectively. The selectivity to the ETA receptor in the cerebrovascular system was approximately two logarithmic units.

Conclusions. The present investigation shows a competitive inhibition of ETB receptor—mediated relaxation in cerebral vessels by clazosentan in therapeutically relevant concentrations. Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid. Furthermore, the present data may be taken to describe the pharmacological properties for an ET receptor antagonist specifically tailored for the treatment of pathological conditions of impaired cerebral blood flow.

Restricted access

Hartmut Vatter, Juergen Konczalla, Stefan Weidauer, Christine Preibisch, Michael Zimmermann, Andreas Raabe and Volker Seifert

Object

The key role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) is increasingly assigned to endothelin (ET)-1. Constriction of the cerebrovasculature by ET-1 is mainly mediated by the ETA receptor but is putatively altered during the development of cerebral vasospasm. Therefore, the aim in the present study was to characterize these alterations, with the emphasis on the ETA receptor.

Methods

Cerebral vasospasm was induced using the rat double-hemorrhage model and proven by perfusion weighted magnetic resonance imaging. Rats were killed on Day 5 after SAH, and immunohistochemical staining for ETA receptors was performed. The isometric force of basilar artery ring segments with (E+, control group) and without (E−, SAH group) endothelial function was measured. Concentration effect curves (CECs) for ET-1 were constructed by cumulative application in the absence and presence of the selective ETA receptor antagonist clazosentan (10−8 or 10−7 M).

Results

The CEC for E+ segments was significantly shifted to the left after SAH by a factor of 3.7, whereas maximum contraction was unchanged. In E− segments, the CECs were not shifted during cerebral vasospasm but the maximum contraction was significantly enhanced. The inhibitory potency of clazosentan yielded a pA2 value of 8.6 ± 0.2. Immunohistochemical staining of the smooth-muscle layer showed no significant increase of ETA receptor expression, but positive staining occurred in the endothelial space after SAH.

Conclusions

The present data indicate an enhanced contractile effect of the smooth-muscle ETA receptors in cases of cerebral vasospasm. The inhibitory potency of clazosentan on this contraction is increased. Furthermore, some evidence for an ETA receptor and an endothelium-dependent vasoactive effect after SAH is provided.

Full access

Matthias Setzer, Hartmut Vatter, Gerhard Marquardt, Volker Seifert and Frank D. Vrionis

Object

In this report, the authors describe their experience in the surgical management of spinal meningiomas at two neurosurgical centers. The results of a literature review are also presented.

Methods

Eighty consecutive patients (22 men and 58 women) with spinal meningiomas who had undergone an operation at two specific neurosurgical centers were included in this study. Functional outcomes were evaluated using univariate and multivariate analyses. A review of the literature yielded an additional 651 patients with spinal meningiomas from 9 large studies.

Results

On multivariate analysis, the variable of a poor preoperative neurological state (p < 0.02, odds ratio [OR] 13.6, 95% confidence interval [CI] 2.6–71.4) and invasion of the arachnoid/pia mater (p < 0.03, OR 15.2, 95% CI 2.5–90.4) were independent predictors of a poor outcome, whereas invasion of the arachnoid/pia (p < 0.02, OR 8.9, 95% CI 2.2–35) and duration of symptoms (p < 0.001, OR 1.12/month, 95% CI 1.05–1.2) predicted no improvement (stable or deteriorated condition). The Cox proportional hazards regression analysis showed three significant predictor variables for recurrence: invasion of the arachnoid/pia (p < 0.05; hazard ratio [HR] 1.8, 95% CI 1.2–3.6), Simpson resection grade (p < 0.012, HR 6.8, 95% CI 1.5–3.0), and histological tumor grade (Grade I; p < 0.001, HR 0.001–0.17).

Conclusions

Because of the excellent outcome of surgery for benign spinal meningiomas and the association between duration of symptoms and neurological compromise with a poor functional outcome, early operation is the treatment of choice. In cases of malignant transformation, adjuvant therapies must be considered.

Full access

Erdem Güresir, Patrick Schuss, Hartmut Vatter, Andreas Raabe, Volker Seifert and Jürgen Beck

Object

The aim of this study was to analyze decompressive craniectomy (DC) in the setting of subarachnoid hemorrhage (SAH) with bleeding, infarction, or brain swelling as the underlying pathology in a large cohort of consecutive patients.

Methods

Decompressive craniectomy was performed in 79 of 939 patients with SAH. Patients were stratified according to the indication for DC: 1) primary brain swelling without or 2) with additional intracerebral hematoma, 3) secondary brain swelling without rebleeding or infarcts, and 4) secondary brain swelling with infarcts or 5) with rebleeding. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months (mRS Score 0–3 favorable vs 4–6 unfavorable).

Results

Overall, 61 (77.2%) of 79 patients who did and 292 (34%) of the 860 patients who did not undergo DC had a poor clinical grade on admission (World Federation of Neurosurgical Societies Grade IV–V, p < 0.0001). A favorable outcome was attained in 21 (26.6%) of 79 patients who had undergone DC. In a comparison of favorable outcomes in patients with primary (28.0%) or secondary DC (25.5%), no difference could be found (p = 0.8). Subgroup analysis with respect to the underlying indication for DC (brain swelling vs bleeding vs infarction) revealed no difference in the rate of favorable outcomes. On multivariate analysis, acute hydrocephalus (p = 0.009) and clinical signs of herniation (p = 0.02) were significantly associated with an unfavorable outcome.

Conclusions

Based on the data in this study the authors concluded that primary as well as secondary craniectomy might be warranted, regardless of the underlying etiology (hemorrhage, infarction, or brain swelling) and admission clinical grade of the patient. The time from the onset of intractable intracranial pressure to DC seems to be crucial for a favorable outcome, even when a DC is performed late in the disease course after SAH.

Restricted access

Erdem Güresir, Hartmut Vatter, Patrick Schuss, Ági Oszvald, Andreas Raabe, Volker Seifert and Jürgen Beck

Object

The object of this study was to describe the rapid closure technique in decompressive craniectomy without duraplasty and its use in a large cohort of consecutive patients.

Methods

Between 1999 and 2008, supratentorial rapid closure decompressive craniectomy (RCDC) was performed 341 times in 318 patients at the authors' institution. Cases were stratified as 1) traumatic brain injury, 2) subarachnoid hemorrhage, 3) intracerebral hemorrhage, 4) cerebral infarction, and 5) other. A large bone flap was removed and the dura mater was opened in a stellate fashion. Duraplasty was not performed—that is, the dura was not sutured, and a dural substitute was neither sutured in nor layed on. The dura and exposed brain tissue were covered with hemostyptic material (Surgicel). Surgical time and complications of this procedure including follow-up (> 6 months) were recorded. After 3–6 months cranioplasty was performed, and, again, surgical time and any complications were recorded.

Results

Rapid closure decompressive craniectomy was feasible in all cases. Complications included superficial wound healing disturbance (3.5% of procedures), abscess (2.6%) and CSF fistula (0.6%); the mean surgical time (± SD) was 69 ± 20 minutes. Cranioplasty was performed in 196 cases; the mean interval (± SD) from craniectomy to cranioplasty was 118 ± 40 days. Complications of cranioplasty included epidural hematoma (4.1%), abscess (2.6%), wound healing disturbance (6.1%), and CSF fistula (1%).

Compared with the results reported in the literature for decompressive craniectomy with duraplasty followed by cranioplasty, there were no significant differences in the frequency of complications. However, surgical time for RCDC was significantly shorter (69 ± 20 vs 129 ± 43 minutes, p < 0.0001).

Conclusions

The present analysis of the largest series reported to date reveals that the rapid closure technique is feasible and safe in decompressive craniectomy. The surgical time is significantly shorter without increased complication rates or additional complications. Cranioplasty after a RCDC procedure was also feasible, fast, safe and not impaired by the RCDC technique.

Restricted access

Patrick Schuss, Erdem Güresir, Joachim Berkefeld, Volker Seifert and Hartmut Vatter

Object

Intracranial aneurysms of the anterior circulation might become symptomatic by causing visual deficits. The influence of treatment modality on improvement is still unclear. The objective of this study was to analyze the recovery of visual deficits caused by the mass effect of intracranial aneurysms after surgical clipping or endovascular treatment.

Methods

Between June 1999 and December 2009, 20 patients with unruptured intracranial aneurysms causing visual dysfunction due to compression of the optical nerve were treated at the authors' institution. Visual deficits were recorded at admission and at follow-up. To evaluate a larger number of patients, MEDLINE was searched for published studies involving visual disturbance caused by an aneurysm. A multivariate analysis was performed to find independent predictors for favorable visual outcome.

Results

Nine (75%) of 12 patients treated surgically achieved improvement of visual symptoms, compared with 3 (38%) of 8 patients treated endovascularly. A literature review, including the current series, revealed a total of 165 patients with UIAs causing visual dysfunction. Surgical treatment was associated with a significantly higher rate of visual improvement (p = 0.002) compared with endovascular treatment. According to the multivariate analysis, surgical clipping was the only variable significantly associated with improvement of visual outcome (p = 0.02).

Conclusions

Aneurysm-related visual dysfunction developed from direct mechanical compression may improve after surgical clipping and endovascular coiling. However, based on the present series combined with pooled analysis of data from the literature, the only factor significantly associated with improvement of visual dysfunction was surgical clipping.

Restricted access

Andrew E. Sloan

Restricted access

Ági Oszvald, Erdem Güresir, Matthias Setzer, Hartmut Vatter, Christian Senft, Volker Seifert and Kea Franz

Object

The objective of this study was to analyze whether age influences the outcome of patients with glioblastoma and whether elderly patients with glioblastoma can tolerate the same aggressive treatment as younger patients.

Methods

Data from 361 consecutive patients with newly diagnosed cerebral glioblastoma (2000–2006) who underwent regular follow-up evaluation from initial diagnosis until death were prospectively entered into a database. Patients underwent resection (complete, subtotal, or partial) or biopsy, depending on tumor size, location, and Karnofsky Performance Scale score. Following surgery, all patients underwent adjuvant treatment consisting of radiotherapy, chemotherapy, or combined treatment. Patients older than 65 years of age were defined as elderly (146 total).

Results

Two hundred thirty-four patients underwent tumor resection (complete 26%, subtotal 29%, and partial 45%). One hundred twenty-seven underwent biopsy. Mean patient age was 61 years, and overall survival was 11.6 ± 12.1 months. The overall survival of elderly patients (9.1 ± 11.6 months) was significantly lower than that of younger patients (14.9 ± 16.7 months; p = 0.0001). Stratifying between resection or biopsy, age was a negative prognostic factor in patients undergoing biopsy (4.0 ± 7.1 vs 7.9 ± 8.7 months; p = 0.007), but not in patients undergoing tumor resection (13.0 ± 8.5 vs 13.3 ± 14.5 months; p = 0.86). Survival of elderly patients undergoing complete tumor resection was 17.7 ± 8.1 months.

Conclusions

In this series of patients with glioblastoma, age was a prognostic factor in patients undergoing biopsy, but not in patients undergoing resection. Tumor location and patient clinical status may prohibit extensive resection, but resection should not be withheld from patients only on the basis of age. In elderly patients with glioblastoma, undergoing resection to the extent feasible, followed by adjuvant therapies, is warranted.

Restricted access

Giuseppe Lanzino