Jürgen Konczalla

Natural History of Small Unruptured Anterior Circulation Aneurysms A Prospective Cohort Study

Background and Purpose— The natural history of small unruptured intracranial aneurysms of the anterior circulation in the European population is unclear. Therefore, the management of unruptured intracranial aneurysms <7 mm in the anterior circulation is controversial. Methods— Between June 1999 and June 2012, 384 unruptured intracranial aneurysms of the anterior circulation <7 mm in diameter underwent conservative treatment and regular annual follow-up in our institution. Patient- and aneurysm-specific information, as well as information on aneurysm enlargement and rupture, was entered into a prospectively conducted database. Results— The mean follow-up duration was 48.5±37 months. Three aneurysms enlarged during the follow-up period and were treated by surgical clipping. Three aneurysms were ruptured during the follow-up period. The overall annual incidence of subarachnoid hemorrhage was 0.2% during the follow-up. In the multivariate Cox proportional hazard regression analysis, hypertension (P<0.001; hazard ratio, 2.6; 95% confidence interval, 2.1–3.3) and <50 years of age (P=0.04; hazard ratio, 1.3; 95% confidence interval, 1.01–1.7) were significant independent predictors of aneurysm rupture. Conclusions— The present data indicate that the annual incidence of subarachnoid hemorrhage associated with small anterior circulation unruptured intracranial aneurysms is low in this single-institution prospective cohort study. The natural course varies according to arterial hypertension and patient age.

Endovascular and surgical treatment of internal carotid bifurcation aneurysms: comparison of results, outcome, and mid-term follow-up.

BACKGROUND Aneurysms of the internal carotid artery (ICA) bifurcation are rare, and no studies have compared patient outcomes after endovascular vs surgical treatment. OBJECTIVE To report the safety, efficacy, and follow-up outcome of these 2 treatment options for patients with ICA bifurcation aneurysms. METHODS Patient and aneurysm characteristics, treatment results, and follow-up outcomes (at 30 months) were analyzed from patient records and review of imaging findings. RESULTS A total of 58 patients with ICA bifurcation aneurysms were treated. By interdisciplinary consensus, 30 aneurysms were assigned for coiling and 28 for clipping. Patients who underwent surgical clipping were younger and had larger aneurysms. More patients were assigned to coiling if their aneurysms originated only from the ICA bifurcation or projected superiorly. For the combined angiographic endpoint, complete and nearly complete occlusion (Raymond-Roy I + II), similar rates of 96% (coiling) or 100% (clipping) could be achieved. Raymond-Roy I occlusion occurred more often after clipping (79% vs 41% coiling). Follow-up of the endovascular group showed minor recanalization of the aneurysm neck (Raymond-Roy II) in 42%. One patient (4%) showed a major recanalization (Raymond-Roy III) and needed re-treatment. For incidental findings, no bleeding complications or new persistent neurological deficits occurred during follow-up. CONCLUSION Treatment of ICA bifurcation aneurysms after interdisciplinary assignment to clipping or coiling is effective and safe. Despite significantly more minor recanalizations after coiling, the re-treatment rate was very low, and no bleeding was observed during follow-up. Multivariate analysis revealed that origin only from the ICA bifurcation was an independent predictor of aneurysm recanalization after endovascular treatment.

CHARACTERIZATION OF THE ENDOTHELIN-B RECEPTOR EXPRESSION AND VASOMOTOR FUNCTION DURING EXPERIMENTAL CEREBRAL VASOSPASM

OBJECTIVESeveral investigations suggest a key role of endothelin (ET) in the development of cerebral vasospasm (CVS). In the cerebrovasculature, physiologically ET-dependent constriction is mediated by the ET(A) receptor, whereas activation of the endothelial ET(B) receptor results in relaxation. However, existence of a contractile ET(B) receptor was postulated after subarachnoid hemorrhage (SAH), according to gene expression studies. The aim of the present investigation is, therefore, to characterize the function and the expression of the ET(B) receptor in the cerebrovasculature during CVS. METHODSCVS was induced in the rat double-hemorrhage model and assessed by perfusion-weighted magnetic resonance imaging scans. Rats were sacrificed on Days 3 and 5 after SAH, and immunohistochemical staining for ET(B) receptors was performed. Isometric force of basilar artery ring segments with (E+) and without (E−) endothelial function was measured. Concentration effect curves for the ET(B) receptor agonist, sarafotoxin 6c, were constructed by cumulative application in segments under resting tension and after precontraction. RESULTSImmunoreactivity for the ET(B) receptor was observed exclusively in the endothelium and was not significantly altered after SAH. Under resting tension, sarafotoxin 6c did not induce significant contraction in E+ or E− segments. After precontraction, a significant relaxation was induced by sarafotoxin 6c administration in sham-operated rats (mean maximum effect, 103 ± 10%), which decreased time dependently after SAH (Day 3, 68 ± 3%; Day 5, 42 ± 3%). Endothelium-dependent relaxation induced by acetylcholine, however, was not significantly reduced. CONCLUSIONThe present investigation provides evidence for the loss of the ET(B) receptor-mediated vasomotor function after SAH. Thus, antagonism of the ET(B) receptor may be undesirable for the treatment of CVS.

Non-aneurysmal subarachnoid hemorrhage in 173 patients: a prospective study of long-term outcome.

In some patients with subarachnoid hemorrhage (SAH) a bleeding source cannot be identified. Perimesencephalic (PM) SAH is assumed to have an excellent outcome. Our objective was to analyze the long‐term physical and psychological outcome of patients after non‐aneurysmal SAH.

Ventriculostomy-Related Hemorrhage After Treatment of Acutely Ruptured Aneurysms: The Influence of Anticoagulation and Antiplatelet Treatment

BACKGROUND Endovascular techniques have gained importance in recent years in the treatment of acutely ruptured aneurysms. Sometimes artificial anticoagulation or antiplatelet agents are indicated after endovascular aneurysm occlusion to prevent thromboembolic complications. Because many patients require ventriculostomy secondary to hydrocephalus, we analyzed ventriculostomy-related hemorrhage in patients with and without anticoagulant therapy. METHODS Between January 2007 and December 2013, 444 patients with aneurysmal subarachnoid hemorrhage and acute hydrocephalus received treatment requiring ventriculostomy. Treatment-related complications were entered in a prospectively conducted database and analyzed retrospectively. All patients received low-molecular-weight heparin in prophylactic dosage starting 24 hours after aneurysm treatment. Heparin (dosage depending on patient weight) was administered during all endovascular procedures. RESULTS In 117 of 444 patients (26%), additional anticoagulation or antiplatelet agents were administered after treatment of the ruptured aneurysm. Heparin was used in 70 of 117 patients (60%), acetylsalicylic acid was used in 61 (52%), clopidogrel was used in 25 (21%), and tirofiban was used in 23 (20%). In 42 patients (36%), anticoagulants and antiplatelet drugs were combined. Ventriculostomy-related hemorrhage was observed in 55 patients (12%). A ventriculostomy-related hemorrhage occurred in 28 of 117 patients (24%) with anticoagulation therapy and in 27 of 327 patients (8%) without anticoagulation therapy (P < 0.001). The hemorrhage rate in all patients receiving endovascular treatment was significantly higher than in patients receiving microsurgical treatment (P < 0.05). Hemorrhage was more likely to be observed when ventriculostomy was performed before the additional anticoagulation was started, although this was not statistically significant. No surgical intervention was necessary to treat ventriculostomy-related bleeding. CONCLUSIONS Patients receiving endovascular treatment were at higher risk for ventriculostomy-related hemorrhage, especially when anticoagulation was administered after aneurysm occlusion. Although no clinically relevant external ventricular drain-related hemorrhage occurred, ventriculostomy should be performed before anticoagulation whenever possible.

Erythropoietin prevents delayed hemodynamic dysfunction after subarachnoid hemorrhage in a randomized controlled experimental setting

INTRODUCTION Erythropoietin (EPO) was proven as a promising approach for experimental subarachnoid hemorrhage (SAH). Clinical data are, however, inconclusive so far. A detailed characterization of specific EPO effects could facilitate the design of trials. The aim of the present investigation was, therefore, to characterize these effects on prevention of delayed proximal cerebral vasospasm (CVS), impaired microcirculation and cerebral blood flow (CBF) after experimental SAH. METHODS 27 male Sprague-Dawley rats were randomized in 3 groups: Sham, SAH control, and SAH EPO. SAH was induced by injection of 0.2ml autologous blood into the cisterna magna on days 1 and 2. Animals of the SAH EPO group received 5000iU rh EPO α 6h after the 2nd SAH intravenously. Surviving animals were examined on day 5 by MR perfusion weighted imaging (PWI). Cerebral blood flow (CBF) and volume (CBV) were determined by PWI, proximal CVS by basilar artery (BA) diameter, and neuroprotection by hippocampal cell count (CA1-CA4). RESULTS BA diameter was significantly reduced in both SAH groups, but improved significantly after EPO (Sham: 144±3μm, SAH control: 79±6μm, SAH EPO 109±4μm). The rrCBV ratio was 8.78±0.72 Sham, 5.14±1.73 SAH control, and 6.80±0.44 SAH EPO. The improvement by EPO did not reach statistical significance. RrCBF ratio was also significantly reduced in both SAH groups, but was significantly improved by EPO (Sham: 8.78±0.34, SAH control: 4.26±1.05, SAH EPO 5.85±0.46). Surviving neuronal cells were significantly reduced in SAH controls in all areas, but in SAH EPO only in CA1. CONCLUSION The present data suggest that an EPO application in a timely distance to the SAH is sufficient to prevent delayed proximal CVS, but that the doses were insufficient to improve microcirculation or to be directly neuroprotective.

Endothelin Related Pathophysiology in Cerebral Vasospasm: What Happens to the Cerebral Vessels?

The central role of Endothelin (ET) in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is supported by several investigations. These investigations provided, furthermore, that changes of the ET-receptor expression and function in the wall of the cerebral arteries are a considerable factor for the development of CVS. The biological activity of ET-1 is mediated by two receptor subtypes, named ET(A) and ET(B). Under physiological conditions the dominant vasocontractile effect of ET-1 is mediated by ET(A)-receptors on smooth muscle cells (SMC), which is attenuated by an ET(B)-receptor dependent release of nitric oxide (NO) from endothelial cells (EC). In the physiological cerebrovasculature ECs express exclusively ET(B)- and SMCs only ET(A)-receptors. In case of CVS an increased expression of the ET(B)-receptor could be detected in cerebral vessels. However, the loss of the vasodilative and the missing of a vasocontractile ET(B)-receptor mediated effect was demonstrated. Therefore, any ET(B)-receptor mediated vasoactivity seems to be lost in case of CVS and the biological impact of the increased expression remains unclear so far. The ET(A)-receptor expression seems to be not increased during the development of CVS. Therefore, the proven increase of the ET-dependent vasocontractility seems to be rather by the loss of the ET(B)-receptor mediated effect than by an increased ET(A)-receptor activity. In spite of the more significant changes of the ET(B)-receptor expression the pathophysiological effect of ET, namely the vasoconstriction, seems to be exclusively mediated by the ET(A)-receptor. Therefore, tailored approaches for the treatment of CVS remain to be ET(A)-receptor selective antagonists.

Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma

Abstract Background Tumour resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). To achieve maximum resection, 5-aminolevulinic acid (5-ALA) and intraoperative MRI (iMRI) are used as surgical tools. Aiming at complete tumour re-resection, we started combining iMRI with 5-ALA to find out if this leads to better surgical results. Methods We performed tumour resections in seven patients with rGBM, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients. We assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision. Results Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm3. In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months. Conclusions 5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGBM. However, not all rGBMs exhibit fluorescence after 5-ALA administration. We propose the combined use of 5-ALA and iMRI in the surgery of rGBM.

MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH

Background Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH. Methods We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA. Results 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI. Conclusion Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.

Evaluation of the perforators of the anterior communicating artery (AComA) using routine cerebral 3D rotational angiography

Background Damage to perforating branches of the anterior communicating artery (AComA) is a known complication of surgical or interventional treatment procedures for AComA aneurysm leading to neurologic deficits. In spite of the clinical relevance of these AComA branches, they have not been systematically analyzed using imaging techniques and most of our knowledge is based on post-mortem injection studies or neurosurgical reports. We therefore analyzed three-dimensional rotational angiography (3DRA) images of the AComA, and propose a first imaging definition of the microvascular structures surrounding the AComA. Methods Reconstructed 3D data derived from standard-of-care rotational angiography acquisitions (5 s DSA) were retrospectively analyzed. 20 patients undergoing selective cerebral angiography and 3DRA for therapy assessment were included in our study. 3DRA datasets were reconstructed and displayed using the volume rendering technique (VRT). Additionally, multiplanar reformatted CT-like cross-sectional images (MPR) were used to evaluate the number, size, and origin of the perforators of the AComA. Results Perforating branches of the AComA could be demonstrated in all cases with large interindividual variations in vessel visibility. MPRs appeared to be superior to total VRT volumes in the visualization of the perforating branches of the AComA. Conclusions 3DRA can be used to visualize perforating branches of the AComA in vivo. Since damage to these perforators may result in neurologic deficits, visualization of these vessels prior to surgery or endovascular aneurysm treatment could help in the planning of therapeutic interventions. Further refinement of current imaging techniques will be necessary, however, to increase the reliability of small vessel angiography.