Sylvia Bele

Neuropeptide Y - an early biomarker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Abstract Objectives: In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Methods: Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. Results: The NPY levels were significantly higher in the SAH group than in the control group (p < 0·001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p > 0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence of CV with a sensitivity and specificity of 82% and 72%, respectively. High NPY levels, starting on day 4, significantly correlated with poor Glasgow Outcome Score grading at the follow-up (p < 0·05). Discussion: Our data indicate that NPY is involved in the pathogenesis of SAH-related CV and ischemia. Neuropeptide Y represents an early and reliable biomarker for the prediction of CV and consecutive stroke due to aneurysmal SAH.

The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage.

ObjectiveNeuropeptide Y (NPY), a highly potent vasoconstrictive neuropeptide, is widely expressed in the human brain, regulating vessel diameter and cerebral blood flow. Earlier studies focusing on the possible role of NPY in the context of aneurismal subarachnoid hemorrhage (SAH) and vasospasm have produced conflicting results. However, despite extensive research efforts, the pathophysiological mechanisms underlying the SAH-related vasospasm and delayed cerebral ischemia (DCI) have not been clarified. We, therefore, attempted to investigate the role of NPY in SAH-induced vasospasm in a larger, well documented patient population utilizing modern analytical tools. We focused on the release of the potent vasoconstrictor NPY in cerebrospinal fluid (CSF) and blood, and its correlation to vasospasm and stroke in the early clinical stage.MethodsThirty-seven patients with SAH and a control group consisting of 29 patients were included. Eighteen patients developed stroke, 21 patients met the Doppler sonographical criteria for vasospasm. Twenty-nine patients had aneurysms of the anterior circulation and four patients of the posterior circulation. All patients had ventricular drainage inserted and an arterial catheter. Blood and CSF were drawn daily for NPY analysis during a 10-day interval.ResultsThe levels of NPY in CSF and plasma were significantly higher after SAH than in the control group (p = 0.001). The vasospasm group showed NPY levels in CSF which continuously ranged above the NPY levels of the non-vasospasm group (p = 0.001). Patients with stroke caused by vasospasm had significantly higher levels of NPY (p = 0.001).DiscussionNPY is released excessively into blood and CSF following SAH. Patients with cerebral infarction caused by vasospasm had significantly higher levels of NPY. Our results indicate a certain role for NPY in the pathophysiology of vasospasm due to SAH and justify further studies in this area of research.

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p<0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p<0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.

Ventriculostomy for acute hydrocephalus in critically ill patients on the ICU – Outcome analysis of two different procedures

Abstract Introduction. Burr-hole trephine and insertion of an external ventricular drainage (EVD) is a common procedure in neurosurgical practice. In critically ill patients, the transport to the operating room, OR represents a major risk. Thus, the burr-hole trephine and implantation of an EVD is frequently performed on the Intensive Care Unit (ICU). Since 2004, we have applied two different procedures: the conventional method with a mechanical compressed air or an electric drill, and an alternative method with a manual twist drill, including fixation of the EVD in a skull screw (Bolt Kit, Raumedic AG, Germany). This study was designed to evaluate the outcome of both surgical procedures. Patients and method. In this retrospective analysis we included 166 consecutive patients with acute hydrocephalus due to intracranial hemorrhage that had been operated at our neurosurgical ICU in a six years interval. We reviewed the charts for gender and age, kind of surgical procedure, cerebrospinal fluid (CSF)-infections, duration of drainage, attempts of insertions, wound infections, misplacement rate, post-surgical hemorrhages, revisions, comorbidities and shunt-dependency. Results. In 122 patients we applied the Bolt Kit System, in 44 patients the conventional method was performed. We found a significantly lower rate of CSF-infections and significantly fewer attempts of insertions in the Bolt Kit group (p = 0.002 and p = 0.001, respectively). The rate of wound infections, misplacement, revisions, shunt-dependency and the post-surgical hemorrhages did not differ significantly. Discussion. Our data indicate that the manual drill and the skull screw are safe and feasible tools in the treatment of acute hydrocephalus. Presumably, the direct skin contact is causative for the higher rate of CSF-infections when the conventional method is performed. The skull screw guides the EVD into the ventricle without skin contact. The lower number of insertions needed may be due to the fact that the skull screw allows just one trajectory for the insertion of the EVD.

Windowed Multitaper Correlation Analysis of Multimodal Brain Monitoring Parameters

Although multimodal monitoring sets the standard in daily practice of neurocritical care, problem-oriented analysis tools to interpret the huge amount of data are lacking. Recently a mathematical model was presented that simulates the cerebral perfusion and oxygen supply in case of a severe head trauma, predicting the appearance of distinct correlations between arterial blood pressure and intracranial pressure. In this study we present a set of mathematical tools that reliably detect the predicted correlations in data recorded at a neurocritical care unit. The time resolved correlations will be identified by a windowing technique combined with Fourier-based coherence calculations. The phasing of the data is detected by means of Hilbert phase difference within the above mentioned windows. A statistical testing method is introduced that allows tuning the parameters of the windowing method in such a way that a predefined accuracy is reached. With this method the data of fifteen patients were examined in which we found the predicted correlation in each patient. Additionally it could be shown that the occurrence of a distinct correlation parameter, called scp, represents a predictive value of high quality for the patients outcome.

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data.

Parameter Optimization for Selected Correlation Analysis of Intracranial Pathophysiology

Recently we proposed a mathematical tool set, called selected correlation analysis, that reliably detects positive and negative correlations between arterial blood pressure (ABP) and intracranial pressure (ICP). Such correlations are associated with severe impairment of the cerebral autoregulation and intracranial compliance, as predicted by a mathematical model. The time resolved selected correlation analysis is based on a windowing technique combined with Fourier-based coherence calculations and therefore depends on several parameters. For real time application of this method at an ICU it is inevitable to adjust this mathematical tool for high sensitivity and distinct reliability. In this study, we will introduce a method to optimize the parameters of the selected correlation analysis by correlating an index, called selected correlation positive (SCP), with the outcome of the patients represented by the Glasgow Outcome Scale (GOS). For that purpose, the data of twenty-five patients were used to calculate the SCP value for each patient and multitude of feasible parameter sets of the selected correlation analysis. It could be shown that an optimized set of parameters is able to improve the sensitivity of the method by a factor greater than four in comparison to our first analyses.

Kasuistik: Aneurysmatische Subarachnoidalblutung – Komplizierter Verlauf mit inverser Tako-Tsubo-Kardiomyopathie

We report the case of a patient who suffered a serious subarachnoid hemorrhage with a cardialaffection and development of an inverted Tako-Tsubo-cardiomyopathy. To avoid apparent cerebral ischemia due to severe cerebral vasospasm after exhaustion of conservative therapeutic options a temporarily endovascular therapy with continuous intra-arterial application of Nimodipine was necessary. In the overall protracted and complicated course the special challenge were the therapeutic efforts to avoid apparent cerebral ischemia in context to the significant cardial affection.

Treatment of spontaneous subarachnoid hemorrhage and self-reported neuropsychological performance at 6 months – results of a prospective clinical pilot study on good-grade patients

AIM Limited focus has been placed on neuropsychological patient profiles after spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled study in good-grade sSAH patients to evaluate the time course of treatment-specific differences in cognitive processing after sSAH. MATERIAL AND METHODS Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients received endovascular aneurysm occlusion (EV), 6 patients were treated microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent standardized intensive medical care. No patient experienced serious vasospasm-related ischemic or hemorrhagic complications. All patients were subjected to neuropsychological self-report assessment (36-Item Short Form Health Survey and ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of bleeding (t1) and at the 6-month follow-up (FU; t < sub > 2 < /sub > ). RESULTS From t1 to t < sub > 2 < /sub > , MS and EV patients significantly improved in physical functioning (Pfi; p=.001 each) and the physical component summary (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened. At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of test differences showed a significant alleviation in nutrition disorder in MS (vs. EV p=.009). CONCLUSION All sSAH groups reported a significant deterioration in health. Though both MS and EV patients, improved in several physical items over time, our data suggest a better short-term Pfi, less Pain and improved nutrition disorder in surgically treated patients. pSAH patients performed significantly better in various aspects of physical and psychological functioning than patients with aneurysmal SAH.

Differences in Neuropeptide Y Secretion Between Intracerebral Hemorrhage and Aneurysmal Subarachnoid Hemorrhage.

Background: Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Materials and Methods: Seventy-nine patients were prospectively included: SAH patients (n=66) (historic population) and intracerebral hemorrhage patients (n=13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. Results: NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P<0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Conclusions: Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.