Petra Schödel

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.

Surgical Resection of Brain Metastases—Impact on Neurological Outcome

Brain metastases (BM) develop in about 30% of all cancer patients. Surgery plays an important role in confirming neuropathological diagnosis, relieving mass effects and improving the neurological status. To select patients with the highest benefit from surgical resection, prognostic indices (RPA, GPA) have been formulated which are solely focused on survival without considering neurological improvement. In this study we analyzed the impact of surgical resection on the neurological status in addition to overall survival in 206 BM patients. Surgical mortality and morbidity was 0.0% and 10.3% respectively. New neurologic deficits occurred in 6.3% of all patients. The median overall survival was 6.3 months. Poor RPA class and short time interval between diagnosis of cancer and the occurrence of BM were independent factors predictive for poor survival. Improvement of neurological performance was achieved in 56.8% of all patients, with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis. Notably, the neurological benefits were independent from RPA class. In conclusion, surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival. Considering the low mortality and morbidity rates, resection should be considered as a valid option to increase neurological function and quality of life for patients with BM.

An outcome analysis of two different procedures of burr-hole trephine and external ventricular drainage in acute hydrocephalus

Burr-hole trephine and insertion of external ventricular drainage (EVD) is the most common neurosurgical treatment of acute hydrocephalus. Until 2005, we performed this procedure conventionally in the operating room (OR) using a mechanical drill but in 2004 we started to use a manual drill and a skull screw (Bolt Kit System [BKS], Raumedic, Münchberg, Germany) for creating burr-holes in the Intensive Care Unit (ICU) exclusively. This retrospective study compares the outcomes after both surgical procedures of 312 consecutive patients (190 patients, conventional procedure; 122, the BKS system; total female 171, male 141; mean age 59.0 years) who suffered from acute hemorrhage-related hydrocephalus and who had undergone EVD via a frontal burr-hole from January 2004 until April 2010. We reviewed the charts for surgical procedure, number of attempted insertions, radiological signs of misplacement and procedural-related hemorrhage, cerebrospinal fluid (CSF) infection rate and shunt-dependency. The CSF infection rate, the number of attempted insertions and the procedural-related hemorrhage were significantly lower in the BKS group (p=0.034; p=0.018 and 0.015 respectively). Our data indicate that the application of the manually driven drill and the skull screw in the ICU is safe and effective. In addition, there is no need for transfer and transportation of critically ill patients from the ICU to the OR.

Surgical resection of sporadic and hereditary hemangioblastoma: Our 10-year experience and a literature review

Background: Hemangioblastomas (HBLs) are benign neoplasms that contribute to 1-2.5% of intracranial tumors and 7-12% of posterior fossa lesions in adult patients. HBLs either evolve hereditarily in association with von Hippel–Lindau disease (vHL) or, more prevalently, as solitary sporadic tumors. Only few authors have reported on the clinical presentation and the neurological outcome of HBL. Methods: We retrospectively analyzed the clinical, radiological, surgical, and histopathologic records of 24 consecutive patients (11 men, 13 women; mean age 51.3 years) with HBL of the posterior cranial fossa, who had been treated at our center between 2001 and 2012. We reviewed the current literature, and discussed our findings in the context of previous publications on HBL. The study protocol was approved by the local ethics committee (14-101-0070). Results: Mean time to diagnosis was 14 weeks. The extent of resection (EOR) was total in 20 and near total in 4 patients. Four patients required revision within 24 h because of relevant postoperative bleeding. One patient died within 14 days. One patient required permanent shunting. At discharge, 75% of patients [n = 18, modified Rankin scale (mRS) 0-1] showed no or at least resolved symptoms. Mean follow-up was 21 months. Two recurrences were detected during follow-up. Conclusions: In comparison to other benign entities of the posterior fossa, time to diagnosis was significantly shorter for HBL. This finding indicates the rather aggressive biological behavior of these excessively vascularized tumors. In our series, however, the rate of complete resection was high, and morbidity and mortality rates were within the reported range.

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.

A single neurosurgical center's experience of the resolution of cervical radiculopathy after dorsal foraminotomy and ventral discectomy

Monosegmental cervical disc herniation can be removed either by dorsal foraminotomy and sequesterectomy (Frykholms method) or by a ventral approach with extensive removal of the affected disc with subsequent segmental fusion (modified Clowards method). The choice of method largely depends on the surgeons individual preference and experience. We evaluated the neurological outcomes of both surgical methods in a retrospective series of 100 consecutive patients (50 male, 50 female; mean age=47.7 years) who underwent surgery within a 3-year period. Fifty-one patients (30 male, 21 female; mean age=50.1 years) underwent a dorsal foraminotomy and 49 patients (20 male, 29 female; mean age=45.3 years) underwent surgery by the ventral approach with consecutive segmental fusion. We identified demographic data and analysed the postoperative neurological performance (motor and sensory activity) and the resolution of the radiating and local pain during the in-hospital stay. Patients in the Cloward Group recovered significantly better from cervicobrachialgia (p=0.02), neck pain (p=0.01) and sensory deficits (p=0.003). Furthermore, the Cloward Group showed a trend towards better outcomes for paresis. Complete removal of the affected cervical disc via a ventral approach and segmental fusion results in a superior neurological performance in the short-term compared to a dorsal foraminotomy and nerve root decompression by sequestrectomy. However, assessment of the long-term outcome is required and further studies are required to confirm our results.

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.

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.

Excessive release of endogenous neuropeptide Y into cerebrospinal fluid after treatment of spontaneous subarachnoid haemorrhage and its possible impact on self-reported neuropsychological performance – results of a prospective clinical pilot study on good-grade patients

ABSTRACT Objectives: Neuropsychological dysfunction after treatment of spontaneous subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric disorders. We prospectively analysed the treatment-specific differences in the secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage after sSAH and its impact on cognitive processing. Methods: A total of 26 consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Ventricular CSF was drawn daily from day 1–10. CSF NPY levels were determined with competitive enzyme immunoassay. All patients underwent neuropsychological self-report assessment [36-Item Short Form Health Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of sSAH (day 11–35; t1) and at the 6-month follow-up (t2). Results: At t1, increased mean levels of NPY in CSF significantly correlated with impaired performance in most ISR scores (ISR total p = .018, depression p = .035, anxiety p = .008, nutrition disorder p = .047, supplementary items p = .038) and in several psychological SF-36 items (vitality p = .019, general mental health p = .001, mental component summary p = .025). Discussion: To the best of our knowledge, this study is the first to correlate the levels of endogenous NPY in supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive NPY release into CSF may have a short-term influence on the pathogenesis of neuropsychological deficits. The impact of cerebrovascular manipulation on NPY release has to be further elucidated. Abbreviations: ANOVA: analysis of variance; aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF: cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA: digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up; GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10-Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental health; min: minute/s; min-max: minimum – maximum; ml: millilitre; mRS: modified Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng: nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain; PCS: physical component summary; Pfi: physical functioning; pSAH: perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder; QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations because of emotional problems; Rolph: role limitations due to physical health problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item Short Form Health Survey; Social: social functioning; sSAH: spontaneous subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t1: test in the sub-acute phase after the onset of bleeding (between day 11 and 35 after subarachnoid haemorrhage); (test) t2: test in the short-term (chronic phase) after treatment at 6-month follow-up; test t1 - t2: intergroup development from t1 to t2; Vital: vitality; vs: versus.