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Background: The vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY. Methods: 58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t0), (2) periprocedurally (t1), (3) 6 h postprocedurally (t2), (4) 72 h postprocedurally (t3), and (5) at the 6-week follow-up (FU; t4) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA. Results: Except for time point t0, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t3, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t1, t3, and t4, reaching a climax at FU (0.551 ± 0.304 ng/mL). Conclusion: Our study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients.

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Background: The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL. Methods: Twenty-six 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. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11-35) and at the FU (t2). Results: During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2. Conclusion: Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing.

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The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.

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Background and Purpose: The value of gross-total surgical resection remains debatable in patients with brain metastases (BMs) as most patients succumb to systemic disease progression. In this study, we evaluated the impact of the extent of resection of singular/solitary BM on in-brain recurrence (iBR), focusing on local recurrence (LR) and overall survival (OS) in an interdisciplinary adjuvant treatment setting. Patients and Methods: In this monocentric retrospective analysis, we included patients receiving surgery of one BM and subsequent adjuvant treatment. A radiologist and a neurosurgeon determined in consensus the extent of resection based on magnetic resonance imaging. The OS was calculated using Kaplan-Meier estimates; prognostic factors for LR and OS were analysed by Log rank test and Cox proportional hazards. Results: We analyzed 197 patients. Gross-total resection was achieved in 123 (62.4%) patients. All patients were treated with adjuvant radiotherapy, and 130 (66.0%) received systemic treatment. Ninety-six (48.7%) patients showed iBR with an LR rate of 23.4%. LR was not significantly influenced by the extent of resection (p = 0.139) or any other parameter. The median OS after surgery was 18 (95%CI 12.5-23.5) months. In univariate analysis, the extent of resection did not influence OS (p = 0.6759), as opposed to adjuvant systemic treatment (p < 0.0001) and controlled systemic disease (p = 0.039). Systemic treatment and controlled disease status remained independent factors for OS (p < 0.0001 and p = 0.009, respectively). Conclusions: In this study, the extent of resection of BMs neither influenced the LR nor the OS of patients receiving interdisciplinary adjuvant treatment.

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In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

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The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11-35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

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OBJECTIVE: We attempted to analyze whether early presentation with brain metastases (BM) represents a poor prognostic factor in patients with non-small cell lung cancer (NSCLC), which should guide the treatment team towards less intensified therapy. PATIENTS AND METHODS: In a retrospective bi-centric analysis, we identified patients receiving surgical treatment for NSCLC BM. We collected demographic-, tumor-, and treatment-related parameters and analyzed their influence on further survival. RESULTS: We included 377 patients. Development of BM was precocious in 99 (26.3%), synchronous in 152 (40.3%), and metachronous in 126 (33.4%) patients. The groups were comparable in terms of age (p = 0.76) and number of metastases (p = 0.11), and histology (p = 0.1); however, mutational status significantly differed (p = 0.002). The precocious group showed the worst clinical status as assessed by Karnofsky performance score (KPS) upon presentation (p < 0.0001). Resection followed by postoperative radiotherapy was the predominant treatment modality for precocious BM, while in syn- and metachronous BM surgical and radio-surgical treatment was balanced. Overall survival (OS) did not differ between the groups (p = 0.76). A good postoperative clinical status (KPS ≥ 70) and the application of any kind of adjuvant systemic therapy were independent predictive factors for OS. CONCLUSION: Early BM presentation was not associated with worse OS in NSCLC BM patients.

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BACKGROUND: Brain metastases (BM) frequently cause focal neurological deficits leading to a reduced Karnofsky performance score (KPS). Since KPS is routinely used to guide the choice of adjuvant therapy, we hypothesized that improving KPS by surgical resection may improve the chance for adjuvant treatment and ultimately result in better survival. We therefore analyzed the course of a large cohort undergoing resection of symptomatic brain metastases in the context of further treatment and clinical outcome. PATIENTS AND METHODS: In a bi-centric retrospective analysis we retrieved baseline, clinical, and treatment-related parameters of patients operated on BM between 2010 and 2019. Survival was calculated using Kaplan-Meier estimates; prognostic factors for survival were analyzed by Log-rank test and Cox proportional hazards. RESULTS: We included 750 patients with a median age of 61 (19-87) years. The functional status was significantly improved by surgical resection, with a median preoperative (KPS) of 80 (10-100) increasing to 90 (0-100) after surgery (P < .0001). Moreover, surgery improved the RTOG recursive partitioning analysis (RPA) class from III to I/II in 82 patients. Postoperative local radiotherapy and systemic treatment were associated with significantly longer survival (P < .0001 for each). Systemic treatment was provided significantly more frequently in patients with a fair postoperative clinical status (KPS ≥ 70; P < .0001). The postoperative clinical status, postoperative radiotherapy, systemic treatment, controlled systemic disease and < 4 BM were independent predictors for survival. CONCLUSION: The resection of symptomatic BM may restore clinical status, so enhancing the likelihood of receiving adjuvant treatment, and therefore leading to improved overall survival.

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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.

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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.

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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.

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BACKGROUND: Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. OBJECTIVE: Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. PATIENTS AND METHODS: Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t1) and 6 weeks after treatment (t2). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. RESULTS: Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV (P = 0.038) and LD group (P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). CONCLUSIONS: Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients.

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BACKGROUND: Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. METHODS: Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. RESULTS: Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). CONCLUSIONS: Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

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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.

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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.

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INTRODUCTION: Moyamoya disease (MMD) is an extremely rare neurovascular disorder in Caucasian children. To the best of our knowledge, the aggressive variant including hemorrhagic malignant stroke and consecutive global ischemia has not been reported for this population before. CASE REPORT: We present the case of an 11-year-old girl with sudden neurological deterioration due to intracerebral hemorrhage with early irruption into the ventricular system. MMD with extensive neovascularization was diagnosed by means of computed tomography and magnetic resonance imaging. Despite immediate ventricular drainage, intracranial pressure increased above the mean arterial pressure resulting in malignant bi-hemispheric ischemia. The girl died within 53 h after admission to hospital. DISCUSSION: Intracerebral hemorrhage in young patients is often attributed to vascular malformation. This case shows that MMD may constitute a potential diagnosis in the case of sudden neurological deterioration and loss of consciousness, even in previously healthy children.

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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.

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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.

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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.

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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.

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