The endothelial-enriched lncRNA LINC00607 mediates angiogenic function.

Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis.

Vitamin K Antagonist (Phenprocoumon) and Subarachnoid Hemorrhage: A Single-Center, Matched-Pair Analysis.

BACKGROUND: Demographic changes are leading to an aging society with a growing number of patients relying on anticoagulation, and vitamin K antagonists (VKA) are still widely used. As mortality and functional outcomes are worse in case of VKA-associated hemorrhagic stroke, phenprocoumon treatment seems to be a negative prognostic factor in case of subarachnoid hemorrhage (SAH). The purpose of this study was to analyze whether phenprocoumon treatment does worsen the outcome after non-traumatic SAH. METHODS: All patients treated for non-traumatic SAH between January 2007 and December 2016 in our institution were retrospectively analyzed. After exclusion of patients with anticoagulant or antiplatelet treatment other than phenprocoumon, we analyzed 1040 patients. Thirty-three patients (3%) of those were treated with continuous phenprocoumon. In total, 132 out of all 1007 patients without anticoagulant treatment of the remaining patients were matched as control group (ratio = 1:4). RESULTS: Patients with phenprocoumon treatment were significantly older (66.5 years vs. 53.9 years; p < .0001), and admission status was significantly more often poor (66.7% vs. 41.8%, p = .007) compared to all patients without anticoagulant treatment. Further, bleeding pattern and rates of early hydrocephalus did not differ. Matched-pair analysis revealed a significant higher rate of angio-negative SAH in the study group (p = .001). Overall rates of hemorrhagic or thromboembolic complications did not differ (21.4% vs. 18.8%; NS) but were more often fatal, and 30-day mortality rate was significantly higher in the phenprocoumon group than in patients of the matched-pair control group (33% vs. 24%; p < .001). 30% of the phenprocoumon group and 37% of the matched-pair control group reached favorable outcome. However, poor outcome was strong associated with the reason for phenprocoumon treatment. CONCLUSION: Patients with phenprocoumon treatment at the time of SAH are significantly older, admission status is worse, and 30-day mortality rates are significantly higher compared to patients without anticoagulant treatment. However, outcome at 6 months did not differ to the matched-pair control group but seems to be strongly associated with the underlying cardiovascular disease. Treatment of these patients is challenging and should be performed on an interdisciplinary base in each individual case. Careful decision-making regarding discontinuation and bridging of anticoagulation and close observation is mandatory.

The Role of Losartan as a Potential Neuroregenerative Pharmacological Agent after Aneurysmal Subarachnoid Haemorrhage.

BACKGROUND: Cerebral vasospasm (CVS) remains a major cause of delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage (SAH), making it a life-threatening type of stroke with high morbidity and mortality. Endothelin-1 is known as key player mediating a strong vasocontractile effect. Interestingly, losartan restores the impaired vasorelaxative ET(B1) receptor function in a non-competitive direct fashion. With this study, we aimed to investigate a potential losartan-dependent vasodilatory effect vice versa by inhibiting NO release through L-NAME, thus pushing forward concepts to alleviate vasospasm and possibly prevent ischaemia and neurodegeneration. METHODS: Cerebral vasospasm was induced by the use of an established double-injection rat model. Sprague-Dawley rats were culled on Day 3 after the ictus, and the vasospastic basilar artery was harvested for isometric investigations of the vessel tone. Ring segments were preincubated with and without L-NAME and/or losartan. RESULTS: Preincubation with L-NAME induced dose-dependent vasoconstriction via endothelin-1 in the non-SAH cohort, which was dose-dependently reduced by losartan. After SAH and dose-dependent endothelin-1 administration, maximal contraction was achieved in the control group without losartan. Furthermore, this maximal contraction was significantly decreased in the losartan group and was reversed by L-NAME. CONCLUSIONS: After SAH, losartan was shown to positively influence the ET(B1) receptor pathway in a non-competitive direct agonistic and indirect fashion. Losartan alleviated the maximum contraction triggered by endothelin-1. This effect was resolved due to NO inhibition by L-NAME. Considering this spasmolytic effect of losartan besides its already well-known effects (attenuating cerebral inflammation, restoring cerebral autoregulation and reducing epileptogenic activity) and alleviating early brain injury, losartan seems to have potential as a promising pharmacological agent after SAH.

Pain medication at ictus of subarachnoid hemorrhage-the influence of one-time acetylsalicylic acid usage on bleeding pattern, treatment course, and outcome: a matched pair analysis.

Acetylsalicylic acid (ASA) is a well-known and widely used analgesic for acute pain. Patients with acute headache due to subarachnoid hemorrhage (SAH) are inclined to take ASA in this situation. Due to the antithrombotic effects, ASA intake is related to higher bleeding rates in case of hemorrhage or surgical treatment. Between January 2006 and December 2016, 941 patients without continuous antithrombotic or anticoagulant medication were treated due to SAH in our institution. Fourteen of them (1.5%) had taken ASA as a single dose because of headache within 24 h before hospital admission. A matched pair analysis was performed. Admission status was good in 93% of patients with one-time use of ASA (OTA), but only in 59% of all other patients (p < 0.01). Bleeding pattern did not differ, but half of the patients with OTA had no identifiable bleeding source; this rate was significantly lower in the rest of the patients (p < 0.005). Aneurysm treatment and related complications did not differ between both groups. Cerebral vasospasm was more often only mild and rates of cerebral infarctions were lower in the OTA group but not on a significant level. Eighty-six percent of the OTA group and 84% (p = 0.8) of the matched pair control group reached favorable outcome according to mRS 6 months after SAH. Patients with OTA in case of SAH are usually in good clinical condition and bleeding pattern does not differ. In half of the patients with OTA, no bleeding source was detectable. In the case of aneurysm treatment, related complications did not differ and most of the patients reached favorable outcome. In the case of aneurysm treatment procedure, OTA does not influence treatment course and should not influence treatment decisions.

Influence of ABO blood type on the outcome after non-aneurysmal subarachnoid hemorrhage.

BACKGROUND: In patients with non-aneurysmal subarachnoid hemorrhage (NA-SAH), the etiology is unknown and the bleeding source remains unidentified. However, the ABO blood type system has a profound role in patient's hemostasis and thrombosis. To date, the aspect of ABO blood type in incidence, clinical course, and outcome after NA-SAH has not been investigated. METHODS: In this retrospective analysis, 81 patients with non-traumatic and non-aneurysmal subarachnoid hemorrhage treated between 2010 and 2014 at the author's institution were included. WFNS admission status, cerebral vasospasm, delayed infarction, ventriculoperitoneal shunt necessity, the Fisher grade, and the modified Rankin Scale were analyzed for their association with ABO blood type. Four hundred seventy patients with aneurysmal subarachnoid hemorrhage served as a control group. RESULTS: The AB blood type is more frequent in NA-SAH compared to aneurysmal patients and the German population (OR 2.45, p ≤ 0.05). Furthermore, NA-SAH with AB blood type showed a similar sequelae compared to aneurysmal patients in terms of shunt necessity (OR 2.00, p ≥ 0.05), cerebral vasospasm (OR 1.66, p ≥ 0.05), and delayed infarctions (OR 1.07, p ≥ 0.05). CONCLUSION: The clinical course of NA-SAH AB blood type patients shows similar severity as of aneurysmal subarachnoid hemorrhage. Therefore, patients with AB blood type should be under intensified observation.

Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

BACKGROUND: Poor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH. METHODS: Experimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV. RESULTS: After preincubation with LV 10-4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10-4 M, Emax 65%; LV 10-5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10-4, Emax 76%) and D5 (LV 10-4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels. CONCLUSIONS: LV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.

The Effect of Losartan on Neuroinflammation as Well as on Endothelin-1- and Serotonin-Induced Vasoconstriction in a Double-Haemorrhage Rat Model.

Poor patient outcome after aneurysmal subarachnoid haemorrhage (SAH) is due to a multifactorial process. Delayed cerebral vasospasm, ischemic neurological deficits, and infarction are the most feared acute sequelae triggered by enhanced synthesis of serotonin and endothelin-1 (ET-1). During the past decades, multiple drugs have been analysed for protective effects without resounding success. Therefore, the authors wanted to analyse the potential beneficial role of Losartan (LOS). Male Sprague Dawley rats were randomised into either a group receiving two injections of blood into the cisterna magna (SAH group) or a group receiving two injections of isotonic sodium chloride (sham group). The animals were culled on day five and basilar artery ring segments were used for in vitro tension studies. Sarafotoxin S6c caused a dose-dependent vasorelaxation in sham and SAH segments, which was more pronounced in sham segments. LOS, applied in a concentration of 10−3 M, was able to significantly reduce serotonin- (p < 0.01) and ET-1- (p < 0.05, p < 0.01) mediated vasoconstriction in sham segments. These findings, along with the well-known beneficial effects of LOS on restoring the impaired endothelin-B1-receptor function after SAH, as well as on the neuroprotectional and antiepileptogenic aspects, might be implemented in advancing tailored concepts to sufficiently ameliorate patients' functional outcome after SAH.

Impact of COVID-19 Pandemic on Treatment Management and Clinical Outcome of Aneurysmal Subarachnoid Hemorrhage - A Single-Center Experience.

Background: Previous studies reported decreased volumes of acute stroke admissions during the COVID-19 pandemic. We aimed to examine whether aneurysmal subarachnoid hemorrhage (aSAH) volumes demonstrated similar declines in our department. Furthermore, the impact of the pandemic on disease progression should be analyzed. Methods: We conducted a retrospective study in the neurosurgical department of the university hospital Frankfurt including patients with the diagnosis of aSAH during the first year of the COVID pandemic. One year cumulative volume for aSAH hospitalization procedures was compared to the year before (03/2020 - 02/2021 vs. 03/2019 - 02/2020) and the last 5 pre-COVID-pandemic years (2015-2020). All relevant patient characteristics concerning family history, disease history, clinical condition at admission, active/past COVID-infection, treatment management, complications, and outcome were analyzed. Results: Compared to the 84 hospital admissions during the pre-pandemic years, the number of aSAH hospitalizations (n = 56) declined during the pandemic without reaching significance. No significant difference in the analyzed patient characteristics including clinical condition at onset, treatment, complications, and outcome, between 56 patients with aSAH admitted during the COVID pandemic and the treated patients in the last 5 years in the pre-COVID period were found. In our multivariable analysis, we detected young age (p < 0.05; OR 4.2) and no existence of early hydrocephalus (p < 0.05; OR 0.13) as important factors for a favorable outcome (mRS ≤ 0-2) after aSAH during the COVID pandemic. A past COVID-infection was detected in young patients suffering from aSAH (Age <50years, p < 0.05; OR 10.5) with an increased rate of cerebral vasospasm after aSAH onset (p < 0.05; OR 26). Nevertheless, past COVID-infection did not reach significance as a high-risk factor for unfavorable outcomes. Conclusion: There was a relative decrease in the number of patients with aSAH during the COVID-19 pandemic. Despite the extremely different conditions of hospitalization, there was no impairing significant effect on the treatment and outcome of admitted patients with aSAH. A past COVID infection seemed to be an irrelevant limiting factor concerning favorable outcomes.

Statins Improve Clinical Outcome After Non-aneurysmal Subarachnoid Hemorrhage: A Translational Insight From a Systematic Review of Experimental Studies.

The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in non-aneurysmal (na)SAH in accordance with animal research data illustrating the pathophysiology of naSAH. We systematically searched PubMed using PRISMA-guidelines and selected experimental studies assessing the statin-effect on SAH. Detecting the accordance of the applied experimental models with the pathophysiology of naSAH, we analyzed our institutional database of naSAH patients between 1999 and 2018, regarding the effect of statin treatment in these patients and creating a translational concept. Patient characteristics such as statin-treatment (simvastatin 40 mg/d), the occurrence of cerebral vasospasm (CVS), delayed infarction (DI), delayed cerebral ischemia (DCI), and clinical outcome were recorded. In our systematic review of experimental studies, we found 13 studies among 18 titles using blood-injection-animal-models to assess the statin-effect in accordance with the pathophysiology of naSAH. All selected studies differ on study-setting concerning drug-administration, evaluation methods, and neurological tests. Patients from the Back to Bedside project, including 293 naSAH-patients and 51 patients with simvastatin-treatment, were recruited for this analysis. Patients under treatment were affected by a significantly lower risk of CVS (p < 0.01; OR 3.7), DI (p < 0.05; OR 2.6), and DCI (p < 0.05; OR 3). Furthermore, there was a significant association between simvastatin-treatment and favorable-outcome (p < 0.05; OR 3). However, dividing patients with statin-treatment in pre-SAH (n = 31) and post-SAH (n = 20) treatment groups, we only detected a tenuously significant higher chance for a favorable outcome (p < 0.05; OR 0.05) in the small group of 20 patients with statin post-SAH treatment. Using a multivariate-analysis, we detected female gender (55%; p < 0.001; OR 4.9), Hunt&Hess ≤III at admission (p < 0.002; OR 4), no anticoagulant-therapy (p < 0.0001; OR 0.16), and statin-treatment (p < 0.0001; OR 24.2) as the main factors improving the clinical outcome. In conclusion, we detected a significantly lower risk for CVS, DCI, and DI in naSAH patients under statin treatment. Additionally, a significant association between statin treatment and favorable outcome 6 months after naSAH onset could be confirmed. Nevertheless, unified animal experiments should be considered to create the basis for developing new therapeutic schemes.

Short- and midterm outcome of ruptured and unruptured intracerebral wide-necked aneurysms with microsurgical treatment.

To clip or coil has been matter of debates for several years and is the domain of interdisciplinary decision making. However, the microsurgical outcome has still been elusive concerning wide neck aneurysms (WNA). A retrospective single center study was performed with all patients with ruptured WNA (rWNA) and unruptured WNA (uWNA) admitted to author´s institute between 2007-2017. Microsurgical outcome was evaluated according to Raymond-Roy occlusion grade and follow-up angiography was performed to analyze the stability of neck/aneurysm remnants and retreatment poverty. Of 805 aneurysms, 139 were rWNA (17.3%) and 148 uWNA (18.4%). Complete occlusion was achieved in 102 of 139 rWNA (73.4%) and 112 of 148 uWNA (75.6%). Neck remnants were observed in 36 patients with rWNA (25.9%) and 30 patients with uWNA (20.3%), 1 (0.7%) and 6 (4.1%) patients had aneurysmal remnant, respectively. Overall complication rate was 11.5%. At follow-up (939/1504 months), all remnants were stable except for one, which was further conservatively treated with marginal retreatment rate under 1%. Even the risk of de-novo aneurysm was higher than the risk for remnant growth (2.6% vs 0% in rWNA; 8.7% vs 5.3% in uWNA) without significant difference. Microsurgical clipping is effective for complete occlusion of r/uWNA with low complication. Furthermore, the risk of remnant growth is marginal even lower than the risk of de-novo rate low retreatment rate.

Short- and Long-Term Effects of Rehabilitation after Perimesencephalic Subarachnoid Hemorrhage.

In about 25% of patients with spontaneous subarachnoid hemorrhage (SAH), a bleeding source cannot be identified during radiological diagnostics. Generally, the outcome of perimesencephalic or prepontine (PM) SAH is known to be significantly better than after non-PM SAH. Data about long-term follow-up concerning physical and mental health are scarce, so this study is reports on long-term results. We measured the influence of PM SAH on a quality-of-life modified Rankin (mRs) scale after six months. For long-term follow-up, a SF-36 questionnaire was used. Questionnaires were sent out between 18 and 168 months after ictus. In 37 patients, a long-term follow-up was available (up to 14 years after SAH). Data detected with the SF-36 questionnaire are compared to reference applicability to the standard population. In total, 37 patients were included for further analysis and divided in 2 subgroups; 13 patients (35%) received subsequent rehabilitation after clinical stay and 24 (65%) did not. In the short-term outcome, a significant improvement from discharge until follow-up was identified in patients with subsequent rehabilitation, but not in the matched pair group without rehabilitation. When PM SAH was compared to the standard population, a reduction in quality of life was identified in physical items (role limitations because of physical health problems, physical functioning) as well as in psychological items (role limitations because of emotional problems). Subsequent rehabilitation on PM SAH patients probably leads to an increase in independence and better mRs. While better mRs was shown at discharge in patients without subsequent rehabilitation, the mRs of rehabilitants was nearly identical after rehabilitation. Patients with good mRs also reached high levels of health-related quality of life (HRQoL) without rehabilitation. Thus, subsequent rehabilitation needs to be encouraged on an individual basis. Indication criteria for subsequent rehabilitation should be defined in further studies to improve patient treatment and efficiency in health care.

Beware of Nihilism: Favorable Outcome despite Poor Admission Status in Posterior Circulation Aneurysms after Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: As shown in a previous study, aneurysm location seems to influence prognosis in patients with subarachnoid hemorrhage (SAH). We compared patients with ruptured aneurysms of anterior and posterior circulation, undergoing coil embolization, concerning differences in outcome and prognostic factors. METHODS: Patients with SAH were entered into a prospectively collected database. We retrospectively identified 307 patients with aneurysms of the anterior circulation (anterior cerebral artery, carotid bifurcation, and middle cerebral artery) and 244 patients with aneurysms of the posterior circulation (aneurysms of the basilar artery, posterior inferior cerebellar artery, posterior communicating artery and posterior cerebral artery). All patients underwent coil embolization. The outcome was assessed using the modified Rankin Scale (mRS; favorable [mRS 0-2] vs. unfavorable [mRS 3-6]) 6 months after SAH. RESULTS: In interventionally treated aneurysms of the anterior and posterior circulation, statistically significant risk factors for poor outcome were worse admission status and severe cerebral vasospasm. If compared with patients with ruptured aneurysms of the anterior circulation, patients with aneurysms of the posterior circulation had a significantly poorer admission status, and suffered significantly more often from an early hydrocephalus. Nonetheless, there were no differences in outcome or mortality rate between the two patient groups. CONCLUSION: Patients with a ruptured aneurysm of the posterior circulation suffer more often from an early hydrocephalus and have a significantly worse admission status, possibly related to the untreated hydrocephalus. Nonetheless, the outcome and the mortality rate were comparable between ruptured anterior and posterior circulation aneurysms, treated by coil embolisation. Therefore, despite the poorer admission status of patients with ruptured posterior circulation aneurysms, treatment of these patients should be considered.

Multidrug-resistant organisms (MDROs) in patients with subarachnoid hemorrhage (SAH).

Patient care in a neurointensive care unit (neuro-ICU) is challenging. Multidrug-resistant organisms (MDROs) are increasingly common in the routine clinical practice. We evaluated the impact of infection with MDROs on outcomes in patients with subarachnoid hemorrhage (SAH). A single-center retrospective analysis of SAH cases involving patients treated in the neuro-ICU was performed. The outcome was assessed 6 months after SAH using the modified Rankin Scale [mRS, favorable (0-2) and unfavorable (3-6)]. Data were compared by matched-pair analysis. Patient characteristics were well matched in the MDRO (n = 61) and control (n = 61) groups. In this center, one nurse was assigned to a two-bed room. If a MDRO was detected, the patient was isolated, and the nurse was assigned to the patient infected with the MDRO. In the MDRO group, 29 patients (48%) had a favorable outcome, while 25 patients (41%) in the control group had a favorable outcome; the difference was not significant (p > 0.05). Independent prognostic factors for unfavorable outcomes were worse status at admission (OR = 3.1), concomitant intracerebral hematoma (ICH) (OR = 3.7), and delayed cerebral ischemia (DCI) (OR = 6.8). Infection with MRDOs did not have a negative impact on the outcome in SAH patients. Slightly better outcomes were observed in SAH patients infected with MDROs, suggesting the benefit of individual care.

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

BACKGROUND: Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology. OBJECTIVE: To explore the vitamin D system as a potential treatment for CVS. METHODS: 25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during the months with a peak vs nadir of VitD3 values were analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm/outcome data in SAH patients admitted in 2017. An experimental mice SAH model and cell culture model were used to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25-VitD3). Additionally, the mediators acting in the VitD mechanism were researched and detected. RESULTS: Based on the retrospective analysis demonstrating an increased frequency of vasospasm in SAH patients during the low vitamin D period in winter, we started basic research experiments. Active 1,25-VitD3 hormone attenuated CVS, neurological deficit, and inflammation after intrathecal blood injection in mice. Deletion of the vitamin D receptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments of myeloid and endothelial cells with blood confirmed the anti-inflammatory 1,25-VitD3 effect but also revealed an induction of stroma-cell-derived factor 1α (SDF1α), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1α mimicked the protective effect of 1,25-VitD3 against CVS. From bench to bedside, CVS severity was inversely correlated with vitamin D plasma level, prospectively. Patients with more severe CVS exhibited attenuated expression of SDF1α and 1,25-VitD3-responsive genes on circulating myeloid cells. CONCLUSION: 1,25-VitD3 attenuates CVS after SAH by inducing SDF1α. However, VitD administration should be tested as optional treatment to prevent CVS.

Does aneurysm side influence the infarction side and patients´ outcome after subarachnoid hemorrhage?

BACKGROUND: The prognostic factors and outcome of aneurysms appear to be dependent on its locations. Therefore, we compared left- and right- sided aneurysms in patients with aneurysmal subarachnoid hemorrhage (SAH) in terms of differences in outcome and prognostic factors. METHODS: Patients with SAH were entered into a prospectively collected database. A total of 509 patients with aneurysmal subarachnoid hemorrhage were retrospectively selected and stratified in two groups depending on side of ruptured aneurysm (right n = 284 vs. left n = 225). Midline aneurysms of the basilar and anterior communicating arteries were excluded from the analysis. Outcomes were assessed using the modified Rankin Scale (mRS; favorable (mRS 0-2) vs. unfavorable (mRS 3-6)) six months after SAH. RESULTS: We did not identify any differences in outcome depending on left- and right-sided ruptured aneurysms. In both groups, the significant negative predictive factors included clinical admission status (WFNS IV+V), Fisher 3- bleeding pattern in CT, the occurrence of delayed cerebral ischemia (DCI), early hydrocephalus and later shunt-dependence. The side of the ruptured aneurysm does not seem to influence patients´ outcome. Interestingly, the aneurysm side predicts the side of infarction, with a significant influence on patients´ outcome in case of left-sided infarctions. In addition, the in multivariate analysis side of aneurysm was an independent predictor for the side of cerebral infarctions. CONCLUSION: The side of the ruptured aneurysms (right or left) did not influence patients' outcome. However, the aneurysm-side predicts the side of delayed infarctions and outcome appear to be worse in patients with left-sided infarctions.

A benchmark approach to hemorrhage risk management of cavernous malformations.

OBJECTIVE: Despite the low annual risk of hemorrhage associated with a cavernous malformation (CM) (0.6%-1.1% per year), the risk of rehemorrhage rate and severity of neurologic deficits is significantly higher; therefore, we aimed to evaluate the rupture risk of CMs depending on various factors. METHODS: We retrospectively analyzed medical records of all patients with CM admitted to our institution between 1999 and April 2016. Cavernoma volume, location of the lesion, existence of a developmental venous anomaly (DVA), number of cavernomas, and patient characteristics (sex, age, hypertension, and antithrombotic therapy) were assessed. RESULTS: One hundred fifty-four patients with CM were included; 89 (58%) ruptured CMs were identified. In statistical univariable analysis, the existence of a DVA was significantly higher in the ruptured cavernoma group (p < 0.001; odds ratio [OR] 4.6). A multivariable analysis of all included independent risk factors designated young age (<45 years) (p < 0.05; OR 2.2), infratentorial location (p < 0.01; OR 2.9), and existence of a DVA (p < 0.0001; OR 4.7) with significantly higher risk of rupture in our patient cohort. A separate analysis of these anatomical locations, supratentorial vs infratentorial, indicated that the existence of a DVA (p < 0.01; OR 4.16) in ruptured supratentorial cases and CM volume (≥1 cm3) (p < 0.0001; OR 3.5) in ruptured infratentorial cases were significant independent predictors for hemorrhage. CONCLUSIONS: Young age (<45 years), infratentorial location, and the presence of a DVA are associated with a higher hemorrhage risk. CM volume (≥1 cm3) and the existence of a DVA were independently in accordance with the anatomical location high risk factors for CM rupture.

Continuous Acetylsalicylic Acid Treatment Does Not Influence Bleeding Pattern or Outcome of Aneurysmal Subarachnoid Hemorrhage: A Matched-Pair Analysis.

OBJECTIVE: Demographic changes are leading to an aging society with a growing number of patients with cardiovascular diseases, relying on antiplatelet drugs like acetylsalicylic acid (ASA). Although antiplatelet agents are suspected to be protective not only in the cardiologic but in the neurovascular field, the alteration of the coagulating process could have a major impact on the course and outcome after rupture of intracranial aneurysms. METHODS: Between June 1999 and December 2014, 1422 patients were treated for aneurysmal SAH in our institution, 144 (10.1%) with continuous ASA at the time of aneurysm rupture. A matched-pair analysis was performed. RESULTS: The rate of patients with continuous ASA treatment while rupture of the aneurysm is rising significantly (P < 0.01). Those patients were significantly older than patients without ASA (60 vs. 53 years, P < 0.001). ASA-treated patients more often had aneurysmal rebleeding (4.7% vs. 2.3%, P = 0.3) and treatment-related hemorrhagic complications (13.9% vs. 6.2%, P = 0.06). However, rates were not different in microsurgical or endovascular procedures (16.4% vs. 12.2%, P = 0.6). Favorable outcome (Modified Rankin Scale 0-2) was achieved in 49.3% of the ASA group and 52.1% of the control group (P = 0.7). CONCLUSION: Patients with continuous ASA treatment were significantly older than patients without ASA, but there was no difference in admission status or bleeding pattern. Outcome was not different in the matched-pair analysis. There was no statistical difference in treatment related-complication rates of microsurgical and endovascular procedures. Therefore, ASA use should not influence treatment decision of the ruptured aneurysm.

Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional 'H' therapy in vasospasm treatment.

OBJECTIVE: Secondary brain injury leads to high morbidity and mortality rates in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, evidence-based treatment strategies are sparse. Since heparin has various effects on neuroinflammation, microthromboembolism and vasomotor function, our objective was to determine whether heparin can be used as a multitarget prophylactic agent to ameliorate morbidity in SAH. METHODS: Between June 1999 and December 2014, 718 patients received endovascular treatment after rupture of an intracranial aneurysm at our institution; 197 of them were treated with continuous unfractionated heparin in therapeutic dosages after the endovascular procedure. We performed a matched pair analysis to evaluate the effect of heparin on cerebral vasospasm (CVS), cerebral infarction (CI), and outcome. RESULTS: The rate of severe CVS was significantly reduced in the heparin group compared with the control group (14.2% vs 25.4%; p=0.005). CI and multiple ischemic lesions were less often present in patients with heparin treatment. These effects were enhanced if patients were treated with heparin for >48 hours, but the difference was not significant. Favorable outcome at 6-month follow-up was achieved in 69% in the heparin group and in 65% in the control group. CONCLUSIONS: Patients receiving unfractionated continuous heparin after endovascular aneurysm occlusion have a significant reduction in the rate of severe CVS, have CI less often, and tend to have a favorable outcome more often. Our findings support the potential beneficial effects of heparin as a multitarget therapy in patients with SAH, resulting in an additional 'H' therapy in vasospasm treatment.

Cerebral Vasospasm-Dependent and Cerebral Vasospasm-Independent Cerebral Infarctions Predict Outcome After Nonaneurysmal Subarachnoid Hemorrhage: A Single-Center Series with 250 Patients.

OBJECTIVE: The number of patients with nonaneurysmal subarachnoid hemorrhage (naSAH) has increased during the last decade. Data regarding infarctions in naSAH are still limited. The aim of this study was to identify the rate of cerebral vasospasm (CVS)-dependent and CVS-independent infarctions and their influence on clinical outcomes. METHODS: Between 1999 and 2015, 250 patients suffering from naSAH were analyzed retrospectively. A delayed infarction was analyzed whether it was associated with CVS (CVS-dependent infarction) or not (CVS-independent). RESULTS: A total of 36 patients (14%) had cerebral infarctions. CVS was detected in 54 patients (22%), and 15 (6%) of them developed infarctions (CVS-dependent). Infarctions without signs of CVS (CVS-independent) occurred in 21 patients (8%). Overall, 86% of the patients had favorable outcome. Patients without cerebral infarctions had the best outcome (91% favorable outcome, 5% mortality rate). Patients with CVS-independent infarctions (57%) as well as patients with CVS-dependent infarctions (53%) had a favorable outcome less often. The mortality rate was also significantly greater in patients with CVS-independent (19%) and CVS-dependent infarctions (33%). A further independent predictor was anticoagulative therapy, which increased during study period and was associated with nonperimesencephalic blood distribution. CONCLUSIONS: CVS-dependent and independent infarctions occur in naSAH and contribute to unfavorable outcomes. Whereas CVS-independent infarctions occur in any subgroup, CVS-dependent infarctions seem to be associated with blood pattern (Fisher 3). Anticoagulative therapy seems to be not only a predictor for worse outcome but also for nonperimesencephalic SAH. Accordingly, the proportion of perimesencephalic and nonperimesencephalic SAH changed during the study period (from 2.2:1 to 1:1.7).

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.