Retrospective comparison of long-term functionality and revision rate of two different shunt valves in pediatric and adult patients.

PURPOSE: The most frequent therapy of hydrocephalus is implantation of ventriculoperitoneal shunts for diverting cerebrospinal into the peritoneal cavity. We compared two adjustable valves, proGAV and proGAV 2.0, for complications resulting in revision surgery. METHODS: Four hundred patients undergoing primary shunt implantation between 2014 and 2020 were analyzed for overall revision rate, 1-year revision rate, and revision-free survival observing patient age, sex, etiology of hydrocephalus, implantation site, prior diversion of cerebrospinal fluid, and cause of revision. RESULTS: All data were available of all 400 patients (female/male 208/192). Overall, 99 patients underwent revision surgery after primary implantation. proGAV valve was implanted in 283 patients, and proGAV 2.0 valves were implanted in 117 patients. There was no significant difference between the two shunt valves concerning revision rate (p = 0.8069), 1-year revision rate (p = 0.9077), revision-free survival (p = 0.6921), and overall survival (p = 0.3232). Regarding 1-year revision rate, we observed no significant difference between the two shunt valves in pediatric patients (40.7% vs 27.6%; p = 0.2247). Revision operation had to be performed more frequently in pediatric patients (46.6% vs 24.8%; p = 0.0093) with a significant higher number of total revisions with proGAV than proGAV 2.0 (33 of 59 implanted shunts [55.9%] vs. 8 of 29 implanted shunts [27.6%]; p = 0.0110) most likely due to longer follow-up in the proGAV-group. For this reason, we clearly put emphasis on analyzing results regarding 1-year revision rate. CONCLUSION: According to the target variables we analyzed, aside from lifetime revision rate in pediatric patients, there is no significant difference between the two shunt valves.

Reduced Platelet Activity in Patients with Acute Intracranial Hemorrhage.

BACKGROUND: Acquired platelet dysfunction is a common element of trauma-induced coagulopathy and has been linked to increased mortality. The aim of the study was to describe the prevalence of platelet dysfunction in patients with acute intracranial bleeding. METHODS: Patients diagnosed with acute intracranial bleeding were screened for eligibility. Patients with an urgent need for craniotomy were enrolled in this prospective monocentric study. Platelet function analyses using multiple electrode aggregometry (TRAPtest, ASPItest and ADPtest) and conventional coagulation tests were performed. The area under the aggregation curves of the ASPItest and ADPtest were defined as primary outcome variables. RESULTS: Seventy-seven patients were screened for eligibility, and 49 patients were ultimately enrolled in the study. In 14 patients (29%), clinically relevant platelet dysfunction was observed. Of those, 8 patients were treated with antiaggregatory medication at the time of study inclusion. Six patients (12%) were diagnosed with acute acquired platelet dysfunction. CONCLUSIONS: Decreased platelet function was present in nearly one-third of patients with acute intracranial bleeding. Hemotherapy algorithms for the treatment of coagulopathy in this cohort should incorporate aggregometric measures to enable rapid goal-directed therapy.

Activation of Platelets and Occurrence of Cerebral Vasospasm and Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage in a Prospective Pilot-Trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) often leads to poor outcome. The aim of the study was to assess platelet function in patients after SAH. METHODS: In this prospective observational study in patients suffering from SAH, platelet count and aggregability were assessed by multiple electrode aggregometry (MEA) over 14 days. RESULTS: In 12 of 18 patients, cerebral vasospasms (CVS) were diagnosed; of those, five developed delayed cerebral ischemia (DCI). We observed a significant increase in the platelet count compared to baseline from day 8 onwards (p < 0.037) and, in patients with CVS and DCI, a significant difference in outcome classified by the mRS (p = 0.047). Repeated measures ANOVA determined no differences in platelet aggregability in patients with or without CVS/DCI. CONCLUSIONS: Besides an increase in platelet count, we detected no increase in platelet aggregability. Nevertheless, patients after SAH may have increased platelet aggregability, which is not reflected by MEA.

First clinical experience with the new noninvasive transfontanelle ICP monitoring device in management of children with premature IVH.

We previously introduced a novel noninvasive technique of intracranial pressure (ICP) monitoring in children with open fontanelles. Within this study, we describe the first clinical implementation and results of this new technique in management of children with hydrocephalus caused by intraventricular hemorrhage (IVH). In neonates with posthemorrhagic hydrocephalus (PHH), an Ommaya reservoir was implanted for initial treatment of hydrocephalus. The ICP obtained noninvasively with our new device was measured before and after CSF removal and correlated to cranial ultra-sonographies. Six children with a mean age of 27.3 weeks and mean weight of 1082.3 g suffering from PHH were included in this study. We performed an overall of 30 aspirations due to ventricular enlargement. Before CSF removal, the mean ICP was 15.3 mmHg and after removal of CSF the mean ICP measured noninvasively decreased to 3.4 mmHg, p = 0.0001. The anterior horn width (AHW), which reflects early expansion of the ventricles, was before and after CSF removal 15.1 mm and 5.5 mm, respectively, p < 0.0006. There was a strong correlation between noninvasively measured ICP values and sonographically obtained AHW, r = 0.81. Ultimately, all children underwent ventriculoperitoneal shunt procedures. This is the first study providing proof for a noninvasively ICP-based approach for management of posthemorrhagic hydrocephalus in newborn children.

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.

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature.

OBJECTIVE: Novel treatments are needed to control treatment-resistant status epilepticus (SE). We present a summary of clinical cases where oral topiramate (TPM) was used in refractory SE (RSE) and superrefractory SE (SRSE). METHODS: A review of medical records was carried out to detect TPM administration in SE patients treated in Frankfurt and Marburg between 2011 and 2016. The primary outcome question concerned SE resolution after TPM initiation. RESULTS: In total, TPM was used in 106 of 854 patients having a mean age of 67.4 ± 18.1 years, 61 of whom were female (57.5%). The median latency from SE onset to TPM initiation was 8.5 days. Patients with SE had previously failed a median of five other antiepileptic drugs. The median initial TPM dose was 100 mg/d, which was uptitrated to a median maintenance dose of 400 mg/d. Treatment with TPM was continued for a median time of 12 days. TPM was the last drug provided to 42 of 106 (39.6%) patients, with a resultant response attributed to TPM observed in 29 of 106 (27.4%) patients. A response was attributed to TPM in 21 (31.8%) of 66 RSE cases and eight (20%) of 40 SRSE cases. Treatment-emergent adverse events were attributed to TPM usage in two patients, one each with pancreatitis and hyperchloremic acidosis, and in 38 patients (35.8%), hyperammonemia was seen. Thirty-four of these patients received a combination of TPM and valproate and/or phenobarbital. The intrahospital mortality rate was 22.6% (n = 24). SIGNIFICANCE: The rate of SE cessation attributed to TPM treatment (27.4%) represents a relevant response given the late treatment position of TPM and the treatment latency of more than 8 days. Based on these results and in line with the findings of other case series, TPM can be considered an alternative option for treating RSE and SRSE.

Cerebral Vasospasm Due to Arteriovenous Malformation-Associated Hemorrhage: Impact of Bleeding Source and Pattern.

OBJECTIVE: Cerebral vasospasm (CVS) after a ruptured arteriovenous malformation (AVM) is rarely reported. This study is aimed at evaluating the predictive variables in AVM hemorrhage for CVS. METHODS: A total of 160 patients with ruptured AVMs were admitted to our neurosurgical department from 2002 to 2018. The frequency of cerebral vasospasm after AVM hemorrhage and the impact of AVM-associated aneurysms were evaluated. We compared different bleeding patterns, such as intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or a combination of both (ICH + SAH) and evaluated predictive variables for outcome in last follow-up. RESULTS: A total of 62 (39%) patients had AAA, mostly located prenidal (75.8%). AVMs with ruptured aneurysms often resulted in ICH with SAH component (p < 0.001). Eighty-two patients (51%) presented a SAH component, and CVS occurred in 6 patients (7.3%), mostly due to a ruptured infratentorial AVM (p < 0.03). Infratentorial location and the amount of SAH component (p < 0.001) predicted the incidence of CVS significantly. Cerebral infarction was significantly associated with CVS (p < 0.02). CONCLUSION: SAH component and infratentorial location of ruptured AVMs may harbor a higher risk for CVS. Follow-up with angiographic imaging should be considered in patients with infratentorial AVM hemorrhage and delayed neurologic deterioration to rule out CVS.

Electrode placement accuracy in robot-assisted epilepsy surgery: A comparison of different referencing techniques including frame-based CT versus facial laser scan based on CT or MRI.

BACKGROUND: Precise robotic or stereotactic implantation of stereoelectroencephalography (sEEG) electrodes relies on the exact referencing of the planning images in order to match the patient's anatomy to the stereotactic device or robot. We compared the accuracy of sEEG electrode implantation with stereotactic frame versus laser scanning of the face based on computed tomography (CT) or magnetic resonance imaging (MRI) datasets for referencing. METHODS: The accuracy was determined by calculating the Euclidian distance between the planned trajectory and the postoperative position of the sEEG electrode, defining the entry point error (EPE) and the target point error (TPE). The sEEG electrodes (n = 171) were implanted with the robotic surgery assistant (ROSA) in 19 patients. Preoperative trajectory planning was performed on three-dimensional (3D) MRI datasets. Referencing was accomplished either by performing (A) 1.25-mm slice CT with the patient's head fixed in a Leksell stereotactic frame (CT-frame, n = 49), fused with a 3D-T1-weighted, contrast enhanced- and T2-weighted 1.5 Tesla (T) MRI; (B) 1.25 mm CT (CT-laser, n = 60), fused with 3D-3.0-T MRI; (C) 3.0-T MRI T1-based laser scan (3.0-T MRI-laser, n = 56) or (D) in one single patient, because of a pacemaker, 3D-1.5-T MRI T1-based laser scan (1.5-T MRI-laser, n = 6). RESULTS: In (A) CT-frame referencing, the mean EPE amounted to 0.86 mm and the mean TPE amounted to 2.28 mm (n = 49). In (B) CT-laser referencing, the EPE amounted to 1.85 mm and the TPE to 2.41 mm (n = 60). In (C) 3.0-T MRI-laser referencing, the mean EPE amounted to 3.02 mm and the mean TPE to 3.51 mm (n = 56). In (D) 1.5-T MRI, surprisingly the mean EPE amounted only to 0.97 mm and the TPE to 1.71 mm (n = 6). In 3 cases using CT-laser and 1 case using 3.0 T MRI-laser for referencing, small asymptomatic intracerebral hemorrhages were detected. No further complications were observed. CONCLUSION: Robot-guided sEEG electrode implantation using CT-frame referencing and CT-laser-based referencing is most accurate and can serve for high precision placement of electrodes. In contrast, 3.0-T MRI-laser-based referencing is less accurate, but saves radiation. Most trajectories can be reached if alternative routes over less vascularized brain areas are used. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Infective endocarditis in patients with pyogenic spondylodiscitis: implications for diagnosis and therapy.

OBJECTIVEThe incidence of patients with pyogenic spinal infection is increasing. In addition to treatment of the spinal infection, early diagnosis of and therapy for coexisting infections, especially infective endocarditis (IE), is an important issue. The aim of this study was to evaluate the proportion of coexisting IE and the value of routine transesophageal echocardiography (TEE) in the management of these patients.METHODSThe medical history, laboratory data, radiographic findings, treatment modalities, and results of TEE of patients admitted between 2007 and 2017 were analyzed.RESULTSDuring the abovementioned period, 110 of 255 total patients underwent TEE for detection of IE. The detection rate of IE between those patients undergoing and not undergoing TEE was 33% and 3%, respectively (p < 0.0001). Thirty-six percent of patients with IE needed cardiac surgical intervention because of severe valve destruction. Chronic renal failure, heart failure, septic condition at admission, and preexisting heart condition were significantly associated with coexisting IE. The mortality rate in patients with IE was significantly higher than in patients without IE (22% vs 3%, p = 0.002).CONCLUSIONSTEE should be performed routinely in all patients with spondylodiscitis.

Complication rate of intraarterial treatment of severe cerebral vasospasm after subarachnoid hemorrhage with nimodipine and percutaneous transluminal balloon angioplasty: Worth the risk?

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (SAH). Arterial cerebral vasospasm (CVS) is discussed as the main pathomechanism for DCI. Due to positive effects of per os nimodipine, intraarterial nimodipine application is used in patients with DCI. Further, percutaneous transluminal balloon angioplasty (PTA) is applied in focal high-grade spasm of intracranial arteries. However, clinical benefits of those techniques are unconfirmed in randomized trials so far, and complications might occur. We analyzed the occurrence of new infarcts in patients with severe CVS treated intra-arterially to assess benefits and risks of those techniques in a large single-center collective. MATERIALS AND METHODS: All imaging and clinical data of 88 patients with CVS after SAH and 188 procedures of intraarterial nimodipine infusion and additional PTA in selected cases (18 patients, 20 PTA procedures) treated at our institution were reviewed. In the event of new infarcts after endovascular treatment of CVS, infarct patterns were analyzed to determine the most probable etiology. RESULTS: Fifty-three percent of patients developed new cerebral infarction after intraarterial nimodipine and additional PTA in selected cases. Hereunder 47% were caused by persisting CVS. In 6% of patients, 3% of procedures respectively, new infarcts occurred due to complications of the intraarterial treatment including thromboembolism and arterial dissection. Of those, 3% of patients, 2% of procedures respectively, were assigned to thrombembolic complications of digital substraction angiography for intraarterial nimodipine. 17% of all patients treated with PTA (3/18=17%) showed infarction as a complication of PTA (15% of all PTA procedures). In 1% of patients, etiology of new infarction remained unclear. CONCLUSION: Ischemic complications occur in about 6% of patients treated intraarterially for CVS, 3% of procedures respectively. Further, to date a benefit for patients treated with this therapy could not be proven. Therefore, intraarterial treatment of CVS should be performed only in carefully selected cases.

[Point-of-care Coagulation Testing in Neurosurgery]. / Point-of-Care-Gerinnungsdiagnostik in der Neurochirurgie.

Disorders of the coagulation system can seriously impact the clinical course and outcome of neurosurgical patients. Due to the anatomical location of the central nervous system within the closed skull, bleeding complications can lead to devastating consequences such as an increase in intracranial pressure or enlargement of intracranial hematoma. Point-of-care (POC) devices for the testing of haemostatic parameters have been implemented in various fields of medicine. Major advantages of these devices are that results are available quickly and that analysis can be performed at the bedside, directly affecting patient management. POC devices allow identification of increased bleeding tendencies and therefore may enable an assessment of hemorrhagic risks in neurosurgical patients. Although data regarding the use of POC testing in neurosurgical patients are limited, they suggest that coagulation testing and hemostatic therapy using POC devices might have beneficial effects in this patient population. This article provides an overview of the application of point-of-care coagulation testing in clinical practice in neurosurgical patients.

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

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

Frequency, risk of hemorrhage and treatment considerations for cerebral arteriovenous malformations with associated aneurysms.

BACKGROUND: Data on arteriovenous malformations (AVMs) of the brain with AVM-associated aneurysms (AAA) are scarce. This study addresses the incidence, rate of hemorrhage, treatment strategies and stability during follow-up in a neurovascular center. METHODS: We retrospectively reviewed patients harboring an AVM with at least one AAA treated at our neurovascular center between 2002 and 2013. RESULTS: Of 216 patients, 59 (27.3%) had at least one AAA (n = 92 aneurysms total). Compared to patients without AAA, hemorrhagic presentation occurred more frequently (61.0% versus 43.9%, p = 0.025), and the rate of infratentorial AVMs was higher (37.3% versus 16.6%, p = 0.001). The aneurysm was the origin of the bleeding in most cases, most often categorized as a feeding artery aneurysm. Overall, the first and recurrent hemorrhage were associated with a high mortality and morbidity (15.3% and 39%, respectively). Aneurysms were treated by coiling (n = 21), surgery (n = 18), or embolizaton with liquid embolization agents (n = 11). All aneurysms treated by embolization and surgery remained occluded during follow-up (mean follow-up 39.0 ± 45.0 months). However, in incomplete AVM obliteration, significant recurrence of the treated aneurysm was noted after endovascular coiling (37.5%), which may be related to the persistence of pathological blood flow. CONCLUSION: In our series, AAA was a significant risk factor for hemorrhage and was associated with a poor outcome. It seems worthwhile to consider whether the aneurysm itself is a risk factor or only an epiphenomenon of severely altered hemodynamics induced by these special AVMs and therefore only the most common site of rupture. As the complication rate was low for aneurysm occlusion, we recommend treating these aneurysms whenever possible. Furthermore, obliteration of the AVM should be strived for as this subtype may be associated with an increased risk of hemorrhage.

Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review.

OBJECTIVE: Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population. METHODS: This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017. RESULTS: The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1-57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1-46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001). CONCLUSIONS: SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors.

Natural history of small unruptured anterior circulation aneurysms: a prospective cohort study.

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

Detecting Sepsis in Patients with Severe Subarachnoid Hemorrhage during Critical Care.

Introduction: Sepsis and septic shock continue to have a very high mortality rate. Therefore, the last consensus-based sepsis guideline introduced the sepsis related organ failure assessment (SOFA) score to ensure a rapid diagnosis and treatment of sepsis. In neurosurgical patients, especially those patients with subarachnoid hemorrhage (SAH), there are considerable difficulties in interpreting the SOFA score. Therefore, our study was designed to evaluate the applicability of the SOFA for critical care patients with subarachnoid hemorrhage. Methods: Our retrospective monocentric study was registered (NCT05246969) and approved by the local ethics committee (# 211/18). Patients admitted to the Department of Neurosurgery at the Frankfurt University Hospital were enrolled during the study period. Results: We included 57 patients with 85 sepsis episodes of which 141 patients had SOFA score-positive results and 243 SIRS positive detections. We failed to detect a correlation between the clinical diagnosis of sepsis and positive SOFA or SIRS scores. Moreover, a significant proportion of sepsis that was incorrectly detected via the SOFA score could be attributed to cerebral vasospasms (p < 0.01) or a decrease in Glasgow Coma Scale (p < 0.01). Similarly, a positive SIRS score was often not attributed to a septic episode (49.0%). Discussion: Regardless of the fact that SAH is a rare disease, the relevance of sepsis detection should be given special attention in light of the long duration of therapy and sepsis prevalence. Among the six modules represented by the SOFA score, two highly modules were practically eliminated. However, to enable early diagnosis of sepsis, the investigator's clinical views and synopsis of various scores and laboratory parameters should be highlighted. Conclusions: In special patient populations, such as in critically ill SAH patients, the SOFA score can be limited regarding its applicability. In particular, it is very important to differentiate between CVS and sepsis.

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.

Experimental Induction of Intracranial Aneurysms in Rats: A New Model Utilizing a Genetic Modification within the EDNRA Gene.

The rupture of an intracranial aneurysm (IA) leads to life-threatening subarachnoid hemorrhage. Aside from well-established risk factors, recently published genome-wide association studies of IA revealed the strong association of a common variant near the endothelin receptor type A (EDNRA) gene with IA risk. However, the role of EDNRA in the pathogenesis of IA remains unclear. The aim of this study was to investigate the influence of a genetic modification within the EDNRA gene on IA pathogenesis in a novel in vivo model. Adult wild-type Sprague-Dawley rats (WT rats) and genetically modified rats (EDNRA rats) were used for the induction of IA using arterial hypertension (HT). Animals were stratified into four groups: WT rats without (WT_CTL) and with induction of HT (WT + HT), as well as EDNRA rats without (EDNRA_CTL) and with induction of HT (EDNRA + HT). Blood pressure (BP) was observed for 12 weeks. After the observation period, cerebral arteries were analyzed for morphological (i.e., aneurysmal) changes as well as histological and functional changes by immunofluorescence and functional investigation. In the groups of rats with induction of HT, BP was higher in EDNRA + HT compared with that in WT + HT. No IAs were observed in WT_CTL and EDNRA_CTL but were found in WT + HT and EDNRA + HT. There was no histological difference in the immunofluorescence of EDNRA between all groups. Contractility and potency of endothelin-1 differed between the groups in functional investigation. In summary, we created a new model that is suitable for further studies for better understanding of the role of EDNRA in IA pathogenesis.

Invasive Diagnostic and Therapeutic Management of Cerebral VasoSpasm after Aneurysmal Subarachnoid Hemorrhage (IMCVS)-A Phase 2 Randomized Controlled Trial.

Cerebral vasospasm (CVS) is associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). The most frequently used form of rescue therapy for CVS is invasive endovascular therapy. Due to a lack of prospective data, we performed a prospective randomized multicenter trial (NCT01400360). A total of 34 patients in three centers were randomized to invasive endovascular treatment or conservative therapy at diagnosis of relevant CVS onset. Imaging data was assessed by a neuroradiologist blinded for treatment allocation. Primary outcome measure was development of DCI. Secondary endpoints included clinical outcome at 6 months after SAH. A total of 18 of the 34 patients were treated conservatively, and 16 patients were treated with invasive endovascular treatment for CVS. There was no statistical difference in the rate of cerebral infarctions either at initial or at the follow-up MRI between the groups. However, the outcome at 6 months was better in patients treated conservatively (mRs 2 ± 1.5 vs. 4 ± 1.8, p = 0.005). Invasive endovascular treatment for CVS does not lead to a lower rate of DCI but might lead to poorer outcomes compared to induced hypertension. The potential benefits of endovascular treatment for CVS need to be addressed in further studies, searching for a subgroup of patients who may benefit.