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Johannes Platz, Erdem Güresir, Marlies Wagner, Volker Seifert and Juergen Konczalla

OBJECTIVE

Delayed cerebral ischemia (DCI) has a major impact on the outcome of patients suffering from aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to assess the influence of an additional intracerebral hematoma (ICH) on the occurrence of DCI.

METHODS

The authors conducted a single-center retrospective analysis of cases of SAH involving patients treated between 2006 and 2011. Patients who died or were transferred to another institution within 10 days after SAH without the occurrence of DCI were excluded from the analysis.

RESULTS

Additional ICH was present in 123 (24.4%) of 504 included patients (66.7% female). ICH was classified as frontal in 72 patients, temporal in 24, and perisylvian in 27. DCI occurred in 183 patients (36.3%). A total of 59 (32.2%) of these 183 patients presented with additional ICH, compared with 64 (19.9%) of the 321 without DCI (p = 0.002). In addition, DCI was detected significantly more frequently in patients with higher World Federation of Neurosurgical Societies (WFNS) grades.

The authors compared the original and modified Fisher Scales with respect to the occurrence of DCI. The modified Fisher Scale (mFS) was superior to the original Fisher Scale (oFS) in predicting DCI. Furthermore, they suggest a new classification based on the mFS, which demonstrates the impact of additional ICH on the occurrence of DCI.

After the different scales were corrected for age, sex, WFNS score, and aneurysm site, the oFS no longer was predictive for the occurrence of DCI, while the new scale demonstrated a superior capacity for prediction as compared with the mFS.

CONCLUSIONS

Additional ICH was associated with an increased risk of DCI in this study. Furthermore, adding the presence or absence of ICH to the mFS improved the identification of patients at the highest risk for the development of DCI. Thus, a simple adjustment of the mFS might help to identify patients at high risk for DCI.

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Juergen Konczalla, Sepide Kashefiolasl, Nina Brawanski, Christian Senft, Volker Seifert and Johannes Platz

OBJECT

Subarachnoid hemorrhage (SAH) is usually caused by a ruptured intracranial aneurysm, but in some patients no source of hemorrhage can be detected. More recent data showed increasing numbers of cases of spontaneous nonaneurysmal SAH (NASAH). The aim of this study was to analyze factors, especially the use of antithrombotic medications such as systemic anticoagulation or antiplatelet agents (aCPs), influencing the increasing numbers of cases of NASAH and the clinical outcome.

METHODS

Between 1999 and 2013, 214 patients who were admitted to the authors’ institution suffered from NASAH, 14% of all patients with SAH. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Risk factors were identified based on the outcome.

RESULTS

The number of patients with NASAH increased significantly in the last 15 years of the study period. There was a statistically significant increase in the rate of nonperimesencephalic (NPM)-SAH occurrence and aCP use, while the proportion of elderly patients remained stable. Favorable outcome (mRS 0–2) was achieved in 85% of cases, but patients treated with aCPs had a significantly higher risk for an unfavorable outcome. Further analysis showed that elderly patients, and especially the subgroup with a Fisher Grade 3 bleeding pattern, had a high risk for an unfavorable outcome, whereas the subgroup of NPM-SAH without a Fisher Grade 3 bleeding pattern had a favorable outcome, similar to perimesencephalic (PM)-SAH.

CONCLUSIONS

Over the years, a significant increase in the number of patients with NASAH has been observed. Also, the rate of aCP use has increased significantly. Risk factors for an unfavorable outcome were age > 65 years, Fisher Grade 3 bleeding pattern, and aCP use. Both “PM-SAH” and “NPM-SAH without a Fisher Grade 3 bleeding pattern” had excellent outcomes. Patients with NASAH and a Fisher Grade 3 bleeding pattern had a significantly higher risk for an unfavorable outcome and death. Therefore, for further investigations, NPM-SAH should be stratified into patients with or without a Fisher Grade 3 bleeding pattern. Also, cases of spontaneous SAH should be stratified into NASAH and aneurysmal SAH.

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Juergen Konczalla, Volker Seifert, Juergen Beck, Erdem Güresir, Hartmut Vatter, Andreas Raabe and Gerhard Marquardt

OBJECTIVE

Outcome analysis of comatose patients (Hunt and Hess Grade V) after subarachnoid hemorrhage (SAH) is still lacking. The aims of this study were to analyze the outcome of Hunt and Hess Grade V SAH and to compare outcomes in the current period with those of the pre–International Subarachnoid Aneurysm Trial (ISAT) era as well as with published data from trials of decompressive craniectomy (DC) for middle cerebral artery (MCA) infarction.

METHODS

The authors analyzed cases of Hunt and Hess Grade V SAH from 1980–1995 (referred to in this study as the earlier period) and 2005–2014 (current period) and compared the results for the 2 periods. The outcomes of 257 cases were analyzed and stratified on the basis of modified Rankin Scale (mRS) scores obtained 6 months after SAH. Outcomes were dichotomized as favorable (mRS score of 0–2) or unfavorable (mRS score of 3–6). Data and number needed to treat (NNT) were also compared with the results of decompressive craniectomy (DC) trials for middle cerebral artery (MCA) infarctions.

RESULTS

Early aneurysm treatment within 72 hours occurred significantly more often in the current period (in 67% of cases vs 22% in earlier period). In the earlier period, patients had a significantly higher 30-day mortality rate (83% vs 39% in the current period) and 6-month mortality rate (94% vs 49%), and no patient (0%) had a favorable outcome, compared with 23% overall in the current period (p < 0.01, OR 32), or 29.5% of patients whose aneurysms were treated (p < 0.01, OR 219). Cerebral infarctions occurred in up to 65% of the treated patients in the current period.

Comparison with data from DC MCA trials showed that the NNTs were significantly lower in the current period with 2 for survival and 3 for mRS score of 0–3 (vs 3 and 7, respectively, for the DC MCA trials).

CONCLUSIONS

Early and aggressive treatment resulted in a significant improvement in survival rate (NNT = 2) and favorable outcome (NNT = 3 for mRS score of 0–3) for comatose patients with Hunt and Hess Grade V SAH compared with the earlier period. Independent predictors for favorable outcome were younger age and bilateral intact corneal reflexes. Despite a high rate of cerebral infarction (65%) in the current period, 29.5% of the patients who received treatment for their aneurysms during the current era (2005–2014) had a favorable outcome. However, careful individual decision making is essential in these cases.

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Atul Verma, Subodh Verma, Mohammed Al-Omran and James T. Rutka

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Juergen Konczalla, Johannes Platz, Stephan Fichtlscherer, Haitham Mutlak, Ulrich Strouhal and Volker Seifert

OBJECTIVE

To date, treatment of complex unruptured intracranial aneurysms (UIAs) remains challenging. Therefore, advanced techniques are required to achieve an optimal result in treating these patients safely. In this study, the safety and efficacy of rapid ventricular pacing (RVP) to facilitate microsurgical clip reconstruction was investigated prospectively in a joined neurosurgery, anesthesiology, and cardiology study.

METHODS

Patients with complex UIAs were prospectively enrolled. Both the safety and efficacy of RVP were evaluated by recording cardiovascular events and outcomes of patients as well as the amount of aneurysm occlusion after the surgical clip reconstruction procedure. A questionnaire was used to evaluate aneurysm preparation and clip application under RVP.

RESULTS

Twenty patients (mean age 51.6 years, range 28–66 years) were included in this study. Electrode positioning was easy in 19 (95%) of 20 patients, and removal of electrodes was easily accomplished in all patients (100%). No complications associated with the placement of the pacing electrodes occurred, such as cardiac perforation or cardiac tamponade. RVP was applied in 16 patients. The mean aneurysm size was 11.1 ± 5.5 mm (range 6–30 mm). RVP proved to be a very helpful tool in aneurysm preparation and clip application in 15 (94%) of 16 patients. RVP was used for a mean duration of 60 ± 25 seconds, a mean heart rate of 173 ± 23 bpm (range 150–210 bpm), and a reduction of mean arterial pressure to 35–55 mm Hg. RVP leads to softening of the aneurysm sac facilitating its mobilization, clip application, and closure of the clip blades. In 2 patients, cardiac events were documented that resolved without permanent sequelae in both. In every patient with successful RVP (n = 14) a total or near-total aneurysm occlusion was documented. In the 1 patient in whom the second RVP failed due to pacemaker electrode dislocation, additional temporary clipping was required to secure the aneurysm, but was not as sufficient as RVP. This led to an incomplete clipping of the aneurysm and finally a remnant on postoperative digital subtraction angiography. A pacemaker lead dislocation occurred in 3 (19%) of 16 patients, but intraoperative repositioning requires less than 20 seconds. Outcome was favorable in all patients according to the modified Rankin Scale.

CONCLUSIONS

To the best of the authors’ knowledge this is the first prospective interdisciplinary study of RVP use in patients with UIAs. RVP is an elegant technique that facilitates clip reconstruction in complex UIAs. The safety of the procedure is good. However, because this procedure requires extensive preoperative cardiological workup of the patient and an experienced neurosurgery and neuroanesthesiology team with much cerebrovascular expertise, actually it remains reserved for selected elective cases and highly specialized centers.

Clinical trial registration no.: NCT02766972 (clinicaltrials.gov)

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Sae-Yeon Won, Daniel Dubinski, Markus Bruder, Adriano Cattani, Volker Seifert and Juergen Konczalla

OBJECTIVE

Isolated acute subdural hematoma (aSDH) is increasing in older populations and so is the use of oral anticoagulant therapy (OAT). The dramatic increase of OAT—with direct oral anticoagulants (DOACs) as well as with conventional anticoagulants—is leading to changes in the care of patients who present with aSDH while receiving OAT. The purpose of this study was to determine the management and outcome of patients being treated with OAT at the time of aSDH presentation.

METHODS

In this single-center, retrospective study, the authors analyzed 116 consecutive cases involving patients with aSDH treated from January 2007 to June 2016. The following parameters were assessed: patient characteristics, admission status, anticoagulation status, perioperative management, comorbidities, clinical course, and outcome as determined at discharge and through 6 months of follow-up. Oral anticoagulants were classified as thrombocyte inhibitors, vitamin K antagonists, and DOACs. Patients were stratified based on which type of medication they were taking, and subgroup analyses were performed. Predictors of unfavorable outcome at discharge and follow-up were identified.

RESULTS

Of 116 patients, 74 (64%) had been following an OAT regimen at presentation with aSDH. The patients who were taking oral anticoagulants (OAT group) were significantly older (OR 12.5), more often comatose 24 hours postoperatively (OR 2.4), and more often had ≥ 4 comorbidities (OR 3.2) than patients who were not taking oral anticoagulants (no-OAT group). Accordingly, the rate of unfavorable outcome was significantly higher in patients in the OAT group, both at discharge (OR 2.3) and at follow-up (OR 2.2). Of the patients in the OAT group, 37.8% were taking a thrombocyte inhibitor, 54.1% a vitamin K antagonist, and 8.1% DOACs. In all cases, OAT was stopped on discovery of aSDH. For reversal of anticoagulation, patients who were taking a thrombocyte inhibitor received desmopressin 0.4 μg/kg, 1–2 g tranexamic acid, and preoperative transfusion with 2 units of platelets. Patients following other oral anticoagulant regimens received 50 IU/kg of prothrombin complex concentrates and 10 mg of vitamin K. There was no significant difference in the rebleeding rate between the OAT and no-OAT groups. The in-hospital mortality rate was significantly higher for patients who were taking a thrombocyte inhibitor (OR 3.3), whereas patients who were taking a vitamin K antagonist had a significantly higher 6-month mortality rate (OR 2.7). Patients taking DOACs showed a tendency toward unfavorable outcome, with higher mortality rates than patients on conventional OAT or patients in the vitamin K antagonist subgroup. Independent predictors for unfavorable outcome at discharge were comatose status 24 hours after surgery (OR 93.2), rebleeding (OR 9.8), respiratory disease (OR 4.1), and infection (OR 11.1) (Nagelkerke R2 = 0.684). Independent predictors for unfavorable outcome at follow-up were comatose status 24 hours after surgery (OR 12.7), rebleeding (OR 3.1), age ≥ 70 years (OR 3.1), and 6 or more comorbidities (OR 3.1, Nagelkerke R2 = 0.466). OAT itself was not an independent predictor for worse outcome.

CONCLUSIONS

An OAT regimen at the time of presentation with aSDH is associated with increased mortality rates and unfavorable outcome at discharge and follow-up. Thrombocyte inhibitor treatment was associated with increased short-term mortality, whereas vitamin K antagonist treatment was associated with increased long-term mortality. In particular, patients on DOACs were seriously affected, showing more unfavorable outcomes at discharge as well as at follow-up. The suggested medical treatment for aSDH in both OAT and no-OAT patients seems to be effective and reasonable, with comparable rebleeding and favorable outcome rates in the 2 groups. In addition, prior OAT is not a predictor for aSDH outcome.

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Sae-Yeon Won, Daniel Dubinski, Nina Brawanski, Adam Strzelczyk, Volker Seifert, Thomas M. Freiman and Juergen Konczalla

OBJECTIVE

Acute subdural hematoma (aSDH) is a common disease increasing in prevalence given the demographic growth of the aging population. Yet, the benefit of surgical treatment for aSDH and the subsequent functional outcome in elderly patients (age ≥ 80 years) remain unclear. Therefore, the aims of this study were to evaluate the incidence of aSDH in patients 80 years or older, determine overall functional outcome, identify predictors of an unfavorable or favorable outcome, and establish specific risk factors for seizures.

METHODS

The authors retrospectively analyzed patients 80 years and older who presented with isolated aSDH in the past 10 years at their institution. The following parameters were assessed: baseline characteristics, clinical status on admission and 24 hours after surgery, and clinical course. Functional outcome was assessed at discharge and the 3-month follow-up (FU).

RESULTS

In the period from January 2007 to December 2016, 165 patients with aSDH were admitted to the authors’ institution. Sixty-eight patients (41.2%) were 80 years old or older, and the mean age overall was 85 years (range 80–96 years). The incidence of aSDH in the elderly had significantly increased over past decade, with more than 50% of patients admitted to our institution for aSDH now being 80 years or older. The overall mortality rate was 28% at discharge and 48% at the FU. Independent predictors of an unfavorable outcome at discharge were a GCS score ≤ 8 at 24 hours after operation (p < 0.001) and pneumonia (p < 0.02). At the FU, a GCS score ≤ 8 at 24 hours after operation (p < 0.001) and cumulative comorbidities (≥ 5; p < 0.05) were significant independent predictors. All patients with more than 6 comorbidities had died by the FU. Surgical treatment in comatose compared to noncomatose patients had statistically significant, higher mortality rates at discharge and the FU. Still, 23% of the comatose patients and more than 50% of the noncomatose patients had a favorable outcome at the FU (p = 0.06).

CONCLUSIONS

The number of octo- and nonagenarians with aSDH significantly increased over the last decade. These patients can achieve a favorable outcome, especially those with a noncomatose status and fewer than 5 comorbidities. Surgical and nonsurgical treatment of octo- and nonagenarians during and after discharge should be optimized to increase clinical improvement.

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Hartmut Vatter, Juergen Konczalla, Stefan Weidauer, Christine Preibisch, Michael Zimmermann, Andreas Raabe and Volker Seifert

Object

The key role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) is increasingly assigned to endothelin (ET)-1. Constriction of the cerebrovasculature by ET-1 is mainly mediated by the ETA receptor but is putatively altered during the development of cerebral vasospasm. Therefore, the aim in the present study was to characterize these alterations, with the emphasis on the ETA receptor.

Methods

Cerebral vasospasm was induced using the rat double-hemorrhage model and proven by perfusion weighted magnetic resonance imaging. Rats were killed on Day 5 after SAH, and immunohistochemical staining for ETA receptors was performed. The isometric force of basilar artery ring segments with (E+, control group) and without (E−, SAH group) endothelial function was measured. Concentration effect curves (CECs) for ET-1 were constructed by cumulative application in the absence and presence of the selective ETA receptor antagonist clazosentan (10−8 or 10−7 M).

Results

The CEC for E+ segments was significantly shifted to the left after SAH by a factor of 3.7, whereas maximum contraction was unchanged. In E− segments, the CECs were not shifted during cerebral vasospasm but the maximum contraction was significantly enhanced. The inhibitory potency of clazosentan yielded a pA2 value of 8.6 ± 0.2. Immunohistochemical staining of the smooth-muscle layer showed no significant increase of ETA receptor expression, but positive staining occurred in the endothelial space after SAH.

Conclusions

The present data indicate an enhanced contractile effect of the smooth-muscle ETA receptors in cases of cerebral vasospasm. The inhibitory potency of clazosentan on this contraction is increased. Furthermore, some evidence for an ETA receptor and an endothelium-dependent vasoactive effect after SAH is provided.

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Sae-Yeon Won, Florian Gessler, Daniel Dubinski, Michael Eibach, Bedjan Behmanesh, Eva Herrmann, Volker Seifert, Juergen Konczalla, Stephanie Tritt and Christian Senft

OBJECTIVE

Prophylactic placement of an external ventricular drain (EVD) is often performed prior to resection of a posterior fossa tumor (PFT); however, there is no general consensus regarding the indications. The purpose of this study was to establish a novel grading system for the prediction of required CSF drainage due to symptomatic elevated intracranial pressure (ICP) after resection of a PFT to identify patients who require an EVD.

METHODS

The authors performed a retrospective analysis of data from a prospective database. All patients who had undergone resection of a PFT between 2012 and 2017 at the University Hospital, Goethe University Frankfurt, were identified and data from their cases were analyzed. PFTs were categorized as intraparenchymal (iPFT) or extraparenchymal (ePFT). Prior to resection, patients underwent EVD placement, prophylactic burr hole placement, or neither. The authors assessed the amount of CSF drainage (if applicable), rate of EVD placement at a later time point, and complication rate and screened for factors associated with CSF drainage. By applying those factors, they established a grading system to predict the necessity of CSF drainage for elevated ICP.

RESULTS

A total of 197 patients met the inclusion criteria. Of these 197, 70.6% received an EVD, 15.7% underwent prophylactic burr hole placement, and 29.4% required temporary CSF drainage. In the prophylactic burr hole group, 1 of 32 patients (3.1%) required EVD placement at a later time. Independent predictors for postoperative need for CSF drainage due to symptomatic intracranial hypertension in patients with iPFTs were preoperative hydrocephalus (OR 2.9) and periventricular CSF capping (OR 2.9), whereas semi-sitting surgical position (OR 0.2) and total resection (OR 0.3) were protective factors. For patients with ePFTs, petroclival/midline tumor location (OR 12.2/OR 5.7), perilesional edema (OR 10.0), and preoperative hydrocephalus (OR 4.0) were independent predictors of need for CSF drainage. According to our grading system, CSF drainage after resection of iPFT or ePFT, respectively, was required in 16.7% and 5.1% of patients with a score of 0, in 21.1% and 12.5% of patients with a score of 1, in 47.1% and 26.3% of patients with a score of 2, and in 100% and 76.5% of patients with a score ≥ 3 (p < 0.0001). The rate of relevant EVD complications was 4.3%, and 10.1% of patients were shunt-dependent at 3-month follow-up.

CONCLUSIONS

This novel grading system for the prediction of need for CSF drainage following resection of PFT might be of help in deciding in favor of or against prophylactic EVD placement.

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Johannes Platz, Marlies Wagner, Erdem Güresir, Se-Jong You, Juergen Konczalla, Richard du Mesnil de Rochemont, Joachim Berkefeld and Volker Seifert

OBJECTIVE

Diffusion-weighted MRI was used to assess periprocedural lesion load after repair of unruptured intracranial aneurysms (UIA) by microsurgical clipping (MC) and endovascular coiling (EC).

METHODS

Patients with UIA were assigned to undergo MC or EC according to interdisciplinary consensus and underwent diffusion-weighted imaging (DWI) 1 day before and 1 day after aneurysm treatment. Newly detected lesions by DWI after treatment were the primary end point of this prospective study. Lesions detected by DWI were categorized as follows: A) 1–3 DWI spots < 10 mm, B) > 3 DWI spots < 10 mm, C) single DWI lesion > 10 mm, or D) DWI lesion related to surgical access.

RESULTS

Between 2010 and 2014, 99 cases were included. Sixty-two UIA were treated by MC and 37 by EC. There were no significant differences between groups in age, sex, aneurysm size, occurrence of multiple aneurysms in 1 patient, or presence of lesions detected by DWI before treatment. Aneurysms treated by EC were significantly more often located in the posterior circulation (p < 0.001). Diffusion-weighted MRI detected new lesions in 27 (43.5%) and 20 (54.1%) patients after MC and EC, respectively (not significant). The pattern of lesions detected by DWI varied significantly between groups (p < 0.001). Microembolic lesions (A and B) found on DWI were detected more frequently after EC (A, 14 cases; B, 5 cases) than after MC (A, 5 cases), whereas C and D were rare after EC (C, 1 case) and occurred more often after MC (C, 12 cases and D, 10 cases). No procedure-related unfavorable outcomes were detected.

CONCLUSIONS

According to the specific techniques, lesion patterns differ between MC and EC, whereas the frequency of new lesions found on DWI is similar after occlusion of UIA. In general, the lesion load was low in both groups, and lesions were clinically silent.

Clinical trial registration no.: NCT01490463 (clinicaltrials.gov)