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Andreas Raabe and Volker Seifert

✓ The S-100B protein is a small cytosolic protein that is found in astroglial or Schwann cells. It is highly specific for brain tissue and is increasingly being investigated as a diagnostic tool to assess the neurological damage after head injury, stroke, subarachnoid hemorrhage, and cardiopulmonary bypass.

The authors report on three patients with severe head injury with otherwise normal cerebral perfusion pressure, SaO2, PaCO2, and controlled intracranial pressure (ICP), in whom a secondary excessive increase in serum S-100B was observed. In all cases, the S-100B increase was followed by an increase in ICP. All three patients died within 72 hours after the excessive increase in S-100B. These findings indicate that major secondary brain damage may occur at a cellular level without being identified by current neuromonitoring techniques.

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Jens Fichtner, Erdem Güresir, Volker Seifert, and Andreas Raabe

Object

Catheter-related infection of CSF is a potentially life-threatening complication of external ventricular drainage (EVD). When using EVD catheters, contact between the ventricular system and skin surface occurs and CSF infection is possible. The aim of this analysis was to compare the efficacy of silver-bearing EVD catheters for reducing the incidence of infection with standard nonimpregnated EVD catheters in neurosurgical patients with acute hydrocephalus.

Methods

Two hundred thirty-one consecutive patients were retrospectively reviewed. Of these, 164 were enrolled in the final analysis. Six patient charts were incomplete or missing, 15 patients were excluded because of catheter insertion within the previous 30 days, 6 because of a suspected CSF infection before ventriculostomy, 7 because the catheter was removed < 24 hours after insertion, and 33 patients because of the requirement of bilateral ventriculostomy. The control group with standard nonimpregnated EVD catheters consisted of 90 patients. The study group with silver-bearing EVDs consisted of 74 patients. For assessing the primary outcome, the authors recorded all CSF samples and liquor cell counts routinely obtained in sterile fashion. After removal of the catheters, they also reviewed microbiology reports of the removed catheters to assess colonization of the catheter tips.

Results

The occurrence of a positive CSF culture, colonization of the catheter tip, or liquor pleocytosis (white blood cell count > 4/μl) was ~ 2 times less in the study group with silver-bearing EVD catheters than that in the control group (18.9% compared with 33.7%, p = 0.04). Positive CSF cultures alone occurred 2 times less frequently for microorganisms in the study group (2.7% compared with 4.7%, p = 0.55). Silver-bearing catheters were 4 times less likely to become colonized as nonimpregnated EVDs (1.4% compared with 5.8%, p = 0.14). Liquor pleocytosis was half as likely in the study group (17.6% compared with 30.2%, p = 0.06).

Conclusions

Although of limited sample size and thus underpowered for subgroup analysis, this analysis indicates that EVD catheters impregnated with silver nanoparticles and an insoluble silver salt may reduce the risk of catheter-related infections in neurosurgical patients.

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Andreas Raabe, Jürgen Beck, Stefan Rohde, Joachim Berkefeld, and Volker Seifert

Object

The aim of this study was to investigate the feasibility of integrating three-dimensional rotational angiography (3D-RA) data into a surgical navigation system and to assess its accuracy and potential clinical benefit.

Methods

The study cohort consisted of 16 patients with 16 intracranial aneurysms who had been scheduled for routine or emergency surgery. Rotational angiography data were exported using a virtual reality modeling language file format and imported into the BrainLAB VectorVision2 image-guided surgery equipment. During 3D-RA the position of the head was measured using a special headframe. The authors also determined the accuracy of 3D-RA image guidance and the clinical benefit as judged by the surgeon, including, for example, early identification of branching vessels and the aneurysm.

There was good correspondence between the 3D-RA–based navigation data and the intraoperative vascular anatomy in all cases, with a maximum error of 9° of angulation and 9° of rotation. In eight cases, the surgeon determined that the 3D-RA image guidance facilitated the surgical procedure by predicting the location of the aneurysm or the origin of a branching artery that had been covered by brain tissue and blood clots.

Conclusions

The integration of 3D-RA into surgical navigation systems is feasible, but it currently requires a new perspective-registration technique. The intraoperative 3D view provides useful information about the vascular anatomy and may improve the quality of aneurysm surgery in selected cases.

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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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Rüdiger Gerlach, Gerhard Marquardt, Heimo Wissing, Inge Scharrer, Andreas Raabe, and Volker Seifert

✓ The authors report on a 64-year-old woman with a huge recurrent skull base hemangiopericytoma, in whom they encountered severe difficulty in attaining intraoperative hemostasis. Standard surgical hemostatic methods and the administration of fresh-frozen plasma and prothrombin complex concentrates failed to stop diffuse bleeding from an inoperable tumor remnant. At a critical point during the operation, the intravenous administration of recombinant activated factor VII, combined with mechanical compression, finally led to satisfactory hemostasis. The rationale for using recombinant activated factor VII in situations of uncontrolled bleeding during neurosurgical procedures is discussed, along with the literature in which the use of recombinant activated factor VII as a maneuver of last resort is reported for hemostasis in other surgical fields.

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Erdem Güresir, Patrick Schuss, Hartmut Vatter, Andreas Raabe, Volker Seifert, and Jürgen Beck

Object

The aim of this study was to analyze decompressive craniectomy (DC) in the setting of subarachnoid hemorrhage (SAH) with bleeding, infarction, or brain swelling as the underlying pathology in a large cohort of consecutive patients.

Methods

Decompressive craniectomy was performed in 79 of 939 patients with SAH. Patients were stratified according to the indication for DC: 1) primary brain swelling without or 2) with additional intracerebral hematoma, 3) secondary brain swelling without rebleeding or infarcts, and 4) secondary brain swelling with infarcts or 5) with rebleeding. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months (mRS Score 0–3 favorable vs 4–6 unfavorable).

Results

Overall, 61 (77.2%) of 79 patients who did and 292 (34%) of the 860 patients who did not undergo DC had a poor clinical grade on admission (World Federation of Neurosurgical Societies Grade IV–V, p < 0.0001). A favorable outcome was attained in 21 (26.6%) of 79 patients who had undergone DC. In a comparison of favorable outcomes in patients with primary (28.0%) or secondary DC (25.5%), no difference could be found (p = 0.8). Subgroup analysis with respect to the underlying indication for DC (brain swelling vs bleeding vs infarction) revealed no difference in the rate of favorable outcomes. On multivariate analysis, acute hydrocephalus (p = 0.009) and clinical signs of herniation (p = 0.02) were significantly associated with an unfavorable outcome.

Conclusions

Based on the data in this study the authors concluded that primary as well as secondary craniectomy might be warranted, regardless of the underlying etiology (hemorrhage, infarction, or brain swelling) and admission clinical grade of the patient. The time from the onset of intractable intracranial pressure to DC seems to be crucial for a favorable outcome, even when a DC is performed late in the disease course after SAH.

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Andreas Raabe, Jügen Beck, Mike Keller, Hartmuth Vatter, Michael Zimmermann, and Volker Seifert

Object. Hypervolemia and hypertension therapy is routinely used for prophylaxis and treatment of symptomatic cerebral vasospasm at many institutions. Nevertheless, there is an ongoing debate about the preferred modality (hypervolemia, hypertension, or both), the degree of therapy (moderate or aggressive), and the risk or benefit of hypervolemia, moderate hypertension, and aggressive hypertension in patients following subarachnoid hemorrhage.

Methods. Monitoring data and patient charts for 45 patients were retrospectively searched to identify periods of hypervolemia, moderate hypertension, or aggressive hypertension. Measurements of central venous pressure, fluid input, urine output, arterial blood pressure, intracranial pressure, and oxygen partial pressure (PO2) in the brain tissue were extracted from periods ranging from 1 hour to 24 hours. For these periods, the change in brain tissue PO2 and the incidence of complications were analyzed.

During the 55 periods of moderate hypertension, an increase in brain tissue PO2 was found in 50 cases (90%), with complications occurring in three patients (8%). During the 25 periods of hypervolemia, an increase in brain oxygenation was found during three intervals (12%), with complications occurring in nine patients (53%). During the 10 periods of aggressive hypervolemic hypertension, an increase in brain oxygenation was found during six of the intervals (60%), with complications in five patients (50%).

Conclusions. When hypervolemia treatment is applied as in this study, it may be associated with increased risks. Note, however, that further studies are needed to determine the role of this therapeutic modality in the care of patients with cerebral vasospasm. In poor-grade patients, moderate hypertension (cerebral perfusion pressure 80–120 mm Hg) in a normovolemic, hemodiluted patient is an effective method of improving cerebral oxygenation and is associated with a lower complication rate compared with hypervolemia or aggressive hypertension therapy.

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Erdem Güresir, Hartmut Vatter, Patrick Schuss, Ági Oszvald, Andreas Raabe, Volker Seifert, and Jürgen Beck

Object

The object of this study was to describe the rapid closure technique in decompressive craniectomy without duraplasty and its use in a large cohort of consecutive patients.

Methods

Between 1999 and 2008, supratentorial rapid closure decompressive craniectomy (RCDC) was performed 341 times in 318 patients at the authors' institution. Cases were stratified as 1) traumatic brain injury, 2) subarachnoid hemorrhage, 3) intracerebral hemorrhage, 4) cerebral infarction, and 5) other. A large bone flap was removed and the dura mater was opened in a stellate fashion. Duraplasty was not performed—that is, the dura was not sutured, and a dural substitute was neither sutured in nor layed on. The dura and exposed brain tissue were covered with hemostyptic material (Surgicel). Surgical time and complications of this procedure including follow-up (> 6 months) were recorded. After 3–6 months cranioplasty was performed, and, again, surgical time and any complications were recorded.

Results

Rapid closure decompressive craniectomy was feasible in all cases. Complications included superficial wound healing disturbance (3.5% of procedures), abscess (2.6%) and CSF fistula (0.6%); the mean surgical time (± SD) was 69 ± 20 minutes. Cranioplasty was performed in 196 cases; the mean interval (± SD) from craniectomy to cranioplasty was 118 ± 40 days. Complications of cranioplasty included epidural hematoma (4.1%), abscess (2.6%), wound healing disturbance (6.1%), and CSF fistula (1%).

Compared with the results reported in the literature for decompressive craniectomy with duraplasty followed by cranioplasty, there were no significant differences in the frequency of complications. However, surgical time for RCDC was significantly shorter (69 ± 20 vs 129 ± 43 minutes, p < 0.0001).

Conclusions

The present analysis of the largest series reported to date reveals that the rapid closure technique is feasible and safe in decompressive craniectomy. The surgical time is significantly shorter without increased complication rates or additional complications. Cranioplasty after a RCDC procedure was also feasible, fast, safe and not impaired by the RCDC technique.

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Hartmut Vatter, Michael Zimmermann, Veronika Tesanovic, Andreas Raabe, Lothar Schilling, and Volker Seifert

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature.

Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2).

The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−).

Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

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Hartmut Vatter, Michael Zimmermann, Veronika Tesanovic, Andreas Raabe, Volker Seifert, and Lothar Schilling

Object. The disturbed balance between nitric oxide and endothelin (ET)—1 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ETA receptor—dependent contractile effect, ET-1 also has ETB receptor—mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ETA receptor—selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature.

Methods. Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10−9 to 10−6 M) after a precontraction was induced by prostaglandin F. The inhibition by clazosentan was estimated by the value of the affinity constant (pA2).

The relaxation induced by sarafotoxin S6c, ET-1, and big ET-1 was inhibited in a competitive manner by clazosentan, yielding pA2 values of 7.1, 6.7, and 6.5, respectively. The selectivity to the ETA receptor in the cerebrovascular system was approximately two logarithmic units.

Conclusions. The present investigation shows a competitive inhibition of ETB receptor—mediated relaxation in cerebral vessels by clazosentan in therapeutically relevant concentrations. Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid. Furthermore, the present data may be taken to describe the pharmacological properties for an ET receptor antagonist specifically tailored for the treatment of pathological conditions of impaired cerebral blood flow.