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Johannes Goldberg, Christian Jaeggi, Daniel Schoeni, Pasquale Mordasini, Andreas Raabe, and David Bervini

OBJECTIVE

Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term β-blocker medication.

METHODS

A single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term β-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the β-blocker group was divided into the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker.

RESULTS

Of 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any β-blocker; 65 (12%) received β1-selective β-blocker, and 16 (3%) received any unselective β-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any β-blocker: p = 0.64, β1-selective: p = 0.93, any unselective β-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with β-blocker medication (any β-blocker: p = 0.70, HR 1.19, 95% CI 0.49–2.90; β1-selective: p = 0.78, HR 1.15, 95% CI 0.44–3.00; any unselective β-blocker: p = 0.76, HR 1.37, 95% CI 0.19–10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk for follow-up hemorrhage under any β-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52–3.56).

CONCLUSIONS

In this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.

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Kathleen Seidel, Jürgen Beck, Lennart Stieglitz, Philippe Schucht, and Andreas Raabe

Object

Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1–20 mA) with direct cortical stimulation (DCS)–motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST.

Methods

A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively.

Results

The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11–20 mA, n = 13; 6–10 mA, n = 20; 4–5 mA, n = 30; and 1–3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1–3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits.

Conclusions

Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

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Jitendra Thakur, Christian T. Ulrich, Ralph T. Schär, Kathleen Seidel, Andreas Raabe, and C. Marvin Jesse

The authors present an illustrative technical note on microsurgical resection of ventrolateral completely ossified spinal meningiomas (OSMs) and a literature review of the surgical management of calcified spinal meningiomas or OSMs. These tumors are surgically demanding due to their solid consistency, especially when in a ventrolateral location with dislocation of the spinal cord. A challenging case with significant thoracic cord compression and displacement is described. Due to the firm consistency and the ventrolateral localization of the meningioma, a piecemeal resection was necessary. This could have resulted in a free-floating tumor remnant adherent to the spinal cord, impeding safe tumor resection. To avoid such a remnant, an anchoring burr hole was drilled at the border between the spinal cord and the adamantine tumor mass. Then, a microdissector was placed within the anchoring burr hole and the tumor was gently pulled laterally while drilling away the medial parts of the ossified tumor. This procedure was repeated until separation of the tumor from the spinal cord was possible and a gross-total resection (Simpson grade II) was manageable. Throughout the procedure, continuous intraoperative neurophysiological monitoring was performed.

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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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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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Nicholas C. Bambakidis and Warren R. Selman

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Alessa Schütz, Michael Murek, Lennart Henning Stieglitz, Corrado Bernasconi, Sonja Vulcu, Jürgen Beck, Andreas Raabe, and Philippe Schucht

OBJECTIVE

Decompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient’s explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.

METHODS

In this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR—defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments—was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.

RESULTS

A total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9–2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3–4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.

CONCLUSIONS

Hypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.

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Levin Häni, Sonja Vulcu, Mattia Branca, Christian Fung, Werner Josef Z’Graggen, Michael Murek, Andreas Raabe, Jürgen Beck, and Philippe Schucht

OBJECTIVE

The use of subdural drains after surgical evacuation of chronic subdural hematoma (CSH) decreases the risk of recurrence and has become the standard of care. Halfway through the controlled, randomized TOSCAN (Randomized Trial of Follow-up CT after Evacuation of Chronic Subdural Hematoma) trial, the authors’ institutional guidelines changed to recommend subgaleal instead of subdural drainage. The authors report a post hoc analysis on the influence of drain location in patients participating in the TOSCAN trial.

METHODS

The study involved 361 patients enrolled in the TOSCAN trial. The patients were stratified according to whether they received surgery before (cohort A) or after (cohort B) the change in institutional protocol. An intention-to-treat analysis was performed with surgery for recurrence as the primary endpoint. Secondary endpoints were outcome-based on modified Rankin Scale scores, seizures, infections, parenchymal brain injuries, and hematoma diameter.

RESULTS

Of the 361 patients included in the analysis, 214 were stratified into cohort A (subdural drainage recommended), while 147 were stratified into cohort B (subgaleal drainage recommended). There was a 31.78% rate of crossover from the subdural to the subgaleal drainage insertion site due to technical or anatomical difficulties. No differences in the rates of reoperation (21.5% [cohort A] vs 25.17% [cohort B], OR 0.81, 95% CI 0.50–1.34, p = 0.415), infections (0.47% [cohort A] vs 2.04% [cohort B], OR 0.23, 95% CI 0.02–2.19, p = 0.199), seizures (3.27% [cohort A] vs 2.72% [cohort B], OR 1.21, 95% CI 0.35–4.21, p = 0.765), or favorable outcomes (modified Rankin Scale score 0–3) at 1 and 6 months (91.26% [cohort A] vs 96.43% [cohort B], OR 0.39, 95% CI 0.14–1.07, p = 0.067; 89.90% [cohort A] vs 91.55% [cohort B], OR 0.82, 95% CI 0.39–1.73, p = 0.605) were noted between the two cohorts. Postoperatively, patients in cohort A had more frequent parenchymal brain tissue injuries (2.8% vs 0%, p = 0.041). Postoperative absolute and relative hematoma reduction was similar irrespective of the location of the drain.

CONCLUSIONS

Subgaleal rather than subdural placement of the drain did not increase the risk for reoperation for recurrence of CSHs, nor did it have a negative impact on clinical or radiological outcome. The intention to place a subdural drain was associated with a higher rate of parenchymal injuries.

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Serge Marbacher, Janine-Ai Schläppi, Christian Fung, Jürg Hüsler, Jürgen Beck, and Andreas Raabe

Object

Recent studies in rats have demonstrated that statins may have an inhibitory effect on intracranial aneurysm (IA) development. The purpose of this study was to assess whether long-term statin use is associated with a reduced risk of IA formation in humans.

Methods

This was a single-center case-control study that included consecutive patients admitted to the authors' institution between January 1, 2005, and December 31, 2008. A case was defined as a patient with a cerebral angiography–confirmed diagnosis of IA. Three controls were matched to each case based on age, sex, and index year of hospital admission. The primary exposure of interest was cumulative statin use. Conditional logistic regression was used to assess the relationship between statin intake and incidence of IA.

Results

In total, 1200 patients were included in the study. No overall association was found between statin use and incidence of IA formation (OR 1.08, 95% CI 0.69–1.69), nor when dichotomized into hydrophilic and lipophilic user, or between short (≤12-month) and long (≥36-month) duration of intake. Hypertension and smoking significantly increased the risk of IA development (OR 4.02, 95% CI 2.49–6.45, and OR 1.67, 95% CI 1.02–2.72, respectively).

Conclusions

In contrast to recent experimental reports of the association between statins and a reduction of IA formation, the authors' findings suggest that in humans statins may have no significant beneficial effect on IA suppression.

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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.