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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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Philippe Schucht, Kathleen Seidel, Jürgen Beck, Michael Murek, Astrid Jilch, Roland Wiest, Christian Fung and Andreas Raabe

Object

Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)–guided surgery in patients with glioblastoma adjacent to eloquent tissue.

Methods

The authors prospectively studied 72 consecutive patients who underwent 5-ALA–guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months.

Results

Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11–20 mA, n = 13; 6–10 mA, n = 10; 4–5 mA, n = 13; and 1–3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST.

Conclusions

A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

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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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Jürgen Beck, Christian Fung, Christian T. Ulrich, Michael Fiechter, Jens Fichtner, Heinrich P. Mattle, Marie-Luise Mono, Niklaus Meier, Pasquale Mordasini, Werner J. Z’Graggen, Jan Gralla and Andreas Raabe

OBJECTIVE

Spinal CSF leakage causes spontaneous intracranial hypotension (SIH). The aim of this study was to characterize CSF dynamics via lumbar infusion testing in patients with and without proven spinal CSF leakage in order to explore possible discriminators for the presence of an open CSF leak.

METHODS

This analysis included all patients with suspected SIH who were treated at the authors’ institution between January 2012 and February 2015. The gold standard for “proven” CSF leakage is considered to be extrathecal contrast accumulation after intrathecal contrast injection. To characterize CSF dynamics, the authors performed computerized lumbar infusion testing to measure lumbar pressure at baseline (opening pressure) and at plateau, as well as pulse amplitude, CSF outflow resistance (RCSF), craniospinal elastance, and pressure-volume index.

RESULTS

Thirty-one patients underwent clinical imaging and lumbar infusion testing and were included in the final analysis. A comparison of the 14 patients with proven CSF leakage with the 17 patients without leakage showed a statistically significantly lower lumbar opening pressure (p < 0.001), plateau pressure (p < 0.001), and RCSF (p < 0.001) in the group with leakage. Sensitivity, specificity, and positive and negative predictive values for an RCSF cutoff of ≤ 5 mm Hg/(ml/min) were 0.86, 1.0, 1.0, and 0.89 (area under the curve of 0.96), respectively. The median pressure-volume index was higher (p = 0.003), and baseline (p = 0.017) and plateau (p < 0.001) pulse amplitudes were lower in patients with a proven leak.

CONCLUSIONS

Lumbar infusion testing captures a distinct pattern of CSF dynamics associated with spinal CSF leakage. RCSF assessed by computerized lumbar infusion testing has an excellent diagnostic accuracy and is more accurate than evaluating the lumbar opening pressure. The authors suggest inclusion of RCSF in the diagnostic criteria for SIH.

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Jürgen Beck, Jan Gralla, Christian Fung, Christian T. Ulrich, Philippe Schucht, Jens Fichtner, Lukas Andereggen, Martin Gosau, Elke Hattingen, Klemens Gutbrod, Werner J. Z'Graggen, Michael Reinert, Jürg Hüsler, Christoph Ozdoba and Andreas Raabe

Object

The etiology of chronic subdural hematoma (CSDH) in nongeriatric patients (≤ 60 years old) often remains unclear. The primary objective of this study was to identify spinal CSF leaks in young patients, after formulating the hypothesis that spinal CSF leaks are causally related to CSDH.

Methods

All consecutive patients 60 years of age or younger who underwent operations for CSDH between September 2009 and April 2011 at Bern University Hospital were included in this prospective cohort study. The patient workup included an extended search for a spinal CSF leak using a systematic algorithm: MRI of the spinal axis with or without intrathecal contrast application, myelography/fluoroscopy, and postmyelography CT. Spinal pathologies were classified according to direct proof of CSF outflow from the intrathecal to the extrathecal space, presence of extrathecal fluid accumulation, presence of spinal meningeal cysts, or no pathological findings. The primary outcome was proof of a CSF leak.

Results

Twenty-seven patients, with a mean age of 49.6 ± 9.2 years, underwent operations for CSDH. Hematomas were unilateral in 20 patients and bilateral in 7 patients. In 7 (25.9%) of 27 patients, spinal CSF leakage was proven, in 9 patients (33.3%) spinal meningeal cysts in the cervicothoracic region were found, and 3 patients (11.1%) had spinal cysts in the sacral region. The remaining 8 patients (29.6%) showed no pathological findings.

Conclusions

The direct proof of spinal CSF leakage in 25.9% of patients suggests that spinal CSF leaks may be a frequent cause of nongeriatric CSDH.

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Christian Fung, Mathias Balmer, Michael Murek, Werner J. Z'Graggen, Janine Abu-Isa, Christoph Ozdoba, Matthias Haenggi, Stephan M. Jakob, Andreas Raabe and Jürgen Beck

OBJECT

After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome.

METHODS

This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I–III) and poor (WFNS IV–V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0–3 was considered a good outcome and an mRS score of 4–6 was considered a poor outcome.

RESULTS

Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14–7.46; p = 0.03) and good outcome (OR 4.01, 97.5% CI 1.63–10.53; p = 0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p < 0.001), and poor WFNS grade (p < 0.001) were associated with poor outcome.

CONCLUSIONS

Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.

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Christian Fung, Fabienne Inglin, Michael Murek, Mathias Balmer, Janine Abu-Isa, Werner J. Z’Graggen, Christoph Ozdoba, Jan Gralla, Stephan M. Jakob, Jukka Takala, Jürgen Beck and Andreas Raabe

OBJECT

Current data show a favorable outcome in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) Grade V subarachnoid hemorrhage (SAH) and a rather poor prediction of worst cases. Thus, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. One reason for this lack of differentiation is the use of “negative” or “silent” diagnostic signs as part of the WFNS Grade V definition. The authors therefore reevaluated the WFNS scale by using “positive” clinical signs and the logic of the Glasgow Coma Scale as a progressive herniation score.

METHODS

The authors performed a retrospective analysis of 182 patients with SAH who had poor grades on the WFNS scale. Patients were graded according to the original WFNS scale and additionally according to a modified classification, the WFNS herniation (hWFNS) scale (Grade IV, no clinical signs of herniation; Grade V, clinical signs of herniation). The prediction of poor outcome was compared between these two grading systems.

RESULTS

The positive predictive values of Grade V for poor outcome were 74.3% (OR 3.79, 95% CI 1.94–7.54) for WFNS Grade V and 85.7% (OR 8.27, 95% CI 3.78–19.47) for hWFNS Grade V. With respect to mortality, the positive predictive values were 68.3% (OR 3.9, 95% CI 2.01–7.69) for WFNS Grade V and 77.9% (OR 6.22, 95% CI 3.07–13.14) for hWFNS Grade V.

CONCLUSIONS

Limiting WFNS Grade V to the positive clinical signs of the Glasgow Coma Scale such as flexion, extension, and pupillary abnormalities instead of including “no motor response” increases the prediction of mortality and poor outcome in patients with severe SAH.

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Nicolai Maldaner, Valentin K. Steinsiepe, Johannes Goldberg, Christian Fung, David Bervini, Adrien May, Philippe Bijlenga, Karl Schaller, Michel Roethlisberger, Daniel W. Zumofen, Donato D’Alonzo, Serge Marbacher, Javier Fandino, Rodolfo Maduri, Roy Thomas Daniel, Jan-Karl Burkhardt, Alessio Chiappini, Thomas Robert, Bawarjan Schatlo, Martin A. Seule, Astrid Weyerbrock, Luca Regli, Martin Nikolaus Stienen and for the Swiss SOS Study Group

OBJECTIVE

The objective of this study was to determine patterns of care and outcomes in ruptured intracranial aneurysms (IAs) of the middle cerebral artery (MCA) in a contemporary national cohort.

METHODS

The authors conducted a retrospective analysis of prospective data from a nationwide multicenter registry of all aneurysmal subarachnoid hemorrhage (aSAH) cases admitted to a tertiary care neurosurgical department in Switzerland in the years 2009–2015 (Swiss Study on Aneurysmal Subarachnoid Hemorrhage [Swiss SOS]). Patterns of care and outcomes at discharge and the 1-year follow-up in MCA aneurysm (MCAA) patients were analyzed and compared with those in a control group of patients with IAs in locations other than the MCA (non-MCAA patients). Independent predictors of a favorable outcome (modified Rankin Scale score ≤ 3) were identified, and their effect size was determined.

RESULTS

Among 1866 consecutive aSAH patients, 413 (22.1%) harbored an MCAA. These MCAA patients presented with higher World Federation of Neurosurgical Societies grades (p = 0.007), showed a higher rate of concomitant intracerebral hemorrhage (ICH; 41.9% vs 16.7%, p < 0.001), and experienced delayed cerebral ischemia (DCI) more frequently (38.9% vs 29.4%, p = 0.001) than non-MCAA patients. After adjustment for confounders, patients with MCAA were as likely as non-MCAA patients to experience DCI (aOR 1.04, 95% CI 0.74–1.45, p = 0.830). Surgical treatment was the dominant treatment modality in MCAA patients and at a significantly higher rate than in non-MCAA patients (81.7% vs 36.7%, p < 0.001). An MCAA location was a strong independent predictor of surgical treatment (aOR 8.49, 95% CI 5.89–12.25, p < 0.001), despite statistical adjustment for variables traditionally associated with surgical treatment, such as (space-occupying) ICH (aOR 1.73, 95% CI 1.23–2.45, p = 0.002). Even though MCAA patients were less likely to die during the acute hospitalization (aOR 0.52, 0.30–0.91, p = 0.022), their rate of a favorable outcome was lower at discharge than that in non-MCAA patients (55.7% vs 63.7%, p = 0.003). At the 1-year follow-up, 68.5% and 69.6% of MCAA and non-MCAA patients, respectively, had a favorable outcome (p = 0.676).

CONCLUSIONS

Microsurgical occlusion remains the predominant treatment choice for about 80% of ruptured MCAAs in a European industrialized country. Although patients with MCAAs presented with worse admission grades and greater rates of concomitant ICH, in-hospital mortality was lower and long-term disability was comparable to those in patients with non-MCAA.