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Philippe Schucht, Fadi Ghareeb and Hugues Duffau

Object

A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.

Methods

Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution.

Results

For the central cohort, the median extent of resection was 92% (range 80%–97%), and for the frontal cohort, the median extent of resection was 93% (range 83%–98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001).

Conclusions

Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

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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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Andreas Raabe, Jürgen Beck, Philippe Schucht and Kathleen Seidel

Object

The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4–2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated.

Methods

The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months.

Results

All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r2 = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11–20 mA, 13 patients; 6–10 mA, 8 patients; 4–5 mA, 17 patients; and 1–3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST.

Conclusions

Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

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David Bervini, Christian Jaeggi, Pasquale Mordasini, Philippe Schucht and Andreas Raabe

OBJECTIVE

Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular abnormalities. The hemorrhagic risk associated with the use of long-term antithrombotic medication (ATM) in patients with CCMs is a matter of controversy. The aim of this study was to determine the hemorrhagic risk associated with ATM use in patients diagnosed with one or more CCMs.

METHODS

Demographic, clinical, treatment, and ATM-related information on patients diagnosed with one or more CCMs at a single institution over more than 34 years was retrospectively recorded. Univariate and multivariate descriptive and survival analyses were used to assess potential risk factors associated with CCM-related hemorrhage at presentation and during follow-up (first or subsequent hemorrhage).

RESULTS

A total of 408 patients were included in the analysis and 492 CCMs were followed up after diagnosis, for a total of 1616 lesion-years. Thirty-seven (7.5%) CCMs bled during follow-up, leading to an overall annual rate of CCM-related symptomatic hemorrhage of 2.3% (95% CI 1.7%–3.2%). Eighty-two patients harboring 91 CCMs (16.8%) were on ATM. When stratified for ATM, the annual rates of hemorrhage were 0.7% (95% CI < 0.01% to 4.2%) for the lesions in patients on ATM versus 2.5% (95% CI 1.8%–3.4%) for those not on ATM. ATM was not found to be associated with either an increased risk of CCM-related hemorrhage at presentation (p = 0.355) or an increased risk of CCM-related hemorrhage (first or subsequent hemorrhage) in multivariate descriptive (p = 0.912) and survival (p = 0.145) analyses.

CONCLUSIONS

The use of ATM does not seem to be associated with an increased risk of hemorrhage in patients diagnosed with CCMs.

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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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Raphael Meier, Nicole Porz, Urspeter Knecht, Tina Loosli, Philippe Schucht, Jürgen Beck, Johannes Slotboom, Roland Wiest and Mauricio Reyes

OBJECTIVE

In the treatment of glioblastoma, residual tumor burden is the only prognostic factor that can be actively influenced by therapy. Therefore, an accurate, reproducible, and objective measurement of residual tumor burden is necessary. This study aimed to evaluate the use of a fully automatic segmentation method—brain tumor image analysis (BraTumIA)—for estimating the extent of resection (EOR) and residual tumor volume (RTV) of contrast-enhancing tumor after surgery.

METHODS

The imaging data of 19 patients who underwent primary resection of histologically confirmed supratentorial glioblastoma were retrospectively reviewed. Contrast-enhancing tumors apparent on structural preoperative and immediate postoperative MR imaging in this patient cohort were segmented by 4 different raters and the automatic segmentation BraTumIA software. The manual and automatic results were quantitatively compared.

RESULTS

First, the interrater variabilities in the estimates of EOR and RTV were assessed for all human raters. Interrater agreement in terms of the coefficient of concordance (W) was higher for RTV (W = 0.812; p < 0.001) than for EOR (W = 0.775; p < 0.001). Second, the volumetric estimates of BraTumIA for all 19 patients were compared with the estimates of the human raters, which showed that for both EOR (W = 0.713; p < 0.001) and RTV (W = 0.693; p < 0.001) the estimates of BraTumIA were generally located close to or between the estimates of the human raters. No statistically significant differences were detected between the manual and automatic estimates. BraTumIA showed a tendency to overestimate contrast-enhancing tumors, leading to moderate agreement with expert raters with respect to the literature-based, survival-relevant threshold values for EOR.

CONCLUSIONS

BraTumIA can generate volumetric estimates of EOR and RTV, in a fully automatic fashion, which are comparable to the estimates of human experts. However, automated analysis showed a tendency to overestimate the volume of a contrast-enhancing tumor, whereas manual analysis is prone to subjectivity, thereby causing considerable interrater variability.

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Philippe Schucht, Kathleen Seidel, Michael Murek, Lennart Henning Stieglitz, Natalie Urwyler, Roland Wiest, Maja Steinlin, Kurt Leibundgut, Andreas Raabe and Jürgen Beck

Object

Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents.

Methods

The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation.

Results

The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm3) in 1 patient.

Conclusions

High-frequency train-of-five with a minimal threshold of 1–3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

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Philippe Schucht, Vanessa Banz, Markus Trochsler, Samuel Iff, Anna Katharina Krähenbühl, Michael Reinert, Jürgen Beck, Andreas Raabe, Daniel Candinas, Dominique Kuhlen and Luigi Mariani

OBJECT

In ventriculoperitoneal (VP) shunt surgery, laparoscopic assistance can be used for placement of the peritoneal catheter. Until now, the efficacy of laparoscopic shunt placement has been investigated only in retrospective and nonrandomized prospective studies, which have reported decreased distal shunt dysfunction rates in patients undergoing laparascopic placement compared with mini-laparotomy cohorts. In this randomized controlled trial the authors compared rates of shunt failure in patients who underwent laparoscopic surgery for peritoneal catheter placement with rates in patients who underwent traditional mini-laparotomy.

METHODS

One hundred twenty patients scheduled for VP shunt surgery were randomized to laparoscopic surgery or mini-laparotomy for insertion of the peritoneal catheter. The primary endpoint was the rate of overall shunt complication or failure within the first 12 months after surgery. Secondary endpoints were distal shunt failure, overall complication/ failure, duration of surgery and hospitalization, and morbidity.

RESULTS

The overall shunt complication/failure rate was 15% (9 of 60 cases) in the laparoscopic group and 18.3% (11 of 60 cases) in the mini-laparotomy group (p = 0.404). Patients in the laparoscopic group had no distal shunt failures; in contrast, 5 (8%) of 60 patients in the mini-laparotomy group experienced distal shunt failure (p = 0.029). Intraoperative complications occurred in 2 patients (both in the laparoscopic group), and abdominal pain led to catheter removal in 1 patient per group. Infections occurred in 1 patient in the laparoscopic group and 3 in the mini-laparotomy group. The mean durations of surgery and hospitalization were similar in the 2 groups.

CONCLUSIONS

While overall shunt failure rates were similar in the 2 groups, the use of laparoscopic shunt placement significantly reduced the rate of distal shunt failure compared with mini-laparotomy.

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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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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.