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Berndt Wowra, Alexander Muacevic, Anja Jess-Hempen, John-Martin Hempel, Stefanie Müller-Schunk and Jörg-Christian Tonn

Object. The purpose of the study was to define the therapeutic profile of outpatient gamma knife surgery (GKS) for vestibular schwannoma (VS) by using sequential tumor volumetry to quantify changes following treatment.

Methods. A total of 111 patients met the inclusion criteria. The median follow-up duration was 7 years (range 5–9.6 years). Thirty-seven patients (33%) had undergone surgery before GKS and 10 (9%) had neurofibromatosis Type 2 (NF2). The median VS volume was 1.6 cm3 (range 0.08–8.7 cm3).

The actuarial 6-year tumor control rate after a single GKS treatment was 95%. Tumor swelling was observed in 43 patients (38.7%). Recurrence was significantly associated with NF2 (p < 0.003) and the reduced dose (p < 0.03) delivered to these tumors. The incidence of facial nerve neuropathy was mainly determined by surgery prior to GKS (p < 0.0001). Facial nerve radiation toxicity was mild and transient. No permanent facial nerve toxicity was observed. Trigeminal neuropathy occurred in 13 patients, and this was correlated with the VS volume (p < 0.02). The median hearing loss was −10 dB (range + 20 dB to −70 dB). The risk of hearing loss was correlated with age and transient tumor swelling (p < 0.05) but not with dose parameters or NF2.

Conclusions. Outpatient GKS is feasible, effective, and safe. Its therapeutic profile compares favorably with that of microsurgery.

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Marko Staender, Ulrich Maerz, Jörg Christian Tonn and Ulrich Steude

Object. The authors prospectively evaluated the therapeutic effect of computerized tomography (CT)—guided kryorhizotomy in the treatment of patients with lumbar facet joint syndrome (LFJS) and assessed prognostic factors that predict this effect.

Methods. Between February 2001 and March 2004, CT-guided kryorhizotomy of facet joints was performed in 76 patients with LFJS. A diagnosis was established after three positive CT-guided medial nerve branch blocks. Outcome was determined by evaluating the results of a standardized questionnaire, including visual analog scale (VAS) score, use of medication, ability to work, and physical conditions. Measurement was performed before treatment and repeated postoperatively at 3 days, 3 months, and every 6 months thereafter. On September 2004 all patients underwent clinical reevaluation.

The median follow-up period was 22.5 months (range 6–43 months); the median interval to pain reduction was 6 months (range 0.1–31 months) after the first kryorhizotomy. The mean VAS pain score was 6.7 preoperatively and 2.9, 3.2, and 3.4 at 3 days, 3 months, and 6 months postoperatively, respectively. In 40% of patients pain was reduced for 12 months or longer. In patients in whom there was no prior surgical treatment of the relevant spinal segment, the duration of pain relief was significantly longer than in patients who had previously undergone surgery (p < 0.03). Eighteen patients underwent a second, seven a third, and one a fourth kryorhizotomy. No patient reported any side effect. The use of CT guidance guarantees an exact needle-tip position control and documentation for repeated procedures.

Conclusions. Computerized tomography—guided kryorhizotomy is a minimally invasive and repeatable treatment that yields good long-term results in patients with LFJS.

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Markus Lenski, Annamaria Biczok, Katrin Neufischer, Jörg-Christian Tonn, Josef Briegel and Niklas Thon

Objective

The aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis.

Methods

Retrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors’ intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis.

Results

There were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0).

Conclusions

The level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

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Friedrich-Wilhelm Kreth, Niklas Thon and Jörg-Christian Tonn

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Ardavan Ardeshiri, Ardeshir Ardeshiri, Jennifer Linn, Jörg-Christian Tonn and Peter A. Winkler

Object

The mesencephalic veins drain crucial brainstem areas. Due to the narrowness of the tentorial notch, these veins can become obstructed as a result of herniation or surgery, leading to hemorrhage and severe consequences for the patient. There is little in the literature about the mesencephalic veins. The aim of this study was to perform an exact analysis of their microanatomy.

Methods

Fifty-two cadaveric hemispheres were examined under an operating microscope, and measurements were made with a digital caliper. The authors focused on the basal vein (BV), pontomesencephalic vein (PMV), peduncular vein (PV), lateral mesencephalic vein (LMV), and other smaller veins.

The PMV was identified in 84.6% of specimens (mean diameter 0.54 mm); the PV, in 86.5% (mean diameter 0.86 mm); and the LMV, in 100% (mean diameter 1.07 mm). Four types of LMV were identified on the basis of the vein's course. Other smaller veins were also differentiated according to whether they drained mainly the cerebral peduncle, the lemniscal trigone, or the tectum. These veins and their junctions with other veins were depicted.

Conclusions

A thorough understanding of the microanatomy of the mesencephalic veins is crucial in brainstem surgery in order to avoid brain damage due to venous infarction and subsequent edema. Because knowledge of the course, variations, and outflow system of these veins could improve surgical outcome, they warrant special attention during surgery.

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Jörg-Christian Tonn, Hans Kristian Haugland, Jaakko Saraste, Klaus Roosen and Ole Didrik Laerum

✓ The aim of this study was to investigate the antimigratory and antiinvasive potential of vincristine sulfate (VCR) on human glioma cells and to analyze whether phenytoin (5,5-diphenylhydantoin; DPH) might act synergistically with VCR. Vincristine affects the cytoplasmic microtubules; DPH has been reported to enhance VCR cytotoxicity in murine cells. In two human glioma cell lines, GaMG and D-37MG, we found VCR to reduce monolayer growth and colony formation in a dose-dependent fashion at concentrations of 10 ng/ml and above. Phenytoin increased the cytotoxic and cystostatic effects of VCR in monolayer cells but not in spheroids.

Multicellular spheroids were used to investigate directional migration. A coculture system of GaMG and D-37MG spheroids with fetal rat brain aggregates was used to analyze and quantify tumor cell invasion. A dose-dependent inhibition of migration and invasion by VCR was observed in both cell lines without further enhancement by DPH. Immunofluorescence microscopy with antibodies against α-tubulin revealed dose-dependent morphological alterations in the microtubules when the cells were exposed to VCR but not after incubation with DPH. Based on the combination of standardized in vitro model systems currently in use and the present data, the authors strongly suggest that VCR inhibits migration and invasion of human glioma cells. This is not altered by DPH, which inhibits cell proliferation in combination with VCR.

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Tobias Greve, Veit M. Stoecklein, Franziska Dorn, Sophia Laskowski, Niklas Thon, Jörg-Christian Tonn and Christian Schichor

OBJECTIVE

Intraoperative neuromonitoring (IOM), particularly of somatosensory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs), evolved as standard of care in a variety of neurosurgical procedures. Case series report a positive impact of IOM for elective microsurgical clipping of unruptured intracranial aneurysms (ECUIA), whereas systematic evaluation of its predictive value is lacking. Therefore, the authors analyzed the neurological outcome of patients undergoing ECUIA before and after IOM introduction to this procedure.

METHODS

The dates of inclusion in the study were 2007–2014. In this period, ECUIA procedures before (n = 136, NIOM-group; 2007–2010) and after introduction of IOM (n = 138, IOM-group; 2011–2014) were included. The cutoff value for SSEP/MEP abnormality was chosen as an amplitude reduction ≥ 50%. SSEP/MEP changes were correlated with neurological outcome. IOM-undetectable deficits (bulbar, vision, ataxia) were not included in risk stratification.

RESULTS

There was no significant difference in sex distribution, follow-up period, subarachnoid hemorrhage risk factors, aneurysm diameter, complexity, and location. Age was higher in the IOM-group (57 vs 54 years, p = 0.012). In the IOM group, there were 18 new postoperative deficits (13.0%, 5.8% permanent), 9 hemisyndromes, 2 comas, 4 bulbar symptoms, and 3 visual deficits. In the NIOM group there were 18 new deficits (13.2%; 7.3% permanent, including 7 hemisyndromes). The groups did not significantly differ in the number or nature of postoperative deficits, nor in their recovery rate. In the IOM group, SSEPs and MEPs were available in 99% of cases. Significant changes were noted in 18 cases, 4 of which exhibited postoperative hemisyndrome, and 1 suffered from prolonged comatose state (5 true-positive cases). Twelve patients showed no new detectable deficits (false positives), however 2 of these cases showed asymptomatic infarction. Five patients with new hemisyndrome and 1 comatose patient did not show significant SSEP/MEP alterations (false negatives). Overall sensitivity of SSEP/MEP monitoring was 45.5%, specificity 89.8%, positive predictive value 27.8%, and negative predictive value 95.0%.

CONCLUSIONS

The assumed positive impact of introducing SSEP/MEP monitoring on overall neurological outcome in ECUIA did not reach significance. This study suggests that from a medicolegal point of view, IOM is not stringently required in all neurovascular procedures. However, future studies should carefully address high-risk patients with complex procedures who might benefit more clearly from IOM than others.

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Ardeshir Ardeshiri, Christian Radina, Martin Edlauer, Ardavan Ardeshiri, Alfred Riepertinger, Andreas Nerlich, Jörg-Christian Tonn and Peter A. Winkler

Object

With the introduction of intraoperative CT (iCT) scanning, neurosurgeons can now obtain images of the brain during surgery, offering the possibility of intraoperative resection control and monitoring of potential intraoperative complications. The combination of iCT with neuronavigation makes it possible to update the reference scans intraoperatively when necessary. However, the headholder pins normally used for iCT scanning still show artifacts. In the present study, new polymer pins, producing nearly no artifacts in laboratory tests, are compared with the usual pins with regard to their mechanical and artifact behavior to evaluate their potential use in the clinical routine.

Methods

Pins made of different materials (titanium, Macor, silicon nitride, zirconium oxide, sapphire, polyetheretherketone, and polyparaphenylene copolymer) were used for the fixation of 10 cadaveric heads. Special force sensors measured the fixation pressure of the pins, and histological analysis revealed the penetration depth. Computed tomography scans of a head phantom, fixed with the different pins, were obtained to reveal artifact behavior.

Results

All pins were biocompatible. Pins did not differ significantly in fixation pressures and mechanical behavior. Penetration depths were comparable (maximum 1.4 mm) and did not cause opening of the diploe. Polymer pins made of polyparaphenylene showed the best results in artifact behavior in CT scans.

Conclusions

The authors' results demonstrate that the new polymer pins are comparable in their mechanical behavior to the usual pins but superior in artifact behavior. Therefore, their use in the clinical routine of iCT scanning will be beneficial for the surgeon.

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Christian Schichor, Walter Rachinger, Dominik Morhard, Stefan Zausinger, Thomas J. Heigl, Maximilian Reiser and Jörg-Christian Tonn

Object

In vascular neurosurgery, there is a demand for intraoperative imaging of blood vessels as well as for rapid information about critical impairment of brain perfusion. This study was conducted to analyze the feasibility of intraoperative CT angiography and brain perfusion mapping using an up-to-date multislice CT scanner in a prospective pilot series.

Methods

Ten patients with unruptured aneurysms underwent intraoperative scanning with a 40-slice sliding-gantry CT scanner. Multimodal CT acquisition was obtained in 8 patients consisting of dynamic perfusion CT (PCT) scanning followed by intracranial CT angiography. Two of these patients underwent CT angiography and PCT 2 times in 1 session as a control after repositioning cerebral aneurysm clips. In another 2 patients, CT angiography was performed alone. The quality of all imaging obtained was assessed in a blinded consensus reading performed by an experienced neurosurgeon and an experienced neuroradiologist. A 6-point scoring system ranging from excellent to insufficient was used for quality evaluation of PCT and CT angiography.

Results

In 9 of 10 PCT data sets, the quality was rated excellent or good. In the remaining case, the quality was rated insufficient for diagnostic evaluation due to major streak artifacts induced by the titanium pins of the head clamp. In this particular case, the quality of the related CT angiography was rated good and sufficient for intraoperative decision making. The quality of all 12 CT angiography data sets was rated excellent or good. In 1 patient with an anterior communicating artery aneurysm, PCT scanning led to a repositioning of the clip because of an ischemic pattern of the perfusion parameter maps due to clip stenosis of an artery. The subsequent PCT scan obtained in this patient revealed an improved perfusion of the related vascular territory, and follow-up MR imaging showed only minor ischemia of the anterior cerebral artery territory.

Conclusions

Intraoperative CT angiography and PCT scanning were shown to be feasible with short acquisition time, little interference with the surgical workflow, and very good diagnostic imaging quality. Thus, these modalities might be very helpful in vascular neurosurgery. Having demonstrated their feasibility, the impact of these methods on patients' outcomes has now to be analyzed prospectively in a larger series.