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Maria Teresa Pedro, Gregor Antoniadis, Angelika Scheuerle, Mirko Pham, Christian Rainer Wirtz and Ralph W. Koenig

The diagnostic workup and surgical therapy for peripheral nerve tumors and tumorlike lesions are challenging. Magnetic resonance imaging is the standard diagnostic tool in the preoperative workup. However, even with advanced pulse sequences such as diffusion tensor imaging for MR neurography, the ability to differentiate tumor entities based on histological features remains limited. In particular, rare tumor entities different from schwannomas and neurofibromas are difficult to anticipate before surgical exploration and histological confirmation. High-resolution ultrasound (HRU) has become another important tool in the preoperative evaluation of peripheral nerves. Ongoing software and technical developments with transducers of up to 17–18 MHz enable high spatial resolution with tissue-differentiating properties. Unfortunately, high-frequency ultrasound provides low tissue penetration. The authors developed a setting in which intraoperative HRU was used and in which the direct sterile contact between the ultrasound transducer and the surgically exposed nerve pathology was enabled to increase structural resolution and contrast. In a case-guided fashion, the authors report the sonographic characteristics of rare tumor entities shown by intraoperative HRU and contrast-enhanced ultrasound.

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Christina Rinkler, Frank Heuer, Maria Teresa Pedro, Uwe Max Mauer, Anita Ignatius and Cornelia Neidlinger-Wilke

Object

Environmental alterations resulting in a decrease in the nutrient supply have been associated with intervertebral disc (IVD) degeneration, particularly of the nucleus pulposus (NP). The goal of the present study was to examine the hypothesis that glucose deprivation alters the metabolism of NP cells and their responsiveness to mechanical loading. A possible interaction of glucose supply and hydrostatic pressure (HP) with gene expression by NP cells has not been investigated.

Methods

The influence of glucose supply (physiological concentration: 5 mM, reduction: 0 or 0.5 mM) and cyclic HP loading (2.5 MPa, 0.1 Hz, 30 minutes) on bovine and human NP cell matrix turnover was analyzed by quantitative real-time reverse transcriptase–polymerase chain reaction. Glucose-dependent effects on cell viability were determined by trypan blue exclusion. A glycosaminoglycan (GAG) assay was performed to determine nutritional effects on the protein level.

Results

Glucose reduction resulted in significant downregulations (p < 0.05) of aggrecan, collagen-I, and collagen-II gene expression by bovine NP cells. Exemplary human donors also displayed a similar trend for aggrecan and collagen-II, whereas matrix metalloproteinases (MMPs) tended to be upregulated under glucose deprivation. After HP loading, human NP cells showed individual upregulations of collagen-I and collagen-II expression, while MMP expression tended to be downregulated under glucose reduction relative to a normal glucose supply. Cell viability decreased with glucose deprivation. The GAG content was similar in all groups at Day 1, whereas at Day 3 there was a significant increase under physiological conditions.

Conclusions

Glucose deprivation strongly affected NP cell metabolism. The effects of an altered glucose supply on gene expression were more pronounced than the mechanically induced effects. Data in this study demonstrate that the glucose environment is more critical for disc cell metabolism than mechanical loads. In individual human donors, however, adequate mechanical stimuli might have a beneficial effect on matrix turnover during IVD degeneration.

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Andreas Knoll, Andrej Pal’a, Maria-Teresa Pedro, Ute Bäzner, Max Schneider, Ralph W. König, Christian Rainer Wirtz, Sarah Friedrich, Markus Pauly and Gregor Antoniadis

OBJECTIVE

Intraneural ganglion cysts are rare and benign mucinous lesions that affect peripheral nerves, most frequently the common peroneal nerve (CPN). The precise pathophysiological mechanisms of intraneural ganglion cyst development remain unclear. A well-established theory suggests the spread of mucinous fluid along the articular branch of the peroneal nerve as the underlying mechanism. Clinical outcome following decompression of intraneural ganglion cysts has been demonstrated to be excellent. The aim of this study was to evaluate the correlation between clinical outcome and ultrasound-detected morphological nerve features following decompression of intraneural ganglion cysts of the CPN.

METHODS

Data were retrospectively analyzed from 20 patients who underwent common peroneal nerve ganglion cyst decompression surgery at the Universität Ulm/Günzburg Neurosurgery Department between October 2003 and October 2017. Postoperative clinical outcome was evaluated by assessment of the muscular strength of the anterior tibial muscle, the extensor hallucis longus muscle, and the peroneus muscle according to the Medical Research Council grading system. Hypesthesia was measured by sensation testing. In all patients, postoperative morphological assessment of the peroneal nerve was conducted between October 2016 and October 2017 using the iU22 Philips Medical ultrasound system at the last routine follow-up appointment. Finally, the correlations between morphological changes in nerve ultrasound and postoperative clinical outcomes were evaluated.

RESULTS

During the postoperative ultrasound scan an intraneural hypoechogenic ring structure located at the medial side of the peroneal nerve was detected in 15 (75%) of 20 patients, 14 of whom demonstrated an improvement in motor function. A regular intraneural fasicular structure was identified in 3 patients (15%), who also reported recovery. In 1 patient, a recurrent cyst was detected, and 1 patient showed intraneural fibrosis for which recovery did not occur in the year following the procedure. Two patients (10%) developed neuropathic pain that could not be explained by nerve ultrasound findings.

CONCLUSIONS

The results of this study demonstrate significant recovery from preoperative weakness after decompression of intraneural ganglion cysts of the CPN. A favorable clinical outcome was highly correlated with an intraneural hypoechogenic ring-shaped structure on the medial side of the CPN identified during a follow-up postoperative ultrasound scan. These study results indicate the potential benefit of ultrasound scanning as a prognostic tool following decompression procedures for intraneural ganglion cysts of the CPN.

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Christian Scheller, Stefan Rampp, Marcos Tatagiba, Alireza Gharabaghi, Kristofer F. Ramina, Oliver Ganslandt, Barbara Bischoff, Cordula Matthies, Thomas Westermaier, Maria Teresa Pedro, Veit Rohde, Kajetan von Eckardstein and Christian Strauss

OBJECTIVE

Patient positioning in vestibular schwannoma (VS) surgery is a matter of ongoing discussion. Factors to consider include preservation of cranial nerve functions, extent of tumor resection, and complications. The objective of this study was to determine the optimal patient positioning in VS surgery.

METHODS

A subgroup analysis of a randomized, multicenter trial that investigated the efficacy of prophylactic nimodipine in VS surgery was performed to investigate the impact of positioning (semisitting or supine) on extent of resection, functional outcomes, and complications. The data of 97 patients were collected prospectively. All procedures were performed via a retrosigmoid approach. The semisitting position was chosen in 56 patients, whereas 41 patients were treated while supine.

RESULTS

Complete resection was obtained at a higher percentage in the semisitting as compared to the supine position (93% vs 73%, p = 0.002). Logistic regression analysis revealed significantly better facial nerve function in the early postoperative course in the semisitting group (p = 0.004), particularly concerning severe facial nerve paresis (House-Brackmann grade IV or worse; p = 0.002). One year after surgery, facial nerve function recovered. However, there was still a tendency for better facial nerve function in the semisitting group (p = 0.091). There were no significant differences between groups regarding hearing preservation rates. Venous air embolism with the necessity to terminate surgery occurred in 2 patients in the semisitting position (3.6%). Supplementary analysis with a 2-tailed permutation randomization with 10,000 permutations of treatment choice and a propensity score matching showed either a tendency or significant results for better facial nerve outcomes in the early postoperative course and extent of resection in the semisitting group.

CONCLUSIONS

Although the results of the various statistical analyses are not uniform, the data indicate better results concerning both a higher rate of complete removal (according to the intraoperative impression of the surgeon) and facial nerve function after a semisitting as compared to the supine position. These advantages may justify the potential higher risk for severe complications of the semisitting position in VS surgery. The choice of positioning has to consider all individual patient parameters and risks carefully.

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Christian Scheller, Andreas Wienke, Marcos Tatagiba, Alireza Gharabaghi, Kristofer F. Ramina, Oliver Ganslandt, Barbara Bischoff, Cordula Matthies, Thomas Westermaier, Gregor Antoniadis, Maria Teresa Pedro, Veit Rohde, Kajetan von Eckardstein, Thomas Kretschmer, Johannes Zenk and Christian Strauss

OBJECTIVE

The purpose of this research was to examine the stability of long-term hearing preservation and the regeneration capacity of the cochlear nerve following vestibular schwannoma (VS) surgery in a prospective study.

METHODS

A total of 112 patients were recruited for a randomized multicenter trial between January 2010 and April 2012 to investigate the efficacy of prophylactic nimodipine treatment versus no prophylactic nimodipine treatment in VS surgery. For the present investigation, both groups were pooled to compare hearing abilities in the early postoperative course and 1 year after the surgery. Hearing was examined using pure-tone audiometry with speech discrimination, which was performed preoperatively, in the early postoperative course, and 12 months after surgery and was subsequently classified by an independent otorhinolaryngologist using the Gardner-Robertson classification system.

RESULTS

Hearing abilities at 2 time points were compared by evaluation in the early postoperative course and 1 year after surgery in 102 patients. The chi-square test showed a very strong association between the 2 measurements in all 102 patients (p < 0.001) and in the subgroup of 66 patients with a preserved cochlear nerve (p < 0.001).

CONCLUSIONS

There is no significant change in cochlear nerve function between the early postoperative course and 1 year after VS surgery. The result of hearing performance, as evaluated by early postoperative audiometry after VS surgery, seems to be a reliable prognosticator for future hearing ability.

Clinical trial registration nos.: 2009-012088-32 (clinicaltrialsregister.eu) and DRKS 00000328 (“AkNiPro,” drks-neu.uniklinik-freiburg.de/drks_web/)

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Christian Scheller, Andreas Wienke, Marcos Tatagiba, Alireza Gharabaghi, Kristofer F. Ramina, Oliver Ganslandt, Barbara Bischoff, Johannes Zenk, Tobias Engelhorn, Cordula Matthies, Thomas Westermaier, Gregor Antoniadis, Maria Teresa Pedro, Veit Rohde, Kajetan von Eckardstein, Thomas Kretschmer, Malte Kornhuber, Jörg Steighardt, Michael Richter, Fred G. Barker II and Christian Strauss

OBJECTIVE

In clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled.

METHODS

The patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1–2 mg/hour) and HES (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery.

RESULTS

Pooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22–0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17–0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09–0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated.

CONCLUSIONS

Prophylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept.

Clinical trial registration no.: DRKS 00000328 (https://drks-neu.uniklinik-freiburg.de/drks_web/)

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Christian Scheller, Andreas Wienke, Marcos Tatagiba, Alireza Gharabaghi, Kristofer F. Ramina, Oliver Ganslandt, Barbara Bischoff, Johannes Zenk, Tobias Engelhorn, Cordula Matthies, Thomas Westermaier, Gregor Antoniadis, Maria Teresa Pedro, Veit Rohde, Kajetan von Eckardstein, Thomas Kretschmer, Malte Kornhuber, Jörg Steighardt, Michael Richter, Fred G. Barker II and Christian Strauss

OBJECT

A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results.

METHODS

An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1–2 mg/hr) and hydroxyethyl starch (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically.

RESULTS

Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34–3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18–1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed.

CONCLUSIONS

There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.