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  • By Author: Antoniadis, Gregor x
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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, 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

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.

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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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Ralph W. Koenig, Thomas E. Schmidt, Christian P. G. Heinen, Christian R. Wirtz, Thomas Kretschmer, Gregor Antoniadis and Maria T. Pedro

Object

Surgical treatment of nerve lesions in continuity remains difficult, even in the most experienced hands. The regenerative potential of those injuries can be evaluated by intraoperative electrophysiological studies and/or intraneural dissection. The present study examines the value of intraoperative high-frequency ultrasound as an imaging tool for decision making in the management of traumatic nerve lesions in continuity.

Methods

Intraoperative high-frequency ultrasound was applied to 19 traumatic or iatrogenic nerve lesions of differing extents. The information obtained was correlated with intraoperative electrophysiological, microsurgical intraneural dissection, and histopathological findings in resected nerve segments.

Results

The intraoperative application of high-resolution, high-frequency ultrasound enabled morphological examination of nerve lesions in continuity, with good image quality. The assessment of the severity of the underlying nerve injury matched perfectly with the judgment obtained from intraoperative electrophysiological studies. Both intraneural nerve dissection and neuropathological examination of the resected nerve segments confirmed the sonographic findings. In addition, intraoperative ultrasound proved to be very time efficient.

Conclusions

With intraoperative ultrasound, the extent of traumatic peripheral nerve lesions can be examined morphologically for the first time. It is a promising, noninvasive method that seems capable of assessing the type (intraneural/perineural) and grade of nerve fibrosis. Therefore, in combination with intraoperative neurophysiological studies, intraoperative high-resolution ultrasound may represent a major tool for noninvasive assessment of the regenerative potential of a nerve lesion.

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Ralph W. Koenig, Maria T. Pedro, Christian P. G. Heinen, Thomas Schmidt, Hans-Peter Richter, Gregor Antoniadis and Thomas Kretschmer

High-resolution ultrasonography is a noninvasive, readily applicable imaging modality, capable of depicting real-time static and dynamic morphological information concerning the peripheral nerves and their surrounding tissues. Continuous progress in ultrasonographic technology results in highly improved spatial and contrast resolution. Therefore, nerve imaging is possible to a fascicular level, and most peripheral nerves can now be depicted along their entire anatomical course. An increasing number of publications have evaluated the role of high-resolution ultrasonography in peripheral nerve diseases, especially in peripheral nerve entrapment.

Ultrasonography has been shown to be a precious complementary tool for assessing peripheral nerve lesions with respect to their exact location, course, continuity, and extent in traumatic nerve lesions, and for assessing nerve entrapment and tumors. In this article, the authors discuss the basic technical considerations for using ultrasoniography in peripheral nerve assessment, and some of the clinical applications are illustrated.

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Stefan A. Rath, Slawomir Moszko, Petra M. Schäffner, Giuseppe Cantone, Veit Braun, Hans-Peter Richter and Gregor Antoniadis

Object

Although transpedicular fixation is a biomechanically superior technique, it is not routinely used in the cervical spine. The risk of neurovascular injury in this region is considered high because the diameter of cervical pedicles is very small and their angle of insertion into the vertebral body varies. This study was conducted to analyze the clinical accuracy of stereotactically guided transpedicular screw insertion into the cervical spine.

Methods

Twenty-seven patients underwent posterior stabilization of the cervical spine for degenerative instability resulting from myelopathy, fracture/dislocation, tumor, rheumatoid arthritis, and pyogenic spondylitis. Fixation included 1–6 motion segments (mean 2.2 segments). Transpedicular screws (3.5-mm diameter) were placed using 1 of 2 computer-assisted guidance systems and lateral fluoroscopic control. The intraoperative mean deviation of frameless stereotaxy was < 1.9 mm for all procedures.

Results

No neurovascular complications resulted from screw insertion. Postoperative computed tomography (CT) scans revealed satisfactory positioning in 104 (90%) of 116 cervical pedicles and in all 12 thoracic pedicles. A noncritical lateral or inferior cortical breach was seen with 7 screws (6%). Critical malplacement (4%) was always lateral: 5 screws encroached into the vertebral artery foramen by 40–60% of its diameter; Doppler sonographic controls revealed no vascular compromise. Screw malplacement was mostly due to a small pedicle diameter that required a steep trajectory angle, which could not be achieved because of anatomical limitation in the exposure of the surgical field.

Conclusions

Despite the use of frameless stereotaxy, there remains some risk of critical transpedicular screw malpositioning in the subaxial cervical spine. Results may be improved by the use of intraoperative CT scanning and navigated percutaneous screw insertion, which allow optimization of the transpedicular trajectory.

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Thomas Kretschmer, Gregor Antoniadis, Christian Heinen, Wolfgang Börm, Christian Scheller, Hans-Peter Richter and Ralph W. Koenig

✓In this article the authors attempt to raise awareness of the pitfalls and controversial issues in nerve tumor surgery. In a case-guided format, examples of ambiguous findings, inappropriate tumor removal, repeated surgery, and nerve repairs are provided. The authors also discuss the need to establish a correct diagnosis preoperatively and to avoid the erroneous identification of malignant peripheral nerve sheath tumors (MPNSTs). They emphasize that not all of the principles of soft tissue sarcoma treatment protocols are applicable to MPNST. A situation of repeated surgery for supposedly malignant tumor is described, and an outline of the indications for, and an approach to, repair after lesion removal is given.

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Julia A. Kandenwein, Thomas Kretschmer, Martin Engelhardt, Hans-Peter Richter and Gregor Antoniadis

Object. Surgical therapy for traumatic brachial plexus lesions is still a great challenge in the field of peripheral nerve surgery. The aim of this study was to present the results of different surgical interventions in patients with this lesion type.

Methods. One hundred thirty-four patients with traumatic brachial plexus lesions underwent surgery between January 1991 and September 1999. In more than 50% of the patients, injury was caused by a motorbike accident. Patients underwent surgery a mean of 6.3 months posttrauma. The following surgical techniques were applied: neurolysis for nerve lesions in continuity (27 cases), grafting for lesions in discontinuity (149 cases), and neurotization for root avulsions (67 cases). Sixty-five patients were evaluated for at least 30 months (mean follow up 42.1 months) after surgery.

Function was graded using the Louisiana State University Health Sciences Center classification system. Only 2% of the patients had Grade 3 or better function preoperatively, increasing to 52% postoperatively. The effect of surgical measures on the functional results for different muscles were compared (supra- or infraspinatus, deltoid, biceps, and triceps muscles); the best results were obtained for biceps muscle function (57% of patients with Medical Research Council Grades M3–M5 function). Graft reconstruction yielded a better outcome than neurotization. Surgery within 5 months posttrauma clearly resulted in improved recovery of motor function compared with later interventions. Sural nerve grafts (monofascicular nerves) showed better results.

Conclusions. The results of neurosurgical interventions for brachial plexus lesions are satisfactory, especially when the operation is performed between 3 and 6 months after trauma.