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"König, Ralph"
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Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival
2015
There is rising evidence that in glioblastoma (GBM) surgery an increase of extent of resection (EoR) leads to an increase of patient's survival. Based on histopathological assessments tumor depiction of Gd-DTPA enhancement and 5-aminolevulinic-acid-fluorescence (5-ALA) might be synergistic for intraoperative resection control.
To assess impact of additional use of 5-ALA in intraoperative MRI (iMRI) assisted surgery of GBMs on extent of resection (EoR), progression free survival (PFS) and overall survival (OS).
We prospectively enrolled 33 patients with GBMs eligible for gross-total-resection(GTR) and performed a combined approach using 5-ALA and iMRI. As a control group, we performed a retrospective matched pair assessment, based on 144 patients with iMRI-assisted surgery. Matching criteria were, MGMT promotor methylation, recurrent surgery, eloquent location, tumor size and age. Only patients with an intended GTR and primary GBMs were included. We calculated Kaplan Mayer estimates to compare OS and PFS using the Log-Rank-Test. We used the T-test to compare volumetric results of EoR and the Chi-Square-Test to compare new permanent neurological deficits (nPND) and general complications between the two groups.
Median follow up was 31 months. No significant differences between both groups were found concerning the matching criteria. GTR was achieved significantly more often (p <0.010) using 5-ALA&iMRI (100%) compared to iMRI alone (82%). Mean EoR was significantly (p<0.004) higher in 5-ALA&iMRI-group (99.7%) than in iMRI-alone-group (97.4%) Rate of complications did not differ significantly between groups (21% iMRI-group, 27%5-ALA&iMRI-group, p<0.518). nPND were found in 6% in both groups. Median PFS (6 mo resp.; p<0.309) and median OS (iMRI:17 mo; 5-ALA&iMRI-group: 18 mo; p<0.708)) were not significantly different between both groups.
We found a significant increase of EoR when combining 5-ALA&iMRI compared to use of iMRI alone. Maximizing EoR did not lead to an increase of complications or neurological deficits if used with neurophysiological monitoring in eloquent lesions. No final conclusion can be drawn whether a further increase of EoR benefits patient's progression free survival and overall survival.
Journal Article
PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial
by
Güresir, Erdem
,
Brandecker, Simon
,
Mielke, Dorothee
in
Aneurysms
,
Biomedicine
,
Care and treatment
2022
Background
Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear.
Methods
PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC.
Discussion
This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients.
Trial registration
DRKS DRKS00017650. Registered on 09 June 2019.
Journal Article
Novelties and limitations of tissue-engineered materials in treating traumatic nerve injuries: a mini review
2025
Peripheral nerve injuries remain challenging due to the limited regenerative capacity over long distances and the complexity of repair mechanisms. While autologous nerve grafts are the clinical gold standard, their use is restricted by donor-site morbidity and tissue availability. Tissue-engineered materials such as nerve guidance conduits (NGCs), hydrogels, and bioactive scaffolds offer alternative solutions by providing structural support and delivering trophic, immunomodulatory, or electrical cues. This mini-review categorizes these materials by their functional properties, including drug delivery, cell integration, and electroactivity, and critically assesses their preclinical performance and translational limitations. Natural materials such as collagen and chitosan exhibit good biocompatibility but limited mechanical stability and variability. Synthetic polymers and electroactive materials allow for customization and controlled stimulation but often provoke immune responses or degrade into harmful byproducts. Advanced drug-delivery systems using hydrogels and microspheres enable targeted factor release, yet reproducibility and kinetics remain critical barriers. Cell-integrated constructs, including Schwann cell-like cells and engineered neural tissue, offer high regenerative potential but face challenges in scalability, regulatory classification, and manufacturing. Importantly, many preclinical studies do not benchmark against autografts or address neuroma formation, fibrosis, and delayed regeneration—key issues in human lesions. A summary of preclinical constructs and translational barriers is provided to highlight recurring obstacles such as immune incompatibility, insufficient vascular integration, and regulatory hurdles. Future research must refine model systems, align regulatory strategies, and enhance construct functionality to enable effective clinical translation.
Journal Article
Histopathological Insights on Imaging Results of Intraoperative Magnetic Resonance Imaging, 5-Aminolevulinic Acid, and Intraoperative Ultrasound in Glioblastoma Surgery
by
Scheuerle, Angelika
,
Coburger, Jan
,
Thal, Dietmar
in
Brain cancer
,
Gangrene
,
Nuclear magnetic resonance
2017
Abstract
BACKGROUND: For appropriate use of available intraoperative imaging techniques in glioblastoma (GB) surgery, it is crucial to know the potential of the respective techniques in tumor detection.
OBJECTIVE: To assess histopathological basis of imaging results of intraoperative magnetic resonance imaging (iMRI), 5-aminolevulinic acid (5-ALA), and linear array intraoperative ultrasound (lioUS).
METHODS: We prospectively compared the imaging findings of iMRI, 5-ALA, and lioUS at 99 intraoperative biopsy sites in 33 GB patients during resection control. Histological classification of specimens, tumor load, presence of necrosis, presence of vascular malformations, and O6-methylguanin-DNA methyltransferase (MGMT) promoter state was correlated with imaging findings.
RESULTS: Solid tumor was found in 57%, infiltration zone in 42%, and no tumor in 1% of specimens. However, imaging was negative in iMRI in 49%, using 5-ALA in 17%, and in lioUS in 21%. In positive imaging results, share of solid tumor was highest in 5-ALA (65%) followed by lioUS (60%) and lowest in iMRI (55%). In comparison to 5-ALA, iMRI had a high share of solid tumor in specimens when showing intermediate results. Sensitivity for invasive tumor was higher in 5-ALA (84%) and lioUS (80%) than in iMRI (50%). We found a significant correlation of 5-ALA with classification of specimen, presence of necrosis, and microproliferations. Methylated MGMT promoter correlated with positive findings in 5-ALA. lioUS and iMRI showed no correlations with histopathological findings.
CONCLUSION: All of the assessed established imaging techniques detect infiltrating tumor only to a certain extent. Only 5-ALA showed a significant correlation with histopathological findings. Interestingly, tumor remnants in an MGMT-methylated tumor are more likely to be visible using 5-ALA as in unmethylated tumors.
Journal Article
The value of intraoperative angiography in the time of indocyanine green videoangiography in the treatment of cerebrovascular lesions: Efficacy, workflow, risk-benefit and cost analysis A prospective study
by
Pala, Andrej
,
Durner, Gregor
,
Wirtz, Christian Rainer
in
Aneurysms
,
Angiography
,
Cost analysis
2021
Intraoperative digital subtraction angiography (ioDSA) allows early treatment evaluation after neurovascular procedures. However, the value and efficiency of this procedure has been discussed controversially.
We have evaluated the additional value of hybrid operating room equipped with an Artis Zeego robotic c-arm regarding cost, efficiency and workflow. Furthermore, we have performed a risk-benefit analysis and compared it with indocyanine green (ICG) angiography.
For 3 consecutive years, we examined all neurovascular patients, treated in the hybrid operating theater in a risk-benefit analysis. After using microdoppler and ICG angiography for best operative result, every patient received an additional ioDSA to look for remnants or unfavorable clip placement which might lead to a change of operating strategy or results.
Furthermore, a workflow-analysis reviewing operating steps, staff positioning, costs, technical errors or complications were conducted on randomly selected cases.
54 patients were enrolled in the risk-benefit analysis, 22 in the workflow analysis. The average duration of a cerebrovascular operation was 4 h 58 min 2 min 35 s accounted for ICG angiography, 46 min 4 s for ioDSA. Adverse events occurred during one ioDSA. In risk-benefit analysis, ioDSA was able to detect a perfusion rest in 2 out of 43 cases (4,7%) of aneurysm surgery, which could not have been visualized by ICG angiography before. In arterio-venous-malformation (AVM) surgery, one of 11 examined patients (7,7%) showed a remnant in ioDSA and resulted in additional resection.
The average cost of an ioDSA in Ulm University can be estimated with 1928,00€.
According to our results ioDSA associated complications are low. Relevant findings in ioDSA can potentially avoid additional intervention, however, due to the high costs and lower availability, the main advantage might lie in the treatment of selected patients with complexes neurovascular pathologies since ICG angiography is equally safe but associated with lower costs and better availability.
•On average ioDSA took 46 min and 4 s including preparation and post processing, accounting for 17,0% of the mean operation time.•For aneurysm clipping, ioDSA was able to display a relevant aneurysm rest-perfusion in 2 out of 43 dases (4,7%) which could not be detected with ICG.•In AVM surgery, ioDSA would have displayed an unsuspected AVM remnant in one of 13 cases (7.7%).•ioDSA displays pathologies which are undetectable by other imaging modalities. However, ICG is associated with lower costs and better availability.
Journal Article
Restoring musculocutaneous nerve function in 146 brachial plexus operations – A retrospective analysis
2023
A brachial plexus lesion is a devastating injury often affecting young, male adults after traffic accidents. Therefore, surgical restoration of elbow flexion is critical for establishing antigravity movement of the upper extremity. We analyzed different methods for musculocutaneous reconstruction regarding outcome.
We conducted a retrospective analysis of 146 brachial plexus surgeries with musculocutaneous reconstruction performed at our department from 2013 to 2017. Demographic data, surgical method, donor and graft nerve characteristics, body mass index (BMI) as well as functional outcome of biceps muscle based on medical research council (MRC) strength grades before and after surgery were analyzed. Multivariate analysis was performed using SPSS.
Oberlin reconstruction was the procedure performed most often (34.2%, n = 50). Nerve transfer and autologous repair showed no significant differences regarding outcome (p = 0.599, OR 0.644 CI95% 0.126–3.307). In case of nerve transfers, we found no significant difference whether reconstruction was performed with or without a nerve graft (e.g. sural nerve) (p = 0.277, OR 0.619 CI95% 0.261–1.469). Multivariate analysis identifies patient age as a strong predictor for outcome, univariate analysis indicates that nerve graft length > 15 cm and BMI of > 25 could lead to inferior outcome. When patients with early recovery (n = 19) are included into final evaluation after 24 months, the general success rate of reconstructions is 62,7% (52/83).
Reconstruction of musculocutaneous nerve after brachial plexus injury results in a high rate of clinical improvement. Nerve transfer and autologous reconstruction both show similar results. Young age was confirmed as an independent predictor for better clinical outcome. Prospective multicenter studies are needed to further clarify.
•Relevant clinical improvement of biceps strength (medical research council MRC grades > 3/5) could be achieved in 62,7% of cases.•Nerve transfer and autologous repair showed no significant differences regarding outcome (p = 0.599, OR 0.644 CI95% 0.126–3.307).•For nerve transfers, we found no significant difference whether reconstruction was performed with or without a nerve graft (e.g. sural nerve) (p = 0.277, OR 0.619 CI95% 0.261–1.469).•Nerve graft length of > 15 cm and body mass index (BMI) of > 25 might lead to inferior outcome.
Journal Article
Linear array ultrasound in low-grade glioma surgery: histology-based assessment of accuracy in comparison to conventional intraoperative ultrasound and intraoperative MRI
by
Scheuerle, Angelika
,
Engelke, Jens
,
König, Ralph
in
Adolescent
,
Adult
,
Brain Neoplasms - diagnostic imaging
2015
Introduction
In low-grade glioma (LGG) surgery, intraoperative differentiation between tumor and most likely tumor-free brain tissue can be challenging. Intraoperative ultrasound can facilitate tumor resection. The aim of this study is to evaluate the accuracy of linear array ultrasound in comparison to conventional intraoperative ultrasound (cioUS) and intraoperative high-field MRI (iMRI).
Methods
We prospectively enrolled 13 patients harboring a LGG of WHO Grade II. After assumed near total removal, a resection control was performed using navigated cioUS, navigated lioUS, and iMRI. We harvested 30 navigated biopsies from the resection cavity and compared the histopathological findings with the respective imaging results. Spearman’s rho was calculated to test for significant correlations. Sensitivity and specificity as well as receiver operating characteristics (ROC) were calculated to assess test performance of each imaging modality.
Results
Imaging results of lioUS correlated significantly (
p
< 0.009) with iMRI. Both iMRI and lioUS correlated significantly with final histopathological diagnosis (
p
< 0.006,
p
< 0.014). cioUS did not correlate with other imaging findings or with final diagnosis.
The highest sensitivity for residual tumor detection was found in iMRI (83 %), followed by lioUS (79 %). The sensitivity of cioUS was only 21 %. Specificity was highest in cioUS (100 %), whereas iMRI and lioUS both achieved 67 %. ROC curves showed fair results for iMRI and lioUS and a poor result for cioUS.
Conclusions
Intraoperative resection control in LGGs using lioUS reaches a degree of accuracy close to iMRI. Test results of lioUS are superior to cioUS. cioUS often fails to discriminate solid tumors from “normal” brain tissue during resection control. Only in lesions <10 cc cioUS does show good accuracy.
Journal Article
Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging
by
Senft, Christian
,
Mehdorn, Maximilian
,
Pala, Andrej
in
Adult
,
Aged
,
Brain Neoplasms - diagnostic imaging
2016
BACKGROUND:The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published.
OBJECTIVE:To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging.
METHODS:A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment.
RESULTS:A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas “failed” GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio0.51, P < .01) was positively and eloquent location (odds ratio1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits.
CONCLUSION:GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS.
ABBREVIATIONS:EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization
Journal Article
Contemporary use of intraoperative imaging in glioma surgery: A survey among EANS members
2017
•Survey among EANS members.•Evaluation of the responses of 310 neurosurgeons.•Assessment of distribution and benefit of intraoperative imaging in glioma surgery.•Assessment of tumor control of iMRI, 5-ALA, ultrasound, iCT and Na-Fluorescein(yellow) separate for GB and LGG.•Specific evaluation of usability, orientation for each technique.
In glioma surgery, intraoperative imaging is regarded highly valuable to improve extent of resection. Current distribution of intraoperative imaging techniques is largely unknown. Further, controversy exists which method might be most beneficial.
We performed a web-based survey among members of the European Association of Neurological Surgeons(EANS) from April to May 2017. Our questionnaire included intraoperative MRI(iMRI), 5-aminolevulinic acid(5-ALA), intraoperative ultrasound(iUS),Na-Fluorescein and intraoperative CT(iCT). The value of each method in resection of glioblastoma(GB) and low-grade-glioma(LGG) and their role for intraoperative orientation and usability were rated based on Likert-scales from 1(not valuable/important) to 5(very valuable/important). A total score was calculated based on each sub-score. Mann-Whitney-U-test was used to compare ratings of imaging methods.
Among the 310 participants, iMRI and 5-ALA were regarded as the most valuable intraoperative imaging methods in GB-surgery (iMRIvs.5-ALA,p=0.573;mean 4.05(SE0.149)vs.4.22(SE0.216)). Both were considered significantly more valuable than iUS, Na-Fluorescein and iCT(p≤0.001).Compared to all other methods, iMRI received significantly higher ratings for the resection of LGGs (p<0.01,mean 4.21(SE 0.143)) as well as for intraoperative orientation (mean 4.00(SE0.166)).5-ALA was rated highest regarding intraoperative usability (mean 4.07(SE0.082)). iMRI showed the highest total score compared to all other imaging modalities(p<0.001,mean 15.95(SE 0.484)).
iMRI and 5-ALA were rated most valuable for GB-surgery, while only iMRI reached higher ratings in LGG cases. iMRI was the best imaging method for intraoperative orientation as well as the most valuable method in overall rating. Considering the total score, 5-ALA and iUS received similar values and were rated second highest, followed by Na-Fluorescein and iCT.
Journal Article
Role of intraoperative neurophysiology in primary surgery for obstetrical brachial plexus palsy (OBPP)
by
König, Ralph W.
,
Börm, Wolfgang
,
Richter, Hans-Peter
in
Adolescent
,
Brachial plexus
,
Brachial Plexus - pathology
2006
Management of conducting neuroma-in-continuity in primary surgery for obstetrical brachial plexus palsy (OBPP) is still discussed controversially. We present our experience with intraoperative neurophysiological recordings in the management of lesions in continuity in OBPP.
A series of ten children with lesions in continuity of the upper brachial plexus is presented. Due to recordable compound nerve action potentials (CNAPs) and muscle response to motor stimulation across the neuroma, five children underwent external neurolysis of neuroma only (neurolysis group). Due to lack of recordable CNAPs or muscle response, resection of neuroma and interpositional nerve grafting were performed in another five children (resection and grafting group). Functional recovery after at least 30 months of follow-up was assessed.
There was a marked difference in functional recovery between the neurolysis and the resection and grafting group. Especially, recovery of shoulder function was disappointing after external neurolysis of conducting neuroma-in-continuity. At the end of follow-up, results of shoulder and elbow function after resection of neuroma followed by interpositional nerve grafting were better without exception.
Intraoperative neurophysiological recordings face certain difficulties when used in small children with OBPP. Due to overoptimistic assessment of prognosis after intraoperative CNAP recordings and motor stimulation, the functional results after neurolysis of conducting neuroma-in-continuity are disappointing. Resection of neuroma-in-continuity, conducting or not, offers the best opportunity for maximal functional recovery of the compromised upper limb in OBPP. The role of intraoperative neurophysiological techniques should be confined to the diagnosis of root avulsions.
Journal Article