Jan Coburger

Continuous Local Intra-arterial Nimodipine Administration in Severe Symptomatic Vasospasm After Subarachnoid Hemorrhage

BACKGROUND:Cerebral vasospasm (CV) is a potentially disastrous consequence of subarachnoid hemorrhage despite medical treatment. Nimodipine is a potent drug for vessel relaxation, but side effects may preclude a sufficient dose. OBJECTIVE:To explore whether continuous local intra-arterial nimodipine administration (CLINA) can reverse vasospasm and prevent delayed ischemic neurological deficit. METHODS:Six consecutive subarachnoid hemorrhage patients (5 women; mean age, 47.2 years) with severe CV despite maximum medical therapy underwent CLINA within 2 hours after the onset of clinical symptoms. After anticoagulation, microcatheters were inserted distally in the concerning supra-aortic vessels. Glyceryl trinitrate injection (2 mg) was followed by CLINA (nimodipine 0.4 mg/h for 70-147 hours). Duration of CLINA was determined by neurological status, transcranial Doppler sonography, and partial tissue oxygen pressure values. RESULTS:In all patients, neurological deficits improved or partial tissue oxygen pressure values returned to normal and transcranial Doppler sonography confirmed a reduced blood flow velocity within 12 hours. Magnetic resonance imaging showed no ischemic lesion caused by CV. Neurological outcome was good (modified Rankin Scale score, 0-2) in 3 patients, whereas 1 patient had a moderate clinical outcome (modified Rankin Scale score, 3-4) and 2 patients had a poor outcome (modified Rankin Scale score, 5) because of the SAH. CONCLUSION:Preliminary data show that CLINA is a straightforward, effective, and safe option for patients with severe CV refractory to medical therapy. Dilation of spastic arteries starts within a few hours and is lasting. Indication for CLINA is peripheral and diffuse CV at any location.

Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival.

Background 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. Objective 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). Methods 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. Results 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 (6mo resp.;p<0.309) and median OS(iMRI:17mo;5-ALA&iMRI-group:18mo;p<0.708)) were not significantly different between both groups. Conclusion 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.

Comparison of navigated transcranial magnetic stimulation and functional magnetic resonance imaging for preoperative mapping in rolandic tumor surgery

Navigated transcranial magnetic stimulation (nTMS) is a novel tool for preoperative functional mapping. It detects eloquent cortical areas directly, comparable to intraoperative direct cortical stimulation (DCS). The aim of this study was to evaluate the advantage of nTMS in comparison with functional magnetic resonance imaging (fMRI) in the clinical setting. Special focus was placed on accuracy of motor cortex localization in patients with rolandic lesions. Thirty consecutive patients were enrolled in the study. All patients received an fMRI and nTMS examination preoperatively. Feasibility of the technique and spatial resolution of upper and lower extremity cortical mapping were compared with fMRI. Consistency of preoperative mapping with intraoperative DCS was assessed via the neuronavigation system. nTMS was feasible in all 30 patients. fMRI was impossible in 7 out of 30 patients with special clinical conditions, pediatric patients, central vascular lesions, or compliance issues. The mean accuracy to localize motor cortex of nTMS was higher than in fMRI. In the subgroup of intrinsic tumors, nTMS produced statistically significant higher accuracy scores of the lower extremity localization than fMRI. fMRI failed to localize hand or leg areas in 6 out of 23 cases. Using nTMS, a preoperative localization of the central sulcus was possible in all patients. Verification of nTMS motor cortex localization with DCS was achieved in all cases. The fMRI localization of the hand area proved to be postcentral in one case. nTMS has fewer restrictions for preoperative functional mapping than fMRI and requires only a limited level of compliance. nTMS scores higher on the accuracy scale than fMRI. nTMS represents a highly valuable supplement for the preoperative functional planning in the clinical routine.

Navigated High Frequency Ultrasound: Description of Technique and Clinical Comparison with Conventional Intracranial Ultrasound

OBJECTIVE Conventional curved or sector array ultrasound (cioUS) is the most commonly used intraoperative imaging modality worldwide. Although highly beneficial in various clinical applications, at present the impact of linear array intraoperative ultrasound (lioUS) has not been assessed for intracranial use. We provide a technical description to integrate an independent lioUS probe into a commercially available neuronavigation system and evaluate the use of navigated lioUS as a resection control in glioblastoma surgery. METHODS We performed a prospective study assessing residual tumor detection after complete microsurgical resection using either cioUS or lioUS in 15 consecutive patients. We compared the imaging findings of both ultrasound modalities in 44 sites surrounding the resection cavity. The respective findings were correlated with the histopathologic findings of tissue specimen obtained from those sites. RESULTS Use of cioUS leaded to an additional resection in 9 patients, whereas lioUS detected residual tumor during all surgeries. A further resection was performed at 33 of 44 intraoperative sites (75%) based on results of lioUS alone. Resected tissue was solid tumor in 66% and infiltration zone in 34%. No false-positive or false-negative findings were seen using lioUS. There was no case of a tumor detection in cioUS combined with a negative finding in lioUS. The difference of imaging results between cioUS and lioUS was significant (sign test, P<0.001). CONCLUSIONS lioUS can be used as a safe and precise tool for intracranial image-guided resection control of glioblastomas. It can be integrated in a commercially available navigation system and shows a significant higher detection rate of residual tumor compared with conventional cioUS.

Multi-Institutional Neurosurgical Training Initiative at a Tertiary Referral Center in Mwanza, Tanzania: Where We Are After 2 Years

BACKGROUND The paucity of neurosurgical care in East Africa remains largely unaddressed. A sustained investment in local health infrastructures and staff training is needed to create an independent surgical capacity. The Madaktari organization has addressed this issue by starting initiatives to train local general surgeons and assistant medical officers in basic neurosurgical procedures. We report illustrative cases since beginning of the program in Mwanza in 2009 and focus on the most recent training period. METHODS A multi-institutional neurosurgical training program and a surgical database was created at a tertiary referral center in Mwanza, Tanzania. We collected clinical data on consecutive patients who underwent a neurosurgical procedure between September 9th and December 1st, 2011. All procedures were performed by a local surgeon under the supervision of a visiting neurosurgeon. Since the inception of the training initiative, comprehensive multidisciplinary training courses in Tanzania and an annual visiting fellowship for East African surgeons to travel to a major U.S. medical center have been established. RESULTS At initial visits infrastructure and feasibility of complex case scenarios was assessed. Surgeries for brain tumors and complex spinal cases were performed. During the 3-month training period, 62 patients underwent surgery. Pediatric hydrocephalus comprised 52% of patients, 11% suffered from meningomyelocelia, and 6% presented with an encephalocele. A total of 24% of patients were treated for trauma-related conditions, representing 75% of the adult patients. A total of 10% of patients had surgery because of traumatic spine injury, and 15% of operations were on patients with severe head injury. A total of 6% of patients presented with degenerative spine disease. One patient sustained a fatal perioperative complication. At the end of the training period, the local general surgeon was able to perform all basic neurosurgical cases independently. CONCLUSIONS Neurosurgical care in Tanzania needs to address a diverse, unique disease burden. We found that local surgeons could be enabled to safely perform basic cranial and spinal neurosurgical procedures through immersive, 1-on-1 on-site collaborations, multidisciplinary courses, and educational visiting fellowships.

Factors associated with supportive care needs in glioma patients in the neuro-oncological outpatient setting

Objective of this study aimed at assessing glioma patients’ supportive care needs in a neurosurgical outpatient setting and identifying factors that are associated with needs for support. In three neuro-oncological outpatient departments, glioma patients were assessed for their psychosocial needs using the Supportive Care Needs Survey short-form (SCNS-SF34-G). Associations between clinical, sociodemographic, treatment related factors as well as distress (measured with the distress thermometer) and supportive care needs were explored using multivariable general linear models. One-hundred and seventy three of 244 eligible glioma patients participated, most of them with primary diagnoses of a high-grade glioma (81%). Highest need for support was observed in ‘psychological needs’ (median 17.5, range 5–45) followed by ‘physical and daily living needs’ (median 12.5, range 0–25) and ‘health system and information needs’ (median 11.3, range 0–36). Needs in the psychological area were associated with distress (R2 = 0.36) but not with age, sex, Karnofsky performance status (KPS), extend of resection, currently undergoing chemotherapy and whether guidance during assessment was offered. Regarding ‘health system and information needs’, we observed associations with distress, age, currently undergoing chemotherapy and guidance (R2 = 0.31). In the domain ‘physical and daily living needs’ we found associations with KPS, residual tumor, as well as with distress (R2 = 0.37). Glioma patients in neuro-oncological departments report unmet supportive care needs, especially in the psychological domain. Distress is the factor most consistently associated with unmet needs requiring support and could serve as indicator for clinical neuro-oncologists to initiate support.

Histopathological Insights on Imaging Results of Intraoperative Magnetic Resonance Imaging, 5-Aminolevulinic Acid, and Intraoperative Ultrasound in Glioblastoma Surgery

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.

Contemporary use of intraoperative imaging in glioma surgery: A survey among EANS members

OBJECTIVES 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. PATIENTS AND METHODS 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. RESULTS 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)). CONCLUSION 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.

Linear array ultrasound: a dedicated tool for a dedicated application.

We appreciate the comment by Dr Moiyadi. As an experienced intraoperative ultrasound user, he adds additional clinical information to our article and provides an overview for the reader. Obviously, sector array ultrasound and linear array ultrasound are no competing technologies. At our center, we always have both types of probes draped if we perform a case. Thus, the surgeon can choose the transducer fitting for the respective situation. Our article provides a comparison of both probes solely for the purpose of residual tumor control. Using a strict intraoperative protocol, we harvested histological specimens to compare imaging results of linear array ultrasound, conventional sector array ultrasound, and iMRI. In this specific setting, linear array ultrasound was superior in the detection of residual tumor. In our experience, linear array intraoperative ultrasound is highly beneficial for residual tumor detection, and thus helps us to prevent multiple intraoperative iMRI scans. Only linear array ultrasound allows for high-frequency ultrasound (7– 30 MHz). The high frequency provides a high resolution, which renders a precise tissue differentiation possible. This feature allows for differentiation of skin tumors in dermatology or is used in breast-sparing surgery. However, an increase of frequency leads to a loss of penetration depth. Additionally, the aperture of linear array ultrasound was too large for intracranial use for a long time. Recently, small linear array transducers, as described in our article, became available and are used by many centers. The great potential is the high resolution directly below the tip of the transducer. Hence, the surgeon can literally scan the tissue during resection and detect thin margins of residual tumor. Actual low-frequency sector or curved array ultrasound transducers also allow for intracavital ultrasound. The distance to the tissue of interest can be artificially increased using gel pads, as described byDr. Moiyadi. However, the physical resolution of ultrasound is mainly based on its frequency and thus will be lower in sector array ultrasound. As described previously, intracavital ultrasound reduces artifacts significantly. As nicely described by Selbekk et al., there are many potential artifacts the surgeon should be aware of [1]. Physically, all types of ultrasound devices are affected by these common ultrasound artifacts. Many of them can be reduced with a good imaging setup. A conventional ultrasound with an optimal setup might provide much better images than a high-frequency linear array ultrasound that was poorly adjusted. One of the key features of the intraoperative linear array probe is the hockey stick shape, which allows for an easy introduction in even small resection cavities. This might add to the benefit we found in our study. This shape, to the best of our knowledge, is technically only achievable with a linear array transducer. However, there are curved linear array and sector array transducers on the market that are smaller than the 3D sector matrix array transducer we used as a “conventional” probe in our setup. The main disadvantage of the small linear array transducer is that it provides a very detailed image of a small area of the brain. Especially if it is inserted in a resection cavity it is challenging to retrieve the spot with a small residual tumor. Thus, we recommend using the device in a navigation setup as it was performed in the actual study. Sector array ultrasound provides a much better overview and a better orientation concerning anatomical landmarks, especially at the beginning of surgery if no navigation is used. When the linear array ultrasound is referenced to the neuronavigation system, this overview can be provided by the preoperative or intraoperative MRI images. In this setup, we * Jan Coburger jan.coburger@uni-ulm.de

Evaluation of surgical decision making and resulting outcome in patients with highly eloquent glioblastoma: Results of a multicenter assessment

INTRODUCTION Treatment of glioblastoma(GB) patients amenable only for a subtotal resection(STR) is controversial. Since outcome of patients is affected by surgical management, our aim was to assess surgical decision making and resulting outcome in patients with highly eloquent GBs. PATIENTS AND METHODS We retrospectively assessed GB patients with intended sub-total resection (STR) or stereotactic biopsy (STX) of 3 neurooncological centers operated between 2008 and 2013. A volumetric assessment of overall extent of resection(oEoR), presence of complications, new permanent neurological deficits(nPNDs) was performed. A central reviewer reassessed all cases blinded and gave recommendation on surgical management and on a potential EoR(pEoR) based on imaging data. We compared outcome data using Mann-Whitney-U-test and Sign-Rank-Test. Survival was assessed based on Kaplan-Meier-estimates. RESULTS 97 patients were included. In 17 patients received STX, 70 patients a STR and 10 patients a near total resection (NTR, EoR>95%). Median OS was significantly different from STX patients only if NTR was reached (16 vs. 7 months, p=0.042). The central reviewer recommended a more aggressive strategy(NTR or STR resp.) in 41 patients and a less aggressive strategy in 13 patients. Overall, management recommendation was significantly different to clinical treatment (p<0.001). Mean pEoR was significantly higher than oEoR (85.7% vs. 71.3%, p=0.001). Regarding the different OR subgroups, no significant differences were found in the NTR group(12/13 ties, p=1) and in STX group (14/17 ties, p=0.125). In STR group, a significant difference was found (p=0.001). In 38/69 patients a NTR and in 13/77 patients a STX was recommended. CONCLUSION Surgery in GB patients with intended STR requires precise preoperative planning since potential EoR is mainly underestimated. Especially, patients with lesions amenable for a NTR should not be missed.