Predictive value of IOM in clipping of unruptured intracranial aneurysms - A prospective study from the surgeon's point of view.

Introduction: Intraoperative neuromonitoring (IOM) of motor/somatosensory evoked potentials is a well-established approach for reducing ischemic complications after aneurysm clipping. Research question: To determine the predictive validity of IOM for postoperative functional outcome and its perceived added value for intraoperative real-time feedback of functional impairment in the surgical treatment of unruptured intracranial aneurysms (UIAs). Material and methods: Prospective study of patients scheduled for elective clipping of UIAs between 02/2019-02/2021. Transcranial motor evoked potentials (tcMEP) were used in all cases, a significant decline was defined as loss of ≥50% in amplitude or 50% latency increase. Clinical data were correlated to postoperative deficits. A surgeon's questionnaire was conceived. Results: 47 patients were included, median age 57 years (range 26-76). IOM was successful in all cases. In 87.2%, IOM was stable throughout surgery, although 1 patient (2.4%) demonstrated a permanent postoperative neurological deficit. All patients with an intraoperatively reversible tcMEP-decline (12.7%) showed no surgery-related deficit, regardless of the decline duration (range 0.5-40.0 â€‹min; mean: 13.8). Temporary clipping (TC) was performed in 12 cases (25.5%), with a decline in amplitude in 4 patients. After clip-removal, all amplitudes returned to baseline. IOM provided the surgeon with a higher sense of security in 63.8%. Discussion and conclusion: IOM remains invaluable during elective microsurgical clipping, particularly during TC of MCA and AcomA-aneurysms. It alerts the surgeon of impending ischemic injury and offers a way of maximizing the time frame for TC. IOM has highly increased surgeons' subjective feeling of security during the procedure.

Non-Invasive Mapping for Effective Preoperative Guidance to Approach Highly Language-Eloquent Gliomas-A Large Scale Comparative Cohort Study Using a New Classification for Language Eloquence.

Objective: A considerable number of gliomas require resection via direct electrical stimulation (DES) during awake craniotomy. Likewise, the feasibility of resecting language-eloquent gliomas purely based on navigated repetitive transcranial magnetic stimulation (nrTMS) has been shown. This study analyzes the outcomes after preoperative nrTMS-based and intraoperative DES-based glioma resection in a large cohort. Due to the necessity of making location comparable, a classification for language eloquence for gliomas is introduced. Methods: Between March 2015 and May 2019, we prospectively enrolled 100 consecutive cases that were resected based on preoperative nrTMS language mapping (nrTMS group), and 47 cases via intraoperative DES mapping during awake craniotomy (awake group) following a standardized clinical workflow. Outcome measures were determined preoperatively, 5 days after surgery, and 3 months after surgery. To make functional eloquence comparable, we developed a classification based on prior publications and clinical experience. Groups and classification scores were correlated with clinical outcomes. Results: The functional outcome did not differ between groups. Gross total resection was achieved in more cases in the nrTMS group (87%, vs. 72% in the awake group, p = 0.04). Nonetheless, the awake group showed significantly higher scores for eloquence than the nrTMS group (median 7 points; interquartile range 6-8 vs. 5 points; 3-6.75; p < 0.0001). Conclusion: Resecting language-eloquent gliomas purely based on nrTMS data is feasible in a high percentage of cases if the described clinical workflow is followed. Moreover, the proposed classification for language eloquence makes language-eloquent tumors comparable, as shown by its correlation with functional and radiological outcomes.

Intraoperative neuromonitoring for function-guided resection differs for supratentorial motor eloquent gliomas and metastases.

BACKGROUND: Recent data show differences in intraoperative neuromonitoring (IOM) in relation to the operated brain lesion. Due to the recently shown infiltrative nature of cerebral metastases, this work investigates the differences of IOM for cerebral metastases and glioma resection concerning sensitivity, specificity, and predictive values when aiming on preservation of motor function. METHODS: Between 2006 and 2011 we resected 171 eloquently located tumors (56 metastases, 115 gliomas) associated with the rolandic cortex or the pyramidal tract using IOM via direct cortical motor evoked potentials (MEPs). Postoperatively, MEP data were re-analyzed with respect to surgery-related paresis, residual tumor, and postoperative MRI with two different thresholds for MEP decline (50 and 80 % below baseline). RESULTS: MEP monitoring was successful in 158 cases (92.4 %). MEPs were stable in 54.7 % of all metastases cases and in 65.2 % of all glioma cases (p < 0.0001). After metastases resection, 21.4 % of patients improved and 21.9 % deteriorated in motor function. Glioma patients improved in only 5.4 % and worsened in 31.3 % of cases (p < 0.05). Resection was stopped due to MEP decline in 8.0 % (metastases) and 34.8 % of cases (gliomas) (p < 0.0002). CONCLUSION: There is significant difference between glioma and metastases resection. Post-hoc, metastases show more stable MEPs but a surprisingly high rate of surgery-related paresis and therefore a higher rate of false negative IOM.

Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

OBJECT: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. METHODS: Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. RESULTS: The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). CONCLUSIONS: Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

Changing the clinical course of glioma patients by preoperative motor mapping with navigated transcranial magnetic brain stimulation.

BACKGROUND: Mapping of the motor cortex by navigated transcranial magnetic stimulation (nTMS) can be used for preoperative planning in brain tumor patients. Just recently, it has been proven to actually change outcomes by increasing the rate of gross total resection (GTR) and by reducing the surgery-related rate of paresis significantly in cohorts of patients suffering from different entities of intracranial lesions. Yet, we also need data that shows whether these changes also lead to a changed clinical course, and can also be achieved specifically in high-grade glioma (HGG) patients. METHODS: We prospectively enrolled 70 patients with supratentorial motor eloquently located HGG undergoing preoperative nTMS (2010-2014) and matched these patients with 70 HGG patients who did not undergo preoperative nTMS (2007-2010). RESULTS: On average, the overall size of the craniotomy was significantly smaller for nTMS patients when compared to the non-nTMS group (nTMS: 25.3 ± 9.7 cm(2); non-nTMS: 30.8 ± 13.2 cm(2); p = 0.0058). Furthermore, residual tumor tissue (nTMS: 34.3%; non-nTMS: 54.3%; p = 0.0172) and unexpected tumor residuals (nTMS: 15.7%; non-nTMS: 32.9%; p = 0.0180) were less frequent in nTMS patients. Regarding the further clinical course, median inpatient stay was 12 days for the nTMS and 14 days for the non-nTMS group (nTMS: CI 10.5 - 13.5 days; non-nTMS: CI 11.6 - 16.4 days; p = 0.0446). 60.0% of patients of the nTMS group and 54.3% of patients of the non-nTMS group were eligible for postoperative chemotherapy (OR 1.2630, CI 0.6458 - 2.4710, p = 0.4945), while 67.1% of nTMS patients and 48.6% of non-nTMS patients received radiotherapy (OR 2.1640, CI 1.0910 - 4.2910, p = 0.0261). Moreover, 3, 6, and 9 months survival was significantly better in the nTMS group (p = 0.0298, p = 0.0015, and p = 0.0167). CONCLUSIONS: With the limitations of this study in mind, our data show that HGG patients might benefit from preoperative nTMS mapping.

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

OBJECT: Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. METHODS: The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. RESULTS: The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. CONCLUSIONS: In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

Superiority of tympanic ball electrodes over mastoid needle electrodes for intraoperative monitoring of hearing function.

OBJECT: Recording the auditory brainstem response (ABR) is a common method for monitoring the integrity of auditory pathways during surgery in the cerebellopontine angle. Electrocochleography (ECochG) is an alternative means of intraoperative neuromonitoring. In the present study the authors compared the practicability and prognostic significance of these two methods by performing simultaneous recordings in the operating room. METHODS: Between 2006 and 2011, 125 patients (mean age 55 years) underwent surgery in the cerebellopontine angle. Seventy-one percent of the patients presented with a hearing deficit, and 37% had useful hearing but with slight functional impairment. Auditory brainstem response was recorded with a subdermal needle electrode at the mastoid. For ECochG recording, a noninvasive ball electrode was attached to the tympanic membrane. Amplitudes obtained from both ECochG and ABR audiometry were compared and correlated to pre- and postoperative hearing deficits. RESULTS: Simultaneous intraoperative monitoring via ABR and ECochG was possible in 114 cases (91%). Postoperatively, 42% of patients showed some degree of new hearing deficit, whereas 4% had improvement. The mean amplitudes in ECochG monitoring were significantly higher (0.18 ± 0.04 µV) than the ABR potentials (0.08 ± 0.006 µV; p < 0.05). All waves recorded at the mastoid needle electrode could be recognized in the potentials of the tympanic ball electrode. Hearing outcome correlated more reliably with the relative amplitude changes in Waves III and V in ECochG (III: p = 0.0008, V: p = 0.0015) than in ABR monitoring (III: p = 0.2075, V: p = 0.0398). CONCLUSIONS: Intraoperative monitoring of the auditory system by recording with noninvasive tympanic ball electrodes is more practicable than with subcutaneous needle electrodes at the tragus. Since there is also a reliable correlation between ECochG and clinical outcome, the method can replace common ABR recording during surgery in the cerebellopontine angle.

Reliability of intraoperative neurophysiological monitoring using motor evoked potentials during resection of metastases in motor-eloquent brain regions: clinical article.

OBJECT: Resection of gliomas in or adjacent to the motor system is widely performed using intraoperative neuromonitoring (IOM). For resection of cerebral metastases in motor-eloquent regions, however, data are sparse and IOM in such cases is not yet widely described. Since recent studies have shown that cerebral metastases infiltrate surrounding brain tissue, this study was undertaken to assess the value and influence of IOM during resection of supratentorial metastases in motor-eloquent regions. METHODS: Between 2006 and 2011, the authors resected 206 consecutive supratentorial metastases, including 56 in eloquent motor areas with monitoring of monopolar direct cortically stimulated motor evoked potentials (MEPs). The authors evaluated the relationship between the monitoring data and the course of surgery, clinical data, and postoperative imaging. RESULTS: Motor evoked potential monitoring was successful in 53 cases (93%). Reduction of MEP amplitude correlated better with postoperative outcomes when the threshold for significant amplitude reduction was set at 80% (only > 80% reduction was considered significant decline) than when it was set at 50% (> 50% amplitude reduction was considered significant decline). Evidence of residual tumor was seen on MR images in 28% of the cases with significant MEP reduction. No residual tumor was seen in any case of stable MEP monitoring. Moreover, preoperative motor deficit, recursive partitioning analysis Class 3, and preoperative radiotherapy were independent risk factors for a new surgery-related motor weakness (occurring in 64% of patients with and 11% of patients without radiotherapy, p > 0.01). CONCLUSIONS: Continuous MEP monitoring provides reliable monitoring of the motor system and also influences the course of operation in resection of cerebral metastases. However, in establishing warning criteria, only an amplitude decline > 80% of the baseline should be considered significant.

Surgery of highly eloquent gliomas primarily assessed as non-resectable: risks and benefits in a cohort study.

BACKGROUND: Today, the treatment of choice for high- and low-grade gliomas requires primarily surgical resection to achieve the best survival and quality of life. Nevertheless, many gliomas within highly eloquent cortical regions, e.g., insula, rolandic, and left perisylvian cortex, still do not undergo surgery because of the impending risk of surgery-related deficits at some centers. However, pre and intraoperative brain mapping, intraoperative neuromonitoring (IOM), and awake surgery increase safety, which allows resection of most of these tumors with a considerably low rate of postoperatively new deficits. METHODS: Between 2006 and 2012, we resected 47 out of 51 supratentorial gliomas (92%), which were primarily evaluated to be non-resectable during previous presentation at another neurosurgical department. Out of these, 25 were glioblastomas WHO grade IV (53%), 14 were anaplastic astrocytomas WHO grade III (30%), 7 were diffuse astrocytomas WHO grade II (15%), and one was a pilocytic astrocytoma WHO grade I (2%). All data, including pre and intraoperative brain mapping and monitoring (IOM) by motor evoked potentials (MEPs) were reviewed and related to the postoperative outcome. RESULTS: Awake surgery was performed in 8 cases (17%). IOM was required in 38 cases (81%) and was stable in 18 cases (47%), whereas MEPs changed the surgical strategy in 10 cases (26%). Thereby, gross total resection was achieved in 35 cases (74%). Postoperatively, 17 of 47 patients (36%) had a new motor or language deficit, which remained permanent in 8.5% (4 patients). Progression-free follow-up was 11.3 months (range: 2 weeks - 64.5 months) and median survival was 14.8 months (range: 4 weeks - 20.5 months). Median Karnofsky Performance Scale was 85 before and 80 after surgery). CONCLUSIONS: In specialized centers, most highly eloquent gliomas are eligible for surgical resection with an acceptable rate of surgery-related deficits; therefore, they should be referred to specialized centers.

Predictive value and safety of intraoperative neurophysiological monitoring with motor evoked potentials in glioma surgery.

BACKGROUND: Resection of gliomas in or adjacent to the motor system is widely performed with intraoperative neuromonitoring (IOM). Despite the fact that data on the safety of IOM are available, the significance and predictive value of the procedure are still under discussion. Moreover, cases of false-negative monitoring affect the surgeon's confidence in IOM. OBJECTIVE: To examine cases of false-negative IOM to reveal structural explanations. METHODS: Between 2007 and 2010, we resected 115 consecutive supratentorial gliomas in or close to eloquent motor areas using direct cortical stimulation for monitoring of motor evoked potentials (MEPs). The monitoring data were reviewed and related to new postoperative motor deficit and postoperative imaging. Clinical outcomes were assessed during follow-up. RESULTS: Monitoring of MEPs was successful in 112 cases (97.4%). Postoperatively, 30.3% of patients had a new motor deficit, which remained permanent in 12.5%. Progression-free follow-up was 9.7 months (range, 2 weeks-40.6 months). In 65.2% of all cases, MEPs were stable throughout the operation, but 8.9% showed a new temporary motor deficit, whereas 4.5% (5 patients) presented with permanently deteriorated motor function representing false-negative monitoring at first glance. However, these cases were caused by secondary hemorrhage, ischemia, or resection of the supplementary motor area. CONCLUSION: Continuous MEP monitoring provides reliable monitoring of the motor system, influences the course of operation in some cases, and has to be regarded as the standard for IOM of the motor system. In our series, we found no false-negative MEP results.