Establishment of Different Intraoperative Monitoring and Mapping Techniques and Their Impact on Survival, Extent of Resection, and Clinical Outcome in Patients with High-Grade Gliomas-A Series of 631 Patients in 14 Years.

BACKGROUND: The resection of brain tumors can be critical concerning localization, but is a key point in treating gliomas. Intraoperative neuromonitoring (IONM), awake craniotomy, and mapping procedures have been incorporated over the years. Using these intraoperative techniques, the resection of eloquent-area tumors without increasing postoperative morbidity became possible. This study aims to analyze short-term and particularly long-term outcomes in patients diagnosed with high-grade glioma, who underwent surgical resection under various technical intraoperative settings over 14 years. METHODS: A total of 1010 patients with high-grade glioma that underwent resection between 2004 and 2018 under different monitoring or mapping procedures were screened; 631 were considered eligible for further analyses. We analyzed the type of surgery (resection vs. biopsy) and type of IONM or mapping procedures that were performed. Furthermore, the impact on short-term (The National Institute of Health Stroke Scale, NIHSS; Karnofsky Performance Scale, KPS) and long-term (progression-free survival, PFS; overall survival, OS) outcomes was analyzed. Additionally, the localization, extent of resection (EOR), residual tumor volume (RTV), IDH status, and adjuvant therapy were approached. RESULTS: In 481 patients, surgery, and in 150, biopsies were performed. The number of biopsies decreased significantly with the incorporation of awake surgeries with bipolar stimulation, IONM, and/or monopolar mapping (p < 0.001). PFS and OS were not significantly influenced by any intraoperative technical setting. EOR and RTV achieved under different operative techniques showed no statistical significance (p = 0.404 EOR, p = 0.186 RTV). CONCLUSION: Based on the present analysis using data from 14 years and more than 600 patients, we observed that through the implementation of various monitoring and mapping techniques, a significant decrease in biopsies and an increase in the resection of eloquent tumors was achieved. With that, the operability of eloquent tumors without a negative influence on neurological outcomes is suggested by our data. However, a statistical effect of monitoring and mapping procedures on long-term outcomes such as PFS and OS could not be shown.

Feasibility of intraoperative neuromonitoring and cortical/subcortical mapping in patients with cerebral lesions of highly functional localizations-pathway to case adapted monitoring and mapping procedures.

Background: Intraoperative neuromonitoring (IONM) and mapping procedures via direct cortical stimulation (DCS) are required for resection of eloquently located cerebral lesions. In our neurooncological department, mapping and monitoring are used either combined or separately for surgery of functional lesions. The study aims to provide a practical insight into strengths and pitfalls of intraoperative neuromonitoring and mapping in supratentorial functionally located infiltrating lesions. Methods: IONM and mapping techniques performed in eloquent located brain tumors were analyzed with a focus on neurological outcome and resection results obtained via MRI. Additionally, the surgeons' view on obligatory techniques was explored retrospectively immediately after surgery. To evaluate the impact of the described items, we correlated intraoperative techniques in various issues. Results: Majority of the 437 procedures were performed as awake surgery (53%). Monopolar stimulation was used in 348 procedures and correlated with a postoperative temporary neurological deficit. Bipolar stimulation was performed in 127 procedures, particularly on tumors in the left hemisphere for language mapping. Overall permanent deficit was seen in 2% of the patients; neither different mapping or monitoring modes nor stimulation intensity, localization, or histopathological findings correlated significantly with permanent deficits. Evaluation of post-OP MRI revealed total resection (TR) in 209 out of 417 cases. Marginal residual volume in cases where total resection was assumed but MRI failed to proof TR was found (0.4 ml). Surgeons' post-OP evaluation of obligatory techniques matched in 73% with the techniques actually used. Conclusion: We report 437 surgical procedures on highly functional located brain lesions. Resection without permanent deficit was adequately achievable in 98% of the procedures. Chosen mapping or monitoring techniques mostly depended on localization and vascular conflicts but also in some procedures on availability of resources, which was emphasized by the post-OP surgeons' evaluation. With the present study, we aimed to pave the way to á la carte choice of monitoring and or mapping techniques, reflecting the possibilities of even supratotal resection in eloquent brain tumor lesions and the herewith increased need for monitoring and limiting resources.

Functional Outcome and Overall Survival in Patients with Primary or Secondary CNS Lymphoma after Surgical Resection vs. Biopsy.

BACKGROUND: Central nervous system lymphoma (CNSL) is rare form of brain tumour. It manifests either as primary CNS lymphoma (pCNSL) originating within the central nervous system or as secondary CNS lymphoma (sCNSL), arising as cerebral metastases of systemic lymphoma. For a significant period, surgical resection was considered obsolete due to the favourable response to chemotherapy and the associated risk of postoperative deficits. The objective of the present study was to demonstrate the benefits of resection in CNSL patients, including extended survival and improved postoperative function. METHODS: A retrospective study involving patients diagnosed with either PCNSL or SCNSL that were surgically approached at our neurosurgical department between 2010 and 2022 was conducted. Patients were categorised into three subgroups based on their neurosurgical approach: (1) stereotactical biopsy, (2) open biopsy, (3) resection. We then performed statistical analyses to assess overall survival (OS) and progression-free survival (PFS). Additionally, we examined various secondary factors such as functional outcome via Karnofsky Performance Index (KPS) and prognosis scoring. RESULTS: 157 patients diagnosed with PCNSL or SCNSL were enclosed in the study. Of these, 101 underwent stereotactic biopsy, 21 had open biopsy, and 35 underwent resection. Mean age of the cohort was 64.94 years, with majority of patients being female (54.1%). The resection group showed longest OS at 44 months (open biopsy = 13 months, stereotactic biopsy = 9 months). Calculated median follow-up was 34.5 months. In the Cox regression model, postoperative KPS 70% (p < 0.001) and resection vs. stereotactic biopsy (p = 0.040) were identified as protective factors, whereas older age at diagnosis was identified as a risk factor (p < 0.001). In the one-way analysis of variance, differences in postoperative KPS were found among all groups (p = 0.021), while there was no difference in preoperative KPS among the groups. CONCLUSIONS: Our data show a favourable outcome when resection is compared to either stereotactic or open biopsy. Additionally, the marginally improved postoperative functional status observed in patients who underwent resection, as opposed to in those who underwent biopsy, provides further evidence in favour of the advantages of surgical resection for enhancing neurological deficits.

Resection of Eloquent Located Brain Tumors by Mapping Only-A Feasibility Study.

BACKGROUND: Patients with eloquently located cerebral lesions require surgery that usually employs mapping and monitoring techniques for the preservation of motor and language function. However, in many cases, mapping only might be sufficient, reducing the need for technical and personnel logistics. Here, we report our experiences using a device that can be operated by the surgeon independently, providing mapping techniques but omitting monitoring techniques. METHODS: For monopolar and bipolar cortical/subcortical stimulation, pre-set programs were available and intraoperatively used-two enabling EMG real-time tracking of eight muscles for monopolar (cortical/subcortical) mapping, and two programs for 60 Hz stimulation, one with EMG and one without. Motor mapping was performed under continuous observation of the screened EMG signal and acoustic feedback by the surgeon. For the 60 Hz stimulation, a standard bipolar stimulation probe was connected through a second port. The preoperative application of the subdermal EMG needles, as well as the intraoperative handling of the device, were performed by the surgeons independently. Postoperatively, an evaluation of the autonomous handling and feasibility of the device for the chosen test parameters was conducted. RESULTS: From 04/19-09/21, 136 procedures in patients with eloquently located cerebral lesions were performed by using the "mapping-only" device. Mapping was performed in 82% of the monopolar cases and in 42% of the bipolar cases. Regarding the setup and sufficiency for the cortical/subcortical mapping, the device was evaluated as independently usable for motor and language mapping in 129 procedures (95%). Gross total resection was achieved, or functional limit throughout resection was reached, in 79% of the patients. 13 patients postoperatively suffered from a new neurological deficit. At the 3-6-month follow-up, three patients showed persistent deficit (2%). All of them had language disturbances. The setup time for the device was less than 7 min. CONCLUSIONS: The device was evaluated as sufficient in over 90% of cases concerning monopolar and bipolar mapping, and the setup and handling was sufficient in all patients. With the present data we show that in well-selected cases, a very simple system providing mapping only is sufficient to achieve gross total resection with the preservation of functionality.

The impact of preoperative MRI-based apparent diffusion coefficients on local recurrence and outcome in patients with cerebral metastases.

BACKGROUND: Surgery of single cerebral metastases is standard but frequently fails to achieve local tumour control. Reliable predictors for local tumour progression and overall survival are unknown. MRI-based apparent diffusion coefficients (ADC) correlate with tumour cellularity and invasion. The present study analysed a potential relation between the MRI based apparent diffusion coefficients local recurrence and outcome in patients with brain metastases. METHODS: A retrospective analysis was performed for patients with cerebral metastases and complete surgical resection evaluated by an early postoperative MRI < 72h. Minimal ADC and mean ADC were assessed in preoperative 1,5T-MRI scans by placing regions of interests in the tumour and the peritumoural tissue. RESULTS: Analysis of the relation between ADC values, local progression and outcome was performed in 86 patients with a mean age of 59 years (range 33-83 years). Primary site was NSCLC in 37.2% of all cases. Despite complete resection 33.7% of all patients suffered from local in-brain-progression. There were no significant differences in ADC values in groups based on histology. In the present cohort, the mean ADCmin and the mean ADCmean within the metastasis did not differ significantly between patients with and without a later local in-brain progression (634 × 10-6 vs. 661 × 10-6 mm2/s and 1324 × 10-6 vs. 1361 × 10-6 mm2/s; 1100 × 10-6 vs. 1054 × 10-6 mm2/s; each p > 0.05). Mean ADC values did not correlate significantly with PFS and OAS. CONCLUSION: In the present study analysed ADC values had no significant impact on local in brain progression and survival parameters.

Impact of COVID-19 Epidemic on Psycho-Oncological Distress in Neuro-Oncological Patients.

Up to 40% of neuro-oncological patients already deal with high levels of distress under conventional circumstances. Due to COVID-19, pandemic hospital visitor rules have been restricted and patients did not receive the same level of supporting caregiver network as before COVID. The aim of the present study was to analyse the impact of the COVID pandemic on the prevalence of distress, anxiety and depression in neuro-oncological patients. Patients admitted for brain tumour surgery were screened regarding distress, anxiety and depression. Furthermore, aspects of patients' quality of life and clinical data were covered. Retrospectively available data of patients treated pre-pandemic (group A) and throughout the COVID-19 pandemic (group B) were statistically analysed using Chi-square tests and independent-sample t-tests, and regression analysis was performed to support statistical findings. Data from 110 patients were available. In all, 48 patients were included pre-COVID-19 and 62 during the COVID-19 pandemic. The authors found no significant difference between pre-COVID-19 prevalence of distress (p = 0.112), anxiety (p = 0.385) or depression (p = 0.084). Regression analyses additionally did not show any significant influence of COVID-19 on the above analysed parameter. Analyses of our cohort's data could not underline the negative impact of COVID-19 restrictions, shortcuts of professional and remodelled caregiver support on psycho-oncological outcomes.

Direct Cortical Stimulation in Neurosurgical Emergencies: Single-Center Experience in 2 Patients.

BACKGROUND: Intraoperative neuromonitoring (IONM) is widely used for elective resection of eloquently located brain tumors to increase safety and extent of resection. Owing to the need for specially trained personnel for IONM and the sophisticated, time-consuming technical setup, standard IONM is usually not suitable for emergency situations. We report the use of a device that can be operated by the neurosurgeon autonomously for monopolar brain mapping in 2 emergency cases. METHODS: Both patients were initially scheduled for elective neurosurgery under IONM. Acute neurological deterioration in both cases led to emergency surgery. For monopolar cortical/subcortical stimulation, a standard monopolar probe was connected to a new device enabling electromyography real-time tracking of 8 muscles. Preoperative application of subdermal electromyography needles and intraoperative handling of the device were performed by the neurosurgeons independently. RESULTS: Cortical mapping of the motor cortex was performed in both patients with a threshold of 4 mA in case 1 and 14 mA in case 2. Gross total resection with residual tumor volume of <2 mL in case 1 and subtotal resection with residual tumor volume of 4.2 mL in case 2 were achieved under use of the new device without any new neurological deficit. Grade IV glioblastoma was diagnosed in both patients. CONCLUSIONS: We demonstrate the feasibility of monopolar stimulation in 2 patients undergoing emergency neurosurgery using a device autonomously operated by the surgeon. Owing to fast setup and nondemanding handling, monopolar stimulation could be used during emergency neurosurgery to extend resection with preservation of neurological function in both cases.

Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) is often caused by irruption of intracerebral hemorrhage (ICH) of basal ganglia or thalamus into the ventricular system. Instillation of recombinant tissue plasminogen activator (rtPA) via an external ventricular drainage (EVD) has been shown to effectively decrease IVH volumes while the impact of rtPA instillation on ICH volumes remains unclear. In this series, we analyzed volumetric changes of ICH in patients with and without intrathecal lysis therapy. METHODS: Between 01/2013 and 01/2019, 36 patients with IVH caused by hemorrhage of basal ganglia, thalamus or brain stem were treated with rtPA via an EVD (Group A). Initial volumes were determined in the first available computed tomography (CT) scan, final volumes in the last CT scan before discharge. During the same period, 41 patients with ICH without relevant IVH were treated without intrathecal lysis therapy at our neurocritical care unit (Group B). Serial CT scans were evaluated separately for changes in ICH volumes for both cohorts using OsiriX DICOM viewer. The Wilcoxon signed-rank test was performed for statistical analysis in not normally distributed variables. RESULTS: Median initial volume of ICH for treatment Group A was 6.5 ml and was reduced to 5.0 ml after first instillation of rtPA (p < 0.01). Twenty-six patients received a second treatment with rtPA (ICH volume reduction 4.5 to 3.3 ml, p < 0.01) and of this cohort further 16 patients underwent a third treatment (ICH volume reduction 3.0 ml to 1.5 ml, p < 0.01). Comparison of first and last CT scan in Group A confirmed an overall median percentage reduction of 91.7% (n = 36, p < 0.01) of ICH volumes and hematoma resolution in Group A was significantly more effective compared to non-rtPA group, Group B (percentage reduction = 68%) independent of initial hematoma volume in the regression analysis (p = 0.07, mean 11.1, 95%CI 7.7-14.5). There were no adverse events in Group A related to rtPA instillation. CONCLUSION: Intrathecal lysis therapy leads to a significant reduction in the intraparenchymal hematoma volume with faster clot resolution compared to the spontaneous hematoma resorption. Furthermore, intrathecal rtPA application had no adverse effect on ICH volume.

Impact of Anticipated Awake Surgery on Psychooncological Distress in Brain Tumor Patients.

BACKGROUND: Brain tumor patients present high rates of distress, anxiety, and depression, in particular perioperatively. For resection of eloquent located cerebral lesions, awake surgery is the gold standard surgical method for the preservation of speech and motor function, which might be accompanied by increased psychological distress. The aim of the present study was to analyze if patients who are undergoing awake craniotomy suffer from increased prevalence or higher scores in distress, anxiety, or depression. METHODS: Patients, who were electively admitted for brain tumor surgery at our neurooncological department, were perioperatively screened regarding distress, anxiety, and quality of life using three established self-assessment instruments (Hospital Anxiety and Depression Scale, distress thermometer, and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30-BN20). Screening results were correlated regarding operation technique (awake vs. general anesthesia). Retrospective statistical analyses for nominal variables were conducted using chi-square test. Metric variables were analyzed using the Kruskal-Wallis test, the Mann-Whitney U-test, and independent-samples t-tests. RESULTS: Data from 54 patients (26 male and 28 female) aged 29 to 82 years were available for statistical analyses. A total of 37 patients received primary resection and 17 recurrent tumor resection. Awake surgery was performed in 35 patients. There was no significant difference in awake versus non-awake surgery patients regarding prevalence (of distress (p = 0.465), anxiety (p = 0.223), or depression (p = 0.882). Furthermore, awake surgery had no significant influence on distress thermometer score (p = 0.668), anxiety score (p = 0.682), or depression score (p = 0.630) as well as future uncertainty (p = 0.436) or global health status (p = 0.943). Additionally, analyses revealed that primary or recurrent surgery also did not have any significant influence on the prevalence or scoring of the evaluated items. CONCLUSION: Analyses of our cohort's data suggest that planned awake surgery might not have a negative impact on patients concerning the prevalence and severity of manifestation of distress, anxiety, or depression in psychooncological screening. Patients undergoing recurrent surgery tend to demonstrate increased distress, although results were not significant.

Correction to: Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage.

The author name Kerim Beseoglu has been corrected and the details given in this correction are correct.

Surgical management of spinal meningiomas: focus on unilateral posterior approach and anterior localization.

OBJECTIVESpinal meningiomas (sMNGs) are relatively rare in comparison to intracranial MNGs. sMNGs localized anterior to the denticulate ligament (aMNGs) represent a surgically challenging subgroup. A high perioperative complication rate due to the need for complex surgical approaches has been described. In the present study, the authors report on their surgical experience that involves two institutions in which 207 patients underwent surgery for sMNGs. Special focus was placed on patients with aMNGs that were treated via a unilateral posterior approach (ULPA).METHODSBetween 2005 and 2017, 207 patients underwent resection of sMNGs at one of two institutions. The following characteristics were assessed: tumor size and localization, surgical approach, duration of surgery, grade of resection, peri- and postoperative complication rates, and neurological outcome. Data were compared between the subgroups of patients according to the lesion's relationship to the denticulate ligament and to surgical approach.RESULTSThe authors identified 48 patients with aMNGs, 86 patients with lateral MNGs, and 76 patients with posterior MNGs (pMNGs). Overall, 66.6% of aMNGs and 64% of pMNGs were reached via a ULPA. aMNGs that were approached via a ULPA showed reduced duration of surgery (131 vs 224 minutes, p < 0.0001) and had surgical complication rates and neurological outcomes comparable to those of lesions that were approached via a bilateral approach. No significant differences in complication rate, outcomes, and extent of resection were seen between aMNGs and pMNGs.CONCLUSIONSThe duration of surgery, extent of resection, and outcomes are comparable between aMNGs and pMNGs when removed via a ULPA. Thus, ULPA represents a safe route to achieve a gross-total resection, even in cases of aMNG.

Acceptance and compliance of TTFields treatment among high grade glioma patients.

BACKGROUND: Tumor treating fields (TTFields) significantly prolong both progression-free and overall survival in patients with newly diagnosed glioblastoma (GBM). TTFields are delivered to the brain tumor via skin transducer arrays and should be applied for a minimum of 18 h per day (≥ 75% compliance). This may cause limited acceptance by patients because of obstacles in daily routine. So far, there are limited data on factors influencing therapy acceptance and compliance. METHODS: In this retrospective study, fourty-one patients with primary GBM or recurrent high grade glioma (rHGG) have been treated with TTFields in our department. Compliance reports were generated at the monthly routine check of the device. We investigated demographic data, stage of disease and therapy duration in regard to treatment compliance. RESULTS: Thirty percent of patients with primary diagnosis of GBM were informed about TTFields. Acceptance rate among these patients was 36%. In this study, TTFields were prescribed in newly diagnosed GBM patients (57%) and in rHGG. Mean treatment compliance was 87% in the total population independent of age, sex and stage of disease. Compliance was not negatively correlated with time on treatment. CONCLUSION: TTFields are effective in newly diagnosed GBM, therefore acceptance and compliance is important for GBM treatment. We experienced moderate acceptance rate for TTFields, which is influenced by factors such as social support, comorbidities and independence in daily life. Overall therapy compliance lies above 75% and is not influenced by age, sex, stage of disease or duration of therapy. Improved patient consultation strategies will increase acceptance and compliance for better outcome.

Long term correlation of subthalamic beta band activity with motor impairment in patients with Parkinson's disease.

OBJECTIVES: To investigate the long term association of subthalamic beta activity with parkinsonian motor signs. METHODS: We recruited 15 patients with Parkinson's disease undergoing subthalamic DBS for local field potential recordings after electrode implantation, and at 3 and 8months post-operatively using the implantable sensing enabled Activa PC+S (Medtronic). Three patients dropped out leaving 12 patients. Recordings were conducted ON and OFF levodopa at rest. Beta (13-35Hz) peak amplitudes were extracted, compared across time points and correlated with UPDRS-III hemibody scores. RESULTS: Peaks in the beta frequency band (13-35Hz) in the OFF medication state were found in all hemispheres. Mean beta activity was significantly suppressed by levodopa at all recorded time points (P<0.007) and individual beta power amplitude correlated with parkinsonian motor impairment across time points and dopaminergic states (pooled data; ρ=0.25, P<0.001). CONCLUSIONS: Our results indicate that beta-activity is correlated with parkinsonian motor signs over a time period of 8months. SIGNIFICANCE: Beta-activity may be a chronically detectable biomarker of symptom severity in PD that should be further evaluated under ongoing DBS.

Subthalamic beta dynamics mirror Parkinsonian bradykinesia months after neurostimulator implantation.

BACKGROUND: Exaggerated oscillatory activity in the beta frequency band in the subthalamic nucleus has been suggested to be related to bradykinesia in Parkinson's disease (PD). However, studies seeking correlations between such activity in the local field potential and motor performance have been limited to the immediate postoperative period, which may be confounded by a stun effect that leads to the temporary alleviation of PD deficits. METHODS: Local field potentials were recorded simultaneously with motor performance in PD patients several months after neurostimulator implantation. This was enabled by the chronic implantation of a pulse generator with the capacity to record and transmit local field potentials from deep brain stimulation electrodes. Specifically, we investigated oscillatory beta power dynamics and objective measures of bradykinesia during an upper limb alternating pronation and supination task in 9 patients. RESULTS: Although beta power was suppressed during continuously repeated movements, this suppression progressively diminished over time in tandem with a progressive decrement in the frequency and amplitude of movements. The relationship between changes within local field potentials and movement parameters was significant across patients, and not present for theta/alpha frequencies (5-12 Hz). Change in movement frequency furthermore related to beta power dynamics within patients. CONCLUSIONS: Changes in beta power are linked to changes in movement performance and the sequence effect of bradykinesia months after neurostimulator implantation. These findings provide further evidence that beta power may serve as a biomarker for bradykinesia and provide a suitable substrate for feedback control in chronic adaptive deep brain stimulation. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.