Intraoperative radiotherapy after resection of brain metastases located in the posterior fossa. Analysis of postoperative morbidity and mortality in a single center cohort.

INTRODUCTION: In order to improve surgical outcome and accelerate the adjuvant oncologic therapy, intraoperative Radiotherapy (IORT) has become a treatment option in oncologic surgery for various diseases including glioma and brain metastasis (BM). BMs are often located in the cranial posterior fossa (PF) requiring specific surgical considerations due to its complex anatomy. Up until now, data on IORT for BMs is limited and detailed description in the use of IORT for lesions in the PF is lacking. Our aim is to provide more insight into this emerging treatment strategy. METHODS: We performed a retrospective analysis of patients receiving surgery for BMs and undergoing IORT at our institution. Each patient was discussed at the interdisciplinary tumor board decision before the intervention. Patient characteristics, functional status (Karnofsky Performance Score, KPS) before and after surgery, disease (recursive partitioning analysis, lesion size) and operative parameters were analyzed. Adverse events (AE) were recorded up until 30 days after the intervention and rated according to the Clavien Dindo Rating scale. RESULTS: Nine patients (5 female) were included. None underwent prior radiotherapy (RT). Mean age was 66 ± 11 years. Preoperative median KPS was 80%. Mean BM diameter was 3.2 ± 0.9 cm. There was no statistically significant deterioration of the functional status after the intervention. Two patients experienced AEs with both of them needing revision surgery. CONCLUSION: Surgery for BMs with IORT in the PF seems safe and feasible. Further studies are needed to evaluate the influence of IORT on long-term outcome after BM surgery.

sPinal coRd stimulatiOn coMpared with lumbar InStrumEntation for low back pain after previous lumbar decompression (PROMISE): a prospective multicentre RCT.

INTRODUCTION: Persistent spine pain syndrome type 2 (PSPS2) represents a significant burden to the individual and society. Treatment options include revision surgery, stabilisation surgery of the spine, neuromodulation, analgesics and cognitive behavioural therapy. Nevertheless, structured treatment algorithms are missing as high-level evidence on the various treatments is sparse. The aim of this study is to compare higher frequency neuromodulation with instrumentation surgery in patients suffering from PSPS2. METHODS AND ANALYSIS: The sPinal coRd stimulatiOn coMpared with lumbar InStrumEntation for low back pain after previous lumbar decompression (PROMISE) trial is a prospective randomised rater blinded multicentre study. Patients suffering from PSPS2 with a functional burden of Oswestry Disability Index (ODI) >20 points are randomised to treatment via spinal cord stimulation or spinal instrumentation. Primary outcome is back-related functional outcome according to the ODI 12 months after treatment. Secondary outcomes include pain perception (visual analogue scale), Short Form-36, EuroQOL5D, the amount of analgesics, the length of periprocedural hospitalisation and adverse events. Follow-up visits are planned at 3 and 12 months after treatment. Patients with previous lumbar instrumentation, symptomatic spinal stenosis, radiographical apparent spinal instability or severe psychiatric or systemic comorbidities are excluded from the study. In order to detect a significant difference of ≥10 points (ODI) with a power of 80%, n=72 patients need to be included. The recruitment period will be 24 months with a subsequent 12 months follow-up. The beginning of enrolment is planned for October 2022. ETHICS AND DISSEMINATION: The PROMISE trial is the first randomised rater blinded multicentre study comparing the functional effectiveness of spinal instrumentation versus neuromodulation in patients with PSPS2 in order to achieve high-level evidence for these commonly used treatment options in this severely disabling condition. Patient recruitment will be performed at regular outpatient clinic visits. No further (print, social media) publicity is planned. The study is approved by the local ethics committee (LMU Munich, Germany) and will be conducted according to the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT05466110.

Resection of supratentorial brain metastases with intraoperative radiotherapy. Is it safe? Analysis and experiences of a single center cohort.

Introduction: Intraoperative Radiotherapy (ioRT) is an emerging treatment option in oncologic surgery for various diseases including intraaxial brain lesions to improve surgical outcome and accelerate the adjuvant oncologic therapy. Despite its use in glioma surgery, the application and data regarding ioRT in the treatment of brain metastases (BMs) is sparse. Here were report the largest series of supratentorial BMs treated with resection and ioRT according to functional outcome and adverse events. Methods: We performed a retrospective chart review analysis of patients undergoing surgery for BMs following an interdisciplinary tumor board decision in every case with ioRT at our institution. Patient properties, functional status (Karnofsky Performance Score/KPS) before and after surgery as well as oncologic (disease, recursive partitioning analysis, lesion size) and operative parameters were analyzed until hospital discharge. Adverse events (AE) were recorded until 30 days after surgery and rated according to the Clavien Dindo Grading (CDG) scale. Results: 70 patients (40 female) with various oncologic diseases were identified and analyzed. Six underwent prior RT. Mean age was 66 ± 11 years. Preoperative median KPS was 80% with a mean BM volume of 3.2 ± 1.2 cm3. Nine patients (13%) experienced in total 14 AEs, including 2 cases (3%) of postoperative death (CDG5) and 2 with new postoperative epilepsy necessitating additional pharmacotreatment (CDG2). Five patients suffered from new neurologic deficit (CDG1) not needing further surgical or medical treatment. After surgery, the neurological status in 7 patients (10%) deteriorated while it improved in 21 cases (30%). Patients experiencing AEs had longer hospitalization and poorer postoperative KPS mdn. 90 vs. 80%. There was no statistically significant deterioration of the functional status during the immediate postoperative course in the whole patient cohort. Conclusion: Surgery for supratentorial BMs with ioRT seems safe and feasible. Further studies on the benefit regarding oncologic outcome need to be performed.

Investigation of subdural electrode displacement in invasive epilepsy surgery workup using neuronavigation and intraoperative MRI.

OBJECTIVES: One of the main obstacles of electrode implantation in epilepsy surgery is the electrode shift between implantation and the day of explantation. We evaluated this possible electrode displacement using intraoperative MRI (iopMRI) data and CT/MRI reconstruction. METHODS: Thirteen patients (nine female, four male, median age 26 ± 9.4 years) suffering from drug-resistant epilepsy were examined. After implantation, the position of subdural electrodes was evaluated by 3.0 T-MRI and thin-slice CCT for 3D reconstruction. Localization of electrodes was performed with the volume-rendering technique. Post-implantation and pre-explantation 1.5 T-iopMRI scans were coregistered with the 3D reconstructions to determine the extent of electrode dislocation. RESULTS: Intraoperative MRI at the time of explantation revealed a relevant electrode shift in one patient (8%) of 10 mm. Median electrode displacement was 1.7 ± 2.6 mm with a coregistration error of 1.9 ± 0.7 mm. The median accuracy of the neuronavigation system was 2.2 ± 0.9 mm. Six of twelve patients undergoing resective surgery were seizure free (Engel class 1A, median follow-up 37.5 ± 11.8 months). CONCLUSION: Comparison of pre-explantation and post-implantation iopMRI scans with CT/MRI data using the volume-rendering technique resulted in an accurate placement of electrodes. In one patient with a considerable electrode dislocation, the surgical approach and extent was changed due to the detected electrode shift. ABBREVIATIONS: ECoG: electrocorticography; EZ: epileptogenic zone; iEEG: invasive EEG; iopMRI: intraoperative MRI; MEG: magnetoencephalography; PET: positron emission tomography; SPECT: single photon emission computed tomography; 3D: three-dimensional.

Intraoperative continuous cerebral microcirculation measurement in patients with aneurysmal subarachnoid hemorrhage: preliminary data on the early administration of magnesium sulfate.

BACKGROUND: In patients with subarachnoid hemorrhage (SAH), vasospasm remains one of the major complications. The application of intravenous magnesium sulfate (MgSO4) has been under discussion to prevent cerebral ischemia. Our aim was to examine the impact of early MgSO4 administration on local cerebral microcirculation during microsurgical clipping of SAH-related aneurysms. METHODS: The non-invasive laser-Doppler spectrophotometry system "Oxygen-to-See (O2C)" was used in 14 consecutive patients (11 female, 3 male, median age 56.5±9.7 yrs) with aneurysmatic SAH. A subdural probe measured capillary venous oxygenation (SO2), relative hemoglobin content (rHb), blood cell velocity (velo) and blood flow (flow) in 7 mm tissue depth. Data samples were recorded as baseline immediately before intraoperative application of MgSO4 10% 50 mg/kg body weight and 10 min thereafter. The continuous MgSO4 infusion rate depended on blood pressure (mean arterial pressure > 60-65 mmHg) and lasted a maximum of 60 min. RESULTS: MgSO4 was administered 2.8 (min. 1.6, max. 15.5) hours after onset of symptoms. Median flow increased significantly by 20.8% (5-68%, p = 0.001). Velo increased 4.9% (1-17%), rHb decreased 1.5% (3-34%) and SO2 decreased 9.4% (8-38%) by trend compared to the baseline values. FiO2 correlated positively with velo (rs = 0.712, p = 0.004), whereas arterial HCO3 correlated negatively with SO2 (rs = -0.599, p = 0.024). Of 14 patients, 2 had symptomatic vasospasm. CONCLUSIONS: Our data suggest an increased cerebral blood flow after early intraoperative administration of MgSO4 in patients with SAH. Using a non-invasive laser-Doppler spectrophotometry system, this technique is feasible for continuous real-time monitoring of cerebral microcirculation. TRIAL REGISTRATION: DRKS (German Clinical Trial Registry), DRKS00013047 , retrospectively registered on September 21st, 2017.

Resective surgery for medically refractory epilepsy using intraoperative MRI and functional neuronavigation: the Erlangen experience of 415 patients.

OBJECTIVE: Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome. METHODS: To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]). RESULTS: In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%. CONCLUSIONS: Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.

Risk reduction in dominant temporal lobe epilepsy surgery combining fMRI/DTI maps, neuronavigation and intraoperative 1.5-Tesla MRI.

BACKGROUND: In dominant temporal lobe epilepsy surgery, speech, memory and visual systems are at risk. OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging combined with intraoperative neuronavigation and MRI were investigated retrospectively regarding risk reductions for favorable neurological and seizure outcome. METHODS: Functional imaging risk maps were generated for 14 patients suffering from dominant temporal lobe epilepsy [7 with hippocampal sclerosis (HS), 7 with various lesions] and used for neuronavigation-guided tailored resection. Postoperative neurological and seizure outcome and complications were evaluated. RESULTS: None of the patients had postoperative speech dysfunction despite 2.3/3.6-cm mean hippocampal/neocortical resection. Verbal memory decline was found in 2 of the 14 (14.3%) patients, correlating with surgical lesions in fMRI memory-activated functional areas in the dominant posterior parahippocampal gyrus. Verbal memory scores did not statistically differ between the HS and the lesional group, neither pre- nor postoperatively. A contralateral visual field defect occurred in 1 patient (7.1%). An Engel class I seizure outcome was found in 12 patients (85.7%), and 11 were completely seizure free (78.6%) at a mean follow-up of 19.5 months. CONCLUSION: This retrospectively investigated protocol led to an excellent neurological and seizure outcome and a low complication rate in dominant temporal lobe epilepsy surgery.

Intraoperative use of high-field MRI in hypothalamic hamartomas associated with epilepsy: clinico-pathological presentation of five adult patients.

BACKGROUND: Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity. METHODS: We present a series of five adult patients with drug-resistant epilepsy who had been operated on for HH using neuronavigation and intraoperative 1.5-T magnetic resonance imaging (MRI). In this retrospective investigation, we compared our surgical strategy and postoperative results to existing series. RESULTS: During surgery, we identified remnant HH in the first intraoperative MRI control scan in three out of five patients. After re-segmentation of the residual lesion using neuronavigation, complete resection was achieved in two of the three patients as confirmed by final intraoperative and late follow-up MRI, raising the rate of total resections to four out of five patients. Two patients died during the observation period. One patient suffered from a permanent third nerve palsy and one from a transient monoparesis of the left arm. New endocrinological disturbances included diabetes insipidus centralis in two and secondary hypothyroidism and hypogonadism in one patient. Four out of five patients had favourable seizure control (Engel I or II) after 64.8 (34-83) months of mean follow-up. CONCLUSIONS: Neuronavigation and intraoperative MRI are valuable tools to encounter difficulties while performing surgery in patients with HHs. Intraoperative resection control increases the amount of maximum resection.

Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome.

PURPOSE: To evaluate the value of magnetoencephalography (MEG) source localization in localization of epileptic activities and predicting surgical outcome in frontal lobe epilepsies (FLE). METHODS: Forty-six patients with presurgical MEG evaluation and intractable FLE surgery (28 male patients) were analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was performed for MEG source imaging (MSI). The localization of dipole clusters in relation to the dominant hemisphere, lesions, resection cavity and functional cortex were analyzed. The predictive value of MSI in respect to clinical outcome with long-term postoperative follow up was evaluated. RESULTS: Interictal focal epileptic activities were found in 82.6% (38/46) patients with monofocal activity 81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9% at the mean follow-up of 5.0 ± 4.0 years (median 11.5, range 2-57). Seizure recurrence mainly occurred in the first 1 year after surgery. In the monofocal epileptic activity group, 58.1% (18/31) of the patients were seizure free, predicitng postoperative seizure freedom better than multifocal localization 0% (0/7) (p=0.028). Dipole clusters were completely resected in 70.9% of monofocal activity patients, which had higher seizure free rates compared to partial resection (p=0.002). In patients with surgery in the dominant hemisphere, seizure control was less likely (p=0.006). CONCLUSION: MSI contributes to the clinical prediction of postoperative outcome in FLE patients. MSI may non-invasively disclose early epileptogenic lesions, pointing to a resectable lesion, and it then facilitates shortcut route of presurgical evaluation.

Improved resection in lesional temporal lobe epilepsy surgery using neuronavigation and intraoperative MR imaging: favourable long term surgical and seizure outcome in 88 consecutive cases.

PURPOSE: To investigate the value of intraoperative MR imaging (iopMRI) combined with neuronavigation to avoid intraoperative underestimation of the resection amount during surgery of lesional temporal lobe epilepsy (LTLE) patients. METHODS: We retrospectively investigated 88 patients (40 female, 48 male, mean age 37.2 yrs, from 12 to 69 yrs, 41 left sided lesions) with LTLE operated at our department, including 40.9% gangliogliomas (GG), 26.1% cavernomas (CM), 10.2% dysembryoplastic neuroepithelial tumours (DNT) and 11.4% focal cortical dysplasias (FCD), excluding hippocampal sclerosis. RESULTS: Complete resection was achieved in 85 of 88 patients (96.6%), as proven by postoperative MRI 6 months after surgery. In contrast, the routine first iopMR imaging before closure revealed radical resection in only 66 of these 88 patients (75%). After re-intervention, the second iopMR imaging demonstrated complete resection in 19 more patients. Thus, as a direct effect of iopMRI and neuronavigation, overall resection rate was increased by 21.6%. An excellent seizure outcome Engel Class I was found in 76.1% of patients during a mean follow-up of 26.4 months, irrespective of histological entity (74% in CM, 75% in GG, 78% in DNT and 60% in FCD). No severe postoperative complications occurred; permanent superior visual field defects were detected in 10.2% and permanent dysphasia/dyscalculia in 1.1%. CONCLUSION: Refined surgery using neuronavigation combined with iopMR imaging in LTLE surgery led to radical resection in 96.6% of the patients, due to immediate correction of underestimated resection in 21.6% of patients. This protocol resulted in a favourable seizure outcome and a low complication rate.

Frameless stereotactic functional neuronavigation combined with intraoperative magnetic resonance imaging as a strategy in highly eloquent located tumors causing epilepsy.

BACKGROUND: Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. OBJECTIVES: To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. METHODS: Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. RESULTS: In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). CONCLUSIONS: Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control.

Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging.

OBJECTIVES: Cure from seizures due to cavernomas might be surgically achieved dependent on both, the complete removal of the cavernoma as well as its surrounding hemosiderin rim. High field intraoperative MRI imaging (iopMRI) and neuronavigation might play a crucial role to achieve both goals. We retrospectively investigated the long-term results and impact of intraoperative 1·5T MRI (iopMRI) and neuronavigation on the completeness of surgical removal of a cavernous malformation (CM) and its perilesional hemosiderin rim as well as reduction of surgical morbidity. METHODS: 26 patients (14 female, 12 male, mean age 39·1 years, range: 17-63 years) with CM related epilepsy were identified. Eighteen patients suffered from drug resistant epilepsy (69·2%). Mean duration of epilepsy was 11·9 years in subjects with drug resistant epilepsy (n = 18) and 0·3 years in subjects presenting with first-time seizures (n = 8). We performed 24 lesionectomies and two lesionectomies combined with extended temporal resections. Seven lesions were located extratemporally. RESULTS: Complete CM removal was documented by postsurgical MRI in all patients. As direct consequence of iopMRI, refined surgery was necessary in 11·5% of patients to achieve complete cavernoma removal and in another 11·5% for complete resection of additional adjacent epileptogenic cortex. Removal of the hemosiderin rim was confirmed by iopMRI in 92% of patients. Two patients suffered from mild (7·7%) and one from moderate (3·8%) visual field deficits. Complete seizure control (Engel class 1A) was achieved in 80·8% of patients with a mean follow-up period of 47·7 months. DISCUSSION: We report excellent long-term seizure control with minimal surgical morbidity after complete resection of CM using our multimodal approach.