Jens Gempt, Annette Förschler, Niels Buchmann, Haiko Pape, Yu-Mi Ryang, Sandro M. Krieg, Claus Zimmer, Bernhard Meyer and Florian Ringel
The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function.
Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded.
New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions.
Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.
Nico Sollmann, Anna Kelm, Sebastian Ille, Axel Schröder, Claus Zimmer, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
Awake surgery combined with intraoperative direct electrical stimulation (DES) and intraoperative neuromonitoring (IONM) is considered the gold standard for the resection of highly language-eloquent brain tumors. Different modalities, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), are commonly added as adjuncts for preoperative language mapping but have been shown to have relevant limitations. Thus, this study presents a novel multimodal setup consisting of preoperative navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) as an adjunct to awake surgery.
Sixty consecutive patients (63.3% men, mean age 47.6 ± 13.3 years) suffering from highly language-eloquent left-hemispheric low- or high-grade glioma underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by awake surgery for tumor resection. Both nTMS language mapping and DTI FT data were available for resection planning and intraoperative guidance. Clinical outcome parameters, including craniotomy size, extent of resection (EOR), language deficits at different time points, Karnofsky Performance Scale (KPS) score, duration of surgery, and inpatient stay, were assessed.
According to postoperative evaluation, 28.3% of patients showed tumor residuals, whereas new surgery-related permanent language deficits occurred in 8.3% of patients. KPS scores remained unchanged (median preoperative score 90, median follow-up score 90).
This is the first study to present a clinical outcome analysis of this very modern approach, which is increasingly applied in neurooncological centers worldwide. Although human language function is a highly complex and dynamic cortico-subcortical network, the presented approach offers excellent functional and oncological outcomes in patients undergoing surgery of lesions affecting this network.
Stefanie Bette, Jens Gempt, Thomas Huber, Claire Delbridge, Bernhard Meyer, Claus Zimmer, Jan S. Kirschke and Tobias Boeckh-Behrens
Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients.
A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups.
Patients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8–8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value.
Signal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.
Nico Sollmann, Alessia Fratini, Haosu Zhang, Claus Zimmer, Bernhard Meyer and Sandro M. Krieg
Navigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.
Fifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).
A significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.
nTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.
Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Claus Zimmer, Bernhard Meyer, Florian Ringel and Sandro M. Krieg
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.
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.
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%.
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.
Nico Sollmann, Dominik Weidlich, Barbara Cervantes, Elisabeth Klupp, Carl Ganter, Hendrik Kooijman, Claus Zimmer, Ernst J. Rummeny, Bernhard Meyer, Thomas Baum, Jan S. Kirschke and Dimitrios C. Karampinos
Lumbosacral radicular syndrome (LRS) is a very common condition, often requiring diagnostic imaging with the aim of elucidating a structural cause when symptoms are longer lasting. However, findings on conventional anatomical MRI do not necessarily correlate with clinical symptoms, and it is primarily performed for the qualitative evaluation of surrounding compressive structures, such as herniated discs, instead of to evaluate the nerves directly. The present study investigated the performance of quantitative imaging by using magnetic resonance neurography (MRN) in patients with LRS.
Eighteen patients (55.6% males, mean age 64.4 ± 10.2 years), with strict unilateral LRS matching at least one dermatome and suspected disc herniation, underwent high-resolution 3-T MRN using T2 mapping. On T2 maps, the presumably affected and contralateral unaffected nerves were identified; subsequent regions of interest (ROIs) were placed at preganglionic, ganglionic, and postganglionic sites; and T2 values were extracted. Patients then underwent an epidural steroid injection (ESI) with local anesthetic agents at the site of suspected nerve affection. T2 values of the affected nerves were compared against the contralateral nerves. Furthermore, receiver operating characteristics were calculated based on the measured T2 values and the responsiveness to ESI.
The mean T2 value was 77.3 ± 1.9 msec for affected nerves and 74.8 ± 1.4 msec for contralateral nerves (p < 0.0001). In relation to ESI performed at the site of suspected nerve affection, MRN with T2 mapping had a sensitivity/specificity of 76.9%/60.0% and a positive/negative predictive value of 83.3%/50.0%. Signal alterations in affected nerves according to qualitative visual inspection were present in only 22.2% of patients.
As one of the first of its kind, this study revealed elevated T2 values in patients suffering from LRS. T2 values of lumbosacral nerves might be used as more objective parameters to directly detect nerve affection in such patients.
Jens Gempt, Sandro M. Krieg, Stefanie Hüttinger, Niels Buchmann, Yu-Mi Ryang, Ehab Shiban, Bernhard Meyer, Claus Zimmer, Annette Förschler and Florian Ringel
The aim of surgical glioma treatment is the complete resection of tumor tissue while preserving neurological function. Surgery-related neurological deficits arise from direct damage to the cortical or subcortical structures or from ischemia. The authors aimed to assess the incidence of resection-related ischemia of newly diagnosed or recurrent supratentorial gliomas and the sensitivity of intraoperative neuromonitoring (IOM) of motor evoked potentials (MEPs) for detecting such ischemic events and their influence on neurological motor function.
Between January 2009 and December 2010, 70 patients with tumors in motor-eloquent brain areas underwent intraoperative MEP monitoring during glioma resection and were examined by early postoperative MRI including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping. Postoperative areas of restricted diffusion were assessed by investigators blinded to the course of intraoperative MEPs and the neurological course.
Among the 70 enrolled patients, a MEP amplitude decline below 50% of the baseline level was observed in 21 patients (30%). Sixteen of these patients (76%) had ischemic lesions identified on postoperative MRI scans. Forty-nine patients (70%) showed no decline in MEP amplitude, and only 16 (33%) of these patients harbored ischemic lesions. Moreover, 9 (69%) of 13 patients with a permanent loss of MEP amplitude showed postoperative ischemic lesions. Factors that promoted the occurrence of postoperative infarction were previous radiotherapy and location of the tumor close to the central arteries.
Alterations in the MEP amplitude during tumor resection and postoperative ischemic lesions are associated with postoperative impairment of motor function. Rather than cortical or subcortical structural damage of eloquent brain tissue alone, peri- or postoperative ischemic lesions play a crucial role in the development of surgery-related motor deficits.