Jens Gempt, Julia Gerhardt, Vivien Toth, Stefanie Hüttinger, Yu-Mi Ryang, Maria Wostrack, Sandro M. Krieg, Bernhard Meyer, Annette Förschler and Florian Ringel
Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits.
Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded.
One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003).
This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.
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.
Nico Sollmann, Chiara Negwer, Lorena Tussis, Theresa Hauck, Sebastian Ille, Stefanie Maurer, Katrin Giglhuber, Jan S. Bauer, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
Resection of brain tumors in language-eloquent areas entails the risk of postoperative aphasia. It has been demonstrated via navigated transcranial magnetic stimulation (nTMS) that language function can partially shift to the unaffected hemisphere due to tumor-induced plasticity. Therefore, this study was designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS-based diffusion tensor imaging–fiber tracking (DTI-FT) can be used to predict surgery-related aphasia in patients with brain tumors.
Thirty-eight patients with left-sided perisylvian brain lesions underwent cortical language mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI-FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize nTMS-based IC. Receiver operating characteristics were calculated for the prediction of a postoperative (irrespective of the preoperative state) and a new surgery-related aphasia by the presence of detectable IC.
Language mapping by nTMS was possible in all patients. Seventeen patients (44.7%) suffered from surgery-related worsening of language performance (transient aphasia according to 3-month follow-up in 16 subjects [42.1%]; new permanent aphasia according to 3-month follow-up in 1 patient [2.6%]). Regarding the correlation of aphasia to nTMS-based IC, statistically significant differences were revealed for both evaluated FA values. However, better results were observed for tractography with an FA of 0.2, which led to a specificity of 93% (postoperative aphasia) and 90% (surgery-related aphasia). For postoperative aphasia, the corresponding OR was 0.1282 (95% CI 0.0143–1.1520), and for surgery-related aphasia the OR was 0.1184 (95% CI 0.0208–0.6754).
According to these results, IC detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for surgery-related aphasia, with a specificity of up to 93%. However, because the majority of enrolled patients suffered from transient aphasia postoperatively, it has to be evaluated whether this approach distinctly leads to similar results among patients with permanent language deficits. Despite this restriction, this approach might contribute to individualized patient consultation prior to tumor resection in clinical practice.
Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Tobias Boeckh-Behrens, Bernhard Meyer, Florian Ringel and Sandro M. Krieg
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.
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.
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%).
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.
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.