Dietmar Frey

Preoperative Functional Mapping for Rolandic Brain Tumor Surgery: Comparison of Navigated Transcranial Magnetic Stimulation to Direct Cortical Stimulation

BACKGROUND:Transcranial magnetic stimulation (TMS) is the only noninvasive method for presurgical stimulation mapping of cortical function. Recent technical advancements have significantly increased the focality and usability of the method. OBJECTIVE:To compare the accuracy of a 3-dimensional magnetic resonance imaging-navigated TMS system (nTMS) with the gold standard of direct cortical stimulation (DCS). METHODS:The primary motor areas of 20 patients with rolandic tumors were mapped preoperatively with nTMS at 110% of the individual resting motor threshold. Intraoperative DCS was available from 17 patients. The stimulus locations eliciting the largest electromyographic response in the target muscles (“hotspots”) were determined for both methods. RESULTS:The nTMS and DCS hotspots were located on the same gyrus in all cases. The mean ± SEM distance between the nTMS and DCS hotspots was 7.83 ± 1.18 mm for the abductor pollicis brevis (APB) muscle (n = 15) and 7.07 ± 0.88 mm for the tibialis anterior muscle (n = 8). When a low number of DCS stimulations was performed, the distance between the nTMS and DCS hotspots increased substantially (r = −0.86 for APB). After the exclusion of the cases with < 15 DCS APB responses, the mean ± SEM distance between the hotspots was only 4.70 ± 1.09 mm for APB (n = 8). CONCLUSION:Peritumoral mapping of the motor cortex by nTMS agreed well with the gold standard of DCS. Thus, nTMS is a reliable tool for preoperative mapping of motor function.

A new approach for corticospinal tract reconstruction based on navigated transcranial stimulation and standardized fractional anisotropy values

PURPOSE To establish a novel approach for fiber tracking based on navigated transcranial magnetic stimulation (nTMS) mapping of the primary motor cortex and to propose a new algorithm for determination of an individualized fractional anisotropy value for reliable and objective fiber tracking. METHODS 50 patients (22 females, 28 males, median age 58 years (20-80)) with brain tumors compromising the primary motor cortex and the corticospinal tract underwent preoperative MR imaging and nTMS mapping. Stimulation spots evoking muscle potentials (MEP) closest to the tumor were imported into the fiber tracking software and set as seed points for tractography. Next the individual FA threshold, i.e. the highest FA value leading to visualization of tracts at a predefined minimum fiber length of 110 mm, was determined. Fiber tracking was then performed at a fractional anisotropy value of 75% and 50% of the individual FA threshold. In addition, fiber tracking according to the conventional knowledge-based approach was performed. Results of tractography of either method were presented to the surgeon for preoperative planning and integrated into the navigation system and its impact was rated using a questionnaire. RESULTS Mapping of the motor cortex was successful in all patients. A fractional anisotropy threshold for corticospinal tract reconstruction could be obtained in every case. TMS-based results changed or modified surgical strategy in 23 of 50 patients (46%), whereas knowledge-based results would have changed surgical strategy in 11 of 50 patients (22%). Tractography results facilitated intraoperative orientation and electrical stimulation in 28 of 50 (56%) patients. Tracking at 75% of the individual FA thresholds was considered most beneficial by the respective surgeons. CONCLUSIONS Fiber tracking based on nTMS by the proposed standardized algorithm represents an objective visualization method based on functional data and provides a valuable instrument for preoperative planning and intraoperative orientation and monitoring.

Navigated transcranial magnetic stimulation improves the treatment outcome in patients with brain tumors in motor eloquent locations

BACKGROUND Neurological and oncological outcomes of motor eloquent brain-tumor patients depend upon the ability to localize functional areas and the respective proposed therapy. We set out to determine whether the use of navigated transcranial magnetic stimulation (nTMS) had an impact on treatment and outcome in patients with brain tumors in motor eloquent locations. METHODS We enrolled 250 consecutive patients and compared their functional and oncological outcomes to a matched pre-nTMS control group (n = 115). RESULTS nTMS mapping results disproved suspected involvement of primary motor cortex in 25.1% of cases, expanded surgical indication in 14.8%, and led to planning of more extensive resection in 35.2% of cases and more restrictive resection in 3.5%. In comparison with the control group, the rate of gross total resections increased significantly from 42% to 59% (P < .05). Progression-free-survival for low grade glioma was significantly better in the nTMS group at 22.4 months than in control group at 15.4 months (P < .05). Integration of nTMS led to a nonsignificant change of postoperative deficits from 8.5% in the control group to 6.1% in the nTMS group. CONCLUSIONS nTMS provides crucial data for preoperative planning and surgical resection of tumors involving essential motor areas. Expanding surgical indications and extent of resection based on nTMS enables more patients to undergo surgery and might lead to better neurological outcomes and higher survival rates in brain tumor patients. The impact of this study should go far beyond the neurosurgical community because it could fundamentally improve treatment and outcome, and its results will likely change clinical practice.

Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: Evidence of tumor-induced plasticity

OBJECTIVE This article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients. METHODS Fifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5-10 Hz and 80-120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation. RESULTS In healthy volunteers, language disturbances were almost exclusively induced in the left hemisphere. In patients errors were more frequent and induced at a comparative rate over both hemispheres. Predominantly dysarthric errors were induced in volunteers, whereas semantic errors were most frequent in the patient group. CONCLUSION The right hemispheres increased sensitivity to rnTMS suggests reorganization in language representation in brain tumor patients. SIGNIFICANCE rnTMS is a novel technology for exploring cortical language representation. This study proves the feasibility and safety of rnTMS in patients with brain tumor.

Assessing the functional status of the motor system in brain tumor patients using transcranial magnetic stimulation

BackgroundTranscranial magnetic stimulation (TMS) is being used in the pre-operative diagnostics of patients with tumors in or near the motor cortex. Although the main purpose of TMS in such patients is to map the functional areas of the motor cortex in spatial relation to the tumor, TMS also provides some numerical neurophysiological measurements of the functional status of the patient’s motor system. The aim of this paper is to provide reference values for these neurophysiological measurements from a large and varied clinical sample.MethodsTMS was used in the pre-operative work-up of patients with various types of tumors in or near the motor cortex during a 3-year period. Data was collected prospectively in 100 patients, yet this is a post hoc report.ResultsPatient characteristics had no influence on the neurophysiological parameters. The response latency time was almost never different in the tumorous versus healthy hemisphere, so clinicians should be suspicious if they find interhemispheric differences for latency. A high interhemispheric ratio of resting motor threshold (RMT) or a low interhemispheric ratio of motor evoked potential (MEP) amplitude appear to suggest immanent deterioration of the patient’s motor status.ConclusionIn addition to topographic cortical mapping, TMS also serves as a neurophysiological assessment of the functional status of the patient’s motor system. The results presented here provide clinicians with a set of reference values to contextualize findings in their own tumor patients. Further research is still needed to better understand the full clinical relevance of these neurophysiological parameters.

Presurgical navigated TMS motor cortex mapping improves outcome in glioblastoma surgery: a controlled observational study

The authors report on an observational study designed to isolate the impact of navigated transcranial magnetic stimulation (nTMS) on surgical outcome in glioblastoma treatment. We undertook a controlled observational study to identify the additive impact of presurgical nTMS in patients scheduled for surgical treatment of glioblastoma in or near motor eloquent locations. The trial data is derived from a large university hospital with a differential availability of its nTMS mapping service at its two campuses, both equally served by a single neurosurgical department. When available, the nTMS cortical mapping data and nTMS-based fiber tractography are used for surgical planning and patient counseling as well as intraoperative identification of the primary motor cortex and guidance in subcortical motor mapping. The addition of preoperative nTMS mapping data to a clinical routine already incorporating preoperative fiber tractography and intraoperative neuronavigation and electrophysiology was shown to improve surgical outcomes by increasing the extent of resection, without compromising patient safety or long-term functional outcomes in comparison to the concurrent non-TMS control group. This study is the first to prove that the improved surgical outcomes observed in previous studies after the implementation of nTMS to presurgical work-up are not caused by any overall improvement in patient care or a paradigm shift toward more aggressive resection but by the additional functional data provided by nTMS.

Is the motor system necessary for processing action and abstract emotion words? Evidence from focal brain lesions

Neuroimaging and neuropsychological experiments suggest that modality-preferential cortices, including motor- and somatosensory areas, contribute to the semantic processing of action related concrete words. Still, a possible role of sensorimotor areas in processing abstract meaning remains under debate. Recent fMRI studies indicate an involvement of the left sensorimotor cortex in the processing of abstract-emotional words (e.g., “love”) which resembles activation patterns seen for action words. But are the activated areas indeed necessary for processing action-related and abstract words? The current study now investigates word processing in two patients suffering from focal brain lesion in the left frontocentral motor system. A speeded Lexical Decision Task on meticulously matched word groups showed that the recognition of nouns from different semantic categories – related to food, animals, tools, and abstract-emotional concepts – was differentially affected. Whereas patient HS with a lesion in dorsolateral central sensorimotor systems next to the hand area showed a category-specific deficit in recognizing tool words, patient CA suffering from lesion centered in the left supplementary motor area was primarily impaired in abstract-emotional word processing. These results point to a causal role of the motor cortex in the semantic processing of both action-related object concepts and abstract-emotional concepts and therefore suggest that the motor areas previously found active in action-related and abstract word processing can serve a meaning-specific necessary role in word recognition. The category-specific nature of the observed dissociations is difficult to reconcile with the idea that sensorimotor systems are somehow peripheral or ‘epiphenomenal’ to meaning and concept processing. Rather, our results are consistent with the claim that cognition is grounded in action and perception and based on distributed action perception circuits reaching into modality-preferential cortex.

Functional brain mapping of patients with arteriovenous malformations using navigated transcranial magnetic stimulation: first experience in ten patients

BackgroundIntracranial arteriovenous malformations (AVM) are known to be potent inductors of functional plasticity, and their vasculature makes standard functional imaging difficult. Here we conducted functional mapping of both primary motor cortex and speech related areas in patients with AVM using navigated transcranial magnetic stimulation (nTMS), which has been recently proven as a reliable noninvasive modality of preoperative functional brain mapping.MethodnTMS mapping was performed in ten patients with unruptured intracranial AVMs located in or near eloquent areas. Motor mapping was conducted for six patients with AVMs near the rolandic region, and speech mapping was performed for four patients with left perisylvian AVMs. After the examination, all patients were treated with surgery, radiosurgery or observed with best medical treatment on case-by-case basis.ResultsMotor mapping allowed for delineation of the primary motor cortex, even if the anatomy was severely obscured by the AVM in all cases with rolandic AVMs. No plastic relocation of the primary motor cortex was observed. Repetitive stimulation of the left ventral precentral gyrus led to speech impairments in all four cases that underwent speech mapping. Right hemispheric involvement was observed in one out of four cases and potentially indicated plastic changes. No side effects were observed.ConclusionnTMS allowed for detailed delineation of eloquent areas even within hypervascularized cortical areas. Our observations indicate that nTMS functional mapping is feasible not only in tumorous brain lesions, but also in AVMs.

Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease.

Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future.