Incidence and linguistic quality of speech errors: a comparison of preoperative transcranial magnetic stimulation and intraoperative direct cortex stimulation

Die repetitive navigierte transkranielle Magnetstimulation (rnTMS) ist eine nichtinvasive Methode zur Lokalisierung von spracheloquenten Arealen und wird in der Neurochirurgie zur perioperativen Diagnostik von Hirntumorpatienten verwendet. Bei Operationen in spracheloquenten Bereichen liegt die Herausforderung in der individuellen Varianz der funktionalen Anatomie der Sprache. Die Detektion von Spracharealen bei Hirntumorpatienten erfolgt noch immer über Wachoperationen. Um die Anzahl der Wachoperationen zu verringern, sowie das postoperative Ergebnis von Patienten zu verbessern, werden zuverlässige nicht invasive präoperative Methoden zur Sprachlokalisierung eruiert. Das Ziel unserer Studie war es, die Zuverlässigkeit der präoperativen rnTMS mit der direkten kortikalen Stimulation (DCS) während der Wachoperation zu vergleichen. Methoden: Prospektiv wurden 25 Patienten mit Hirntumoren in spracheloquenten Arealen evaluiert. Die Sprache aller Patienten wurde mit der präoperativen rnTMS, sowie mit der DCS getestet. In beiden Fällen bestand die Aufgabe der Patienten darin, Objekte eines Datensatzes mit 80 Bildern zu benennen. Während der pre - und intraoperativen Stimulation wurden positive und negative Stimulationspunkte erhoben und einer statistischen Vergleichsanalyse unterzogen. Hinsichtlich ihrer räumlichen Überlappung und ihrer anatomischen Verteilung wurden die positiven Sprachpunkte innerhalb der Kraniotomie im gleichen MRT-Datensatz dokumentiert und verglichen. Wir entschieden uns für die Einteilung der sprachpositiven Punkte in ein kortikales Parzellierungssystem (nach Corina) und in folgende linguistische Sprachqualitäten: anomische, semantische, phonologische, performance und Verzögerungssprachfehler. Ergebnisse: Die Überlappung von positiven rnTMS und positiven DCS Punkten zeigte für die rnTMS eine niedrige Sensitivität (35%) und einen niedrigen positiven Vorhersagewert (16%), jedoch eine hohe Spezifität (90%) und einen hohen negativen Vorhersagewert (96%). Innerhalb des exponierten Bereichs wurden mehr als doppelt so viele rnTMS sprachpositive Punkte registriert als bei der DCS. Der hohe negative prädiktive Wert der rnTMS ist zumindest zum Teil mit der großen Anzahl der rnTMS sprachnegativen Punkte erklärbar, die eine höhere Wahrscheinlichkeit haben mit den weniger DCS negativen Punkten übereinzustimmen. Die anatomische Verteilung zeigte für die sprachpositiven DCS Punkte eine 73-prozentige Verteilung in der pars opercularis und der pars triangularis des frontalen Operculums und 24% innerhalb des parietal gelegenen supramarginalen Gyrus, sowie dem dorsalen Teil des oberen temporalen Gyrus. Die rnTMS sprachpositiven Punkte waren gleichmäßig über eine große Anzahl von Gyri verteilt. Innerhalb der Überlappungen gab es keine Korrelation in den linguistischen Fehlerqualitäten. Schlussfolgerung: Mit dem aktuellen rnTMS Protokoll können wir vorhersagen, dass in 90% der zuvor untersuchten rnTMS Areale keine Sprachpositivität zu finden ist. Das aktuelle Protokoll der rnTMS zeigt für die Sprachzuordnung negativer Areale eine gute Reliabilität. Bisher können sprachpositive Punkte mit Hilfe der rnTMS jedoch nicht zuverlässig zugeordnet werden. Hier ist eine Verbesserung des rnTMS Protokolls notwendig. Beispielsweise kann eine postoperative Nachkartierung via rnTMS bei der zuvor durchgeführten DCS die Zuverlässigkeit des rnTMS Protokolls verbessern.The repetitive navigated transcranial magnetic stimulation (rnTMS) is a non-invasive method for localizing speech eloquent areas. In neurosurgery it is an evolving and increasingly utilized tool for the preoperative diagnostic of brain tumor patients. One of the challenges in brain tumor surgery is the ability to precisely localize the speech eloquent areas. These are generally characterized by a significant inter-individual variance of the language-functional anatomy across patients. Therefore reliable methods for non-invasive language evaluation are desirable to considerably improve and support risk stratification and preoperative access planning. The current gold standard for the assessment of speech eloquent areas is the direct cortical stimulation (DCS). It is however only applicable during awake surgery. In order to reduce the necessity of awake surgery, as well as to improve the postoperative outcome in brain tumor surgery in general, this work evaluates the applicability and reliability of the preoperative rnTMS and compares it to the DCS during awake surgery. Methods: For the evaluation of the effectiveness of the rnTMS 25 patients with brain tumors in speech-related areas were prospectively assessed. All patients were preoperatively examined using the rnTMS as well as using DCS during awake surgery afterwards. Each assessment comprised the task to promptly name objects out of a dataset of 80 pictures. In all cases the positive and negative stimulation spots were checked statistically. Language positive spots in the craniotomy were further recorded in the same MRI data set. Subsequently the stored rnTMS and DCS language-positive spots were compared against each other with regard to their spatial correspondence and anatomical distribution. In addition the rnTMS and DCS mappings were classified in a cortical parcelling system (Corina) and finally the performance of both methods was assessed with respect to the following five types of linguistic error qualities: no-response, semantic, hesitation, phonological and performance errors. Results: Statistical analysis of the positive and negative stimulation spots as well as spatial correlation analysis of the rnTMS and DCS language-positive spots in the recorded MRI datasets revealed a sensitivity of 35% and a positive predictive value of 16% for the rnTMS. The specificity and negative predictive value on the other hand were determined to be significantly higher and resulted in values of 90% and 96%, respectively. Regarding the anatomical distribution 73% of the DCS speech-positive points were located in the pars opercularis and the pars triangularis in the frontal operculum. In the supramarginal gyrus as well as the dorsal part of the upper temporal gyrus 24% of the DCS positives spots could be evaluated. Comparing the rnTMS speech positivity to DCS, more spots were distributed over a large number of gyri. No correlation in the error quality within the overlaps could be found. Conclusion: With the herein established rnTMS protocol we were able to predict language negativity in the vast majority of the previously examined rnTMS areas. However, compared to DCS, with regard to assessment of positive language points the established rnTMS protocol lacked accuracy. Nontheless, rnTMS can be considered a reliable diagnostic tool to allocate essential language sites with simultaneous postoperative re-mapping via rnTMS. Future improvement of the protocol might possibly aid in reliable language point assignment

Specific DTI seeding and diffusivity-analysis improve the quality and prognostic value of TMS-based deterministic DTI of the pyramidal tract

Object: Navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI) is used preoperatively in patients with eloquent-located brain lesions and allows analyzing non-invasively the spatial relationship between the tumor and functional areas (e.g. the motor cortex and the corticospinal tract [CST]). In this study, we examined the diffusion parameters FA (fractional anisotropy) and ADC (apparent diffusion coefficient) within the CST in different locations and analyzed their interrater reliability and usefulness for predicting the patients' motor outcome with a precise approach of specific region of interest (ROI) seeding based on the color-coded FA-map. Methods: Prospectively collected data of 30 patients undergoing bihemispheric nTMS mapping followed by nTMS-based DTI fiber tracking prior to surgery of motor eloquent high-grade gliomas were analyzed by 2 experienced and 1 unexperienced examiner. The following data were scrutinized for both hemispheres after tractography based on nTMS-motor positive cortical seeds and a 2nd region of interest in one layer of the caudal pons defined by the color-coded FA-map: the pre- and postoperative motor status (day of discharge und 3months), the closest distance between the tracts and the tumor (TTD), the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC). The latter as an average within the CST as well as specific values in different locations (peritumoral, mesencephal, pontine). Results: Lower average FA-values within the affected CST as well as higher average ADC-values are significantly associated with deteriorated postoperative motor function (p=0.006 and p=0.026 respectively). Segmental analysis within the CST revealed that the diffusion parameters are especially disturbed on a peritumoral level and that the degree of their impairment correlates with motor deficits (FA p=0.065, ADC p=0.007). No significant segmental variation was seen in the healthy hemisphere. The interrater reliability showed perfect agreement for almost all analyzed parameters. Conclusions: Adding diffusion weighted imaging derived information on the structural integrity of the nTMS-based tractography results improves the predictive power for postoperative motor outcome. Utilizing a second subcortical ROI which is specifically seeded based on the color-coded FA map increases the tracking quality of the CST independently of the examiner's experience. Further prospective studies are needed to validate the nTMS-based prediction of the patient's outcome. Keywords: Navigated transcranial magnetic stimulation (nTMS), Brain tumor surgery, Glioma, Motor outcome, Diffusion tensor imaging, Fractional anisotropy, Apparent diffusion coefficien

Resection of Motor Eloquent Metastases Aided by Preoperative nTMS-Based Motor Maps-Comparison of Two Observational Cohorts.

IntroductionPreoperative mapping of motor areas with navigated transcranial magnetic stimulation (nTMS) has been shown to improve surgical outcomes for peri-Rolandic lesions and, in particular, for gliomas. However, the impact of this technique on surgical outcomes for peri-Rolandic metastatic lesions is yet unknown.ObjectiveTo investigate the impact of nTMS on surgical outcomes for peri-Rolandic metastatic lesions, various clinical parameters were analyzed in our international study group.MethodsTwo prospectively enrolled cohorts were compared by investigating patients receiving preoperative nTMS (2010-2015; 120 patients) and patients who did not receive preoperative nTMS (2006-2015; 130 patients). Tumor location, pathology, size, and preoperative deficits were comparable.ResultsThe nTMS group showed a lower rate of residual tumor on postoperative magnetic resonance imaging (odds ratio 0.3025; 95% confidence interval 0.1356-0.6749). On long-term follow-up, surgery-related paresis was decreased in the nTMS group (nTMS vs. non-nTMS; improved: 30.8 vs. 13.1%, unchanged: 65.8 vs. 73.8%, worse: 3.4 vs. 13.1% of patients; p = 0.0002). Moreover, the nTMS group received smaller craniotomies (nTMS: 16.7 ± 8.6 cm2 vs. non-nTMS: 25.0 ± 17.1 cm2; p < 0.0001). Surgical time differed significantly between the two groups (nTMS: 128.8 ± 49.4 min vs. non-nTMS: 158.0 ± 65.8 min; p = 0.0002).ConclusionThis non-randomized study suggests that preoperative motor mapping by nTMS may improve the treatment of patients undergoing surgical resection of metastases in peri-Rolandic regions. These findings suggest that further evaluation with a prospective, randomized trial may be warranted

Resection of Motor Eloquent Metastases Aided by Preoperative nTMS-Based Motor Maps-Comparison of Two Observational Cohorts.

IntroductionPreoperative mapping of motor areas with navigated transcranial magnetic stimulation (nTMS) has been shown to improve surgical outcomes for peri-Rolandic lesions and, in particular, for gliomas. However, the impact of this technique on surgical outcomes for peri-Rolandic metastatic lesions is yet unknown.ObjectiveTo investigate the impact of nTMS on surgical outcomes for peri-Rolandic metastatic lesions, various clinical parameters were analyzed in our international study group.MethodsTwo prospectively enrolled cohorts were compared by investigating patients receiving preoperative nTMS (2010-2015; 120 patients) and patients who did not receive preoperative nTMS (2006-2015; 130 patients). Tumor location, pathology, size, and preoperative deficits were comparable.ResultsThe nTMS group showed a lower rate of residual tumor on postoperative magnetic resonance imaging (odds ratio 0.3025; 95% confidence interval 0.1356-0.6749). On long-term follow-up, surgery-related paresis was decreased in the nTMS group (nTMS vs. non-nTMS; improved: 30.8 vs. 13.1%, unchanged: 65.8 vs. 73.8%, worse: 3.4 vs. 13.1% of patients; p = 0.0002). Moreover, the nTMS group received smaller craniotomies (nTMS: 16.7 ± 8.6 cm2 vs. non-nTMS: 25.0 ± 17.1 cm2; p < 0.0001). Surgical time differed significantly between the two groups (nTMS: 128.8 ± 49.4 min vs. non-nTMS: 158.0 ± 65.8 min; p = 0.0002).ConclusionThis non-randomized study suggests that preoperative motor mapping by nTMS may improve the treatment of patients undergoing surgical resection of metastases in peri-Rolandic regions. These findings suggest that further evaluation with a prospective, randomized trial may be warranted

Towards a tractography-based risk stratification model for language area associated gliomas

Objectives: Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. Methods: We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. Results: In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 – 129.06; temporal stem: OR: 21.96; CI: 2.93 – 164.41) was associated with a higher-risk of persisting aphasia. Conclusions: Tractography of language pathways can help to determine the individual aphasia risk profile presurgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries