Introduction
Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is ...accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value.
Methods
The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications.
Results
nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here.
Conclusion
At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.
Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, ...sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.
Highlights • This large, multicenter series describes the safety of pre-operative navigated TMS mapping in 733 neurosurgical patients. • Navigated TMS was well-tolerated overall; the median VAS score ...was 0 with monopulse TMS and 5 with repetitive TMS. • The safety profile of navigated TMS in neurosurgical patients was excellent, with no persistent headaches reported and no provoked seizures in the series.
Lesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation ...(nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS.
Subjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared.
nTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects.
Maps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions.
•Navigated TMS is a safe, noninvasive method for lesion-based mapping of language pathways.•nTMS is safe, well-tolerated by patients, and can be performed in a lab environment.•nTMS-based language maps correlate well with maps from direct cortical stimulation.•nTMS maps are less well correlated with maps from magnetoencephalographic imaging.•nTMS is useful for interrogating language pathways for research and clinical purposes.
In patients with gliomas, changes in hemispheric specialization for language determined by magnetoencephalography (MEG) were analyzed to elucidate the impact of treatment and tumor recurrence on ...language networks. Demonstration of reorganization of language networks in these patients has significant implications on the prevention of postoperative functional loss and recovery. Whole‐brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 patients with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index (LI), a measure derived from the task. The initial scan was performed prior to resection; patients subsequently underwent surgery and adjuvant treatment. A second scan was performed upon recurrence prior to repeat resection. The relationship between the shift in LI between scans and demographics, anatomic location, pathology, and adjuvant treatment was analyzed. Laterality shifts were observed between scans; the median percent change was 29.1% across all patients. Laterality shift magnitude and relative direction were associated with the initial position of language dominance; patients with increased lateralization experienced greater shifts than those presenting more bilateral representation. A change in LI from left or right to bilateral (or vice versa) occurred in 23.3% of patients; complete switch occurred in 5.5% of patients. Patients with tumors within the language‐dominant hemisphere experienced significantly greater shifts than those with contralateral tumors. The majority of patients with glioma experience shifts in language network organization over time which correlate with the relative position of language lateralization and tumor location.
Preoperative mapping of cortical structures prior to neurosurgical intervention can provide a roadmap of the brain with which neurosurgeons can navigate critical cortical structures. In patients ...undergoing surgery for brain tumors, preoperative mapping allows for improved operative planning, patient risk stratification, and personalized preoperative patient counseling. Navigated transcranial magnetic stimulation (nTMS) is one modality that allows for highly accurate, image-guided, non-invasive stimulation of the brain, thus allowing for differentiation between eloquent and non-eloquent cortical regions. Motor mapping is the best validated application of nTMS, yielding reliable maps with an accuracy similar to intraoperative cortical mapping. Language mapping is also commonly performed, although nTMS language maps are not as highly concordant with direct intraoperative cortical stimulation maps as nTMS motor maps. Additionally, nTMS has been used to localize cortical regions involved in other functions such as facial recognition, calculation, higher-order motor processing, and visuospatial orientation. In this review, we evaluate the growing literature on the applications of nTMS in the preoperative setting. First, we analyze the evidence in support of the most common clinical applications. Then we identify usages that show promise but require further validation. We also discuss developing nTMS techniques that are still in the experimental stage, such as the use of nTMS to enhance postoperative recovery. Finally, we highlight practical considerations when utilizing nTMS and, importantly, its safety profile in neurosurgical patients. In so doing, we aim to provide a comprehensive review of the role of nTMS in the neurosurgical management of a patient with a brain tumor.
Despite profound medico-socio-legal consequences of traumatic brain injury (TBI) from intimate partner violence and domestic violence (IPV/DV), the incidence and acute outcomes of concurrent ...IPV/DV-TBI are not well understood. We examined US IPV/DV patients with/without TBI (IPV/DV-TBI; non-TBI) using the National Trauma Data Bank. We hypothesized IPV/DV-TBI would be associated with elevated morbidity.
National Trauma Data Bank Trauma Quality Programs Participant Use Files years 2018 to 2021 were queried for patients aged ≥18 years with IPV/DV using International Classification of Diseases, Tenth Revision external cause codes. TBI/non-TBI was defined using International Classification of Diseases, Tenth Revision diagnosis codes. TBI severity was defined by the Glasgow Coma Scale (severe = 3-8, moderate = 9-12, and mild = 13-15). Outcomes were intensive care unit (ICU) admission, in-hospital mortality, length of stay (LOS), and discharge home. Multivariable regressions examined associations between TBI and outcomes, controlling for sociodemographic and injury severity variables.
Of 3891 IPV/DV-related cases, 31.1% were IPV/DV-TBI. Cranial injuries included skull fracture (30.2%), subdural (19.8%), subarachnoid (13.4%), and epidural (1.1%) hemorrhage, contusion (8.1%), and cerebral edema (3.3%). In IPV/DV-TBI, mild/moderate/severe TBI proportions were 87.4%/4.3%/8.3%, with mean LOS 11.5 ± 10.9/14.4 ± 27.3/5.0 ± 7.7-days and mortality 0.9%/22.5%/28.6%, respectively. Compared with non-TBI, IPV/DV-TBI had more female (77.2%/64.6%, P < .001) and fewer Black patients (28.9%/36.6%, P < .001), more ICU admissions (20.9%/7.5%, P < .001) and mortality (4.1%/1.8%, P < .001), longer LOS (5.3 ± 9.5/4.5 ± 6.4-days, P = .008), and decreased discharge home (79.8%/83.8%, P = .005). Multivariable regressions confirmed the associations between TBI and ICU admission (adjusted odds ratio aOR = 4.29, 95% CI 3.46-5.33), mortality (aOR = 3.20 1.99-5.15), LOS (adjusted mean difference = +1.22 0.68-1.76), and inability to discharge home (aOR = 0.57 0.46-0.71).
One-third of US IPV/DV-related trauma cases have TBI, comprising predominantly female patients. Black patients with IPV/DV-related trauma were overrepresented compared with US census estimates. IPV/DV-TBI had increased ICU admissions, LOS, in-hospital mortality, and inability to discharge home compared with non-TBI. Investigating morbidity risk factors and providing sociomedical resources during acute care are critically needed in this vulnerable population.
Object
Direct cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two ...such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging.
Methods
Patients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively.
Results
Transcranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study.
Conclusions
Maps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.
Within the primary motor cortex, navigated transcranial magnetic stimulation (nTMS) has been shown to yield maps strongly correlated with those generated by direct cortical stimulation (DCS). ...However, the stimulation parameters for repetitive nTMS (rTMS)-based language mapping are still being refined. For this purpose, the present study compares two rTMS protocols, which differ in the timing of pulse train onset relative to picture presentation onset during object naming. Results were the correlated with DCS language mapping during awake surgery.
Thirty-two patients with left-sided perisylvian tumors were examined by rTMS prior to awake surgery. Twenty patients underwent rTMS pulse trains starting at 300ms after picture presentation onset (DELAYED TMS), whereas another 12 patients received rTMS pulse trains starting at the picture presentation onset (ONSET TMS). These rTMS results were then evaluated for correlation with intraoperative DCS results as gold standard in terms of differential consistencies in receiver operating characteristics (ROC) statistics. Logistic regression analysis by protocols and brain regions were conducted.
Within and around Broca's area, there was no difference in sensitivity (ONSET TMS: 100%, DELAYED TMS: 100%), negative predictive value (NPV) (ONSET TMS: 100%, DELAYED TMS: 100%), and positive predictive value (PPV) (ONSET TMS: 55%, DELAYED TMS: 54%) between the two protocols compared to DCS. However, specificity differed significantly (ONSET TMS: 67%, DELAYED TMS: 28%). In contrast, for posterior language regions, such as supramarginal gyrus, angular gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation showed greater specificity (ONSET TMS: 92%, DELAYED TMS: 20%), NPV (ONSET TMS: 92%, DELAYED TMS: 57%) and PPV (ONSET TMS: 75%, DELAYED TMS: 30%) with comparable sensitivity (ONSET TMS: 75%, DELAYED TMS: 70%). Logistic regression analysis also confirmed the greater fit of the predictions by rTMS that had the pulse train onset coincident with the picture presentation onset when compared to the delayed stimulation. Analyses of differential disruption patterns of mapped cortical regions were further able to distinguish clusters of cortical regions standardly associated with semantic and pre-vocalization phonological networks proposed in various models of word production. Repetitive nTMS predictions by both protocols correlate well with DCS outcomes especially in Broca's region, particularly with regard to TMS negative predictions.
With this study, we have demonstrated that rTMS stimulation onset coincident with picture presentation onset improves the accuracy of preoperative language maps, particularly within posterior language areas.
Moreover, immediate and delayed pulse train onsets may have complementary disruption patterns that could differentially capture cortical regions causally necessary for semantic and pre-vocalization phonological networks.
•rTMS stimulation onset improves accuracy particularly within posterior language areas.•Immediate and delayed pulse train onsets may have complementary disruption patterns.•rTMS language mapping has a high specificity for negative response maps.•Analysis of disruption patterns could capture semantic and phonological networks.
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