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.
Objective 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. Methods 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. Results 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. Conclusion 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.
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.
Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumorrelated seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs.
Despite increasing reliance on endovascular therapy with posterior circulation aneurysms, there is a role for microsurgical therapy. Microsurgery remains a competitive, primary therapy for superior cerebellar artery, P1 posterior cerebral artery, distal anteroinferior cerebellar artery, and posteroinferior cerebellar artery aneurysms. Microsurgery has become a secondary therapy for P2 posterior cerebral artery, basilar trunk, proximal anteroinferior cerebellar artery, vertebrobasilar junction, and vertebral artery aneurysms when endovascular therapy is unfavorable. The preferred therapy for basilar bifurcation aneurysms remains unclear. Collaborative, multidisciplinary teams are strengthened and results are improved by offering competitive treatment alternatives for patients to consider and select. Rather than abandoning the posterior circulation prematurely, aneurysm surgeons should maintain technical proficiency with these lesions.
Object Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI. Methods Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI. Results Fourteen male and 7 female patients (17–53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p > 0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p < 0.05) than the initial MEG scan. Conclusions A rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as “mild” by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.
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