Postoperative Language Deficits Research Articles

What effects does awake craniotomy have on functional and survival outcomes for glioblastoma patients?

Neurosurgeons adopt several different surgical approaches to deal with glioblastomas (GB) located in or near eloquent areas. Some attempt maximal safe resection by awake craniotomy (AC), but doubts persist concerning the real benefits of this type of surgery in this situation. We performed a retrospective study to evaluate the extent of resection (EOR), functional and survival outcomes after AC of patients with GB in critical locations. Forty-six patients with primary GB treated with the Stupp regimen between 2004 and 2019, for whom brain mapping was feasible, were included. We assessed EOR, postoperative language and/or motor deficits three months after AC, progression-free survival (PFS) and overall survival (OS). Complete resection was achieved in 61% of the 46GB patients. The median PFS was 6.8months (CI 6.1; 9.7) and the median OS was 17.6months (CI 14.8; 34.1). Three months after AC, more than half the patients asymptomatic before surgery remained asymptomatic, and one third of patients with symptoms before surgery experienced improvements in language, but not motor functions. The risk of postoperative deficits was higher in patients with preoperative deficits or incomplete resection. Furthermore, the presence of postoperative deficits was an independent predictive factor for shorter PFS. AC is an option for the resection of GB in critical locations. The observed survival outcomes are typical for GB patients in the Stupp era. However, the success of AC in terms of the recovery or preservation of language and/or motor functions cannot be guaranteed, given the aggressiveness of the tumor.

STMO-09 Recovery from speech deficit after injury to frontal aslant tract in glioma surgery

BACKGROUND: The frontal aslant tract (FAT) is a white matter fiber connecting the superior frontal gyrus to the lateral inferior frontal gyrus. Damage to FAT in dominant hemisphere can lead to speech deficits which, in most cases, resolve within weeks to months. However, little is known about mechanisms of recovery and factors for predicting permanent language deficits. METHODS: Eighteen patients with glioma (age ranged 24 to 78, 10 glioblastomas and 8 lower grade gliomas) located in the medial frontal lobe in the dominant hemisphere involving the supplementary motor area (SMA) and FAT were included. FAT was visualized using diffusion tensor imaging tractography in pre- and postoperative MRI. Postoperative language deficit, resected area of FAT and surrounding brain regions including the cingulate gyrus and corpus callosum (CC) were retrospectively reviewed. RESULTS: In 17 of 18 cases, postoperative language deficits were observed. Speech deficits resolved within a month in 12 cases, while recovery was incomplete in five cases. In two patients without complete recovery, CC located beneath SMA was removed because of tumor infiltration. Other two patients had substantial injury of middle third portion of FAT. The last case had preceding infarction in the contralateral frontal white matter including FAT. In cases with complete language recovery, transcallosal fibers connecting the contralateral SMA to the ipsilateral inferior frontal gyrus were detected by postoperative DTI-tractography. These fibers were damaged anywhere along its length in patients without complete language recovery, indicating that they may play an important role in recovery after FAT injury. CONCLUSION: Injury to CC or middle third portion of FAT can cause permanent language disorder. Transcallosal fibers from contralateral SMA seems to be involved in the recovery from language deficit after injury to FAT. In glioma surgery involving dominant SMA or FAT, these fibers should be preserved to avoid permanent speech deficit.

The impact of high functional connectivity network hub resection on language task performance in adult low- and high-grade glioma.

Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance. Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN). Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus. Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.

Plasticity in language cortex and white matter tracts after resection of dominant inferior parietal lobule arteriovenous malformations: a combined fMRI and DTI study.

The dominant inferior parietal lobe (IPL) contains cortical and subcortical structures that serve language processing. A high incidence of postoperative short-term aphasia and good potential for language reorganization have been observed. The authors' goal was to study the plasticity of the language cortex and language-related fibers in patients with brain arteriovenous malformations (BAVMs) located in the IPL. A total of 6 patients who underwent microsurgical treatment of an IPL BAVM were prospectively recruited between September 2016 and May 2018. Blood oxygen level-dependent functional MRI (BOLD-fMRI) and diffusion tensor imaging (DTI) were performed within 1 week before and 6 months after microsurgery. Language-related white matter (WM) eloquent fiber tracts and their contralateral homologous fiber tracts were tracked. The Western Aphasia Battery was administered to assess language function. The authors determined the total number of fibers and mean fractional anisotropy (FA) indices for each individual tract. In addition, they calculated the laterality index (LI) between the activated language cortex voxels in the lesional and contralesional hemispheres and compared these indices between the preoperative and postoperative fMR and DT images. Of the 6 patients with IPL BAVMs, all experienced postoperative short-term language deficits, and 5 (83.3%) recovered completely at 6 months after surgery. Five patients (83.3%) had right homologous reorganization of BOLD signal activations in both Broca's and Wernicke's areas. More fibers were observed in the arcuate fasciculus (AF) in the lesional hemisphere than in the contralesional hemisphere (1905 vs 254 fibers, p = 0.035). Six months after surgery, a significantly increased number of fibers was seen in the right hemispheric AF (249 fibers preoperatively vs 485 postoperatively, p = 0.026). There were significantly more nerve fibers in the postoperative left inferior frontooccipital fasciculus (IFOF) (874 fibers preoperatively vs 1186 postoperatively, p = 0.010). A statistically significant increase in right hemispheric dominance of Wernicke's area was observed. The overall functional LI showed functional lateralization of Wernicke's area in the right hemisphere (LI ≤ -0.20) in all patients. The authors' findings provide evidence for the functional reorganization by recruiting the right hemispheric homologous region of Broca's and Wernicke's areas, right hemispheric AFs, and left hemispheric IFOFs following resection of IPL BAVMs.Clinical trial registration no.: NCT02868008 (clinicaltrials.gov).

Refined Functional Magnetic Resonance Imaging and Magnetoencephalography Mapping Reveals Reorganization in Language-Relevant Areas of Lesioned Brains

Neurosurgical decisions regarding interventions close to brain areas with language-related functions remain highly challenging because of the risk of postoperative dysfunction. To minimize these risks, improvements in the preoperative mapping of language-related regions are required, especially as space-occupying lesions often lead to altered cortical topography and language area reorganization. The degree of deviation and language area reorganization were investigated in 26 functional magnetic resonance imaging- and magnetoencephalography-dissociable cortical sub-areas displaying language-related activations in each of 18 patients with brain lesions and 3 healthy volunteers (during visual language tasks). Both modalities showed good congruency of the language areas. The mean spatial distance of the centroids and maxima was 9.06 mm and 10.58 mm, respectively, allowing us to define more specific anatomical positions. Postoperatively, language abilities increased in 11% (2 of 18) of the patients, remained unchanged in 83% (15 of 18) of the patients, and decreased in 6% (1 of 18) of the patients, respectively. Signs of language function reorganization detected on both functional magnetic resonance imaging and magnetoencephalography were present in 29% (5 of 17) of the patients. Attenuation of neurovascular coupling was found postoperatively in 17% (3 of 18) of the patients. Monohemispheric language processing cannot be assumed always in patients with brain lesions. The more detailed subdivision of language-relevant brain areas shown in this study can help to achieve more radical tumor resection without postoperative language deficits.

Localization of Expressive Language Cortex in a 2-Year-Old Child Using High-Gamma Electrocorticography

Cortical stimulation mapping is the gold standard for presurgical language mapping; however, it cannot be reliably performed in very young patients. Language mapping using noninvasive modalities is also challenging in very young patients. Although utility of language mapping using power of high-gamma in electrocorticographic recordings was demonstrated in adults and older children, there is a gap of knowledge in the ability of this procedure for localizing language-specific cortex in very young patients. We describe a case of a 2-year-old patient who, to our knowledge, is the youngest person to undergo successful high-gamma electrocorticographic presurgical language mapping for localization of the expressive language cortex (Broca area). The surgical plan was to resect a cortical tuber within the left inferior frontal gyrus and there was a strong concern about postoperative language deficit after resection. Presurgical language mapping using noninvasive modalities were attempted without success. Cortical stimulation mapping was not feasible in this patient. Therefore, high-gamma electrocorticography was the only viable option for language mapping, and it successfully localized the expressive language cortex. The patient underwent surgery for resection of the IFG tuber based on results of high-gamma electrocorticography and had no postoperative language deficit. High-gamma electrocorticography can be used for localizing language-specific cortex, especially Broca's area, in very young patients.

Prediction of postoperative deficits using an improved diffusion-weighted imaging maximum a posteriori probability analysis in pediatric epilepsy surgery.

This study is aimed at improving the clinical utility of diffusion-weighted imaging maximum a posteriori probability (DWI-MAP) analysis, which has been reported to be useful for predicting postoperative motor, language, and visual field deficits in pediatric epilepsy surgery. The authors determined the additive value of a new clustering mapping method in which average direct-flip distance (ADFD) reclassifies the outliers of original DWI-MAP streamlines by referring to their minimum distances to the exemplar streamlines (i.e., medoids). The authors studied 40 children with drug-resistant focal epilepsy (mean age 8.7 ± 4.8 years) who had undergone resection of the presumed epileptogenic zone and had five categories of postoperative deficits (i.e., hemiparesis involving the face, hand, and/or leg; dysphasia requiring speech therapy; and/or visual field cut). In pre- and postoperative images of the resected hemisphere, DWI-MAP identified a total of nine streamline pathways: C1 = face motor area, C2 = hand motor area, C3 = leg motor area, C4 = Broca's area-Wernicke's area, C5 = premotor area-Broca's area, C6 = premotor area-Wernicke's area, C7 = parietal area-Wernicke's area, C8 = premotor area-parietal area, and C9 = occipital lobe-lateral geniculate nucleus. For each streamline of the identified pathway, the minimal ADFD to the nine exemplars corrected the pathway membership. Binary logistic regression analysis was employed to determine how accurately two fractional predictors, Δ1-9 (postoperative volume change of C1-9) and γ1-9 (preoperatively planned volume of C1-9 resected), predicted postoperative motor, language, and visual deficits. The addition of ADFD to DWI-MAP analysis improved the sensitivity and specificity of regression models for predicting postoperative motor, language, and visual deficits by 28% for Δ1-3 (from 0.62 to 0.79), 13% for Δ4-8 (from 0.69 to 0.78), 13% for Δ9 (from 0.77 to 0.87), 7% for γ1-3 (from 0.81 to 0.87), 1% for γ4-8 (from 0.86 to 0.87), and 24% for γ9 (from 0.75 to 0.93). Preservation of the eloquent pathways defined by preoperative DWI-MAP analysis with ADFD (up to 97% of C1-4,9) prevented postoperative motor, language, and visual deficits with sensitivity and specificity ranging from 88% to 100%. The present study suggests that postoperative functional outcome substantially differs according to the extent of resected white matter encompassing eloquent cortex as determined by preoperative DWI-MAP analysis. The preservation of preoperative DWI-MAP-defined pathways may be crucial to prevent postoperative deficits. The improved DWI-MAP analysis may provide a complementary noninvasive tool capable of guiding the surgical margin to minimize the risk of postoperative deficits for children.

Surgery of language-eloquent tumors in patients not eligible for awake surgery: the impact of a protocol based on navigated transcranial magnetic stimulation on presurgical planning and language outcome, with evidence of tumor-induced intra-hemispheric plasticity

ObjectivesAwake surgery and intraoperative monitoring represent the gold standard for surgery of brain tumors located in the perisylvian region of the dominant hemisphere due to their ability to map and preserve the language network during surgery. Nevertheless, in some cases awake surgery is not feasible. This could increase the risk of postoperative language deficit. Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI fiber tracking (DTI-FT) provide a preoperative mapping and reconstruction of the cortico-subcortical language network. This can be used to plan and guide the surgical strategy to preserve the language function. The objective if this study is to describe the impact of a non-invasive preoperative protocol for mapping the language network through the nTMS and nTMS-based DTI-FT in patients not eligible for awake surgery and thereby operated under general anesthesia for suspected language-eloquent brain tumors. Patients and methodsWe reviewed clinical data of patients not eligible for awake surgery and operated under general anaesthesia between 2015 and 2016. All patients underwent nTMS language cortical mapping and nTMS-based DTI-FT of subcortical language fascicles. The nTMS findings were used to plan and guide the maximal safe resection of the tumor. The impact on postoperative language outcome and the accuracy of the nTMS-based mapping in predicting language deficits were evaluated. ResultsTwenty patients were enrolled in the study. The nTMS-based reconstruction of the language network was successful in all patients. Interestingly, we observed a significant association between tumor localization and the cortical distribution of the nTMS errors (p = 0.004), thereby suggesting an intra-hemispheric plasticity of language cortical areas, probably induced by the tumor itself. The nTMS mapping disclosed the true-eloquence of lesions in 12 (60%) of all suspected cases. In the remaining 8 cases (40%) the suspected eloquence of the lesion was disproved. The nTMS-based findings guided the planning and surgery through the visual feedback of navigation. This resulted in a slight reduction of the postoperative language performance at discharge that was completely recovered after one month from surgery. The accuracy of the nTMS-based protocol in predicting postoperative permanent deficits was significantly high, especially for false-eloquent lesions (p = 0.04; sensitivity 100%, specificity 57.14%, negative predictive value 100%, positive predicitive value 50%). ConclusionsThe nTMS-based preoperative mapping allows for a reliable visualization of the language network, being also able to identify an intra-hemispheric tumor-induced cortical plasticity. It allows for a customized surgical strategy that could preserve post-operative language function. This approach should be considered as a support for neurosurgeons whenever approaching patients affected by suspected language-eloquent tumors but not eligible for awake surgery.

Book Review

Case selection for surgical treatment of language-area brain arteriovenous malformations (L-BAVMs) remains difficult. This study aimed to determine the surgical outcomes and risk factors for postoperative language deficits (LDs) in patients with L-BAVMs.Patients with L-BAVMs who underwent microsurgical resection between September 2012 and June 2016 were reviewed. All patients had undergone preoperative functional magnetic resonance imaging and diffusion tensor imaging. Both functional and angioarchitectural factors were analyzed regarding the postoperative LD. Functional factors included the eloquence involved, the side of blood-oxygenation level-dependent signal activation and the white-matter fibers (anterior segment, long segment [LS], and posterior segment of arcuate fasciculus, and the inferior fronto-occipital fasciculus) involved.Sixty-nine patients with L-BAVMs were reviewed. Postoperative short- and long-term LD was found in 32 (46.4%) and 14 (20.3%) patients, respectively. Twelve of the 14 patients with Geschwind's territory L-BAVMs (85.7%) had short-term LD, compared with 10 (34.5%) in Wernicke's and 10 (38.5%) in Broca's area. LS involvement (P = 0.001) and larger nidus size (P = 0.017) were independent risk factors for the short-term LD. Meanwhile, nidus size (P = 0.007), preoperative LD (P = 0.008), and LS involvement (P = 0.028) were independent risk factors for long-term LD.L-BAVMs located in Geschwind's territory can cause a high incidence of LD. LS involvement and larger nidus size are risk factors for postoperative short- and long-term LD, and preoperative LD is a risk factor for postoperative, long-term LD.

Brain Arteriovenous Malformations Located in Language Area: Surgical Outcomes and Risk Factors for Postoperative Language Deficits

Case selection for surgical treatment of language-area brain arteriovenous malformations (L-BAVMs) remains difficult. This study aimed to determine the surgical outcomes and risk factors for postoperative language deficits (LDs) in patients with L-BAVMs. Patients with L-BAVMs who underwent microsurgical resection between September 2012 and June 2016 were reviewed. All patients had undergone preoperative functional magnetic resonance imaging and diffusion tensor imaging. Both functional and angioarchitectural factors were analyzed regarding the postoperative LD. Functional factors included the eloquence involved, the side of blood-oxygenation level-dependent signal activation and the white-matter fibers (anterior segment, long segment [LS], and posterior segment of arcuate fasciculus, and the inferior fronto-occipital fasciculus) involved. Sixty-nine patients with L-BAVMs were reviewed. Postoperative short- and long-term LD was found in 32 (46.4%) and 14 (20.3%) patients, respectively. Twelve of the 14 patients with Geschwind's territory L-BAVMs (85.7%) had short-term LD, compared with 10 (34.5%) in Wernicke's and 10 (38.5%) in Broca's area. LS involvement (P= 0.001) and larger nidus size (P= 0.017) were independent risk factors for the short-term LD. Meanwhile, nidus size (P= 0.007), preoperative LD (P= 0.008), and LS involvement (P= 0.028) were independent risk factors for long-term LD. L-BAVMs located in Geschwind's territory can cause a high incidence of LD. LS involvement and larger nidus size are risk factors for postoperative short- and long-term LD, and preoperative LD is a risk factor for postoperative, long-term LD.

Is fluorescence-guided surgery with 5-ala in eloquent areas for malignant gliomas a reasonable and useful technique?

IntroductionHigh-grade gliomas surgery in eloquent areas must achieve two pivotal aims: oncological efficacy and preservation of unimpaired neurological functions or improvement of impaired neurological functions. Here, we evaluated the safety and the usefulness of 5-ALA fluorescence-guided surgery in eloquent areas. Material and methodsSingle center, retrospective and consecutive series of adult patients operated on for a supratentorial glioblastoma between November 2012 and November 2015. ResultsFifty-one patients with a glioblastoma located within an eloquent area were included: 24 patients operated on with 5-ALA (5-ALA group), and 27 patients operated on under white light (control group). Preoperative motor and language deficits were similar in the 5-ALA group (50%, 37.5%) as in the control group (59.3%, 55.6%) (P=0.510; P=0.200). Three-month postoperative motor and language deficits rates were similar in the 5-ALA group (12.5%, 12.5%) as in the control group (29.6%, 14.8%) (P=0.180; P=0.990). The extent of resection did not significantly vary between groups (P=0.280). The overall survival did not significantly vary between groups (P=0.080) but the progression-free survival was significantly higher in the 5-ALA group than in the control group (P=0.020). The 12-month progression-free survival was significantly higher in 5-ALA group (60%) than in control group (21%; P=0.006). In multivariate analysis, the 5-ALA was an independent prognostic factor associated with progression-free survival (P=0.030). Conclusion5-ALA fluorescence-guided surgery for glioblastoma located in eloquent areas is effective to improve progression-free survival. To preserve functional outcomes, it requires the routine use of intraoperative functional mapping to respect functional boundaries.

The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality: A Retrospective Diffusion Tensor Imaging Study.

Using diffusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits. This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes. Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records. The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P < .001) deficits, respectively. The left SLF LTD was also significantly associated with the occurrence rate of new postoperative language deficits (P = .003), and the LTD threshold that best predicted this occurrence was 1 cm (P < .001). Kaplan–Meier log-rank survival analyses in patients having high-grade tumors demonstrated a significantly higher mortality for patients with a left SLF LTD <1 cm (P = .01). Measuring tumor proximity to major white matter tracts using DTI can inform clinicians of the likelihood of postoperative functional deficits. A distance of 1 cm or less from eloquent white matter structures most significantly predicts the occurrence of new deficits with current surgical and imaging techniques.

Lateralization of language function in epilepsy patients: A high-density scalp-derived event-related potentials (ERP) study

Language functional magnetic resonance imaging (fMRI) represents the clinical standard for language lateralization assessment in presurgical epilepsy evaluation, but still many patients experience postoperative language deficits. Event-related potentials (ERPs), especially the negative component around and after 400ms, are related to language processing and could therefore represent a complementary method of language lateralization assessment. Scalp EEG was recorded from 64 locations in 36 epilepsy patients and 37 controls during three visually presented language tasks: A short-term language memory task (differentiation memorized vs. unknown words), a phonological task (detection of rhymes in word pairs), and a semantic decision task (differentiation words vs. pseudowords). ERPs were analyzed in the 300ms-800ms epoch. Language fMRI was routinely obtained in patients. ERPs were significantly more negative over the left compared to the right hemisphere in all three tasks in patients and controls. Laterality indices showed highest concordance with fMRI for the Word/Pseudoword Task. ERPs of language processing were lateralized to the left hemisphere in the majority of epilepsy patients and controls. In patients, single-subject laterality indices showed high concordance with fMRI results. Results indicate that scalp-derived ERPs are a promising tool to investigate lateralization of language function in epilepsy patients.

Functional Reconstruction of Motor and Language Pathways Based on Navigated Transcranial Magnetic Stimulation and DTI Fiber Tracking for the Preoperative Planning of Low Grade Glioma Surgery: A New Tool for Preservation and Restoration of Eloquent Networks.

Surgery of low-grade gliomas (LGGs) in eloquent areas still presents a challenge. New technologies have been introduced to enable the performance of "functional", customized preoperative planning aimed at maximal resection, while reducing the risk of postoperative deficits. We describe our experience in the surgery of LGGs in eloquent areas using preoperative planning based on navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging (DTI) tractography. Sixteen patients underwent preoperative planning, using nTMS and nTMS-based DTI tractography. Motor and language functions were mapped. Preoperative data allowed for tailoring of the surgical strategy. The impact of these modalities on surgical planning was evaluated. Influence on functional outcome was analyzed in comparison with results in a historical control group. In 12 patients (75 %), nTMS added useful information on functional anatomy and surgical risks. Surgical strategy was modified in 9 of 16 cases (56 %). The nTMS "functional approach" provided a good outcome at discharge, with a decrease in postoperative motor and/or language deficits, as compared with controls (6 vs. 44 %; p = 0.03). The functional preoperative mapping of speech and motor pathways based on nTMS and DTI tractography provided useful information, allowing us to plan the best surgical strategy for radical resection; this resulted in improved postoperative neurological results.

A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients.

Navigated transcranial magnetic stimulation (nTMS) has recently been introduced as a non-invasive tool for functional mapping of cortical language areas prior to surgery. It correlates well with intraoperative neurophysiological monitoring (IONM) findings, allowing defining the best surgical strategy to preserve cortical language areas during surgery for language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping and postoperative language deficits are often caused by injury to subcortical language pathways. Nowadays, the only way to preoperatively visualize language subcortical white matter tracts consists in DTI fiber tracking (DTI-FT). However, standard DTI-FT is based on anatomical landmarks that vary interindividually and can be obscured by the presence of the tumor itself. It has been demonstrated that combining nTMS with DTI-FT allows for a more reliable visualization of the motor pathway in brain tumor patients. Nevertheless, no description about such a combination has been reported for the language network. The aim of the present study is to describe and assess the feasibility and reliability of using cortical seeding areas defined by error type-specific nTMS language mapping (nTMS-positive spots) to perform DTI-FT in patients affected by language-eloquent brain tumors. We describe a novel technique for a nTMS-based DTI-FT to visualize the complex cortico-subcortical connections of the language network. We analyzed quantitative findings, such as fractional anisotropy values and ratios, and the number of visualized connections of nTMS-positive spots with subcortical pathways, and we compared them with results obtained by using the standard DTI-FT technique. We also analyzed the functional concordance between connected cortical nTMS-positive spots and subcortical pathways, and the likelihood of connection for nTMS-positive vs. nTMS-negative cortical spots. We demonstrated, that the nTMS-based approach, especially what we call the “single-spot” strategy, is able to provide a reliable and more detailed reconstruction of the complex cortico-subcortical language network as compared to the standard DTI-FT. We believe this technique represents a beneficial new strategy for customized preoperative planning in patients affected by tumors in presumed language eloquent location, providing anatomo-functional information to plan language-preserving surgery.

Vascular risk factors in Alzheimer disease and mild cognitive impairment

Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent.Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task.Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values.Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.

Mapping of language brain areas in patients with brain tumors.

Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them.

P61. Preoperative repetitive navigated transcranial magnetic stimulation for language mapping and outcome improvement in brain tumor patients

Objective Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet, we also need data that show whether preoperative rTMS for language mapping also has an impact on the patients' clinical course and functional outcomes as it was proved for motor mapping. Methods We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011–2013) with mapping results not being available for the surgeon, and matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013–2014), but mapping results were taken into account during awake mapping and tumor resection via implementation into the neuronavigation system. In addition, cortical language maps were generated by analyzing preoperative rTMS data. Results Mean craniotomy sizes were significantly smaller in patients of GROUP 2 (GROUP 1 vs. GROUP 2: 50.1±16.8cm 2 vs. 41.6±10.4cm 2 , p =0.0373), and postoperative language deficits were found significantly more often in patients of GROUP 1 ( p =0.0153), although preoperative language status did not differ between groups ( p =0.7576). Additionally, there was a trend towards less unexpected tumor residuals (GROUP 1 vs. GROUP 2: 32.0% vs. 16.0%, p =0.1853), shorter surgery duration (240.3±53.2min vs. 215.5±48.5min, p =0.0914), and higher postoperative KPS scores (80 vs. 90, p =0.2102) in GROUP 2 patients. Conclusion In general, the clinical course and functional outcomes of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. Furthermore, reliable and precise language maps can be generated by rTMS in brain tumor patients, and this approach has once again proven to be safe, effective, and well-tolerable for the individual subject. However, more patients have to be enrolled for more definite data.

The impact of preoperative language mapping by repetitive navigated transcranial magnetic stimulation on the clinical course of brain tumor patients.

BackgroundLanguage mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet we also need data that show whether patients benefit clinically from preoperative rTMS for language mapping.MethodsWe enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011–2013), with the mapping results not being available for the surgeon, and we matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013–2014), but the mapping results were taken into account during tumor resection. Additionally, cortical language maps were generated by analyzing preoperative rTMS and intraoperative direct cortical stimulation (DCS) data.ResultsMean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576). Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2.ConclusionsThe present study provides a first hint that the clinical course of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. However, a significant difference between both groups was only found for craniotomy extents and postoperative deficits, but not for other clinical parameters, which only showed a trend toward better results in GROUP 2. Therefore, multicenter trials with higher sample sizes are needed to further investigate the distinct impact of rTMS language mapping on the clinical course of brain tumor patients.

Usage of fMRI for pre-surgical planning in brain tumor and vascular lesion patients: task and statistical threshold effects on language lateralization.

Background and purposeFunctional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent.Materials and methodsImaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task.ResultsBrain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values.ConclusionOur results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.