Differentiating IDH-mutant astrocytomas and 1p19q-codeleted oligodendrogliomas using DSC-PWI: high performance through cerebral blood volume and percentage of signal recovery percentiles.

OBJECTIVE: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. METHODS: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010-2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. RESULTS: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. CONCLUSIONS: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. CLINICAL RELEVANCE STATEMENT: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. KEY POINTS: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification.

Deeply 3D-T1-TFE hypointense voxels are characteristic of phase-rim lesions in multiple sclerosis.

OBJECTIVES: The development of new drugs for the treatment of progressive multiple sclerosis (MS) highlights the need for new prognostic biomarkers. Phase-rim lesions (PRLs) have been proposed as markers of progressive disease but are difficult to identify and quantify. Previous studies have identified T1-hypointensity in PRLs. The aim of this study was to compare the intensity profiles of PRLs and non-PRL white-matter lesions (nPR-WMLs) on three-dimensional T1-weighted turbo field echo (3DT1TFE) MRI. We then evaluated the performance of a derived metric as a surrogate for PRLs as potential markers for risk of disease progression. METHODS: This study enrolled a cohort of relapsing-remitting (n = 10) and secondary progressive MS (n = 10) patients for whom 3 T MRI was available. PRLs and nPR-WMLs were segmented, and voxel-wise normalized T1-intensity histograms were analyzed. The lesions were divided equally into training and test datasets, and the fifth-percentile (p5)-normalized T1-intensity of each lesion was compared between groups and used for classification prediction. RESULTS: Voxel-wise histogram analysis showed a unimodal histogram for nPR-WMLs and a bimodal histogram for PRLs with a large peak in the hypointense limit. Lesion-wise analysis included 1075 nPR-WMLs and 39 PRLs. The p5 intensity of PRLs was significantly lower than that of nPR-WMLs. The T1 intensity-based PRL classifier had a sensitivity of 0.526 and specificity of 0.959. CONCLUSIONS: Profound hypointensity on 3DT1TFE MRI is characteristic of PRLs and rare in other white-matter lesions. Given the widespread availability of T1-weighted imaging, this feature might serve as a surrogate biomarker for smoldering inflammation. CLINICAL RELEVANCE STATEMENT: Quantitative analysis of 3DT1TFE may detect deeply hypointense voxels in multiple sclerosis lesions, which are highly specific to PRLs. This could serve as a specific indicator of smoldering inflammation in MS, aiding in early detection of disease progression. KEY POINTS: • Phase-rim lesions (PRLs) in multiple sclerosis present a characteristic T1-hypointensity on 3DT1TFE MRI. • Intensity-normalized 3DT1TFE can be used to systematically identify and quantify these deeply hypointense foci. • Deep T1-hypointensity may act as an easily detectable, surrogate marker for PRLs.

Understanding language and cognition after brain surgery - Tumour grade, fine-grained assessment tools and, most of all, individualized approach.

Cognitive performance influences the quality of life and survival of people with glioma. Thus, a detailed neuropsychological and language evaluation is essential. In this work, we tested if an analysis of errors in naming can indicate semantic and/or phonological impairments in 87 awake brain surgery patients. Secondly, we explored how language and cognition change after brain tumour resection. Finally, we checked if low-tumour grade had a protective effect on cognition. Our results indicated that naming errors can be useful to monitor semantic and phonological processing, as their number correlated with scores on tasks developed by our team for testing these domains. Secondly, we showed that - although an analysis at a whole group level indicates a decline in language functions - significantly more individual patients improve or remain stable when compared to the ones who declined. Finally, we observed that having LGG, when compared with HGG, favours patients' outcome after surgery, most probably due to brain plasticity mechanisms. We provide new evidence of the importance of applying a broader neuropsychological assessment and an analysis of naming errors in patients with glioma. Our approach may potentially ensure better detection of cognitive deficits and contribute to better postoperative outcomes. Our study also shows that an individualized approach in post-surgical follow-ups can reveal reassuring results showing that significantly more patients remain stable or improve and can be a promising avenue for similar reports. Finally, the study captures that plasticity mechanisms may act as protective in LGG versus HGG after surgery.

Eating-induced seizures: A semiological sign of the right temporal pole.

OBJECTIVE: Eating-induced seizures (EIS) are a rare form of reflex seizures. The objective of this study was to report a series of cases of EIS involving patients admitted to our epilepsy unit, and to analyze the clinical characteristics, etiology, and treatment response of this type of infrequent seizure. METHODS: We performed a single-center retrospective analysis of all consecutive patients diagnosed with epilepsy with eating-induced seizures between 2008 and 2020. RESULTS: We included eight patients (six women) with mean age 54.75 years (range: 40-79), and mean age at epilepsy onset 30.75 years (range: 9-58 years). EIS were triggered during a meal in 5/8 (at dinner 1/8, at breakfast in 1/8, and without time preference in 3/8), by a certain flavor in 1/8, by eating different textures or drinking soft drinks in 1/8, and by slicing food in 1/8. All patients suffered nonreflex seizures and 3/8 other types of reflex seizures. In 6/8 of patients, EIS originated in the right hemisphere. In 5/8, the EIS progressed to impaired awareness with oromandibular automatisms. In 6/8, the epilepsy was drug-resistant. Temporopolar encephalocele was the most frequent etiology, in 4/8. Three of the eight underwent surgical treatment, with Engel IA 1 year in 3/3. Three of the eight were treated with vagal stimulation therapy, with McHugh A 1 year in 2/3. SIGNIFICANCE: In our series, eating-induced seizures were observed in patients with focal epilepsy. It was frequently drug-resistant and started predominantly in the right hemisphere, due to temporal pole involvement in half of the patients.

The role of the anterior insular cortex in self-monitoring: A novel study protocol with electrical stimulation mapping and functional magnetic resonance imaging.

Becoming aware of one's own states is a fundamental aspect for self-monitoring, allowing us to adjust our beliefs of the world to the changing context. Previous evidence points out to the key role of the anterior insular cortex (aIC) in evaluating the consequences of our own actions, especially whenever an error has occurred. In the present study, we propose a new multimodal protocol combining electrical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI) to explore the functional role of the aIC for self-monitoring in patients undergoing awake brain surgery. Our results using a modified version of the Stroop task tackling metacognitive abilities revealed new direct evidence of the involvement of the aIC in monitoring our performance, showing increased difficulties in detecting action-outcome mismatches when stimulating a cortical site located at the most posterior part of the aIC as well as significant BOLD activations at this region during outcome incongruences for self-made actions. Based on these preliminary results, we highlight the importance of assessing the aIC's functioning during tumor resection involving this region to evaluate metacognitive awareness of the self in patients undergoing awake brain surgery. In a similar vein, a better understanding of the aIC's role during self-monitoring may help shed light on action/outcome processing abnormalities reported in several neuropsychiatric disorders such as schizophrenia, anosognosia for hemiplegia or major depression.

Inferior fronto-occipital fascicle displacement in temporoinsular gliomas using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Brain tumors can result in displacement or destruction of important white matter tracts such as the inferior fronto-occipital fascicle (IFOF). Diffusion tensor imaging (DTI) can assess the extent of this effect and potentially provide neurosurgeons with an accurate map to guide tumor resection; analyze IFOF displacement patterns in temporoinsular gliomas based on tumor grading and topography in the temporal lobe; and assess whether these patterns follow a predictable pattern, to assist in maximal tumor resection while preserving IFOF function. METHODS: Thirty-four patients with temporal gliomas and available presurgical MRI were recruited. Twenty-two had insula infiltration. DTI deterministic region of interest (ROI)-based tractography was performed using commercial software. Tumor topographic imaging characteristics analyzed were as follows: location in the temporal lobe and extent of extratemporal involvement. Qualitative tractographic data obtained from directional DTI color maps included type of involvement (displaced/edematous-infiltrated/destroyed) and displacement direction. Quantitative tractographic data of ipsi- and contralateral IFOF included whole tract volume, fractional anisotropy, and fractional anisotropy of a 2-dimensional coronal ROI on the tract at the point of maximum tumor involvement. RESULTS: The most common tract involvement pattern was edematous/infiltrative displacement. Displacement patterns depended on main tumor location in the temporal lobe and presence of insular involvement. All tumors showed superior displacement pattern. In lateral tumors, displacement tendency was medial. In medial tumors, displacement tendency was lateral. When we add insular involvement, the tendency was more medial displacement. A qualitative and quantitative assessment supported these results. CONCLUSIONS: IFOF displacement patterns are reproducible and suitable for temporoinsular gliomas presurgical planning.

New-onset non-lesional aphasic status epilepticus. Clinical description, diagnostic clues, and treatment algorithm.

OBJECTIVES: De novo aphasic status epilepticus (ASE) in patients without a previous history of epilepsy and without cerebral lesions (aphasic NOSE) is rare. The aim of the study is to describe its clinical characteristics, etiologies, and outcome. MATERIALS & METHODS: Single-center study including consecutive patients presenting to the emergency department between 2011 and 2019 with acute aphasia, which was finally diagnosed as aphasic NOSE. Subsequent episodes of aphasia (>5 min) were recorded and divided into confirmed ASE and postictal aphasic episodes (non-ASE). Clinical characteristics of the two types of episodes were compared. RESULTS: Nineteen patients were included, suffering fifty episodes of epileptic aphasia, episodes per patient 2.6 (range 1-7). Fifteen patients (71.4%) were women, mean age at ASE onset was 66.05 years old (SD 6.3). Nine (47%) patients died, 6 of them (66.7%) during the aphasic episode. Ictal EEG was available in 37 episodes, confirming the diagnosis of ASE in 12 episodes; in 8 episodes, the EEG fulfilled the criteria of possible ASE. The most frequent etiologies were inflammatory and vascular. Comparing ASE with non-ASE episodes, ASE was longer than non-ASE (225 vs 65 h, p .024) and was treated more frequently with BZD (76 vs 24%, p .001) but with a longer delay (22.2 vs 1.5 h, p .06). CONCLUSIONS: ASE is a treatable, highly relapsing emergency, with the subsequent relapses ASE or postictal aphasia. EEG is diagnostic in half of the patients, while in others imaging techniques are also useful. Benzodiazepines should be administered. Persistent aphasia, of more than 65 hours' duration, is highly suggestive of ASE.

Primary extraosseous dural chondrosarcoma: a case report.

BACKGROUND: Dural chondrosarcoma is a very rare intracranial tumor, given that meninges do not normally contain cartilaginous tissue from which it can originate. We present a case of primary extraosseous dural chondrosarcoma. CASE PRESENTATION: A 48-year-old woman presented to our tertiary center neurosurgery consultation with progressive headache, vomiting, vertigo, and gait instability of 5 months' duration. An initial brain CT revealed a large parietal mass with gross calcifications and subtle hyperostosis of the inner table. Subsequent brain MRI showed a heterogeneous expansive lesion with a honey-comb enhancement. Discussion of intra- or extra-axial location was warranted, and finally, initial presurgical suspicion of meningioma arose although some atypical imaging features were detected. The differential diagnosis included solitary fibrous tumor-hemangiopericytoma and dural metastasis. Total resection of the lesion was performed, extra-axial origin was confirmed, and pathology resulted in a primary dural chondrosarcoma. CONCLUSION: The importance of this case presentation lies in the unusual nature of the final diagnosis, the brief literature review and differential diagnosis with emphasis on imaging pearls, as well as the useful reminder for physicians to consider less frequent diseases when key findings do not unambiguously lead to the usual suspects.

Risk of Developing Epilepsy after Autoimmune Encephalitis.

BACKGROUND: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. OBJECTIVE: To assess the risk of developing epilepsy in AE and study related risk factors. MATERIALS AND METHODS: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. RESULTS: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). CONCLUSIONS: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE.

Lower Locus Coeruleus MRI intensity in patients with late-life major depression.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. METHODS: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. RESULTS: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). CONCLUSION: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.

RNA sequencing and Immunohistochemistry Reveal ZFN7 as a Stronger Marker of Survival than Molecular Subtypes in G-CIMP-negative Glioblastoma.

PURPOSE: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials. EXPERIMENTAL DESIGN: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes. RESULTS: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes. CONCLUSIONS: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

The black box of global aphasia: Neuroanatomical underpinnings of remission from acute global aphasia with preserved inner language function.

OBJECTIVE: We studied an unusual case of global aphasia (GA) occurring after brain tumor removal and remitting one-month after surgery. After recovering, the patient reported on her experience during the episode, which suggested a partial preservation of language abilities (such as semantic processing) and the presence of inner speech (IS) despite a failure in overt speech production. Thus, we explored the role of IS and preserved language functions in the acute phase and investigated the neuroanatomical underpinnings of this severe breakdown in language processing. METHOD: A neuropsychological and language assessment tapping into language production, comprehension, attention and working memory was carried out both before and three months after surgery. In the acute stage a simplified protocol was tailored to assess the limited language abilities and further explore patient's performance on different semantic tasks. The neuroanatomical dimension of these abrupt changes was provided by perioperative structural neuroimaging. RESULTS: Language and neuropsychological performance were normal/close to normal both before and three months after surgery. In the acute stage, the patient presented severe difficulties with comprehension, production and repetition, whereas she was able to correctly perform tasks that requested conceptual analysis and non-verbal operations. After recovering, the patient reported that she had been able to internally formulate her thoughts despite her overt phonological errors during the episode. Structural neuroimaging revealed that an extra-axial blood collection affected the middle frontal areas during the acute stage and that the white matter circuitry was left-lateralized before surgery. CONCLUSIONS: We deemed that the global aphasia episode was produced by a combination of the post-operative extra-axial blood collection directly impacting left middle frontal areas and a left-lateralization of the arcuate and/or uncinated fasciculi before surgery. Additionally, we advocate for a comprehensive evaluation of linguistic function that includes the assessment of IS and non-expressive language functions in similar cases.

White-matter pathways and semantic processing: intrasurgical and lesion-symptom mapping evidence.

In the present study, we aimed to test the association between the correct function of the left ventral white matter pathways and semantic processing (dual stream models for language processing, Hickok & Poeppel, 2004), using a new set of language tasks during intraoperative electrical stimulation at white matter level. Additionally, we evaluated brain regions needed for correct performance on the different semantic tasks using lesion-symptom analyses (voxel lesion-symptom mapping and track-wise lesion analysis) in a sample of 62 candidates for the awake brain surgery. We found that electrical stimulation in the vicinity of the inferior longitudinal and inferior fronto-occipital fasciculi disturbed performance on semantic processing tasks. Individuals presented with significantly more semantic paraphasias during brain tumor resection than during the electrical stimulation at the cortex level. Track-wise analyses confirmed the role of these left ventral pathways in semantic processing: a significant relationship was observed between the probability of inferior fronto-occipital fasciculus disconnection/damage and the semantic matching tasks, as well as the number of semantic paraphasias in naming. Importantly, the same analyses for the total score of the Boston Naming Test confirmed significant relationships between this test score and the integrity of the inferior fronto-occipital, inferior longitudinal and uncinate fasciculi. This was further supported by the results of VLSM analyses showing a significant relationship between BNT and the presence of lesion within left middle and inferior temporal gyri. The present findings provide new intraoperative evidence for the role of the white-matter ventral pathways in semantic processing, while at the same time emphasizing the need to include a broader assessment of semantic-conceptual aspects during the awake neurosurgical intervention. This approach will ensure better preservation of functional tissue in the tumoral vicinity and therefore substantially diminish post-surgical language impairments.

Magnetic resonance spectroscopy in posterior fossa tumours: the tumour spectroscopic signature may improve discrimination in adults among haemangioblastoma, ependymal tumours, medulloblastoma, and metastasis.

OBJECTIVES: Assessing a posterior fossa tumour in an adult can be challenging. Metastasis, haemangioblastoma, ependymal tumours, and medulloblastoma are the most common diagnostic possibilities. Our aim was to evaluate the contribution of magnetic resonance spectroscopy (MRS) in the diagnosis of these entities. METHODS: We retrospectively evaluated 56 consecutive patients with a posterior fossa tumour and histological diagnosis of ependymal tumour, medulloblastoma, haemangioblastoma, and metastasis in which good-quality spectra at short (TE 30 ms) or/and intermediate (TE, 136 ms) TE were available. Spectra were compared using the Mann-Whitney U non-parametric test in order to select the spectral datapoints and the intensity ratios that showed significant differences between groups of lesions. Performance of these datapoints and their ratios were assessed with ROC curves. RESULTS: The most characteristic signatures on spectroscopy were high choline (Cho) in medulloblastoma (p < 0.001), high myoinositol (mIns) in ependymal tumours (p < 0.05), and high lipids (LIP) in haemangioblastoma (p < 0.01) and metastasis (p < 0.01). Selected ratios between normalised intensity signals of resonances provided accuracy values between 79 and 95% for pairwise comparisons. Intensity ratio NI3.21ppm/3.55ppm provided satisfactory discrimination between medulloblastoma and ependymal tumours (accuracy, 92%), ratio NI2.11ppm/1.10ppm discriminated ependymal tumours from haemangioblastoma (accuracy, 94%), ratio NI3.21ppm/1.13ppm discriminated haemangioblastoma from medulloblastoma (accuracy, 95%), and ratio NI1.28ppm/2.02pmm discriminated haemangioblastoma from metastasis (accuracy, 83%). CONCLUSIONS: MRS may improve the non-invasive diagnosis of posterior fossa tumours in adults. KEY POINTS: • High choline suggests a medulloblastoma in a posterior fossa tumour. • High myoinositol suggests an ependymal lesion in a posterior fossa tumour. • High lipids suggest a metastasis or a haemangioblastoma in a posterior fossa tumour.

Is a pretreatment radiological staging system feasible for suggesting the optimal extent of resection and predicting prognosis in glioblastoma? An observational study.

To assess the value of resection in glioblastoma based on pre-surgical tumor characteristics and a subsequent staging system. The lack of a staging system for glioblastoma hinders the analysis of treatment outcome. We classified 292 uniformly treated glioblastoma patients as stage I, II, or III based on tumor size, location, and eloquence and then analyzed the impact of the extent of resection. We classified 62% of patients as stage I, 25.3% as stage II, and 12.7% as stage III. Gross total resection (GTR) was performed mainly in stage I rather than stage II or III patients (79.2% vs. 14.6% vs. 6.3%; P < 0.001). Overall survival (OS) was 17.7, 14.6, and 10.8 months for stage I, II, and III patients, respectively (P = 0.005). Longer OS was significantly associated with greater extent of resection, younger age, KPS ≥ 70%, MGMT methylation, lower stage, and tumor ≤ 5 cm. In the subgroups of stage I (P = 0.04) and stage II (P < 0.001)-but not stage III-patients, GTR and partial resection (PR) were associated with longer OS. We constructed several multivariable models including different variables, and greater extent of resection, smaller tumor size, and MGMT methylation consistently emerged as independent markers of longer OS. This staging system provides a feasible tool for comparison of results. We confirmed the value of partial resection in stage I and II patients, in contrast to some reports suggesting that biopsy only is sufficient when gross total resection cannot be safely achieved.

Involvement of the middle frontal gyrus in language switching as revealed by electrical stimulation mapping and functional magnetic resonance imaging in bilingual brain tumor patients.

Neural basis of language switching and the cognitive models of bilingualism remain controversial. We explored the functional neuroanatomy of language switching implementing a new multimodal protocol assessing neuropsychological, functional magnetic resonance and intraoperative electrical stimulation mapping results. A prospective series of 9 Spanish-Catalan bilingual candidates for awake brain surgery underwent a specific language switching paradigm implemented both before and after surgery, throughout the electrical stimulation procedure and during functional magnetic resonance both pre- and postoperatively. All patients were harboring left-hemispheric intrinsic brain lesions and were presenting functional language-related activations within the affected hemisphere. Language functional maps were reconstructed on the basis of the intraoperative electrical stimulation results and compared to the functional magnetic resonance findings. Single language-naming sites (Spanish and Catalan), as well as language switching naming sites were detected by electrical stimulation mapping in 8 patients (in one patient only Spanish related sites were detected). Single naming points outnumbered the switching points and did not overlap with each other. Within the frontal lobe, the single language naming sites were found significantly more frequently within the inferior frontal gyrus as compared to the middle frontal gyrus [X2 (1) = 20.3, p < .001]. Contrarily, switching naming sites were distributed across the middle frontal gyrus significantly more often than within the inferior frontal gyrus [X2 (1) = 4.1, p = .043]. Notably, there was not always an overlap between functional magnetic resonance and electrical stimulation mapping findings. After surgery, patients did not report involuntary language switching and their neuropsychological scores did not differ significantly from the pre-surgical examinations. Our results suggest a functional division of the frontal cortex between naming and language switching functions, supporting that non-language specific cognitive control prefrontal regions (middle frontal gyrus) are essential to maintain an effective communication together with the classical language-related sites (inferior frontal gyrus).

Brain metastasis of carcinoma ex pleomorphic adenoma of the parotid gland: case report and review of the literature.

We present an extremely infrequent case of brain metastasis of a parotid tumor. To our knowledge, this is the second case reported of a brain metastasis of a malignant parotid tumor, carcinoma ex pleomorphic adenoma. Pleomorphic adenoma represents 60% of tumors of the parotid gland, and although it is a benign tumor, it can transform into carcinoma ex pleomorphic adenoma in 5% of cases, one of the most aggressive neoplasms of the salivary glands. We want to note the need for an accurate diagnostic. Thanks to aggressive surgical management, our patient survived more than 1½ years.

Words are not enough: nonword repetition as an indicator of arcuate fasciculus integrity during brain tumor resection.

OBJECTIVE Subcortical electrical stimulation during brain surgery may allow localization of functionally crucial white matter fibers and thus tailoring of the tumor resection according to its functional limits. The arcuate fasciculus (AF) is a white matter bundle connecting frontal, temporal, and parietal cortical areas that is often disrupted by left brain lesions. It plays a critical role in several cognitive functions related to phonological processing, but current intraoperative monitoring methods do not yet allow mapping of this tract with sufficient precision. In the present study the authors aimed to test a new paradigm for the intraoperative monitoring of the AF. METHODS In this report, the authors studied 12 patients undergoing awake brain surgery for tumor resection with a related risk of AF damage. To preserve AF integrity and the cognitive processes sustained by this tract in the intraoperative context, the authors used real word repetition (WR) and nonword repetition (NWR) tasks as complements to standard picture naming. RESULTS Compared with the errors identified by WR or picture naming, the NWR task allowed the detection of subtle errors possibly related to AF alterations. Moreover, only 3 patients demonstrated phonological paraphasias in standard picture naming, and in 2 of these patients the paraphasias co-occurred with the total loss of WR and NWR ability. Before surgery, lesion volume predicted a patient's NWR performance. CONCLUSIONS The authors suggest that monitoring NWR intraoperatively may complement the standard naming tasks and could permit better preservation of the important language production functions subserved by the AF.

Morphological derivation overflow as a result of disruption of the left frontal aslant white matter tract.

The frontal aslant tract (FAT) is a recently described major connection between the preSMA and Broca's area, whose functional role remains undefined. In this study we examined a patient presenting a morphological overregularization strategy in a verb generation task during awake surgery. This specific language deficit coincided with brain tumor resection at the level of the left FAT. During the task execution the patient formed the non-existent verbs by applying a morphological derivation rule to the given nouns, instead of retrieving the appropriate verbs. DTI results confirmed left FAT damage. Neuropsychological follow-up showed that this morphological derivation impairment partially persisted after surgery, whereas the results on a wide spectrum of other language-related tasks remained satisfactory. Additionally, we compared the pre- and the post-operational fMRI activation maps for the same verb generation task. We discuss the potential role of the left FAT in the morphological derivation process and in lexical retrieval.

Multicentre evaluation of the INTERPRET decision support system 2.0 for brain tumour classification.

In a previous study, we have shown the added value of (1) H MRS for the neuroradiological characterisation of adult human brain tumours. In that study, several methods of MRS analysis were used, and a software program, the International Network for Pattern Recognition of Tumours Using Magnetic Resonance Decision Support System 1.0 (INTERPRET DSS 1.0), with a short-TE classifier, provided the best results. Since then, the DSS evolved into a version 2.0 that contains an additional long-TE classifier. This study has two objectives. First, to determine whether clinicians with no experience of spectroscopy are comparable with spectroscopists in the use of the system, when only minimum training in the use of the system was given. Second, to assess whether or not a version with another TE is better than the initial version. We undertook a second study with the same cases and nine evaluators to assess whether the diagnostic accuracy of DSS 2.0 was comparable with the values obtained with DSS 1.0. In the second study, the analysis protocol was flexible in comparison with the first one to mimic a clinical environment. In the present study, on average, each case required 5.4 min by neuroradiologists and 9 min by spectroscopists for evaluation. Most classes and superclasses of tumours gave the same results as with DSS 1.0, except for astrocytomas of World Health Organization (WHO) grade III, in which performance measured as the area under the curve (AUC) decreased: AUC = 0.87 (0.72-1.02) with DSS 1.0 and AUC = 0.62 (0.55-0.70) with DSS 2.0. When analysing the performance of radiologists and spectroscopists with respect to DSS 1.0, the results were the same for most classes. Having data with two TEs instead of one did not affect the results of the evaluation.