Miran Skrap

Pathological switching between languages after frontal lesions in a bilingual patient

Cerebral lesions may alter the capability of bilingual subjects to separate their languages and use each language in appropriate contexts. Patients who show pathological mixing intermingle different languages within a single utterance. By contrast, patients affected by pathological switching alternate their languages across different utterances (a self contained segment of speech that stands on its own and conveys its own independent meaning). Cases of pathological mixing have been reported after lesions to the left temporoparietal lobe. By contrast, information on the neural loci involved in pathological switching is scarce. In this paper a description is given for the first time of a patient with a lesion to the left anterior cingulate and to the frontal lobe—also marginally involving the right anterior cingulate area—who presented with pathological switching between languages in the absence of any other linguistic impairment. Thus, unlike pathological mixing that typically occurs in bilingual aphasia, pathological switching may be independent of language mechanisms.

Low-grade glioma surgery in eloquent areas: Volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients - Clinical article

OBJECT A growing number of published studies have recently demonstrated the role of resection in overall survival (OS) for patients with gliomas. In this retrospective study, the authors objectively investigated the role of the extent of resection (EOR) in OS in patients with low-grade gliomas (LGGs). METHODS Between 1998 and 2011, 190 patients underwent surgery for LGGs. All surgical procedures were conducted under corticosubcortical stimulation. The EOR was established by analyzing the pre- and postoperative volumes of the gliomas on T2-weighted MRI studies. The difference between the preoperative tumor volumes was also investigated by measuring the volumetric difference between the T2- and T1-weighted MRI images (ΔVT2T1) to evaluate how the diffusive tumor-growing pattern affected the EOR achieved. RESULTS The median preoperative tumor volume was 55 cm(3), and in almost half of the patients the EOR was greater than 90%. In this study, patients with an EOR of 90% or greater had an estimated 5-year OS rate of 93%, those with EOR between 70% and 89% had a 5-year OS rate of 84%, and those with EOR less than 70% had a 5-year OS rate of 41% (p < 0.001). New postoperative deficits were noted in 43.7% of cases, while permanent deficits occurred in 3.16% of cases. There were 41 deaths (21.6%), and the median follow-up was 4.7 years. A further volumetric analysis was also conducted to compare 2 different intraoperative protocols (Series 1 [intraoperative electrical stimulation alone] vs Series 2 [intraoperative stimulation plus overlap of functional MRI/fiber tracking diffusion tensor imaging data on a neuronavigation system]). Patients in Series 1 had a median EOR of 77%, while those in Series 2 had a median EOR of 90% (p = 0.0001). Multivariate analysis showed that OS is influenced not only by EOR (p = 0.001) but also by age (p = 0.003), histological subtype (p = 0.005), and the ΔVT2T1 value (p < 0.0001). Progression-free survival is similarly influenced by histological subtype (fibrillary astrocytoma, p = 0.003), EOR (p < 0.0001), and ΔVT2T1 value (p < 0.0001), as is malignant progression-free survival (p = 0.003, p < 0.0001, and p < 0.0001, respectively). Finally, the study shows that the higher the ΔVT2T1 value, the less extensive the currently possible resection, highlighting an apparent correlation between the ΔVT2T1 value itself and EOR (p < 0.0001). CONCLUSIONS The EOR and the ΔVT2T1 values are the strongest independent predictors in improving OS as well as in delaying tumor progression and malignant transformation. Furthermore, the ΔVT2T1 value may be useful as a predictive index for EOR. Finally, due to intraoperative corticosubcortical mapping and the overlap of functional data on the neuronavigation system, major resection is possible with an acceptable risk and a significant increase in expected OS.

O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Specific impairments of rule induction in different frontal lobe subgroups

The neural correlates of inductive reasoning are still poorly understood. In order to explore them, we administered a revised version of the Brixton test, a rule attainment task, to a group of 40 patients with a focal frontal brain lesion of mixed aetiology and to 43 control subjects. To interpret an impairment on the test as suggesting an inductive reasoning deficit a number of alternative hypotheses need first to be considered, namely whether the Brixton impairment could be explained by: (i) a working memory deficit; (ii) a monitoring deficit; (iii) a difficulty in applying an already induced rule; (iv) greater impulsivity. The patients with left lateral (LL) frontal lesions were significantly impaired on the Brixton test; more importantly they were the only group in which none of the alternative hypotheses we explored proved able to explain the flawed performance. In sharp contrast, right lateral lesion patients did not make significantly more errors on the Brixton test than controls, but they produced three times more capture errors (a sign of impaired monitoring processes). The results were interpreted as suggesting functional dissociations between inductive reasoning, monitoring and working memory and a localisation of key processes for induction in left lateral frontal cortex and in right lateral cortex for monitoring and checking.

The neural basis of temporal preparation: Insights from brain tumor patients

When foreperiods (FPs) of different duration vary on a trial-by-trial basis equiprobably but randomly, the RT is faster as the FP increases (variable FP effect), and becomes slower as the FP on the preceding trial gets longer (sequential effects). It is unclear whether the two effects are due to a common mechanism or to two different ones. Patients with lesions on the right lateral prefrontal cortex do not show the typical FP effect, suggesting a deficit in monitoring the FP adequately [Stuss, D. T., Alexander, M. P., Shallice, T., Picton, T. W., Binns, M. A., Macdonald, R., et al. (2005). Multiple frontal systems controlling response speed. Neuropsychologia, 43, 396-417]. The aim of this study was two-fold: (1) to replicate this neuropsychological result testing cerebral tumor patients before and after surgical removal of the tumor located unilaterally in the prefrontal, premotor or parietal cortex, respectively and (2) to investigate whether the sequential effects would change together with the FP effect (supporting single-process accounts) or the two effects can be dissociated across tumor locations (suggesting dual-process views). The results of an experiment with a variable FP paradigm show a significant reduction of the FP effect selectively after excision of tumors on right prefrontal cortex. On the other hand, the sequential effects were reliably reduced especially after surgical removal of tumors located in the left premotor region, despite a normal FP effect. The latter dissociation between the two effects supports a dual-process account of the variable FP phenomena. This study demonstrates that testing acute cerebral tumor patients represents a viable neuropsychological approach for the fractionation and localisation of cognitive processes.

Meditation-related activations are modulated by the practices needed to obtain it and by the expertise: an ALE meta-analysis study

The brain network governing meditation has been studied using a variety of meditation practices and techniques practices eliciting different cognitive processes (e.g., silence, attention to own body, sense of joy, mantras, etc.). It is very possible that different practices of meditation are subserved by largely, if not entirely, disparate brain networks. This assumption was tested by conducting an activation likelihood estimation (ALE) meta-analysis of meditation neuroimaging studies, which assessed 150 activation foci from 24 experiments. Different ALE meta-analyses were carried out. One involved the subsets of studies involving meditation induced through exercising focused attention (FA). The network included clusters bilaterally in the medial gyrus, the left superior parietal lobe, the left insula and the right supramarginal gyrus (SMG). A second analysis addressed the studies involving meditation states induced by chanting or by repetition of words or phrases, known as “mantra.” This type of practice elicited a cluster of activity in the right SMG, the SMA bilaterally and the left postcentral gyrus. Furthermore, the last analyses addressed the effect of meditation experience (i.e., short- vs. long-term meditators). We found that frontal activation was present for short-term, as compared with long-term experience meditators, confirming that experts are better enabled to sustain attentional focus, rather recruiting the right SMG and concentrating on aspects involving disembodiment.

Surgery of insular nonenhancing gliomas: volumetric analysis of tumoral resection, clinical outcome, and survival in a consecutive series of 66 cases.

BACKGROUND Despite intraoperative technical improvements, the insula remains a challenging area for surgery because of its critical relationships with vascular and neurophysiological functional structures. OBJECTIVE To retrospectively investigate the morbidity profile in insular nonenhancing gliomas, with special emphasis on volumetric analysis of tumoral resection. METHODS From 2000 to 2010, 66 patients underwent surgery. All surgical procedures were conducted under cortical-subcortical stimulation and neurophysiological monitoring. Volumetric scan analysis was applied on T2-weighted magnetic resonance images (MRIs) to establish preoperative and postoperative tumoral volume. RESULTS The median preoperative tumor volume was 108 cm. The median extent of resection was 80%. The median follow-up was 4.3 years. An immediate postoperative worsening was detected in 33.4% of cases; a definitive worsening resulted in 6% of cases. Patients with extent of resection of > 90% had an estimated 5-year overall survival rate of 92%, whereas those with extent of resection between 70% and 90% had a 5-year overall survival rate of 82% (P < .001). The difference between preoperative tumoral volumes on T2-weighted MRI and on postcontrast T1-weighted MRI ([T2 - T1] MRI volume) was computed to evaluate the role of the diffusive tumoral growing pattern on overall survival. Patients with preoperative volumetric difference < 30 cm demonstrated a 5-year overall survival rate of 92%, whereas those with a difference of > 30 cm had a 5-year overall survival rate of 57% (P = .02). CONCLUSION With intraoperative cortico-subcortical mapping and neurophysiological monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up.

Glioma-Associated Stem Cells: A Novel Class of Tumor-Supporting Cells Able to Predict Prognosis of Human Low-Grade Gliomas

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239–1253

Semantic access dysphasia resulting from left temporal lobe tumours.

Unlike semantic degradation disorders, the mechanisms and the anatomical underpinnings of semantic access disorders are still unclear. We report the results of a case series study on the effects of temporal lobe gliomas on semantic access abilities of a group of 20 patients. Patients were tested 1–2 days before and 4–6 days after the removal of the tumour. Their semantic access skills were assessed with two spoken word-to-picture matching tasks, which aimed to separately control for rate of presentation, consistency and serial position effects (Experiment 1) and for word frequency and semantic distance effects (Experiment 2). These variables have been held to be critical in characterizing access in contrast to degraded-store semantic deficits, with access deficits characterized by inconsistency of response, better performance with slower presentation rates and with semantically distant stimuli, in the absence of frequency effects. Degradation deficits show the opposite pattern. Our results showed that low-grade slowly growing tumours tend not to produce signs of access problems. However, high-grade tumours especially within the left hemisphere consistently produce strong semantic deficits of a clear access type: response inconsistency and strong semantic distance effects in the absence of word frequency effects were detected. However, effects of presentation rate and serial position were very weak, suggesting non-refractory behaviour in the tumour patients tested. This evidence, together with the results of lesion overlapping, suggests the presence of a type of non-refractory semantic access deficit. We suggest that this deficit could be caused by the disconnection of posterior temporal lexical input areas from semantic system.

LANGUAGE DISORDERS IN BILINGUAL PATIENTS AFTER THALAMIC LESIONS

Abstract Three bilingual patients with ischemic or tumoral brain lesions localized in the left thalamus have been submitted to a thorough neurolinguistic analysis by means of the Bilingual Aphasia Test (BAT). They all presented with language impairments which included reduced verbal fluency; phonemic, semantic and verbal paraphasias; grammatical errors (e.g. omission and addition of free grammatical morphemes); greater disruption of comprehension as opposed to repetition; and disorders of written language. In all patients, the most disrupted linguistic levels concerned morphology and syntax, more in L2 than in L1. One patient also presented with several mixing phenomena and major difficulties in translating sentences.