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The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function

The aim of the study was to assess different outcome measures in a cohort of ambulant boys with Duchenne muscular dystrophy (DMD) over 12 months in order to establish the spectrum of possible changes in relation to age and steroid treatment.

BACKGROUND Diffuse infiltrative low-grade gliomas of the cerebral hemispheres in the adult are a group of tumors with distinct clinical, histological and molecular characteristics, and there are still controversies in management. METHODS The scientific evidence of papers collected from the literature was evaluated and graded according to EFNS guidelines, and recommendations were given accordingly. RESULTS AND CONCLUSIONS WHO classification recognizes grade II astrocytomas, oligodendrogliomas and oligoastrocytomas. Conventional MRI is used for differential diagnosis, guiding surgery, planning radiotherapy and monitoring treatment response. Advanced imaging techniques can increase the diagnostic accuracy. Younger age, normal neurological examination, oligodendroglial histology and 1p loss are favorable prognostic factors. Prophylactic antiepileptic drugs are not useful, whilst there is no evidence that one drug is better than the others. Total/near total resection can improve seizure control, progression-free and overall survival, whilst reducing the risk of malignant transformation. Early post-operative radiotherapy improves progression-free but not overall survival. Low doses of radiation are as effective as high doses and better tolerated. Modern radiotherapy techniques reduce the risk of late cognitive deficits. Chemotherapy can be useful both at recurrence after radiotherapy and as initial treatment after surgery to delay the risk of late neurotoxicity from large-field radiotherapy. Neurocognitive deficits are frequent and can be caused by the tumor itself, tumor-related epilepsy, treatments and psychological distress.

We have previously shown that the sustained expression of MARK4L transcripts in glioma and neural progenitors (NHNPs) declines after exposure to antisense MARK4L oligonucleotides in glioblastoma cell lines. Array-CGH confirmed the genomic duplication of MARK4L identified by FISH in a glioblastoma cell line. This background together with literature data on the exogenous association of MARK4 with interphase centrosome prompted us to investigate the sub-cellular localization of the endogenous MARK4L protein aiming at achieving insights on its possible role in the pathomechanisms of glioma.

This article describes the rationale, indications, and modality for intraoperative brain mapping for safe and effective surgical removal of tumors located within functional brain areas.

OBJECT: It has been hypothesized that specific brain regions involved in face naming may exist in the brain. To spare these areas and to gain a better understanding of their organization, the authors studied patients who underwent surgery by using direct electrical stimulation mapping for brain tumors, and they compared an object-naming task to a famous face-naming task. METHODS: Fifty-six patients with brain tumors (39 and 17 in the left and right hemispheres, respectively) and with no significant preoperative overall language deficit were prospectively studied over a 2-year period. Four patients who had a partially selective famous face anomia and 2 with prosopagnosia were not included in the final analysis. RESULTS: Face-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Among 35 patients whose dominant left hemisphere was studied, 26 face-naming specific areas (that is, sites of interference in face naming only and not in object naming) were found. These face naming-specific sites were significantly detected in 2 regions: in the left frontal areas of the superior, middle, and inferior frontal gyri (p < 0.001) and in the anterior part of the superior and middle temporal gyri (p < 0.01). Variable patterns of interference were observed (speech arrest, anomia, phonemic, or semantic paraphasia) probably related to the different stages in famous face processing. Only 4 famous face-naming interferences were found in the right hemisphere. CONCLUSIONS: Relative anatomical segregation of naming categories within language areas was detected. This study showed that famous face naming was preferentially processed in the left frontal and anterior temporal gyri. The authors think it is necessary to adapt naming tasks in neurosurgical patients to the brain region studied.

The aim of this study was to investigate the suitability of the North Star Ambulatory Assessment as a possible outcome measure in multicentric clinical trials. More specifically we wished to investigate the level of training needed for achieving a good interobserver reliability in a multicentric setting. The scale was specifically designed for ambulant children with Duchenne Muscular Dystrophy and includes 17 items that are relevant for this cohort. Thirteen Italian centers participated in the study. In the first phase of the study we provided two training videos and an example of the scale performed on a child. After the first session of training, all the 13 examiners were asked to send a video with an assessment performed in their centre and to score all the videos collected. There were no difficulties in performing the items and in obtaining adequate videos with a hand held camera but the results showed a poor interobserver reliability (<.5). After a second training session with review and discussion of the videos previously scored, the same examiners were asked to score three new videos. The results of this session had an excellent interobserver reliability (.995). The level of agreement was maintained even when the same videos were rescored after a month, showing a significant intra-observer reliability (.95). Our results suggest that the NSAA is a test that can be easily performed, completed in 10 min and can be used in a multicentric setting, providing that adequate training is administered. © 2009.

Objective: We report, for the first time, the occurrence of interference between a Cavitron ultrasonic surgical aspirator (CUSA) and intraoperative brain mapping performed by direct electrical stimulation (DES). METHODS: Intraoperative polygraphic recordings (electrocorticogram and electromyogram) were gathered from a 44-year-old patient harboring a recurrent Grade II oligoastrocytoma operated on with the aid of a CUSA and DES. RESULTS: Simultaneous use of CUSA and DES at the subcortical level in proximity to the corticospinal tract brought about the abolition of previously evident motor responses. This abolition was fully reversible after the CUSA was turned off. An analogous pattern of motor response inhibition was evident when the DES was applied cortically and the CUSA was used subcortically close to motor pathways. Interestingly, the authors had already observed a similar phenomenon in many patients when the CUSA was used for resection of lesions located within or in proximity to subcortical language pathways. In this setting, the CUSA induced transient speech disturbances that were confirmed afterwards by the DES. This interference with language and motor mapping might be interpreted as a transitory inhibition of axonal conduction. CONCLUSION: The clinical significance of this interference is relevant when the CUSA and DES are used simultaneously for motor mapping because the CUSA can decrease the sensitivity of the brain mapping technique. Further studies will be required to determine the neurophysiological mechanism underlying this interference.

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b = 1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST = 95%, language tracts = 97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a hig

OBJECTIVE: Subcortical stimulation can be used to identify functional language tracts during resection of gliomas located close to or within language areas or pathways. The objective of the present study was to investigate the feasibility of the routine use of subcortical stimulation for identification of language tracts in a large series of patients with gliomas and to determine the influence that subcortical language tract identification exerted on the extent of surgery and on the appearance of immediate and definitive postoperative deficits. METHODS: Subcortical stimulation for language tract identification was systematically used during surgical removal of 88 gliomas (44 high-grade and 44 low-grade gliomas) involving language pathways. Procedures were performed during asleep/awake craniotomy. Subcortical stimulation was continuously alternated with surgical resection in a back-and-forth fashion. Language performances were tested by neuropsychological language evaluation preoperatively and at 3, 30, and 90 days after surgery. RESULTS: Language tracts were identified in 59% of patients, with differences according to tumor location but not according to histological grade. Language tract identification influenced the ability to reach a complete tumor removal in low-grade gliomas, in which tracts were documented inside the peripheral mass of the tumor. Identification of language tracts was associated with a higher occurrence of transient postoperative deficits (67.3% of cases), but a low occurrence of definitive morbidity (2.3% of cases). A pattern of typical language disturbances related to the phonological and semantic system can be identified according to tumor location, with preservation being important for the maintenance of language integrity. CONCLUSION: Our study supports the routine use of subcortical stimulation for language tract identification as a reliable tool for guiding surgical removal of gliomas in or in close proximity to language areas or pathways

Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-beta1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation

OBJECTIVE: Intraoperative localization of speech is problematic in patients who are fluent in different languages. Previous studies have generated various results depending on the series of patients studied, the type of language, and the sensitivity of the tasks applied. It is not clear whether languages are mediated by multiple and separate cortical areas or shared by common areas. Globally considered, previous studies recommended performing a multiple intraoperative mapping for all the languages in which the patient is fluent. The aim of this work was to study the feasibility of performing an intraoperative multiple language mapping in a group of multilingual patients with a glioma undergoing awake craniotomy for tumor removal and to describe the intraoperative cortical and subcortical findings in the area of craniotomy, with the final goal to maximally preserve patients' functional language. METHODS: Seven late, highly proficient multilingual patients with a left frontal glioma were submitted preoperatively to a battery of tests to evaluate oral language production, comprehension, and repetition. Each language was tested serially starting from the first acquired language. Items that were correctly named during these tests were used to build personalized blocks to be used intraoperatively. Language mapping was undertaken during awake craniotomies by the use of an Ojemann cortical stimulator during counting and oral naming tasks. Subcortical stimulation by using the same current threshold was applied during tumor resection, in a back and forth fashion, and the same tests. RESULTS: Cortical sites essential for oral naming were found in 87.5% of patients, those for the first acquired language in one to four sites, those for the other languages in one to three sites. Sites for each language were distinct and separate. Number and location of sites were not predictable, being randomly and widely distributed in the cortex around or less frequently over the tumor area. Su