Mechanisms of glioblastoma replication: Ca2+ flares and Cl- currents.

Glioblastoma (GBM) is amongst the deadliest types of cancers, with no resolutive cure currently available. GBM cell proliferation in the patient's brain is a complex phenomenon controlled by multiple mechanisms. The aim of this study was to determine whether the ionic fluxes controlling cell duplication could represent a target for GBM therapy. In this work, we combined multi-channel Ca2+ and Cl- imaging, optical tweezers, electrophysiology and immunohistochemistry to describe the role of ion fluxes in mediating the cell volume changes that accompany mitosis of U87 GBM cells. We identified three main steps: (i) in round GBM cells undergoing mitosis, during the transition from anaphase to telophase and cytokinesis, large Ca2+ flares occur, reaching values of 0.5-1 µM; (ii) these Ca2+ flares activate Ca2+-dependent Cl- channels, allowing the entry of Cl- ions; (iii) to maintain osmotic balance, GBM cells swell to complete mitosis. This sequence of steps was validated by electrophysiological experiments showing that Cl- channels are activated either directly or indirectly by Ca2+, and by additional live-cell imaging experiments. Cl- channel blockers with different molecular structures, such as niflumic acid and carbenoxolone, blocked GBM replication by arresting GBM cells in a round configuration. These results describe the central role of Ca2+ flares and Cl- fluxes during mitosis and show that inhibition of Ca2+-activated Cl- channels blocks GBM replication, opening the way to new approaches for the clinical treatment of GBM. Implications: Our work identifies ionic fluxes occurring during cell division as targets for devising novel therapies for the glioblastoma treatment.

Motor or non-motor speech interference? A multimodal fMRI and direct cortical stimulation mapping study.

We retrospectively analyzed data from 15 patients, with a normal pre-operative cognitive performance, undergoing awake surgery for left fronto-temporal low-grade glioma. We combined a pre-surgical measure (fMRI maps of motor- and language-related centers) with intra-surgical measures (MNI-registered cortical sites data obtained during intra-operative direct electrical stimulation, DES, while they performed the two most common language tasks: number counting and picture naming). Selective DES effects along the precentral gyrus/inferior frontal gyrus (and/or the connected speech articulation network) were obtained. DES of the precentral gyrus evoked the motor speech arrest, i.e., anarthria (with apparent mentalis muscle movements). We calculated the number of shared voxels between the lip-tongue and overt counting related- and silent naming-related fMRI maps and the Volumes of Interest (VOIs) obtained by merging together the MNI sites at which a given speech disturbance was observed, normalized on their mean the values (i.e., Z score). Both tongue- and lips-related movements fMRI maps maximally overlapped (Z = 1.05 and Z = 0.94 for lips and tongue vs. 0.16 and -1.003 for counting and naming) with the motor speech arrest seed. DES of the inferior frontal gyrus, pars opercularis and the rolandic operculum induced speech arrest proper (without apparent mentalis muscle movements). This area maximally overlapped with overt counting-related fMRI map (Z = -0.11 and Z = 0.09 for lips and tongue vs. 0.9 and 0.0006 for counting and naming). Interestingly, our fMRI maps indicated reduced Broca's area activity during silent speech compared to overt speech. Lastly, DES of the inferior frontal gyrus, pars opercularis and triangularis evoked variations of the output, i.e., dysarthria, a motor speech disorder occurring when patients cannot control the muscles used to produce articulated sounds (phonemes). Silent object naming-related fMRI map maximally overlapped (Z = -0.93 and Z = -1.04 for lips and tongue vs. -1.07 and 0.99 for counting and naming) with this seed. Speech disturbances evoked by DES may be thought of as selective interferences with specific recruitment of left inferior frontal gyrus and precentral cortex which are differentiable in terms of the specific interference induced.

Preoperative plasticity in the functional naming network of patients with left insular gliomas.

Plasticity could take place as a compensatory process following brain glioma growth. Only a few studies specifically explored plasticity in patients affected by a glioma invading the left insula; even more, plasticity of the insular cortex in task-based functional language network is almost unexplored. In the current study, we explored potential plasticity in a consecutive series of 22 patients affected by a glioma centered to the left insula, by comparing their preoperative object-naming functional network with that of a group of healthy controls. After having controlled for demographic variables, fMRI results showed that patients vs. controls activated a cluster in the right, contralesional pars triangularis including the Broca's area. On the other hand, controls did not significantly activate any brain region more than patients. At behavioral level, patients retained a generally preserved naming performance as well as a proficient language processing profile. These findings suggest that involvement of language-specific areas in the healthy hemisphere could help compensate for the left, affected insula, thus allowing preservation of the naming functions. Results are commented in relation to lesion site, naming performance, and potential relevance for neurosurgery.

An "epileptic scent": Olfactory auras in tumor-related epilepsy.

OBJECTIVES: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras. MATERIALS AND METHODS: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts. RESULTS: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222). DISCUSSION: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras. CONCLUSIONS: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.

Cognitive reserve and individual differences in brain tumour patients.

The aim of the paper is to determine the effects of the cognitive reserve on brain tumour patients' cognitive functions and, specifically, if cognitive reserve helps patients cope with the negative effects of brain tumours on their cognitive functions. We retrospectively studied a large sample of around 700 patients, diagnosed with a brain tumour. Each received an MRI brain examination and performed a battery of tests measuring their cognitive abilities before they underwent neurosurgery. To account for the complexity of cognitive reserve, we construct our cognitive reserve proxy by combining three predictors of patients' cognitive performance, namely, patients' education, occupation, and the environment where they live. Our statistical analysis controls for the type, side, site, and size of the lesion, for fluid intelligence quotient, and for age and gender, in order to tease out the effect of cognitive reserve on each of these tests. Clinical neurological variables have the expected effects on cognitive functions. We find a robust positive effect of cognitive reserve on patients' cognitive performance. Moreover, we find that cognitive reserve modulates the effects of the volume of the lesion: the additional negative impact of an increase in the tumour size on patients' performance is less severe for patients with higher cognitive reserve. We also find substantial differences in these effects depending on the cerebral hemisphere where the lesion occurred and on the cognitive function considered. For several of these functions, the positive effect of cognitive reserve is stronger for patients with lesions in the left hemisphere than for patients whose lesions are in the right hemisphere. The development of prevention strategies and personalized rehabilitation interventions will benefit from our contribution to understanding the role of cognitive reserve, in addition to that of neurological variables, as one of the factors determining the patients' individual differences in cognitive performance caused by brain tumours.

Meningioma-Related Epilepsy: A Happy Ending?

(1) Background: More than one-third of patients with meningiomas experience at least one seizure during the course of their disease, and in the 20-50% of cases, seizure represents the onset symptom. After surgery, up to 30% of patients continue to have seizures, while others may experience them later; (2) Methods: The study analyzed retrospectively the risk factors for pre-operative seizures in a large cohort of 358 patients who underwent surgery for newly diagnosed brain meningioma; (3) Results: We identified age, peritumor edema, and location as risk factors for seizure at the onset. Patients with seizures differed from patients without seizures for the following characteristics: younger average age, lower pre-operative Karnofsky Performance Status (KPS), location on the convexity, lower Simpson Grade, lower incidence of pre-operative neurological deficits, and higher incidence of pre-operative peritumor edema. After 24 months, 88.2% of patients were classified as Engel class Ia, and no correlation with disease progression was observed; (4) Conclusions: Meningioma-related epilepsy has generally a positive outcome following surgery and it seems not to be linked to disease progression, even if further studies are needed.

Machine learning to improve interpretability of clinical, radiological and panel-based genomic data of glioma grade 4 patients undergoing surgical resection.

BACKGROUND: Glioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line treatment in GG4 tumors. Although Stupp combination can prolong survival, prognosis of treated adult patients with GG4 still remains unfavorable. The introduction of innovative multi-parametric prognostic models may allow refinement of prognosis of these patients. Here, Machine Learning (ML) was applied to investigate the contribution in predicting overall survival (OS) of different available data (e.g. clinical data, radiological data, or panel-based sequencing data such as presence of somatic mutations and amplification) in a mono-institutional GG4 cohort. METHODS: By next-generation sequencing, using a panel of 523 genes, we performed analysis of copy number variations and of types and distribution of nonsynonymous mutations in 102 cases including 39 carmustine wafer (CW) treated cases. We also calculated tumor mutational burden (TMB). ML was applied using eXtreme Gradient Boosting for survival (XGBoost-Surv) to integrate clinical and radiological information with genomic data. RESULTS: By ML modeling (concordance (c)- index = 0.682 for the best model), the role of predicting OS of radiological parameters including extent of resection, preoperative volume and residual volume was confirmed. An association between CW application and longer OS was also showed. Regarding gene mutations, a role in predicting OS was defined for mutations of BRAF and of other genes involved in the PI3K-AKT-mTOR signaling pathway. Moreover, an association between high TMB and shorter OS was suggested. Consistently, when a cutoff of 1.7 mutations/megabase was applied, cases with higher TMB showed significantly shorter OS than cases with lower TMB. CONCLUSIONS: The contribution of tumor volumetric data, somatic gene mutations and TBM in predicting OS of GG4 patients was defined by ML modeling.

Parietal/premotor lesions effects on visuomotor cognition in neuro-oncology patients: A multimodal study.

BACKGROUND: Assessing prior to surgery the functionality of brain areas exposed near the tumor requires a multimodal approach that combines the use of neuropsychological testing and fMRI tasks. Paradigms based on motor imagery, which corresponds to the ability to mentally evoke a movement, in the absence of actual action execution, can be used to test sensorimotor areas and the functionality of mental motor representations. METHODS: The most commonly used paradigm is the Limb Laterality Recognition Task (LLRT), requiring judgments about whether a limb belongs to the left or right side of the body. The group studied included 38 patients with high-grade (N = 21), low-grade (N = 11) gliomas and meningiomas (N = 6) in areas anterior (N = 21) and posterior (N = 17) to the central sulcus. Patients before surgery underwent neuropsychological assessment and fMRI. They performed the LLRT as an fMRI task. Accuracy, and neuroimaging data were collected and combined in a multimodal study. Structural MRI data analyses were performed by subtracting the overlap of volumes of interest (VOIs) plotted on lesions from the impaired patient group vs the overlap of VOIs from the spared group. The fMRI analyses were performed comparing the impaired patients and spared group. RESULTS: In general, patients were within normal limits on many neuropsychological screening tests. Compared with the control group, 17/38 patients had significantly different performance. The subtraction between the VOIs overlay of the impaired patients' group vs. the VOIs overlay of the spared group revealed that the areas maximally involved by lesions in the impaired patients' group were the right postcentral gyrus, right inferior parietal lobe, right supramarginal gyrus, right precentral gyrus, paracentral lobule, left postcentral gyrus, right superior parietal lobe, left inferior parietal lobe, and left superior and middle frontal gyrus. Analysis of the fMRI data showed which of these areas contributes to a correct LLRT performance. The task (vs. rest) in the group comparison (spared vs. impaired patients) activated a cluster in the left inferior parietal lobe. CONCLUSION: Underlying the altered performance at LLRT in patients with lesions to the parietal and premotor areas of the right and left hemispheres is a difference in activation of the left inferior parietal lobe. This region is involved in visuomotor processes and those related to motor attention, movement selection, and motor planning.

Clinical applicability of arterial spin labeling magnetic resonance imaging in patients with possible idiopathic normal pressure hydrocephalus: A prospective preliminary study.

PURPOSE: idiopathic Normal Pressure Hydrocephalus (iNPH) patients have a global reduction of cerebral blood flow (CBF) and Arterial Spin Label (ASL) MRI allows a global evaluation of CBF without the injection of contrast agents. This work aims to assess the qualitative evaluation agreement of ASL CBF colored maps between different neuroradiologists and by correlating these data to the Tap Test. METHODS: Thirty - seven patients with the diagnosis of possible iNPH were consecutively submitted to a diagnostic MRI on a 1.5 Tesla Magnet before and after the lumbar infusion test and the Tap Test. Twenty - seven patients improved after the Tap Test and were addressed to surgery while 10 patients did not improve. All the MRI examinations included a 3D-Pulsed ASL sequence. Two different neuroradiologists independently reviewed all ASL images. They were asked to give a score (0 not improved; 1 improved) to global perfusion image quality by comparing ASL images obtained after the Tap Test to those obtained before. Comparison between inter- and intra-reader qualitative scores were performed with Cohen's kappa. RESULTS: Inter-reader agreement between the two neuroradiologists showed that qualitative scores were attributed similarly by two readers (k = 0.83). This technique has a good PPV (90.5 %; CI 95 %, 72.7-97.1 %), NPV (50 %; CI 95 %, 34.1-65.6 %), SN (70.37 %; CI 95 %, 49.8-86.2 %) SP (80 %; CI 95 %, 44.4-97.5 %) and accuracy (73 %; CI 95 %, 55.9-86.2 %) when considered in the setting of possible iNPH patients. CONCLUSION: ASL-MRI seems to be a promising non-invasive technique in the preoperative selection of patients affected by possible iNPH.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Continuous Real-Time Neuropsychological Testing during Resection Phase in Left and Right Prefrontal Brain Tumors.

BACKGROUND: Executive functions are multi-component and are based on large-scale brain networks. For patients undergoing brain surgery in the prefrontal cortex, resection in the anterior prefrontal sites is assisted by continuous monitoring of their performance on several tasks measuring components of executive functions. In this study, we did not test patients during direct cortical stimulation, but during resection itself. We chose tests routinely used to assess executive functions and included them in a protocol for left (LH) and right (RH) hemisphere prefrontal resections. This protocol is meant to be used during real-time neuropsychological testing (RTNT)-an already established monitoring technique. METHODS: We retrospectively reviewed a consecutive series of 29 adult patients with glioma in the superior and middle frontal areas who performed the RTNT sequence throughout the resection phase. The testing protocol comprised 10 tests for LH frontal resections and 9 tests for RH frontal resections. RESULTS: RH patients showed a median performance on RTNT with significantly lower scores for visuo-spatial attention and emotion processing (95% Confidence Interval Lower bound of 66.55 and 82.57, respectively, χ2 (7) = 32.8, p < 0.001). LH patients showed a median performance on RTNT, with significantly lower scores for selective attention and working memory (95% Confidence Interval Lower bound of 51.12, χ2 (5) = 20.31 p < 0.001) and minimum scores for the same task and for the Stroop test (χ2 (5) = 17.86, p < 0.005). The delta for accuracy between the first and the last RTNT run was not statistically significant (RH patients: χ2 (7) = 10.49, p > 0.05, n.s.; LH patients: χ2 (5) = 3.35, p > 0.05, n.s.). Mean extent of resection was 95.33% ± 9.72 for the RH group and 94.64% ± 6.74 for the LH group. Patients showed good performance post- vs. pre-surgery. The greater difference in the number of LH patients scoring within the normal range was found for the symbol-digit modality test (83.3% to 62%), Stroop test (100% to 77%) and short-term memory (84.61% to 72.72%) and working memory (92.3% to 63.63%). For RH patients, the main changes were observed on the clock drawing test (100% to 77.7%) and cognitive estimation (100% to 72.7%). CONCLUSIONS: Frontal RTNT offers continuous and reliable feedback on the patients' cognitive status during resection in frontal areas.

Effect of Dexmedetomidine versus Propofol on Intraoperative Seizure Onset During Awake Craniotomy: A Retrospective Study.

OBJECTIVE: The effect of dexmedetomidine (DEX) compared with propofol on intraoperative seizures (IOSs) detected using electrocorticography during awake craniotomy for resection of brain tumors is unknown. This investigation aimed to compare IOS rate in patients receiving DEX versus propofol as sedative agent. METHODS: In this retrospective single-center study, awake craniotomies performed from January 2014 to December 2019 were analyzed. All IOSs detected by electrocorticography along with vital signs were recorded. RESULTS: Of 168 adults enrolled in the study, 58 were administered DEX and 110 were administered propofol. IOSs occurred more frequently in the DEX group (22%) versus the propofol group (11%) (P = 0.046). A higher incidence of bradycardia was also observed in the DEX group (P < 0.001). Higher incidence of hypertension and a higher mean heart rate were recorded in the propofol group (P = 0.006 and P < 0.001, respectively). No serious adverse events requiring active drug administration were noted in either group. At univariate regression analysis, DEX demonstrated a tendency to favor IOS onset but without statistical significance (odds ratio = 2.36, P = 0.051). Patients in both groups had a similar epilepsy outcome at the 1-year postoperative follow-up. CONCLUSIONS: IOSs detected with electrocorticography during awake craniotomy occurred more frequently in patients receiving DEX than propofol. However, patients receiving DEX were not shown to be at a statistically significant greater risk for IOS onset. DEX is a valid alternative to propofol during awake craniotomy in patients affected by tumor-related epilepsy.

MDS-UDPRS-III in the diagnosis of idiopathic Normal Pressure Hydrocephalus and identification of candidates for Ventriculo-Peritoneal Shunting surgery. Results from a retrospective large cohort of patients.

OBJECTIVES: To evaluate the entity of extrapyramidal signs, characterize them and evaluate the dynamics of change by the mean of MDS-UPDRS-III in iNPH patients after the TT to determine if this tool may help the diagnosis of iNPH and the identification of candidates for Ventriculo-Peritoneal Shunting. MATERIALS AND METHODS: We retrospectively collected data from 120 patients with the initial diagnosis of possible iNPH; they underwent neurological examination by the means of MDS-UPDRS-III and other scales before and after Tap Test (TT). They were then classified as defined iNPH (57), probable iNPH (35), and NOT-iNPH (28) based on the clinical response after the Tap Test and VPS. RESULTS: After the Tap Test, defined and probable iNPH groups improved by 3.35 (2.57-4.12, p < 0.001) and 3.43 (2.43-4.4, p < 0.001) points on MDS-UPDRS-III respectively; NOT-iNPH did not improve significantly on MDS-UPDRS-III and on any other variable studies. Defined iNPH also shifted significantly from asymmetric prevalence of symptoms to a more symmetric form (from 70% before to 57% after). CONCLUSION: extrapyramidal signs improved significantly after the Tap Test in definite and probable iNPH patients. MDS-UPDRS-III may be a useful complementary tool in the diagnosis of iNPH and identification of candidates for Ventriculo-Peritoneal Shunting.

Resting-state functional-MRI in iNPH: can default mode and motor networks changes improve patient selection and outcome? Preliminary report.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant. METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded. RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038). CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.

Risk Factors for Intraoperative Seizures in Glioma Surgery: Electrocorticography Matters.

PURPOSE: Few and contradictory data are available regarding intraoperative seizures during surgery for low-grade gliomas. Aim of this study was to evaluate possible risk factors for the occurrence of IOS. METHODS: The authors performed a retrospective analysis of 155 patients affected by low-grade gliomas and tumor-related epilepsy, who underwent surgery in our Department, between 2007 and 2018. A statistical analysis was performed by means of univariate and multivariate regression to evaluate any possible correlation between seizure occurrence and several demographic, clinical, neurophysiological, and histopathological features. RESULTS: Intraoperative seizure occurred in 39 patients (25.16%) with a total of 62 seizure events recorded. Focal seizures were the prevalent seizure type: among them, 39 seizures did not show motor signs, being those with only electrographic and/or with cognitive features the most represented subtypes. Twenty-six seizures occurring during surgery were not spontaneous: direct cortical stimulation with Penfield paradigm was the most prevalent evoking factor. The univariate analysis showed that the following prognostic factors were statistically associated with the occurrence of intraoperative seizure: the awake technique ( P = 0.01) and the interictal epileptiform discharges detected on the baseline electrocorticography (ECoG) ( P < 0.001). After controlling for confounding factors with multivariate analysis, the awake surgery and the epileptic ECoG pattern kept statistical significance. CONCLUSIONS: The awake surgery procedure and the epileptic ECoG pattern are risk factors for intraoperative seizure. ECoG is mandatory to detect electrographic seizures or seizures without motor signs.

Normal-appearing white matter structural integrity in incidentally discovered low-grade gliomas: a single institution study.

BACKGROUND: Incidentally discovered low-grade gliomas (iLGGs) are poorly reported in the literature and little is still known about their effects on white-matter structure. In this study, we investigated whether iLLG growth in either hemisphere could affect main white-matter association tracts and cortico-spinal tract. METHODS: We retrospectively analyzed white-matter integrity in a group of 18 patients with iLGG having a mostly preserved cognitive status [1]. We identified two groups of patients, 13 having iLGG in left hemisphere (LH) and five in right hemisphere (RH) and maximum lesion overlap in inferior frontal gyrus and in medial frontal areas, respectively. A group of healthy controls (N.=20) was included. We carried out a univariate analysis of variance to inspect potential effect of interaction between hemisphere harboring the lesion (i.e., LH or RH) and hemisphere taken into account on number of streamlines and fractional anisotropy (FA) of reconstructed white-matter tracts. RESULTS: The sole significant interaction concerned left arcuate fasciculus, with patients with iLGG in LH having a lower number of streamlines than healthy controls; interaction involving FA was not significant for any of the fascicles. Lack of any other significant findings indicates overall preserved white matter. CONCLUSIONS: iLGG size and growth pattern could explain why white-matter status did not markedly differ with respect to the healthy controls. Findings therefore support evidence that iLGGs represent the earlier phase in natural history of LGGs and are discussed in a clinical perspective and in support to safe early surgery.

Fast or Slow? A Comparison Between Two Transcranial Electrical Stimulation Techniques for Eliciting Motor-Evoked Potentials During Supratentorial Surgery.

PURPOSE: During intraoperative neurophysiological monitoring of motor pathways, two types of transcranial electrical stimulation are available, i.e., constant-current and constant-voltage stimulation. Few previous studies, performed only during spinal surgery, analyzed and compared them during intraoperative neurophysiological monitoring. The aim of our study was to compare these two stimulation techniques for eliciting motor-evoked potentials during intraoperative neurophysiological monitoring in a group of patients affected by supratentorial lesions. METHODS: Supratentorial lesions from 16 patients were retrospectively collected and analyzed. Motor-evoked potentials were performed only from transcranial electrical stimulation because the inability to place the subdural strip electrodes correctly did not permit to perform direct cortical stimulation. At the beginning of surgery, in each patient, motor-evoked potentials were monitored by using both "fast-charge" constant-voltage and "slow-charge" constant-current stimulation. Several neurophysiological parameters were collected and compared between the two stimulation techniques by means of statistical analysis. RESULTS: "Fast-charge" constant-voltage stimulation allowed statistically higher efficiency rates for eliciting motor-evoked potentials compared with "slow-charge" constant-current stimulation, both for upper and lower limbs. We also found that threshold and maximal charge as well as charge density were significantly lower during constant-voltage stimulation, thus lowering the potential tissue damage. CONCLUSIONS: "Fast-charge" constant-voltage transcranial electrical stimulation is feasible and safe during intraoperative neurophysiological monitoring for supratentorial surgery and may be preferable to "slow-charge" constant-current stimulation.

Primary Leptomeningeal Medulloblastoma in Adults: A Diagnostic Challenge-Case Report and Systematic Review.

Primary leptomeningeal medulloblastoma (PL-MB) in adults is a rare disease with a severe prognosis. A 35-year-old woman presented with headaches, diplopia, and gait ataxia, with triventricular hydrocephalus and descent of the cerebellar tonsils beyond the foramen magnum. Endoscopic third ventriculostomy was performed. Six months later, headaches recurred. Dilatation of the supratentorial ventricular system and massive cerebellar swelling without contrast-enhancing nodularities were reported. Occipitocervical decompression with duraplasty was performed. A bioptic diagnosis of PL-MB was made. Craniospinal irradiation and chemotherapy were administered. After 18 months, no recurrence was observed. Few cases of PL-MB have been reported: patients die before treatment or within a few days after surgery. Our long-term survival could be ascribable to a slow clinical presentation and an early diagnosis that allowed surgical treatment and the administration of a combined chemoradiotherapy protocol. Cerebellar swelling, even without associated enhancing lesions, with or without hydrocephalus, should be a neuroradiological alarm sign, and PL-MB should be considered.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Incidental low grade glioma in young female: An indolent lesion? A case report and a literature review.

OBJECTIVE: The wide use of brain MRI has led to an increased diagnosis of incidental low-grade gliomas (LGGs). There is no consensus regarding the surgical treatment of incidental LGGs, nor even when we deal with a young woman who wants to plan a pregnancy. We performed a literature review on the topic of cognitive testing and pregnancy in LGGs. Results on the patients' cognitive status are poorly addressed: if, after surgery, neuropsychological deficits were to arise, this would greatly complicate the management of a child by a mother who is an oncological patient, and, moreover, has developed cognitive alterations that may compromise the abilities to look after a baby. We also report the case of a 30-years old woman with a diagnosis of incidental LGG who underwent a first surgery for a right-frontal oligodendroglioma METHODS: The patient underwent two awake surgeries and in both performed the Real Time Neuropsychological Testing (RTNT). We acquired clinical and MRI data. This paper also reports a literature review on the topic of cognitive testing and pregnancy in LGGs highlighting a lack of adequate data about this issue. RESULTS: No deterioration of neuropsychological performances was documented during surgery. During the follow-up, she became pregnant and, despite an increased growth rate of the lesion, she did not accuse any symptom or sign of evolution in high-grade glioma (HGG). She underwent a second awake surgery with RTNT. Performance was maintained within the normal range. CONCLUSIONS: We concluded that, in our experience, pregnancy could induce an increased growth rate of LGG, not influencing the prognosis.