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Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called ‘nephrosclerosis’ (NS), on CKD progression is often unpredictable, particularly in elderly population. We have conducted a prospective, observational study to define renal function patterns and outcomes in elderly CKD individuals with or without NS. Three hundred four individuals with an already established CKD were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time trajectories in estimated glomerular filtration rate (eGFR) (CKD-Epi) were computed over a 4-year follow-up. In addition, we analyzed the occurrence of a composite outcome of doubling of serum creatinine levels, eGFR reduction ≥25% and/or the need of chronic renal replacement therapy. CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%). In the whole cohort, the average estimated annual GFR slope was 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with others (1.4 vs 3.4 mL/min/1.73 m2; p

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

BACKGROUND AND AIMS Chronic haemodialysis (HD) patients are notoriously at high risk for cardiovascular mortality and morbidity. Omentin-1 (OME-1) is an adipocytokine produced by adipose tissue, whose levels are altered in various dysmetabolic conditions, such as obesity and type 2 diabetes mellitus. Beyond this, nowadays there is evidence indicating that this cytokine plays a crucial role in the genesis and progression of systemic atherosclerosis since it may inhibit plaque formation. With this background in mind, we run a pilot investigation to evaluate the possible correlation between circulating OME-1 levels and mean intimal thickness (IMT) in a small, homogeneous cohort of patients treated by HD (‘HD patients’). METHOD From a source cohort of 45 HD patients, we selected 27 individuals suitable to be enrolled. These patients had a dialysis vintage > 6 mo., were on a regular 4 h/3 times week HD regimen and had stable clinical conditions. OME-1 levels were measured in their blood by the ELISA together with common laboratory and clinical parameters before starting a mid-week HD session. All the patients then underwent carotid Doppler ultrasound for IMT measurement. A total of 18 healthy subjects were the controls. RESULTS In the whole cohort, mean IMT values were 0.75 ± 0.12 mm. However, 8/27 patients (29.6%) presented a pathological IMT (>1 mm). Circulating OME-1 levels in the whole HD cohort were increased as compared with controls [763 (367–1423) versus 371 (228–868) ng/mL; P = 0.03]. However, HD patients with pathological IMT presented, on average, lower OME-1 levels as compared with others [483.25 (168.7–1743) versus 1155 (286–2324); P = 0.05]. In ROC analyses, OME-1 values ≤ 840 ng/mL held an 83.3 sensitivity and 66.7 specificity (AUC 0.716, 95% confidence interval 0.506–0.946) in identifying HD patients with pathological carotid thickening. CONCLUSION OME-1 may play a direct role in the atherosclerosis process also in HD patients. Further studies on larger and more heterogeneous HD cohorts are needed to confirm the usefulness of OME-1 plasma levels as potential biomarkers for diagnosing subclinical atherosclerosis and for stratifying the risk of atherosclerosis progression in high-CV risk in HD patients.

The increased prevalence of chronic kidney disease (CKD) in elderly patients recognizes, as main cause, the long-term exposure to atherosclerosis and hypertension. Chronic ischemic damage due to critical renal arterial stenosis induces oxidative stress and intra-renal inflammation, resulting in fibrosis and microvascular remodelling, that is the histological picture of atherosclerotic renal vascular disease (ARVD). The concomitant presence of a long history of hypertension may generate intimal thickening and luminal narrowing of renal arteries and arterioles, glomerulosclerosis, interstitial fibrosis and tubular atrophy, more typically expression of hypertensive nephropathy. These complex mechanisms contribute to the development of CKD and the progression to End Stage Kidney Disease. In elderly CKD patients, the distinction among these nephropathies may be problematic; therefore, ischemic and hypertensive nephropathies can be joined in a unique clinical syndrome defined as atherosclerotic nephropathy. The availability of novel diagnostic procedures, such as intra-vascular ultrasound and BOLD-MRI, in addition to traditional imaging, have opened new scenarios, because these tools allow to identify ischemic lesions responsive to renal revascularization. Indeed, although trials have deflated the role of renal revascularization on the renal outcomes, it should be still used to avoid dialysis initiation and/or to reduce blood pressure in selected elderly patients at high risk. Nonetheless, lifestyle modifications (smoking cessation, increased physical activity), statins and antiplatelet use, as well as cautious use of renin-angiotensin system inhibitors, remain the main therapeutic approach aimed at slowing the renal damage progression. Mesenchymal stem cells and Micro-RNA are promising target of anti-fibrotic therapy, which might provide potential benefit in ARVD patients, though safety and efficacy profile in humans is unknown too.

Left ventricular hypertrophy (LVH) is remarkably prevalent among end-stage kidney disease (ESKD) on chronic dialysis and has a strong prognostic value for adverse outcomes. In experimental models, the endogenous cardiotonic steroid Marinobufagenin (MBG) promotes cardiac hypertrophy and accelerates uremic cardiomyopathy. In this study, we investigated the possible relationships between MBG, LV geometry and cardiac dysfunction in a clinical setting of ESKD.Plasmatic MBG was measured in 46 prevalent ESKD patients (n = 30 HD, n = 16 PD) together with a thorough laboratory, clinical, bioimpedance and echocardiography assessment. Different patterns of LV geometry were defined by left ventricular mass index (LVMi) and ventricular morphology. Diastolic dysfunction was diagnosed by the ASE/EACVI criteria.MBG levels were significantly higher in ESKD patients than in healthy controls (p = 0.001) and more elevated in PD than in HD (p = 0.02). At multivariate analyses, E/e' (β = 0.38; p = 0.009) and LVMi (β = 0.42; p = 0.02) remained the sole independent predictors of MBG. A statistically significant trend in MBG levels (p = 0.01) was noticed across different patterns of LV geometry, with the highest values found in eccentric LVH. MBG levels were higher in the presence of diastolic dysfunction (p = 0.01) and this substance displayed a remarkable diagnostic capacity in distinguish patients with normal LV geometry, LV hypertrophy and, particularly, eccentric LVH (AUC 0.888; p 0.0001) and diastolic dysfunction (AUC 0.79; p = 0.001).Deranged plasma MBG levels in ESKD patients on chronic dialysis reflect alterations in LV structure and function. MBG may, thus, candidate as a novel biomarker for improving cardiac assessment in this high-risk population.

Background and Aims Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney disease (ESKD) is often unpredictable, particularly in older populations. We run a prospective, observational study to define renal function patterns and outcomes in elderly individuals with or without NS-related CKD. Method 304 elderly patients with already established CKD (mean age 69±4 y; mean eGFR 44.2±19.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’ clinic were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction≥ 25% and/or ESKD needing dialysis or kidney transplantation. Results CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients. Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p Conclusion Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions. Therapeutic efforts to delay CKD progression in older populations should go beyond just optimizing blood pressure control and focus more on concomitant diseases.

Background and Aims Several evidences demonstrate that chronic dialysis treatment alters troponin levels, even in the absence of an acute myocardial event, although the underlying causes remain largely unclear. In this small pilot study, we aimed at analyzing high sensitivity troponin T (HsTnT) in a cohort of dialysis patients to identify the potential clinical predictors. Method HsTnT levels were measured together with common laboratory and clinical parameters in 39 chronic dialysis patients (middle age: 65±12 aa; 82% M; 30 in hemodialysis and 9 in peritoneal dialysis). The patients underwent also a complete echocardiography assessment. Results HsTnT levels were higher than normal reference values (median 46.1 ng/L IQR 33.5-84.3),but showing no differences between hemodialysis and peritoneal dialysis patients (p=0.19). At correlation analyses, HsTnT were strongly associated with beta2-MCG (R=0.43; p=0.008), Hemoglobin (r=-0.47; p=0.002) and, in particular, with some echocardiography parameters such as ejection fraction (R=-0.29; p=0.05), E/E’ratio (R=0.56; p=0.006) and LAVI (R=0.41; p=0.05) Figure 1. Conclusion In a small cohort of dialysis patients, high HsTnt levels were at the crossroad between the severity of functional heart dysfunction and anemia. Larger studies are advocated to further clarify the role of HsTnT as a potential biomarker reflecting the anemic cardiorenal syndrome which characterizes uremic subjects.

Intradialytic hypotension (IDH) is a sudden and often serious complication of chronic hemodialysis (HD). In this prospective study, we aimed at evaluating the clinical predictors of IDH in a homogeneous cohort of chronic HD patients, with a particular focus on marinobufagenin (MBG), an endogenous cardiotonic steroid which alterations have previously been involved in various cardiovascular disorders. MBG levels in HD patients were significantly higher than in controls (p = 0.03), remained unchanged throughout a single HD session and were not correlated with the absolute or partial fluid loss achieved. During a 30-day follow-up, 19 patients (65.5%) experienced at least one IDH (73 total episodes). An inverse correlation was found between baseline MBG and the number of IDH (R = –0.55; p = 0.001). HD patients experiencing IDH presented remarkably lower baseline MBG as compared to others (p = 0.008) with a statistically significant trend during HD (p = 0.02). At Kaplan-Meier analyses, HD patients with lower MBG manifested a four-to-six fold increased risk of IDH during follow-up (crude Hazard Ratio ranging from 4.37 to 6.68). At Cox regression analyses, MBG measurement at different time points resulted the strongest time-dependent predictors of IDH among all the variables considered (HR ranging from 0.068 to 0.155; p: 0.002 to

Objective: Available biomarkers for monitoring primary glomerulonephritides (GNs), often lack the ability to assess longitudinal changes and have great variability with poor sensitivity. Accruing evidence has demonstrated that Neutrophil Gelatinase-Associated Lipocalin (NGAL), holds promising capacities in predicting renal function worsening in various renal diseases. We aimed at analysing urinary NGAL (uNGAL) levels in a cohort of individuals with biopsy-proven GNs in order to evaluate its ability to reflect the entity of renal damage and to predict disease evolution overtime. Methods: We enrolled 61 consecutive GNs patients still naive to pathogenic therapy. uNGAL levels were measured at baseline and patients prospectively followed until the manifestation of a combined outcome of doubling of baseline serum creatinine and/or end-stage kidney disease requiring permanent dialysis support. Results: Median uNGAL levels were 107 [35-312] ng/mL. At univariate and multivariate analyses an inverse correlation was found between eGFR and uNGAL levels (p=0.001). Progressor subjects showed exceedingly increased baseline uNGAL values as compared with non-progressors (p

The decision-making process of the individual is analogous to the collapse of a quantum system at the moment of measurement, whereby quantum system we mean the decision-maker, his mental processes and the environmental context that influences him in his choices. Classical probability depends on the lack of information, quantum probability is instead intrinsic to the system to be studied, meaning that the system, consisting of the decision-maker and the context, is in a superposition of states, each with its own amplitude of probability. Only the measurement process (the decision) selects in the decision maker a specific state among those in which he was overlapping. We demonstrated on a Noisy Intermediate –Scale Quantum Processor the model of the “order effect”, one of the most important cognitive bias.

Purpose: Gut dysbiosis has been described in advanced, but not in initial stages of CKD. Considering the relevant impact of gut dysbiosis on renal and cardiovascular risk, its diagnosis and treatment are clinically relevant. Methods: We designed, open-label, placebo-controlled intervention study (ProbiotiCKD) to evaluate gut microbiota metabolism in a cohort of KDIGO CKD patients (n = 28) at baseline and after a randomly assigned treatment with probiotics or placebo. Gut microbiota status was evaluated on:. Results: Basal mean fecal Lactobacillales and Bifidobacteria concentrations were abnormally low in both groups, while urinary indican and 3-MI levels were, indicating a mixed (fermentative and putrefactive) dysbiosis. After treatment, mean fecal Lactobacillales and Bifidobacteria concentrations were increased, only in the probiotics group (p < 0.001). Conversely, mean urinary indican and 3-MI levels only in the group treated with probiotics (p < 0.001). Compared to placebo group, significant improvements of C-reactive protein (p < 0.001), iron (p < 0.001), ferritin (p < 0.001), transferrin saturation (p < 0.001), β2-microglobulin (p < 0.001), serum iPTH and serum calcium were observed only in the probiotics group. Conclusions: ProbiotiCKD is the first intervention study demonstrating that an intestinal mixed dysbiosis is present even in early CKD stage and can be effectively corrected by the novel mode of administration of high-quality probiotics with improvement of inflammatory indices, iron status and iPTH stabilization.

Data concerning the neural basis of noun and verb processing are inconsistent. Some authors assume that action-verb processing is based on frontal areas while nouns processing relies on temporal regions; others argue that the circuits processing verbs and nouns are closely interconnected in a predominantly left-lateralized fronto-temporal-parietal network; yet, other researchers consider that the primary motor cortex plays a crucial role in processing action verbs. In the present study, one hundred and two patients with a tumour either in the right or left hemisphere were submitted to picture naming of objects and actions before and after surgery. To test the effect of specific brain regions in object and action naming, patients' lesions were mapped and voxel-lesion-symptom mapping (VLSM) was computed. Behavioural results showed that left-brain damaged patients were significantly more impaired than right brain-damaged patients. The VLSM showed that these two grammatical classes are segregated in the left hemisphere. In particular, scores in naming of objects correlated with damage to the anterior temporal region, while scores in naming of actions correlated with lesions in the parietal areas and in the posterior temporal cortex. In addition, VLSM analyses carried out on non-linguistic tasks were not significant, confirming that the regions associated with deficits in object and action naming were not generally engaged in all cognitive tasks. Finally, the involvement of subcortical pathways was investigated and the inferior longitudinal fasciculus proved to play a role in object naming, while no specific bundle was identified for actions., Highlights • One-hundred and two patients were examined and their lesions analysed. • An anatomical dissociation between noun and verb has been demonstrated • Posterior temporal and parietal, not frontal regions, are involved in action naming • Temporal regions are involved in naming objects.

The cortical and subcortical neural correlates underlying item and order information in verbal short-term memory (STM) were investigated by means of digit span in 29 patients with direct electrical stimulation during awake surgery for removal of a neoplastic lesion. Stimulation of left Broca's area interfered with span, producing significantly more item than order errors, as compared to the stimulation of the supramarginal/angular gyrus, which also interfered with span but, conversely, produced more order than item errors. Similarly, stimulation of the third segment of the left superior longitudinal fasciculus (SLF-III), also known as anterior segment of the arcuate fascicle (AF), produced more order than item errors. Therefore, we obtained two crucial results: first, we were able to distinguish between content and order information storage. Second, we demonstrated that the SLF-III is involved in transferring order information from Geschwind's area to Broca's area. In a few patients, we demonstrated that also order information of nonverbal material was disrupted by left supramarginal gyrus stimulation. Order information is thus likely stored in the supramarginal gyrus, possibly independently from the nature of the material. Hum Brain Mapp 38:3011-3024, 2017. © 2017 Wiley Periodicals, Inc.

The mechanism of action of fibroblast growth factor-23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long-term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation.

The relationship between verbal-auditory short-term memory (STM) and language is an open area of debate and contrasting hypotheses have been proposed, suggesting either that STM would strongly rely on language-related processes, or that it depends on a dedicated system related to language, but independent from it. In this study we examined 103 patients undergoing surgery for glioma resection in the left or right hemisphere, and we conducted a VLSM analysis on their behavioral performance on auditory-verbal STM, as well as on more general verbal and nonverbal tasks. The aim was to investigate whether the anatomical correlates of auditory-verbal STM were part of the language system or they were spatially segregated from it. VLSM results showed that digit span scores were linked to lesions in both the left supramarginal gyrus and superior-posterior temporal areas, as reported in the literature on patients with a selective deficit of auditory-verbal STM. Conversely, other verbal tasks involved areas only partly overlapping with those found for digit span, with repetition being affected by lesions in more anterior regions in the parietal, temporal, and frontal lobes, and word comprehension by lesions in a network including cortical and subcortical pathways in the temporal lobe. The present results, thus, show that auditory-verbal STM neural correlates are only partially overlapping with those supporting comprehension and production: while the left posterior–superior temporal cortex, involved in speech perception, takes part in both functions, the left supramarginal gyrus has a consistent and specific role only in STM, supporting the hypothesis of interacting but segregated networks.

Emotion processing impairments are common in patients undergoing brain surgery for fronto-temporal tumour resection, with potential consequences on social interactions. However, evidence is controversial concerning side and site of lesions causing such deficits. This study investigates visual and auditory emotion recognition in brain tumour patients with the aim of clarifying which lesion sites are related to impairments in emotion processing from different modalities. Thirty-four patients were evaluated, before and after surgery, on facial expression and emotional prosody recognition; voxel-based lesion–symptom mapping (VLSM) analyses were performed on patients’ post-surgery MRI images. Results showed that patients’ performance decreased after surgery in both visual and auditory modalities, but, in general, recovered 3 months after surgery. In facial expression recognition, left brain-damaged patients showed greater post-surgery deterioration than right brain-damaged ones, whose performance specifically decreased for sadness and fear. VLSM analysis revealed two segregated areas in the left hemisphere accounting for post-surgery scores for happy (fronto-temporo-insular region) and surprised (middle frontal gyrus and inferior fronto-occipital fasciculus) facial expressions. Our findings demonstrate that surgical removal of tumours in the fronto-temporal region produces impairment in facial emotion recognition with an overall recovery at 3 months, suggesting a partially different representation of positive and negative emotions in the left and right hemispheres for visually – but not auditory – presented emotions; moreover, we show that deficits in specific expression recognition are associated with discrete lesion locations.

Neuropsychological and neuroimaging studies yielded controversial results concerning the specific role of the insula in recognizing the facial expression of disgust. To verify whether the insula has a selective role in facial disgust processing, emotion recognition was studied in thirteen patients during intraoperative stimulation of the insula in awake surgery performed for removal of a glioma close to this structure. Direct electrical stimulation of the left insula produced a general decrease in emotion recognition but only in the case of disgust there was a statistically significant detrimental effect (p=0.004). Happiness and anger were the best and the worst recognized emotion, respectively. The worst baseline performance with anger and, partly, fear could be explained with the involvement of the left temporal regions, striatum, and the connection between the striatum and the frontal lobe, as suggested in previous studies. Therefore, upon these intra-operative evidences, we argue for a selective role of the left insula in disgust recognition, although a (non significant) decrease in the recognition of other negative emotions was found. However, additional networks can develop, as demonstrated by the fact that disgust recognition was not impaired after surgery even in patients with insular resection in the current as in previous studies.

OBJECT Intraoperative language mapping is traditionally performed with low-frequency bipolar stimulation (LFBS). High-frequency train-of-five stimulation delivered by a monopolar probe (HFMS) is an alternative technique for motor mapping, with a lower reported seizure incidence. The application of HFMS in language mapping is still limited. Authors of this study assessed the efficacy and safety of HFMS for language mapping during awake surgery, exploring its clinical impact compared with that of LFBS. METHODS Fifty-nine patients underwent awake surgery with neuropsychological testing, and LFBS and HFMS were compared. Frequency, type, and site of evoked interference were recorded. Language was scored preoperatively and 1 week and 3 months after surgery. Extent of resection was calculated as well. RESULTS High-frequency monopolar stimulation induced a language disturbance when the repetition rate was set at 3 Hz. Interference with counting (p = 0.17) and naming (p = 0.228) did not vary between HFMS and LFBS. These results held true when preoperative tumor volume, lesion site, histology, and recurrent surgery were considered. Intraoperative responses (1603) in all patients were compared. The error rate for both modalities differed from baseline values (p < 0.001) but not with one another (p = 0.06). Low-frequency bipolar stimulation sensitivity (0.458) and precision (0.665) were slightly higher than the HFMS counterparts (0.367 and 0.582, respectively). The error rate across the 3 types of language errors (articulatory, anomia, paraphasia) did not differ between the 2 stimulation methods (p = 0.279). CONCLUSIONS With proper setting adjustments, HFMS is a safe and effective technique for language mapping.

A previous study reporting on 44 patients who underwent awake surgery for a left frontal or temporal glioma resection demonstrated the removal of the uncinate fasciculus to have consequences on language 3 months post-surgery. At this time-point, patients with a temporal glioma who had undergone uncinate removal showed the worst overall performance with a significant impairment in naming of famous faces and objects compared to patients without removal. Also, verbal fluency was mildly impaired. We report a longer-term follow-up (9–12 months) in a selected group of 17 patients (six female, age range 27–64) who did not suffer any tumour recurrence in this timeframe. MRI and DTI were performed before and after surgery. While verbal fluency on categorical cue and object naming recovered to the same level as before surgery, proper naming remained significantly impaired even after 12 months (P = 0.032) in patients with uncinate removal, demonstrating this structure to be crucial for that function and supporting the hypothesis that subcortical connectivity is relevant to allow plasticity. We thus argued that the left frontal and temporal poles connected by means of the uncinate fasciculus constitute a dedicated circuit for naming of unique entities.

Resection of tumors involving language pathways requires the intraoperative identification of cortical and subcortical sites mediating the various language components, which determines the extent of resection (EOR). One of the critical point is which test(s) has to be performed during subcortical mapping. Object naming is the most used one, but it may have the limit to miss other components of language such as verb naming and generation, or comprehension of words or sentences, potentially resulting in permanent post operative deficits. Patients can be submitted intraoperatively to complex batteries of tests, resulting in limited performance and high chance of intraoperative fatigue, resulting in poor mapping. We revised our experience on subcortical language mapping in a series of patients with language pathways gliomas, in which two strategies for subcortical mapping were applied: in a first group only naming was used; in the second group, object naming was prevalently used but integrated with other tests (verb naming and generation, comprehension of words or sentences, number recognition and calculation). Results were evaluated as immediate and permanent deficits by applying a large neuropsychological testing, and as EOR (on volumetric FLAIR or post Gd T1 images). The first group was composed of 221 gliomas (168 LGGs, 53 HGGs); 130 were frontal, 21 in the insula, 58 temporal, and 12 parietal. Object naming was applied for subcortical mapping in all cases; 198 patients had immediate post operative deficits. Neuropsychological evaluation at 1 months showed complete recovery in 199 patients, a mild impairment was documented in 22 patients (12 posterior temporal tumors, 6 parietal tumors, and 4 posterior insular tumors); at 3 months evaluation, 15 patients still showed a mild impairment, mainly those whose tumors were located in the posterior temporal and parietal location. EOR was total and subtotal in 48.9% and 41.5% of cases. Fatigue was observed in 12% of patients with large volume tumors. The second group was composed of 179 gliomas (155 LGGs, 24 HGGs); 61 were frontal, 38 insular, 45 temporal and 11 parietal. Object naming was used for initial mapping and for locating main subcortical tracts (IFOF, ARC, UNC); in addition, when the initial portion of these tracts was identified, other tests were applied during subcortical mapping. 165 patients had immediate post operative deficits, only 2 patients had a mild impairment at 1 and 3 months evaluation. EOR was total and subtotal in 49.6% and 47.4% of cases. Patient fatigue was shown in 9% of patients. Object naming can be safely used during subcortical mapping for resection of tumors in frontal lobe; resection of tumors in posterior temporal, insular and parietal areas requires the use of a larger battery of tests, which did not influence the chance to reach a total or subtotal resection, nor results in a higher chance of patient fatigue.

Intraoperative language mapping is standard for resection of gliomas involving language pathways, because it enables a maximal safe tumor removal. Intraoperative language mapping is a demanding procedure requiring a good level of patient collaboration, a complex peri-operative organization, and may cause patient fatigue. The selection of patients to submit to such a procedure is critical. The efficacy of intraoperative mapping is widely recognized for Low Grade Gliomas, the use for surgical removal of high grade gliomas (HGGs) is still under debate. We evaluated the efficacy of the use of intraoperative language mapping for resection of HGGs involving language pathways, to identify for which subtype of patients is highly recommended, and for which can be optional. 2 groups were included. In the first group (126 patients) removal was performed asleep, with the aid of neurophysiological monitoring. In the second group (157 patients) resection was performed awake with the aid of cortical and subcortical language mapping and neurophysiological monitoring. Patients and tumor characteristics (location, radiological appearance on conventional MR, pattern of tract dislocation/infiltration in DTI FT images) were considered. Results were evaluated as immediate/permanent deficits (by neuropsychological evaluation) and extent of resection (on volumetric gadolinium enhanced T1 weighted MR images). In the first group, 65 tumors were frontal, 61 temporal. 108 were involving the cortex, 18 were deep seated. DTI depicted the Tract located at the tumor periphery in 111 patients, inside the tumor in the remaining. 32 patients had pre-operative mild or moderate language deficits. Resection was continued till microscopically normal parenchyma was encountered. Total resection was achieved in 97.6% of cases. In 35 (27.8%) of patients, immediate post-operative deficits were observed, which remained as permanent in 16 patients. 87.5% of patients with pre-operative language deficits recovered in the post operative period. Patients who developed permanent deficits were those with deep seated tumors. In the second group of tumors, 72 were frontal, and 85 temporal, 112 superficial, 45 were not reaching the cortex. DTI depicted the tract located in the tumor periphery in 128 patients, inside the tumor in the remaining. 25 patients had pre operative mild language deficits. Resection was continued till functional boundaries were reached. Immediate post operative language deficits were shown in 41 (26.1%) patients, with complete recovery within a month in all patients. Total resection was reached in 96.1% of cases. Removal of language pathways tumors does not strictly requires the use of subcortical language mapping when the tumor reach the surface. Resection of deep seated tumors or of tumors with infiltrated tracts (as depicted by DTI) requires the use of subcortical mapping to achieve a safe tumor removal.

BACKGROUND: Glioma surgery has been changed from one,relying on anatomical references, to a new one aimed at recognizing, with the aid of intraoperative neurophysiology, the different neural structures on the basis of their functional properties, to maximally resect the tumor and preserve patient functional integrity. This approach called functional neurooncological surgery needs to be maximally and safely extended to enlarge the population of patients who will benefit from surgery. Intraoperative neurophysiology offers the surgeon various stimulation protocols, whose efficiency is based on the ability to recognize the essential sites at cortical and subcortical level, with the highest possible resolution in most clinical conditions. This ability faces the neural structures excitability that depends on patients characteristics and tumor features. The key point is the integration of the choice of the stimulation protocols with the clinical context. METHODS: Intraoperative neurophysiological protocols used in the study were the 60Hz-technique (Low Frequency-LF) and the train-of-five-or pulse technique (To5), delivered alternatively by bipolar or monopolar probe. In 620 patients with tumors involving the corticospinal-tract and in 450 patients with tumors involving language areas and tracts, the use of these stimulation protocols was tailored to the clinical context defined by patient characteristics (clinical history, seizures control, antiepileptic drug therapy, previous treatments) and tumor features (defined by MR-imaging: volume, location, degree of infiltration on volumetric FLAIR images, degree of tracts involvement in DTI-FT images). The effect was evaluated on the feasibility of mapping (number of cases in which a reliable mapping was feasible), number of intraoperative seizures, the impact on immediate and permanent morbidity, the extent of resection (by volumetric analysis), the number of patients treated, and by neuropsychological evaluation (immediately after surgery and at 3-6 months). RESULTS: By integrating the choice of the probe and the stimulating protocol with patient clinical history and tumor characteristics, the best “probe-frequency match” to be applied in different clinical conditions was identified. According to clinical and imaging criteria various risk groups of patients were identified (either in the group of tumors involving the motor or language tracts) and the most adequate stimulation protocols for each group was reported. This integrative approach allows increasing the extent of resection, keeping patient functional integrity, and strongly expanding the number of patients who benefit from surgery CONCLUSIONS: The integration of stimulation modalities with clinical context enhances resection extent and safety, and largely expands the population of patients who benefit from surgical treatment SECONDARY CATEGORY: n/a.

Background Music is one of the most sophisticated and fascinating functions of the brain. Yet, how music is instantiated within the brain is not fully characterized. Singing is a peculiar aspect of music, in which both musical and linguistic skills are required to provide a merged vocal output. Identifying the neural correlates of this process is relevant for both clinical and research purposes. Case Description An adult white man with a presumed left temporal glioma was studied. He is a professional opera singer. A tailored music evaluation, the Montreal Battery of Evaluation of Amusia, was performed preoperatively and postoperatively, with long-term follow-up. Intraoperative stimulation mapping (ISM) with awake surgery with a specific music evaluation battery was used to identify and preserve the cortical and subcortical structures subserving music, along with standard motor-sensory and language mapping. A total resection of a grade I glioma was achieved. The Montreal Battery of Evaluation of Amusia reported an improvement in musical scores after the surgery. ISM consistently elicited several types of errors in the superior temporal gyrus and, to a lesser extent, in the inferior frontal operculum. Most errors occurred during score reading; fewer errors were elicited during the assessment of rhythm. No spontaneous errors were recorded. These areas did not overlap with eloquent sites for counting or naming. Conclusions ISM and a tailored music battery enabled better characterization of a specific network within the brain subserving score reading independently from speech with long-term clinical impact.

We describe how a neuropsychological evaluation in patients with brain tumors should be performed, specifically in the case of low-grade gliomas. Neuropsychological examination is crucial before starting any treatment as well as during the follow-up, since it can improve neurosurgery techniques and reveal potential cognitive effects of chemotherapy and radiotherapy, besides planning rehabilitation. We underline that sensitive and wide-ranging tests are required; specific tasks based on the lesion site should be added. Moreover, some tests can provide additional information about the evolution of the tumor. A careful, thorough examination improves quality of life. © Springer Science+Business Media, LLC. 2012.

Resection of language pathways tumors requires intraoperative identification of cortical and subcortical language essential sites. Language mapping is traditionally performed with LowFrequency(60Hz) stimulation. In patients with previous treatment or long history of seizures, the use of LF may be problematic and results in inadequate mapping. HighFrequency(HF)(To5) stimulation represents an alternative strategy. We present our experience with HF stimulation for language mapping in patients with gliomas involving language pathways. Efficacy of mapping was compared with LF, and clinical impact (percentage of immediate and permanent deficits) and Extent-of-Resection(EOR)) was also reported. 80 patients were included (49 were frontal, 21 temporal). HF (repetition rate of 3Hz) identified language sites in all patients. In patients with long history of seizures, high doses of antiepileptic drugs (AEDs), previous treatments, in whom LF induced seizures and was inadequate for mapping, HF efficiently identified language sites at cortical and subcortical level. In patients (30 cases) in whom LF and HF were compared, HF induced positive language responses in the same sites as LF, in frontal and temporal lobes. Intraoperative seizures were 24% with LF, 2% with HF, also in patients with previous history of seizures, high doses of AEDs. Percentage of immediate and permanent deficits were 78% and 2%, also in patients in whom only HF was used. EOR was total in 82%. HF(To5, repetition rate of 3Hz) represents an efficient alternative stimulation strategy for language mapping, particularly in patients with long history of seizures and high AEDs, associated with a low risk of intraoperative seizures.