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The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline., (© 2024. The Author(s).)

We compared choroid plexus (ChP) manual segmentation on non-contrast-enhanced (non-CE) sequences and reference standard CE T1- weighted (T1w) sequences in 61 multiple sclerosis patients prospectively included. ChP was separately segmented on T1w, T2-weighted (T2w) fluid-attenuated inversion-recovery (FLAIR), and CE-T1w sequences. Inter-rater variability assessed on 10 subjects showed high reproducibility between sequences measured by intraclass correlation coefficient (T1w 0.93, FLAIR 0.93, CE-T1w 0.99). CE-T1w showed higher signal-to-noise ratio and contrast-to-noise ratio (CE-T1w 23.77 and 18.49, T1w 13.73 and 7.44, FLAIR 13.09 and 10.77, respectively). Manual segmentation of ChP resulted 3.073 ± 0.563 mL (mean ± standard deviation) on T1w, 3.787 ± 0.679 mL on FLAIR, and 2.984 ± 0.506 mL on CE-T1w images, with an error of 28.02 ± 19.02% for FLAIR and 3.52 ± 12.61% for T1w. FLAIR overestimated ChP volume compared to CE-T1w (p < 0.001). The Dice similarity coefficient of CE-T1w versus T1w and FLAIR was 0.67 ± 0.05 and 0.68 ± 0.05, respectively. Spatial error distribution per slice was calculated after nonlinear coregistration to the standard MNI152 space and showed a heterogeneous profile along the ChP especially near the fornix and the hippocampus. Quantitative analyses suggest T1w as a surrogate of CE-T1w to estimate ChP volume.Relevance statement To estimate the ChP volume, CE-T1w can be replaced by non-CE T1w sequences because the error is acceptable, while FLAIR overestimates the ChP volume. This encourages the development of automatic tools for ChP segmentation, also improving the understanding of the role of the ChP volume in multiple sclerosis, promoting longitudinal studies.Key points • CE-T1w sequences are considered the reference standard for ChP manual segmentation.• FLAIR sequences showed a higher CNR than T1w sequences but overestimated the ChP volume.• Non-CE T1w sequences can be a surrogate of CE-T1w sequences for manual segmentation of ChP., (© 2024. The Author(s).)

Importance: The prognosis of overall survival (OS) in patients with glioblastoma (GBM) may depend on the underlying structural connectivity of the brain., Objective: To examine the association between white matter tracts affected by GBM and patients' OS by means of a new tract density index (TDI)., Design, Setting, and Participants: This prognostic study in patients with a histopathologic diagnosis of GBM examined a discovery cohort of 112 patients who underwent surgery between February 1, 2015, and November 30, 2020 (follow-up to May 31, 2023), in Italy and 70 patients in a replicative cohort (n = 70) who underwent surgery between September 1, 2012, and November 30, 2015 (follow-up to May 31, 2023), in Germany. Statistical analyses were performed from June 1, 2021, to May 31, 2023. Thirteen and 12 patients were excluded from the discovery and the replicative sets, respectively, because of magnetic resonance imaging artifacts., Exposure: The density of white matter tracts encompassing GBM., Main Outcomes and Measures: Correlation, linear regression, Cox proportional hazards regression, Kaplan-Meier, and prediction analysis were used to assess the association between the TDI and OS. Results were compared with common prognostic factors of GBM, including age, performance status, O6-methylguanine-DNA methyltransferase methylation, and extent of surgery., Results: In the discovery cohort (n = 99; mean [SD] age, 62.2 [11.5] years; 29 female [29.3%]; 70 male [70.7%]), the TDI was significantly correlated with OS (r = -0.34; P < .001). This association was more stable compared with other prognostic factors. The TDI showed a significant regression pattern (Cox: hazard ratio, 0.28 [95% CI, 0.02-0.55; P = .04]; linear: t = -2.366; P = .02). and a significant Kaplan-Meier stratification of patients as having lower or higher OS based on the TDI (log-rank test = 4.52; P = .03). Results were confirmed in the replicative cohort (n = 58; mean [SD] age, 58.5 [11.1] years, 14 female [24.1%]; 44 male [75.9%]). High (24-month cutoff) and low (18-month cutoff) OS was predicted based on the TDI computed in the discovery cohort (accuracy = 87%)., Conclusions and Relevance: In this study, GBMs encompassing regions with low white matter tract density were associated with longer OS. These findings indicate that the TDI is a reliable presurgical outcome predictor that may be considered in clinical trials and clinical practice. These findings support a framework in which the outcome of GBM depends on the patient's brain organization.

Background: Paediatric-onset multiple sclerosis (POMS) therapeutic approach derives from of adult-onset multiple sclerosis (AOMS) tailored algorithms., Objectives: To evaluate in a common clinical scenario the efficacy and safety of alemtuzumab (ALZ) in POMS and AOMS., Methods: All patients switching from natalizumab (NTZ) to ALZ for safety concerns (high anti-John Cunningham Virus Antibody Index value, anti-JCV Index) were enrolled in this single-centre, retrospective, case-control open-label study., Results: Ten POMS and 27 AOMS were followed up for 51.3 months. After month 12, we found a lower risk of clinical or radiological relapses among AOMS patients and among patients with older age at ALZ (both p  < 0.05). Survival analysis revealed an increased risk of relapse in POMS compared with AOMS (logrank p  = 0.00498) and patients starting ALZ before age 22.75 years than the elder ones (logrank p  = 0.0018). Survival analysis did not disclose any difference between AOMS and POMS (logrank p  = 0.27) in terms of progression independent of any relapse activity (PIRA). In addition, no evidence of relapse-associated worsening was observed. Autoimmune events were reported by 5 AOMS and no POMS (29.4% versus 0.0%, p  = 0.057), and survival analysis was not significant (logrank p  = 0.0786)., Conclusion: ALZ seems more effective in AOMS than in POMS following NTZ. These findings underrate ALZ effectiveness when shifting from NTZ in POMS., Competing Interests: M.P. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy and Novartis; consultancy for Novartis, Biogen Italy and Sanofi Genzyme; board membership Sanofi Genzyme, Novartis and Biogen Italy. M.G., A.M., V.M.A., F.D.N., G.Z., M.N. and S.S. have nothing to disclose. P.P. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis and Roche; consultancy for Novartis, Biogen Italy, Sanofi Genzyme and Roche. F.R. report grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis; consultancy for Novartis, Biogen Italy and Sanofi Genzyme. P.G. reports grant from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, Roche and Bristol Myers Squibb; consultancy for Novartis, Biogen Italy, Sanofi Genzyme, Roche and Bristol Myers Squibb; board membership Sanofi Genzyme, Novartis, Biogen Italy, Roche, Merck Serono and Bristol Myers Squibb., (© The Author(s), 2023.)

Resting state fMRI has been used in many studies to investigate the impact of brain tumours on functional connectivity (FC). However, these studies have so far assumed that FC is stationary, disregarding the fact that the brain fluctuates over dynamic states. Here we utilised resting state fMRI data from 33 patients with high-grade gliomas and 33 healthy controls to examine the dynamic interplay between resting-state networks and to gain insights into the impact of brain tumours on functional dynamics. By employing Hidden Markov Models, we demonstrated that functional dynamics persist even in the presence of a high-grade glioma, and that patients exhibited a global decrease of connections strength, as well as of network segregation. Furthermore, through a multivariate analysis, we demonstrated that patients' cognitive scores are highly predictive of pathological dynamics, thus supporting our hypothesis that functional dynamics could serve as valuable biomarkers for better understanding the traits of high-grade gliomas., (© 2023. The Author(s).)

Background: Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain's functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS)., Materials and Methods: We included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson's correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS., Results: 99 patients were included (70 males, mean age 62  years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema ( p  < 0.001). 5 main patterns of GBM core distribution across functional networks were found, while edema localization was less classifiable. ANOVA showed significant differences between mean overlap percentages, separately for GMNs and WMNs ( p -values<0.0001). Core-N12 overlap predicts higher OS, although its inclusion does not increase the explained OS variance., Discussion and Conclusion: Both GBM core and edema preferentially overlap with specific GMNs and WMNs, especially associative networks, and GBM core follows five main distribution patterns. Some inter-related GMNs and WMNs were co-lesioned by GBM, suggesting that GBM distribution is not independent of the brain's structural and functional organization. Although the involvement of ventral frontoparietal tracts (N12) seems to have some role in predicting survival, network-topology information is overall scarcely informative about OS. fMRI-based approaches may more effectively demonstrate the effects of GBM on brain networks and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2023 Sansone, Pini, Salvalaggio, Gaiola, Volpin, Baro, Padovan, Anglani, Facchini, Chioffi, Zagonel, D’Avella, Denaro, Lombardi and Corbetta.)

Gliomas are amongst the most common primary brain tumours in adults and are often associated with poor prognosis. Understanding the extent of white matter (WM) which is affected outside the tumoral lesion may be of paramount importance to explain cognitive deficits and the clinical progression of the disease. To this end, we explored both direct (i.e., tractography based) and indirect (i.e., atlas-based) approaches to quantifying WM structural disconnections in a cohort of 44 high- and low-grade glioma patients. While these methodologies have recently gained popularity in the context of stroke and other pathologies, to our knowledge, this is the first time they are applied in patients with brain tumours. More specifically, in this work, we present a quantitative comparison of the disconnection maps provided by the two methodologies by applying well-known metrics of spatial similarity, extension, and correlation. Given the important role the oedematous tissue plays in the physiopathology of tumours, we performed these analyses both by including and excluding it in the definition of the tumoral lesion. This was done to investigate possible differences determined by this choice. We found that direct and indirect approaches offer two distinct pictures of structural disconnections in patients affected by brain gliomas, presenting key differences in several regions of the brain. Following the outcomes of our analysis, we eventually discuss the strengths and pitfalls of these two approaches when applied in this critical field., (© 2022. The Author(s).)

Though the assessment of cognitive functions is proven to be a reliable prognostic indicator in patients with brain tumors, some of these functions, such as cognitive control, are still rarely investigated. The objective of this study was to examine proactive and reactive control functions in patients with focal brain tumors and to identify lesioned brain areas more at "risk" for developing impairment of these functions. To this end, a group of twenty-two patients, candidate to surgery, were tested with an AX-CPT task and a Stroop task, along with a clinical neuropsychological assessment, and their performance was compared to that of a well-matched healthy control group. Although overall accuracy and response times were similar for patients and control groups, the patient group failed more on the BX trials of the AX-CPT task and on the incongruent trials of the Stroop task, specifically. Behavioral results were associated with the damaged brain areas, mostly distributed in right frontal regions, by means of a lesion-symptom mapping multivariate approach. This analysis showed that a white matter cluster in the right prefrontal area was associated with lower d'-context values on the AX-CPT, which reflected the fact that these patients rely more on later information (reactive processes) to respond to unexpected and conflicting stimuli, than on earlier contextual cues (proactive processes). Taken together, these results suggest that patients with brain tumors present an imbalance between proactive and reactive control strategies in high interfering conditions, in association with right prefrontal white matter lesions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A few 18 F-FDG PET/CT studies have revealed the presence of brain hypermetabolism in the brain stem and cervical spinal cord of patients within the amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) continuum. We aimed to investigate this finding through a hybrid PET/MRI system, allowing a more precise depiction of the spatial pattern of metabolic changes in the brain stem and cervical spinal cord. Methods: Twenty-eight patients with a diagnosis of ALS or a diagnosis of the behavioral variant of FTD plus motoneuron disease, as well as 13 control subjects, underwent 18 F-FDG PET/MRI. Mean normalized 18 F-FDG uptake in the midbrain/pons, medulla oblongata, and cervical spinal cord as defined on the individual's MRI scans were compared between groups. Furthermore, the associations between regional 18 F-FDG uptake and clinical and demographic characteristics-including gene mutation, type of onset (bulbar, spinal, dementia), and clinical characteristics-were investigated. Results: A significant ( P < 0.005) increment in glucose metabolism in the midbrain/pons and medulla oblongata was found in ALS/FTD patients (spinal-ALS and FTD-motor neuron disease subgroups) in comparison to controls. No relevant associations between clinical and metabolic features were reported, although medulla oblongata hypermetabolism was associated with shortened survival ( P < 0.001). Conclusion: Increased glucose metabolism in the brain stem might be due to neuroinflammation, one of the key steps in the pathogenic cascade that leads to neurodegeneration in ALS/FTD. 18 F-FDG PET/MRI could be a valuable tool to assess glial changes in the ALS/FTD spectrum and could serve as a prognostic biomarker. Large prospective initiatives would likely shed more light on the promising application of PET/MRI in this setting., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Assessment of impaired/preserved cortical regions in brain tumours is typically performed via intraoperative direct brain stimulation of eloquent areas or task-based functional MRI. One main limitation is that they overlook distal brain regions or networks that could be functionally impaired by the tumour. This study aims (i) to investigate the impact of brain tumours on the cortical synchronization of brain networks measured with resting-state functional magnetic resonance imaging (resting-state networks) both near the lesion and remotely and (ii) to test whether potential changes in resting-state networks correlate with cognitive status. The sample included 24 glioma patients (mean age: 58.1 ± 16.4 years) with different pathological staging. We developed a new method for single subject localization of resting-state networks abnormalities. First, we derived the spatial pattern of the main resting-state networks by means of the group-guided independent component analysis. This was informed by a high-resolution resting-state networks template derived from an independent sample of healthy controls. Second, we developed a spatial similarity index to measure differences in network topography and strength between healthy controls and individual brain tumour patients. Next, we investigated the spatial relationship between altered networks and tumour location. Finally, multivariate analyses related cognitive scores across multiple cognitive domains (attention, language, memory, decision making) with patterns of multi-network abnormality. We found that brain gliomas cause broad alterations of resting-state networks topography that occurred mainly in structurally normal regions outside the tumour and oedema region. Cortical regions near the tumour often showed normal synchronization. Finally, multi-network abnormalities predicted attention deficits. Overall, we present a novel method for the functional localization of resting-state networks abnormalities in individual glioma patients. These abnormalities partially explain cognitive disabilities and shall be carefully navigated during surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and peritumoral brain tissues may be measured by magnetic resonance imaging (MRI)., Methods: Pre-operative MRI was combined with immune phenotyping of intraoperative tumor tissue based on flow cytometry of myeloid cell populations that are associated with immune suppression, namely, microglia and bone marrow-derived macrophages (BMDM). These cell populations were measured from the central and marginal areas of the lesion identified intraoperatively with 5-aminolevulinic acid-guided surgery. MRI features (volume, mean and standard deviation of signal intensity, and fractality) were derived from all MR sequences (T1w, Gd+ T1w, T2w, FLAIR) and ADC MR maps and from different tumor areas (contrast- and non-contrast-enhancing tumor, necrosis, and edema). The principal components of MRI features were correlated with different myeloid cell populations by Pearson's correlation., Results: We analyzed 126 samples from 62 GBM patients. The ratio between BMDM and microglia decreases significantly from the central core to the periphery. Several MRI-derived principal components were significantly correlated (p <0.05, r range: [-0.29, -0.41]) with the BMDM/microglia ratio collected in the central part of the tumor., Conclusions: We report a significant correlation between structural MRI clinical imaging and the ratio of recruited vs. resident macrophages with different immunomodulatory activities. MRI features may represent a novel tool for investigating the microenvironment of GBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salvalaggio, Silvestri, Sansone, Pinton, Magri, Briani, Anglani, Lombardi, Zagonel, Della Puppa, Mandruzzato, Corbetta and Bertoldo.)

Rhinocerebral mucormycosis (RCM) may result in severe intracranial ischemic and hemorrhagic lesions. Both computed tomography (CT) and magnetic resonance imaging (MRI) play an essential role in the diagnosis of RCM, but whereas CT is better for assessing bone erosion, MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion. Specific CT and MRI techniques, such as CT angiography or enhanced MR angiography, and more advanced MRI sequences such as gadolinium-3D Black Blood imaging, contribute to the assessment of the extension of vascular invasion.In this pictorial review, we describe specific CT and MRI signs of RCM, mainly focusing on its life-threatening complications due to vascular involvement.

Diffusion-based biophysical models have been used in several recent works to study the microenvironment of brain tumours. While the pathophysiological interpretation of the parameters of these models remains unclear, their use as signal representations may yield useful biomarkers for monitoring the treatment and the progression of this complex and heterogeneous disease. Up to now, however, no study was devoted to assessing the mathematical stability of these approaches in cancerous brain regions. To this end, we analyzed in 11 brain tumour patients the fitting results of two microstructure models (Neurite Orientation Dispersion and Density Imaging and the Spherical Mean Technique) and of a signal representation (Diffusion Kurtosis Imaging) to compare the reliability of their parameter estimates in the healthy brain and in the tumoral lesion. The framework of our between-tissue analysis included the computation of 1) the residual sum of squares as a goodness-of-fit measure 2) the standard deviation of the models' derived metrics and 3) models' sensitivity functions to analyze the suitability of the employed protocol for parameter estimation in the different microenvironments. Our results revealed no issues concerning the fitting of the models in the tumoral lesion, with similar goodness of fit and parameter precisions occurring in normal appearing and pathological tissues. Lastly, with the aim of highlight possible biomarkers, in our analysis we briefly discuss the correlation between the metrics of the three techniques, identifying groups of indices which are significantly collinear in all tissues and thus provide no additional information when jointly used in data-driven analyses., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The pressure cooker technique was originally ideated to obtain wedge-flow conditions during arteriovenous malformation or arteriovenous fistula embolisation. The anti-reflux plug created with coils or glue around the tip of a detachable microcatheter enables a continuous injection with a more in-depth penetration. Here we describe two illustrative cases performed with a variation of the technique that we describe as the hand-compression pressure cooker technique.

Background: Radiological parameters predicting the postoperative neurological outcome after resection of a spinal meningioma (SM) are poorly studied, with controversial results., Methods: Observational multicenter cohort (2011-2018) of adult patients undergoing surgery for resection of SM. Tumor-canal volume ratio (TCR), the areas related to the cord and tumor occupancy at maximum compression, the presence of dural tail, calcifications, signs of myelopathy, and postoperative cord expansion were compared with the modified McCormick scale (mMCS) preoperative and at follow-up., Results: In the cohort ( n = 90 patients), cord and tumor occupancy as well as cord compression and tumor volume showed a correlation with preoperative mMCS ( p < 0.05, R -0.23; p < 0.001, R 0.35; p < 0.005, R -0.29; p < 0.001, R 0.42). Cord occupancy had a strong correlation with cord compression ( p < 0.001, R 0.72). Tumor occupancy and TCR were correlated with relative outcome at follow-up ( p < 0.005 R 0.3; p < 0.005 R 0.29). No correlation was found between cord re-expansion and clinical outcome at follow-up. Finally, a correlation was shown between preoperative signs of cord myelopathy and mMCS ( p < 0.05 R 0.21) at follow-up., Conclusions: Larger tumors showed lower preoperative functional status and a worse clinical outcome. Moreover, preoperative T2 cord signal changes are correlated with a poorer outcome.

Dementia in Lewy Body Diseases (Parkinson's disease and dementia with Lewy Bodies) affects progression of disabilities, quality of life and well-being. Understanding its pathogenetic mechanisms is critical to properly implement disease-modifying strategies. It has been hypothesized that synuclein- and amyloid-pathology act synergistically aggravating cognitive decline in elderly patients but their precise contribution to dementia is debated. In this study, we aimed at exploring if presence of amyloid deposits influences clinical, cognitive and neuroanatomical correlates of mental decline in a cohort of 40 Parkinson's disease patients with normal cognition ( n = 5), mild cognitive impairment ( n = 22), and dementia ( n = 13) as well as in Dementia with Lewy Bodies ( n = 10). Patients underwent simultaneous 3 T PET/MRI with [ 18 F]-flutemetamol and were assessed with an extensive baseline motor and neuropsychological examination, which allowed level II diagnosis of mild cognitive impairment and dementia. The role of amyloid positivity on each cognitive domain, and on the rate of conversion to dementia at 1-year follow-up was explored. A Kaplan Meier and the Log Rank (Mantel-Cox) test were used to assess the pairwise differences in time-to-develop dementia in Parkinson's disease patients with and without significant amyloidosis. Furthermore, the presence of an Alzheimer's dementia-like morphological pattern was evaluated using visual and automated assessment of T 1 -weighted and T 2 -weighted MRI images. We observed similar percentage of amyloid deposits in Parkinson's disease dementia and dementia with Lewy Bodies cohorts (50% in each group) with an overall prevalence of 34% of significant amyloid depositions in Lewy Body Diseases. PET amyloid positivity was associated with worse global cognition (Montreal Cognitive Assessment and Mini Mental State Examination), executive and language difficulties. At 12-month follow-up, amyloid positive Parkinson's disease patients were more likely to have become demented than those without amyloidosis. Moreover, there was no difference in the presence of an Alzheimer's disease-like atrophy pattern and in vascular load (at Fazekas scale) between Lewy Body Diseases with and without significant amyloid deposits. Our findings suggest that in Lewy Body Diseases, amyloid deposition enhances cognitive deficits, particularly attention-executive and language dysfunctions. However, the large number of patients without significant amyloid deposits among our cognitively impaired patients indicates that synuclein pathology itself plays a critical role in the development of dementia in Lewy Body Diseases., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of Vò Euganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways for low-risk, high-risk, and confirmed Coronavirus Disease 19 (COVID-19) patients to accomplish three main targets: guarantee a safe pathway for non-COVID-19 patients, ensure health personnel safety, and maintain an efficient workload. Thus, an additional pathway was created with the aid of a trailer-mounted Computed Tomography (CT) scanner devoted to positive patients. We evaluated the performance of our approach from February 21 through April 12 in terms of workload (e.g., number of CT examinations) and safety (COVID-19-positive healthcare workers). There was an average of 72.2 and 17.8 COVID-19 patients per day in wards and the Intensive Care Unit (ICU), respectively. A total of 176 high-risk and positive patients were examined. High Resolution Computed Tomography (HRCT) was one of the most common exams, and 24 pulmonary embolism scans were performed. No in-hospital transmission occurred in the DDI neither among patients nor among health personnel. The weekly number of in-patient CT examinations decreased by 27.4%, and the surgical procedures decreased by 29.5%. Patient screening and dedicated diagnostic pathways allowed the maintenance of high standards of care while working in safety.

Background and Purpose: Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects., Materials and Methods: Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm 2 ). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm 2 ) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation., Results: Single-shell diffusion MR imaging-based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging-based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns., Conclusions: In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging-based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient's outcome., (© 2020 by American Journal of Neuroradiology.)

Background: Neurocysticercosis is the most frequent parasitic disease of the central nervous system, and its incidence in the developed countries is increasing due to immigration and travels from endemic areas. The intraventricular location has been found to involve up to 61.3% of the patients; moreover, only 22 cases of migrating intraventricular cyst have been reported so far. Despite the rarity of the condition in western countries, its occurrence generates some concerns and the aim of this paper is to update the information concerning pathogenesis, clinical presentation, diagnosis and management of this entity., Methods and Results: All the pertinent literature was analysed, focused on the cases of migrating intraventricular neurocysticercosis and its peculiar features. An illustrative case regarding a 14-year-old girl is also presented., Conclusions: Migrating intraventricular neurocysticercosis is a pathognomonic entity usually presenting with hydrocephalus, and its treatment is mainly surgical, preferring an endoscopic approach. When the resection of the intraventricular cyst is not performed, an accurate follow-up is mandatory to detect clinical changes due to a recurrent hydrocephalus or to the effect of the dying cyst on the surrounding area. In case of permanent shunt placement, the cysticidal and steroid treatment is recommended to reduce the risk of shunt failure.

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao's brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

Despite network studies of the human brain have brought consistent evidence of brain regions with diverse functional roles, the neuropsychological approach has mainly focused on the functional specialization of individual brain regions. Relatively few neuropsychological studies try to understand whether the severity of cognitive impairment across multiple cognitive abilities can be related to focal brain injuries. Here we approached this issue by applying a latent variable modeling of the severity of cognitive impairment in brain tumor patients, followed by multivariate lesion-symptom methods identifying brain regions critically involved in multiple cognitive abilities. We observed that lesions in confined left lateral prefrontal areas including the inferior frontal junction produced the most severe cognitive deficits, above and beyond tumor histology. Our findings support the recently suggested integrated albeit modular view of brain functional organization, according to which specific brain regions are highly involved across different sub-networks and subserve a vast range of cognitive abilities. Defining such brain regions is relevant not only theoretically but also clinically, since it may facilitate tailored tumor resections and improve cognitive surgical outcomes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Unruptured brain arteriovenous malformations (AVMs) represent a complex disease in young healthy adults. Most often AVMs are clinically silent but also can display a neurologic syndrome due to hypoperfusion/hypometabolism in perilesional brain tissue called steal phenomenon., Case Description: A 34-year-old woman was admitted to a secondary neurologic center complaining of a right hemiparesis and secondarily generalized seizures. Computed tomography scan and magnetic resonance imaging of the brain showed a left prerolandic AVM without signs of acute or previous bleedings. Digital subtraction angiography confirmed a left juxta-central AVM, with a diffuse pattern, fed by hypertrophic rolandic branches from the left middle cerebral artery. An 18 F-fluorodeoxyglucose positron emission tomography-magnetic resonance imaging scan was performed 3 days after the critical episode. A significant hypometabolism in parenchymal regions ipsilaterally to the AVM was detected. Two embolization sessions were performed by means of N-butyl cyanoacrylate glue. At the end of the second procedure, a decrease of the shunt-flow and AVM size was observed. Six months later, 18 F-fluorodeoxyglucose positron emission tomography-magnetic resonance imaging scan showed persistent hypometabolism located in the AVM area, with a significant improvement of the cortical hemispheric hypometabolism. The patient was asymptomatic and was sent to stereotactic radiosurgery to complete the treatment., Conclusions: In clinical practice, irritative symptoms in patients with unruptured AVMs could lead to erroneous evaluations. In case of fluctuating clinical syndromes, like our case, establishing that symptoms are related to a steal phenomenon is usually difficult., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In vestibular schwannoma surgery, the preservation of facial and cochlear nerves is of paramount concern regarding to their effect on patients' quality of life. The rate of nerve function preservation has increased with advancements in surgical technique and neuroimaging and the introduction of intraoperative neuromonitoring. The preoperative depiction of anatomical issues between the nerves and tumor could help in surgical planning. Many studies investigating advanced imaging for cranial nerves detection, in particular diffusion tensor imaging, have been reported in the past decade. A systematic review of the reported data evaluating preoperative facial nerve fiber tracking, followed by intraoperative verification, was conducted. Seventeen studies with 223 patients (mean age, 47.5 years; range 17-77; male/female ratio 1:1.4) met our inclusion criteria. Preoperative facial nerve fiber tracking was obtained for 214 patients (96%), and subsequent intraoperative verification revealed a correct prediction for 187 cases (85.5%). The results from the present review have confirmed that preoperative fiber tracking for facial nerve identification during large vestibular schwannoma surgery is valuable and reliable. However, the included studies were not comparable in terms of images, acquisitions, or postprocessing elaboration. Larger series and homogenous magnetic resonance imaging parameters are required to strengthen these findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cortical lesions (CLs) are typical of multiple sclerosis (MS) and have been recently incorporated in MS diagnostic criteria. Thus, the 'no evidence of disease activity' (NEDA) definition should now include CLs. The aim of this study was to evaluate the NEDA3 + CL status in natalizumab- or fingolimod-treated relapsing remitting MS (RMS) patients., Methods: Natalizumab- or fingolimod-treated RMS patients were enrolled in a 2-year longitudinal study based on clinical and magnetic resonance imaging (MRI) evaluations performed respectively biannually and annually. CLs were detected by double inversion recovery. The NEDA3 + CL condition was evaluated at baseline (T0) and at the end of the first (T1) and second (T2) year., Results: Of the 137 RMS patients included in the study, 86 were propensity-matched. At T2, the annualized relapse rate was lower on natalizumab ( p = 0.021), but the effect on white matter lesions ( p = 0.29) and the proportion of NEDA-3 patients ( p = 0.14) were similar in the two treatment arms. At T2, 11.6% natalizumab- and 62.8% fingolimod-treated patients had new CLs ( p < 0.001) and a higher proportion of natalizumab-treated patients (55.8% versus 11.6%, p < 0.001) achieved the NEDA3 + CL status (hazard ratio 5.2, p < 0.001)., Conclusion: The incorporation of CLs in the NEDA-3 definition highlighted the higher efficacy of natalizumab versus fingolimod in suppressing disease activity in RMS patients., Competing Interests: Conflict of interest statement: MP reports grants and personal fees from Novartis, grants and personal fees from Almirall, grants and personal fees from Biogen Idec, grants and personal fees from Sanofi Genzyme, grants from Teva, outside the submitted work. CC, ES and MA have nothing to disclose. SZ reports grants from Sanofi Genzyme, grants from Almirall, outside the submitted work. FR serves as an advisory board member of Biogen Idec and Sanofi Genzyme and has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, Teva and Bayer Schering Pharma. PP has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva. PG reports grants and personal fees from Novartis, grants and personal fees from Almirall, grants and personal fees from Biogen Idec, grants and personal fees from Sanofi Genzyme, grants and personal fees from Teva, grants and personal fees from Merck Serono, grants from University of Padova, grants from the Italian Ministry of Public Health, grants from the Veneto Region of Italy, and grants from the Italian Association for Multiple Sclerosis, outside the submitted work.

Background The clinical criteria for cluster headache (CH) are included in Chapter 3 of the International Classification of Headache Disorders, 3rd beta edition (ICHD-III). CH may sometimes be secondary to other pathologies. Case reports We report two patients in whom the clinical features of CH initially fulfilled the ICHD-III criteria, but who later presented some radical modifications in headache natural history as a result of a secondary pathology. The first case of CH was secondary to a pontine cavernous angioma and the second to a cerebral venous thrombosis. Conclusion We highlight the importance of clinical modifications of CH that could suggest clinical investigations should be performed or repeated to exclude a secondary pathology in a previously diagnosed cluster headache. Some of the pathological mechanisms of CH and brain lesions are discussed.

Background: Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly., Methods: We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease., Results: Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities., Conclusions: Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking., Methods: Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients., Results: Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST., Conclusion: Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST. © 2015 Wiley Periodicals, Inc. Head Neck 38: 673-679, 2016., (© 2015 Wiley Periodicals, Inc.)