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In this paper we present the case of a child with early left thalamic vascular damage who subsequently developed a language disorder. At 3 years and 8 months, her language was poor and unintelligible and showed phonetic, phonological and morpho-syntactic disorders. She did not exhibit any signs of mental retardation. After specific speech therapy, she improved in all linguistic skills. Given the lack of reports on thalamic lesions in children, this paper describes the effect of a thalamic injury in the earliest phases of language acquisition in a child who showed consistent phonological disorders. This case seems to confirm early hemispheric specialisation and the importance of a timely therapy. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging and transcranial magnetic stimulation were used to examine a 34 year-old right-handed patient, who, at the age of 6 years, had experienced sudden right hemiplegia, seizures, and stupor during a bout of measles encephalitis, followed by incomplete distal right motor recovery. Morphological MRI showed massive unilateral enlargement of the left ventricle, associated with extreme thinning of the white and gray matter, with partial preservation of the pyramidal tract. Functional MRI and transcranial magnetic stimulation revealed reorganization of the motor cortices, and integrity of the corticospinal pathway, respectively. Our findings indicate that complete hand motor recovery may require functional connections between the motor cortical areas and cortical-subcortical structures, in addition to the retained integrity of the primary sensorimotor area and pyramidal tract. [ABSTRACT FROM AUTHOR]

Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count < 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections. [ABSTRACT FROM AUTHOR]

• Multidisciplinary rehabilitation in people with multiple sclerosis may improve their level of activity in daily activities. • The fMRI results revealed a significant reduction in the activity of brain areas related to task-specific networks. • Brain activity also increases in not specific task areas, such as medial prefrontal area that is a connectivity core network. Multiple sclerosis (MS) is characterized by a range of symptoms, including motor, sensorimotor and cognitive impairments, that limit the quality of life. A multidisciplinary rehabilitation approach in people affected by multiple sclerosis was recently reported to improve the functional abilities of MS patients in daily activities. The purpose of the study was to assess the effect of multidisciplinary rehabilitation on the whole brain of MS patients by means of functional magnetic resonance imaging (fMRI). Thirty individuals affected by MS (49.9 ± 12.1 years; disease duration: 16.0 ± 8.5 years) with a medium-high severity of disease were enrolled. The fMRI examination assessed a range of action-related tasks involving passive movement, mental simulation of action and miming of action triggered by external stimuli, such as object photography. The three tasks were performed using each arm separately. The fMRI acquisitions were performed at T1 (inclusion in the study), T2 (3 months later, at the start of rehabilitation) and T3 (after 3 months of multidisciplinary rehabilitation). The fMRI results revealed a significant reduction in the activity of brain areas related to task-specific networks as well as the activation of cerebral regions not usually involved in task-specific related network, such as the medial prefrontal area. The effectiveness of multidisciplinary rehabilitation on activity and participation has been established in previous studies. Our study sheds new light on the effect of such treatment on brain reorganization. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiform (GBM), a malignant brain tumour, has a very often poor prognosis. The therapeutic approach is represented by surgery followed by radiotherapy and chemotherapy. Hypoxia is a factor that causes a reduction of both radiotherapy and chemotherapy effectiveness in GBM and other cancers. Through the use of [64Cu][Cu(ATSM)], a hypoxia-targeting positron emission tomography (PET) radiotracer, is possible to identify the presence of hypoxic areas within a lesion and therefore modulate the therapeutic approach according to the findings.Case Presentation: In this case report, we observed an increase of radiotracer uptake from early acquisition to late acquisition in hypoxia sites and high correlation between [64Cu][Cu(ATSM) PET/CT results and expression of the hypoxia marker HIF-1α.Conclusions: [64Cu][Cu(ATSM) PET/CT represents a valid opportunity to reveal in vivo hypoxic areas in GBM lesion which can guide clinicians on selecting GMB patient's therapeutic scheme. [ABSTRACT FROM AUTHOR]

We report a case of a 19-year-old male referred to the Endocrine Unit because of gynecomastia. Initial investigation revealed elevated levels of estradiol (E2) along with secondary hypogonadism (hypotestosteronemia and severe oligoasthenoteratozoospermia (OAT)) despite normal testicular volume (12 mL) and secondary sexual characteristics. Surprisingly, an ultrasound examination revealed a small hypoechoic mass (1.1 cm) with intense intralesional vascularization within the right testicle, even though tumor markers were normal. Surgical removal of testicular mass led to the identification of Leydigioma, and the patient showed regression of gynecomastia during the nine-month follow-up. Unexpectedly, hypergonadotropinemia manifested along with normal testosterone (T) levels and significant improvement in OAT. Magnetic resonance imaging (MRI) showed pituitary hyperplasia (PH). Gynecomastia represents an atypical manifestation of Leydig cell tumors and typically resolves after surgical removal. However, unilateral orchiectomy may determine compensatory PH. Currently, it is uncertain whether the shift from hypogonadotropic to permanent hypergonadotropinemia was the only factor responsible for the high sperm count occurring in our patient. Further research is needed to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Cortical hubs play a fundamental role in the functional architecture of brain connectivity at rest. However, the anatomical scaffold underlying their centrality is still under debate. Certainly, the brain function and anatomy are significantly entwined through synaptogenesis and pruning mechanisms that continuously reshape structural and functional connections. Thus, if hubs are expected to exhibit a large number of direct anatomical connections with the rest of the brain, such a dense wiring is extremely inefficient in energetic terms. In this work, we investigate these aspects on fMRI and DTI data from a set of know resting-state networks, starting from the hypothesis that to promote integration, functional, and anatomical connections link different areas at different scales or hierarchies. Thus, we focused on the role of functional hubs in this hierarchical organization of functional and anatomical architectures. We found that these regions, from a structural point of view, are first linked to each other and successively to the rest of the brain. Thus, functionally central nodes seem to show few strong anatomical connections. These findings suggest an efficient strategy of the investigated cortical hubs in exploiting few direct anatomical connections to link functional hubs among each other that eventually reach the rest of the considered nodes through local indirect tracts. Hum Brain Mapp 38:5141-5160, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in diagnosing vascular parkinsonism (VaP) due to its broad criteria, which have led to misdiagnoses and variations in prevalence estimates. It presents a case study of a 67-year-old man with lower-body predominant parkinsonism, highlighting the importance of a comprehensive diagnostic approach. The article emphasizes the complexity of diagnosing VaP and the need for refined criteria and specific biomarkers for accurate identification. [Extracted from the article]

Background and Objective: Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ. Methods: We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography–tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ. Results: Our data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ. Conclusions: The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation. [ABSTRACT FROM AUTHOR]

Simple Summary: Within a multicentric clinical trial context for the treatment of recurrent high-grade brain tumors, the aim of our study was to assess the potential added value of multiparametric MRI harmonization to improve a classification problem based on radiomics analysis. We confirmed that harmonization reduced the so-called "scanner effect" related to the variability of multiparametric MRI protocol settings between the participating centers and improved the predictive performance of radiomics-based classification model. Radiomics features extracted from MRI perfusion gave the best accuracy for the classification between radionecrosis and tumor progression. Interestingly, our study revealed that radiomics features extracted from T1-weigthed MRI alone, before any injection of contrast product reached accuracies close to the perfusion model. In this study, a radiomics analysis was conducted to provide insights into the differentiation of radionecrosis and tumor progression in multiparametric MRI in the context of a multicentric clinical trial. First, the sensitivity of radiomic features to the unwanted variability caused by different protocol settings was assessed for each modality. Then, the ability of image normalization and ComBat-based harmonization to reduce the scanner-related variability was evaluated. Finally, the performances of several radiomic models dedicated to the classification of MRI examinations were measured. Our results showed that using radiomic models trained on harmonized data achieved better predictive performance for the investigated clinical outcome (balanced accuracy of 0.61 with the model based on raw data and 0.72 with ComBat harmonization). A comparison of several models based on information extracted from different MR modalities showed that the best classification accuracy was achieved with a model based on MR perfusion features in conjunction with clinical observation (balanced accuracy of 0.76 using LASSO feature selection and a Random Forest classifier). Although multimodality did not provide additional benefit in predictive power, the model based on T1-weighted MRI before injection provided an accuracy close to the performance achieved with perfusion. [ABSTRACT FROM AUTHOR]

• Pediatric Huntington disease (PHD) with Highly Expanded (HE) CAG mutations affects brain and peripheral organs. • The liver is one affected peripheral organ showing steatosis in HE-PHD. • Higher the mutation size in HE-PHD, earlier the liver steatosis in childhood HD life. [ABSTRACT FROM AUTHOR]

Objective: Several evidences demonstrated the role of white matter (WM) lesions in the pathogenesis of Vascular Parkinsonism (VP), a clinical entity characterized by parkinsonism, postural instability, marked gait difficulty and poor response to levodopa. However, the involvement of normal appearing white matter (NAWM) in VP still remains unknown. This study aimed to investigate the microstructural integrity of NAWM in VP compared to Parkinson's disease (PD) and controls using neuroimaging approach.Methods: Magnetic resonance imaging data were acquired from 50 participants (15 VP, 20 PD and 15 controls). Diffusion tensor imaging (DTI) and Tract-based spatial statistics (TBSS) were performed to assess microstructural NAWM changes. In order to evaluate the relationship between specific fiber tract involvement and clinical picture, diffusion alterations were correlated with clinical features.Results: Compared to PD patients and controls, significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in NAWM of corpus callosum, internal and external capsule, and corona radiata were present in VP. By contrast, DTI metrics were normal in NAWM-PD and controls. A significant correlation was found between FA and MD of anterior third of corpus callosum and clinical variables (postural instability, freezing-of-gait and symmetry of parkinsonism).Conclusions: This study improves the knowledge on WM pathology in VP, as our results demonstrate that NAWM damage occurs in VP, but not in PD nor in controls. NAWM damage might relate to clinical picture and suggest that non-clearly-visible WM alterations may contribute to the physiopathology of this vascular disease. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the imaging counterpart of two functional domains (ocular motor dysfunction and postural instability) in progressive supranuclear palsy (PSP) patients classified according to the new clinical diagnostic criteria.Methods: Forty-eight patients with probable PSP-Richardson's syndrome (PSP-RS), 30 with probable PSP-parkinsonism (PSP-P), 37 with Parkinson's disease (PD), and 38 controls were enrolled. For each functional domain, PSP patients were stratified by two certainty levels: vertical supranuclear gaze palsy (O1) and slowness of vertical saccades (O2) for ocular motor dysfunction; early unprovoked falls and tendency to fall on the pull-test for postural instability. Voxel-based morphometry (VBM), whole-brain fractional anisotropy (FA) and MR planimetric measurements were analysed and compared across patient groups.Results: O1 was present in 64%, and O2 in 36% of all PSP patients. All PSP-RS patients showed early unprovoked falls. TBSS whole-brain analysis revealed that superior cerebellar peduncles (SCPs) were the only structures with significantly lower FA values in PSP-RS compared with PSP-P patients. PSP/O1 patients had lower FA values in midbrain than PSP/O2 patients. By contrast, VBM revealed no differences in grey matter volume between PSP patient groups. MR Planimetric measurements confirmed atrophy of midbrain and SCPs, in line with DTI findings.Conclusions: Our study demonstrates that SCPs were significantly more damaged in patients with PSP-RS in comparison with PSP-P patients, thus suggesting the role of SCPs in developing postural instability. Midbrain damage was less severe in O2 than in O1 patients, suggesting that the degree of vertical ocular dysfunction reflects the severity of midbrain atrophy. [ABSTRACT FROM AUTHOR]

Introduction: Several structural and functional neuroimaging studies have shown that the Supplementary Motor Area (SMA) is affected by tau pathology in patients with Progressive Supranuclear Palsy (PSP). The aim of the study was to investigate the biochemical profile of SMA in PSP patients, using proton magnetic resonance spectroscopy (1H-MRS).Methods: Sixteen PSP patients and 18 healthy controls participated in this study. 1H-MRS was performed by using a Point RESolving Spectroscopy (PRESS) single-voxel sequence implemented on a 3-T scanner. A voxel of 25 × 25 × 15 mm involving the right and left SMA was acquired in all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine with phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), glutamate + glutamine (Glx), glutathione (GSH), myo-Inositol (mI) and Scyllo-Inositol (Scyllo) were calculated using a version 6.3-1K of the fitting program LCModel. Comparative analysis was performed on both absolute concentrations and ratio values relative to Cr.Results: PSP patients showed a significant decrease in Scyllo concentration and Scyllo/Cr ratio values in SMA, compared to controls, whereas no difference between groups was found for the other ratio values. Of note, the attention and working memory functions were positively related to Scyllo and Scyllo/Cr values in PSP patients.Conclusions: Our study demonstrates that Scyllo and Scyllo/Cr were significantly reduced in the SMA of PSP patients. Because Scyllo seems to be able to protect against formation of toxic fibrils of amyloid-beta fragments and tau oligomers deposition, these preliminary findings may open new perspectives to investigate Scyllo as a new potential disease-modifying therapy for PSP. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease is a rare, neurodegenerative disease caused by an expanded CAG repeat mutation in the huntingtin gene. Compared with adult-onset Huntington's disease, juvenile Huntington's disease (onset ≤20 years) is even rarer and has not been studied extensively. We aimed to further characterise juvenile Huntington's disease by examining the effect of CAG repeat size on disease presentation, progression, and survival.Methods: We did a retrospective analysis of patients with juvenile Huntington's disease aged 20 years or younger, according to the length of their CAG repeat and who had disabling psychiatric symptoms (with motor symptoms) or motor symptoms alone, and of patients with adult-onset Huntington's disease manifesting aged 30-60 years with 40 or more CAG repeats, from the REGISTRY and ENROLL-HD platforms and from two institutional databases (Lega Italiana Ricerca Huntington Foundation and the Instituto Neurociencias de Buenos Aires and the Sanatorio de la Trinidad Mitre). Patients with psychiatric but no motor symptoms were excluded. We compared symptoms at onset and longitudinally in patients with juvenile Huntington's disease with highly expanded (HE subgroup) or low expansion (LE subgroup) mutations, grouped by hierarchical clustering analysis. We also compared disease progression (longitudinal change in Unified Huntington's Disease Rating Scale-Total Motor Score) and survival of patients with juvenile and adult-onset Huntington's disease.Findings: We extracted medical records from 580 patients entered into the studies or databases between June 23, 2004, and March 31, 2018, of whom 36 patients met our definition of juvenile Huntington's disease and 197 for adult-onset Huntington's disease. According to caregiver reports, gait disturbance was more often a first presenting symptom in the HE subgroup (eight [80%] of 10 patients) than in the LE subgroup (seven [27%] of 26 patients; p=0·0071), whereas loss of hand dexterity was more common in the LE subgroup (11 [42%] of 26 patients) than in the HE subgroup (0 [0%] of 10 patients; p=0·0160). Compared with the LE subgroup, development delay (0 [0%] in the LE subgroup vs nine [90%] in the HE subgroup; p<0·0001), severe gait impairment (nine [35%] in the LE subgroup vs nine [90%] in the HE subgroup; p=0·0072), and seizures (three [11%] in the LE subgroup vs eight [80%] in the HE subgroup; p<0·0001) prevailed over time in the HE subgroup. Disease progression was more rapid in juvenile Huntington's disease (n=14) than in adult-onset Huntington's disease (n=52; generalised estimating equation model, p=0·0003). Of 121 deceased patients, median survival was shorter in the juvenile Huntington's disease (n=17) cohort than in adult-onset Huntington's disease (n=104) cohort (hazard ratio 2·18 [95% CI 1·08-4·40]; p=0·002).Interpretation: Patients with HE juvenile Huntington's disease differ clinically from patients with LE juvenile Huntington's disease or adult-onset Huntington's disease, suggesting reclassification of this particularly aggressive form of Huntington's disease might be required.Funding: Lega Italiana Ricerca Huntington Foundation and IRCCS Ospedale Casa Sollievo della Sofferenza. [ABSTRACT FROM AUTHOR]

Introduction: Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD.Methods: Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images.Results: The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients.Conclusion: The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the thalamic biochemical profile in patients with essential tremor (ET), using proton magnetic resonance spectroscopy (1H-MRS), and to explore the correlations between clinical and biochemical data.Methods: Sixteen patients with ET and 14 healthy controls participated in this study. After conventional MR imaging, single-voxel 1H-MRS (TR = 2000 ms; TE = 28 ms) was performed by using a PROBE-SV system implemented on a 3-T scanner. A voxel of 10 × 10 × 15 mm involving the ventrointermediate (Vim) nucleus was acquired in each thalamus of all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine + phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), and glutamate + glutamine (Glx) were calculated using a version 6.3-1 K of the fitting program LCModel for each voxel. Comparative and correlation analyses were performed on the NAA, Cr, Cho, and Glx concentrations, as well as on the values of the NAA/Cr, a neural density marker, Cho/Cr, a membrane marker, and Glx/Cr, an intracellular neurotransmitter marker.Results: Patients with ET showed a significant increase in Glx concentration and Glx/Cr ratio values in both thalami, compared to healthy controls, whereas no difference inter-group was found for the other metabolites and NAA/Cr and Cho/Cr ratio values. Of note, the tremor severity was positively related to increased Glx concentrations and Glx/Cr ratio values in ET group.Conclusions: Our study shows that 1H-MRS can highlight in vivo metabolic abnormalities in the thalami of ET patients, supporting the evidence that the increase of thalamic glutamatergic transmission can play a role in developing of tremor in ET. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (1H-MRS).Methods: Fourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123I-ioflupane, and a short-echo single-voxel 1H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated.Results: DAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls.Conclusions: This study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that 1H-MRS can help differentiate patients with tPD from those with rET. [ABSTRACT FROM AUTHOR]

Objectives: More than a year has passed since the initial outbreak of SARS‐CoV‐2, which caused many hospitalizations worldwide due to COVID‐19 pneumonia and its complications. However, there is still a lack of information detailing short‐ and long‐term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID‐19 patients at mid‐term follow‐ups. Methods: A total of 407 consecutive COVID‐19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X‐ray was subsequently selected, and was scheduled to undergo a mid‐term chest CT study, which was evaluated for specific lung alterations and morphological patterns. Results: The most frequently observed lung CT alterations, in order of frequency, were ground‐glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non‐specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). Conclusions: Our work showed that recovered COVID‐19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. Advances in knowledge: This slow recovery process should be kept in mind when determining the follow‐up phases in order to improve the long‐term management of patients affected by COVID‐19. [ABSTRACT FROM AUTHOR]

Ongoing signals from one׳s own body (interoception) allow experience of self-feeling. In early studies interoception strictly referred to the awareness of visceral sensation but recent theories have expanded this concept to denote the ongoing status of the body. Here we asked left and right focal brain-damaged patients to answer questions about their interoceptive feelings, and correlated their responses to a quantitative measure of their lesions (voxel-based symptom-lesion mapping). By these means we could reveal that three key structures contribute to building up the feeling of self, namely insula (interoceptive modulator), amygdala (emotional modulator) and putamen (motor modulator). This brain network may be necessary for the integrity of self-feeling. A dysfunction of this network might impair perception of the inner body state, and also account for psychological disturbances, such as the somatic symptom disorders, in which individuals experience subjective symptoms suggesting physical illness or injury despite medical test results which are normal, and clinical examination do not disclose relevant medical conditions. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Bone mineral density (BMD) result has a low predictive value on patients' risk for future fractures. Thus, new approaches for examining patients at risk for developing osteoporosis would be desirable. Magnetic resonance (MR) investigations in cancellous bone have been shown to yield useful quantitative information on both trabecular-bone microstructure and bone marrow composition. This work was undertaken to address the hypothesis that the effective internal magnetic field gradient (IMFG), a new MR parameter, discriminates between healthy, osteopenic and osteoporotic postmenopausal women, classified on the basis of bone mineral density (BMD) criteria. The work builds on preliminary results indicating that IMFG, measured in trabecular-bone pores and quantified by spin-echo decay and water diffusion MR near the bone–bone marrow interface depends on both the bone marrow water rate of diffusion and the magnetic susceptibility difference (ΔX) between water and bone. Materials and methods: MR relaxometry, MR spectroscopy and diffusion-weighted MR imaging of the heel was performed in fifty-five women (mean age, 62.9±6.6years) at 3T. Moreover, in order to study the reproducibility of IMFG measurement, five young women (mean age 31.0±3.2years; age range, 28–36years) were scanned and rescanned. The study protocol was approved by the local Ethics Committee. Quantitative Computer Tomography (QCT) of the L1–L3 vertebral segments was performed to classify the postmenopausal women into three groups according to QCT BMD: healthy (n=8); osteopenic (n=25); and osteoporotic (n=22). In all subjects, BMD T-scores, marrow fat content (Mfc), T2*, apparent diffusion coefficient (ADC) and IMFG (estimated from the additional spin-echo decay due to diffusion of water in local magnetic field gradients), were assessed in the whole calcaneus as well as in three calcaneal subregions: subtalar, tuber calcaneus, and cavum calcaneus. Between-group comparisons to assess group differences and Pearson correlation analysis were performed. Short and long-term coefficients of variation (CVS and CVL, respectively) were evaluated in young subjects. Results: Reproducibility of the IMFG measurement was satisfactory. No significant difference was found in the IMFG measurement performed in both calcaneus and subtalar calcaneal region between the two separate sessions comprised of five young women. Mfc did not significantly differ between groups. The IMFG in the subtalar region was significantly different between all three groups (P <0.01), being greatest in healthy women, intermediate in those with osteopenia, and lowest in osteoporotic subjects. Conversely neither T2* nor ADC is able to discriminate healthy subjects from those with osteopenia and osteoporosis. Increased inter-trabecular space, as it typically occurs in patients with osteoporosis, modifies water diffusion, conferring higher ADC values, thereby lowering the IMFG. Conclusion: The IMFG measured in the calcaneal subtalar region shows a high ability in identifying healthy subjects. The new quantitative MR method based on measurement of the IMFG may provide a new means for assessing patients with osteoporosis. [Copyright &y& Elsevier]

Abstract: Emotion or stress can jeopardize decision-making relevance and cognitive functioning. In this paper we examine plan continuation error (PCE), an erroneous behavior defined as a “failure to revise a flight plan despite emerging evidence that suggests it is no longer safe” (Orasanu et al., 2001). Our hypothesis is that negative emotional consequences attached to the go-around decision provoke a temporary impairment of the decision-making process and favor PCE. We investigated this hypothesis with a simplified landing task in which two possible contributors to those emotions, namely the uncertainty of a decision outcome and the reward/punishment, associated to the outcome were manipulated. A behavioral experiment (n =12) and a second one (n =6) using functional magnetic resonance imaging (fMRI) were conducted. Behavioral results of both studies showed the effectiveness of the financial incentive to bias decision making toward a more risky and less rational behavior from a safety point of view. Neuroimaging data showed that the PCE behavior was underpinned by the contribution of brain circuitry of emotion and reward during the decision-making process. Taken together, behavioral and fMRI result support the hypothesis that PCE can be provoked by a temporary impairment of rational decision-making due to the negative emotional consequences attached with the go-around. [Copyright &y& Elsevier]

Abstract: In aeronautics, plan continuation error (PCE) represents failure to revise a flight plan despite emerging evidence suggesting that it is no longer safe. Assuming that PCE may be associated with a shift from cold to hot reasoning, we hypothesized that this transition may result from a large range of strong negative emotional influences linked with the decision to abort a landing and circle for a repeat attempt, referred to as a “go-around”. We investigated this hypothesis by combining functional neuroimaging with an ecologically valid aviation task performed under contextual variation in incentive and situational uncertainty. Our goal was to identify regional brain activity related to the sorts of conservative or liberal decision-making strategies engaged when participants were both exposed to a financial payoff matrix constructed to bias responses in favor of landing acceptance, while they were simultaneously experiencing maximum levels of uncertainty related to high levels of stimulus ambiguity. Combined with the observed behavioral outcomes, our neuroimaging results revealed a shift from cold to hot decision making in response to high uncertainty when participants were exposed to the financial incentive. Most notably, while we observed activity increases in response to uncertainty in many frontal regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), less overall activity was observed when the reward was combined with uncertainty. Moreover, participants with poor decision making, quantified as a lower discriminability index d'', exhibited riskier behavior coupled with lower activity in the right DLPFC. These outcomes suggest a disruptive effect of biased financial incentive and high uncertainty on the rational decision-making neural network, and consequently, on decision relevance. [Copyright &y& Elsevier]

Abstract: Recent theories have hypothesized that semantic representations of action verbs and mental representations of action may be supported by partially overlapping, distributed brain networks. An fMRI experiment in healthy participants was designed to identify the common and specific regions in three different tasks from a common set of object drawings (manipulable man-made objects (MMO) and biological objects (MBO)): the generation of action words (GenA), the mental simulation of action (MSoA) and the mime of an action with the right hand (MimA). A fourth task, object naming (ON), was used as control for input/output effects. A null conjunction identified a common neural network consisting of nine regions distributed over premotor, parietal and occipital cortices. Within this common network, GenA elicited significantly more activation than either ON or MSoA in the left inferior frontal region, while MSoA elicited significantly more activation than either ON or GenA in the left superior parietal lobule. Both MSoA and GenA activated the left inferior parietal lobule more than ON. Furthermore, the left superior parietal cortex was activated to a greater extent by MMO than by MBO regardless of the tasks. These results suggest that action-denoting verbs and motor representations of the same actions activate a common frontal–parietal network. The left inferior parietal cortex and the left superior parietal cortex are likely to be involved in the retrieval of spatial–temporal features of object manipulation; the former might relate to the grasping and manipulation of any object while the latter might be linked to specific object-related gestures. [Copyright &y& Elsevier]

The "Spazio Huntington—A Place for Children" program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children's Yale–Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes. The magnetic resonance imaging contributed to confirm the suspicious clinical observation by highlighting very initial striatum abnormalities in PHD. Spazio Huntington is a program to prospectively study PHD, the most atypical face of HD, and may represent the basis to recruit PHD patients in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Pediatric-onset Huntington's disease (POHD) exhibits a phenotype different from adult-onset HD (AOHD), with hypokinetic movement disorders (eg, rigidity, bradykinesia, and dystonia) rather than chorea typical of AOHD., Objectives: The aim was to identify pathophysiology-based biomarkers specific to POHD (≥60 CAG repeats)., Methods: Simultaneous hybrid imaging using [ 18 F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography plus magnetic resonance imaging (FDG-PET/MRI) and clinical assessment using standardized Huntington's disease (HD) scales were employed. Exploratory longitudinal analyses were also performed., Results: Striatal volume loss was remarkable and more severe in POHD (n = 5) than in AOHD (n = 14). Widespread, significantly altered glucose metabolism occurred in several different POHD cortical areas and thalamus, but not AOHD cortex, consistent with differences in clinical progression., Conclusions: POHD patients' brains exhibited distinct morphologic and metabolic traits compared to AOHD patients' brains, with longitudinal changes mirroring clinical progression. Hybrid FDG-PET/MRI highlighted a variable regional brain dysfunction in vivo, as a biological consequence of highly expanded CAG repeats. Findings provide further evidence that POHD is a distinct disease from AOHD., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB., Methods: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected., Results: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep 
learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only., Conclusion: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747)., (© The Author(s) 2023. Published by Oxford University Press.)

Lung ultrasound (LUS) has rapidly emerged in COVID-19 diagnosis and for the follow-up during the acute phase. LUS is not yet used routinely in lung damage follow-up after COVID-19 infection. We investigated the correlation between LUS score, and clinical and laboratory parameters of severity of SARS-COV-2 damage during hospitalization and at follow-up visit. Observational retrospective study including all the patients discharged from the COVID-19 wards, who attended the post-COVID outpatient clinic of the IRCCS Policlinico San Matteo in April-June 2020. 115 patients were enrolled. Follow-up visits with LUS score measurements were at a median of 38 days (IQR 28-48) after discharge. LUS scores were associated with the length of hospitalization (p < 0.001), patients' age (p = 0.036), use of non-invasive ventilation (CPAP p < 0.001 or HFNC p = 0.018), administration of corticosteroids therapy (p = 0.030), and laboratory parameters during the acute phase (WBC p < 0.001, LDH p < 0.001, CRP p < 0.001, D-dimer p = 0.008, IL-6 p = 0.045), and inversely correlated with lymphocyte count (p = 0.007). We found correlation between LUS score and both LDH (p = 0.001) and the antibody anti-SARS-CoV-2 titers (p value = 0.008). Most of these finding were confirmed by dichothomizing the LUS score (≤ 9 or > 9 points). We found a significantly higher LUS score at the follow-up in the patients with persistent dyspnea (7.00, IQR 3.00-11.00) when compared to eupnoeic patients (3.00, IQR 0-7.00 p < 0.001). LUS score at follow-up visit correlates with more severe lung disease. These findings support the hypothesis that ultrasound could be a valid tool in the follow-up medium-term COVID-19 lung damage., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose: We aimed to determine the origin and genetic characteristics of Huntington disease (HD) in the Middle East., Methods: We performed genetic and genealogical analyses to establish the ancestral origin of the HTT pathgenic variant from a large kindred from Oman (hereafter called the OM-HD-01 pedigree) by single-nucleotide polymorphism and dense haplotype analysis genotyping., Results: We traced the oldest ancestry of the largest, eight-generation, OM-HD-01 pedigree (n = 302 subjects, with 54 showing manifest HD) back to sub-Saharan Africa and identified a unique HD haplotype carried by all pedigree members, which consisted of portions of the C6 and C9 haplotypes and was carried by all affected members. Such a unique HD haplotype was of African origin and appeared to be associated with large CAG repeat expansions on average and high frequency of juvenile-onset HD. Three other families from the same area were also identified and found carrying a Caucasian HD haplotype A, also shared by most families of Arab ancestry., Conclusion: Mutated HTT spread into Middle East with a unique haplotype of African origin, appeared to be associated with juvenile-onset, a HD condition frequently occurring in Black Africans, and may have a significant impact on further development of novel targeted genetic therapies.

A 19-year-old man with epilepsy underwent ictal F-FDG PET/MRI, showing a 5 mm heterotopic nodule in the periventricular white matter, adjacent to the frontal horn of the left lateral ventricle (SUVmax, 5.5; glucidic cerebral metabolic rate, 0.317 μmol/mL). A repeated F-FDG PET/MRI, during seizure freedom, showed, at visual analysis, subtle decrease of the nodule metabolism. SUVmax and glucidic cerebral metabolic rate were clearly reduced to 3.7 and 0.226, respectively. Ictal F-FDG PET/MRI could be useful in epilepsy because of the added value of SUVmax and cerebral metabolic rate of glucose analysis to understand the relationship between heterotopy and epilepsy.

Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes., Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease., Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001)., Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, inducing dopaminergic depletion in the striatum. Recently, subcortical nuclei shape analysis based on T1 imaging has been used in PD pathology. The present study aimed to test the hypothesis that changes in local volume detectable with T1-weighted imaging are concomitant with PD and may be used as biomarkers. We compared 21 PD patients and 20 control subjects using gray matter density and subcortical nuclei volume and shape. We also tested correlations between these parameters and clinical scales. A linear discriminant analyses was carried out using global volume and local atrophy. The differences revealed between the 2 groups were volume differences in the putamen and shape differences in the putamen and the caudate nucleus. A correlation was found between shape and motor symptoms. The discriminant analysis performed using local atrophy values led to the best classification. Our results show that shape analysis contributes valuable information to investigations concerning PD patients and helps to discriminate these patients from control subjects., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

Objective: A long-lasting neuroinflammatory cascade may lead to the progression of brain damage, favoring neurodegeneration and cognitive impairment in patients with traumatic brain injury (TBI), but the potential mechanisms underlying this sequence of events remain elusive. Here we aimed to evaluate the impact of interleukin (IL)-18, a proinflammatory cytokine elevated in post-acute head injury and associated with neurodegeneration, on the long-term outcome of patients with chronic TBI., Methods: The serum content of IL-18 was evaluated in 16 patients with severe TBI, during their rehabilitation phase, and in a matched group of 16 healthy controls. The disability of the enrolled patients was evaluated by means of the Glasgow Outcome Scale, Levels of Cognitive Functioning, and the Disability Rating Scale., Results: The circulating levels of IL-18 were significantly increased in chronic TBI patients, as compared to healthy subjects, and correlated with the patients' cognitive impairment and disability severity., Conclusions: IL-18 may contribute to the long-term outcome and neurodegeneration in TBI patients. Even though further studies are needed to understand the molecular mechanisms underlying the effects of IL-18 on TBI progression and its associated drop in cognitive function, a possible role of this cytokine as a therapeutic target in TBI can be envisaged., (© 2013 S. Karger AG, Basel.)