150 results on '"Mortilla, M."'
Search Results
102. Molecular genetics of Alzheimer's disease in Italian families
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Sorbi, S., Nacmias, B., Mortilla, M., and Forleo, P.
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- 1994
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103. Imaging e spettroscopia RM dell'idrogeno dell'encefalo in soggetti con LES ad esordio pediatrico
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Mortilla, M., Ermini, M., Nistri, M., Dal Pozzo, G., and Falcini, F.
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Nel 30–60% dei soggetti con LES ad esordio pediatrico è stato descritto un coinvolgimento del SNC. In studi precedenti sono state riscontrate alterazioni metaboliche tramite indagine con SPECT cerebrale.Sono stati studiati con Risonanza Magnetica (Imaging e Spettroscopia 23 soggetti (18 F e 5 M; età media 15, 4 anni; range 8–27) con LES, 20 controlli di età e sesso adeguati, 5 soggetti con forma giovanile di dermatomiosite (5 F), 2 con sclerosi sistemica (1 F e 1 M) e 1 con malattia di Behçet (1 F). Altre 2 ragazze con LES erano state sottoposte all'esame RM, ma sono state escluse dallo studio per il rilievo di grossi artefatti dovuti alla presenza di apparecchio metallico ortodontico fisso.Gli esami sono stati effettuati con apparecchio Philips ACS-NT (Best, Olanda) 1,5T. Sono state eseguite scansioni assiali spin eco T2 e FLAIR, scansioni sagittali turbo T2 (5mm di spessore) e spettroscopia dell'idrogeno di un singolo volume 70times50times20mm (TE 272ms, TR 2000ms) posizionato sulla sostanza bianca sopraventricolare.16 pazienti affetti da LES presentavano dati anamnestici e clinici di coinvolgimento del SNC: tra questi soltanto 9 hanno mostrato alterazioni all'esame di Imaging preliminare (atrofia e/o piccole lesioni focali della sostanza bianca). Anche in 2 dei pazienti senza sintomi neuropsichiatrici il quadro neuroradiologico è risultato alterato. L'indagine spettroscopica ha evidenziato una correlazione tra l'attività della malattia e la diminuzione dell'N-acetilaspartato espresso come rapporto NAA/Cr.11 pazienti sono stati esaminati durante la presenza di sintomi neuropsichiatrici: tra questi 5 pazienti sottoposti a un prolungato periodo di trattamento con corticosteroidi per un coinvolgimento sistemico della malattia più marcato hanno mostrato il più basso valore del rapporto NAA/Cr. 2 tra essi hanno mostrato il quadro neuroradiologico nella norma.Dunque la Risonanza Magnetica per immagini e la Spettroscopia possono essere indagini non invasive da utilizzare in soggetti con LES pediatrico sia per rilevare un coinvolgimento precoce dell'encefalo sia per monitorizzare la gravità della malattia. more...
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- 1997
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104. Peak width of skeletonized mean diffusivity (PSMD) and cognitive functions in relapsing-remitting multiple sclerosis
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Claudia Vinciguerra, Maria Pia Amato, V Nardone, Claudia Niccolai, Jian Zhang, R. Tappa Brocci, M. L. Stromillo, Antonio Giorgio, Luisa Pastò, M. Mortilla, N. De Stefano, Vinciguerra, C., Giorgio, A., Zhang, J., Nardone, V., Tappa Brocci, R., Pasto, L., Niccolai, C., Stromillo, M. L., Mortilla, M., Amato, M. P., and De Stefano, N. more...
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Multiple Sclerosis ,Cognitive Neuroscience ,Grey matter ,050105 experimental psychology ,White matter ,03 medical and health sciences ,Behavioral Neuroscience ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Atrophy ,Cognition ,DTI ,MRI ,Multiple sclerosis ,PSMD ,Multiple Sclerosis, Relapsing-Remitting ,Visual memory ,medicine ,Verbal fluency test ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Multiple sclerosi ,Neuroradiology ,business.industry ,05 social sciences ,Neuropsychology ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,medicine.anatomical_structure ,Diffusion Tensor Imaging ,Neurology ,Neurology (clinical) ,business ,Nuclear medicine ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
Peak width of skeletonized mean diffusivity (PSMD) is a new MRI marker, which has shown clinical relevance in some neurological conditions and, in preliminary data, in multiple sclerosis (MS). We aimed here to investigate, in a group of relapsing-remitting MS (RRMS) patients, the relationship between PSMD and cognitive performances, in comparison with other MRI measures. RRMS patients (n= 60) and normal controls (n= 15) underwent a 3T MRI examination. MRI-based white matter (WM) lesion volume, microstructural integrity (assessed with Tract-Based Spatial Statistics of diffusion tensor imaging [DTI] images) and brain volumes (i.e., total brain, grey matter [GM] and WM) were computed. In addition, PSMD was calculated through “skeletonization” of WM tracts and diffusion histograms. Cognition was evaluated with Rao’s Brief Repeatable Battery (BRB), which incorporated tests of verbal and visual memory, attention, concentration, information processing speed and verbal fluency. PSMD closely correlated with symbol digit modalities test (SDMT) (r = −0.70, p< 0.001)and, to a lesser extent, with verbal and visual memory tests. Multiple regression analysis showed that PSMD explained SDMT variance (R2= 0.54, p< 0.001) more than other MRI measures. Results point out the relevance of microstructural damage, as assessed by PSMD, as a reliable marker of cognition in MS, especially in explaining dysfunction in information processing speed. © 2020, Springer Science+Business Media, LLC, part of Springer Nature. more...
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- 2020
105. Evaluation of cervical spinal cord atrophy using a modified SIENA approach.
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Luchetti L, Prados F, Cortese R, Gentile G, Calabrese M, Mortilla M, De Stefano N, and Battaglini M
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- Humans, Female, Male, Middle Aged, Adult, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, Aged, Atrophy pathology, Magnetic Resonance Imaging methods, Cervical Cord diagnostic imaging, Cervical Cord pathology
- Abstract
Spinal cord (SC) atrophy obtained from structural magnetic resonance imaging has gained relevance as an indicator of neurodegeneration in various neurological disorders. The common method to assess SC atrophy is by comparing numerical differences of the cross-sectional spinal cord area (CSA) between time points. However, this indirect approach leads to considerable variability in the obtained results. Studies showed that this limitation can be overcome by using a registration-based technique. The present study introduces the Structural Image Evaluation using Normalization of Atrophy on the Spinal Cord (SIENA-SC), which is an adapted version of the original SIENA method, designed to directly calculate the percentage of SC volume change over time from clinical brain MRI acquired with an extended field of view to cover the superior part of the cervical SC. In this work, we compared SIENA-SC with the Generalized Boundary Shift Integral (GBSI) and the CSA change. On a scan-rescan dataset, SIENA-SC was shown to have the lowest measurement error than the other two methods. When comparing a group of 190 Healthy Controls with a group of 65 Multiple Sclerosis patients, SIENA-SC provided significantly higher yearly rates of atrophy in patients than in controls and a lower sample size when measured for treatment effect sizes of 50%, 30% and 10%. Our findings indicate that SIENA-SC is a robust, reproducible, and sensitive approach for assessing longitudinal changes in spinal cord volume, providing neuroscientists with an accessible and automated tool able to reduce the need for manual intervention and minimize variability in measurements., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicola De Stefano reports financial support was provided by National Recovery and Resilience Plan (PNRR), and also relationship with Biogen, Merck, Novartis, Sanofi, Roche, Teva, FISM that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Rosa Cortese reports a relationship with Roche, Merck Serono, Janssen, Novartis, Sanofi that includes: speaking and lecture fees and travel reimbursement. Ferran Prados reports a relationship with National Institute for Health and Care Research (NIHR) Biomedical Research Centres (BRC) at University College London (UCL) that includes: employment, funding grants, speaking and lecture fees, and travel reimbursement. Massimiliano Calabrese reports a relationship with Roche, Sanofi Genzyme, Merck Serono, Biogen Idec, Teva, and Novartis Pharma that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.) more...
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- 2024
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106. A multidisciplinary non-invasive approach to monitor response to intravenous immunoglobulin treatment in neurodegenerative Langerhans cell histiocytosis: a real-world study.
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Trambusti I, Barba C, Mortilla M, Rizzi S, Romano K, Coniglio ML, Lucenteforte E, Tondo A, Guerrini R, and Sieni E
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- Humans, Male, Female, Evoked Potentials, Somatosensory, Treatment Outcome, Child, Preschool, Child, Adolescent, Neurodegenerative Diseases drug therapy, Neurodegenerative Diseases diagnosis, Infant, Adult, Evoked Potentials, Auditory, Brain Stem, Immunoglobulins, Intravenous therapeutic use, Immunoglobulins, Intravenous administration & dosage, Histiocytosis, Langerhans-Cell drug therapy, Histiocytosis, Langerhans-Cell diagnosis, Magnetic Resonance Imaging
- Abstract
Aims: Early detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients., Methods: Patients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.5 g/kg IVIG. The diagnostic protocol included structural 3T MRI, neurological examination, brainstem auditory evoked potentials (BAEPs) and SEPs., Results: Twenty-two patients were followed for 5.2 years (median) from the first MRI evidence of ND-LCH. Eleven patients received IVIG for 1.7 years (median). At treatment start neurological examination was abnormal in 10 patients, of whom two had severe clinical impairment and four had abnormal BAEPs. At last follow-up, 1/11 remained stable and 7/11 improved, while worsening of neurological or neurophysiological findings, or both, occurred in 3/11. Risk factors for worsening were a severe clinical or MRI ND-LCH at treatment initiation and prolonged exposure to LCH. Of the 11 untreated patients, none improved and three worsened., Conclusions: Using a standardized diagnostic protocol, we demonstrated that IVIG treatment can lead to clinical stabilization or improvement in all pauci-symptomatic patients with an MRI grading of less than 4., 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 © 2024 Trambusti, Barba, Mortilla, Rizzi, Romano, Coniglio, Lucenteforte, Tondo, Guerrini and Sieni.) more...
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- 2024
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107. Radiomic- and dosiomic-based clustering development for radio-induced neurotoxicity in pediatric medulloblastoma.
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Piffer S, Greto D, Ubaldi L, Mortilla M, Ciccarone A, Desideri I, Genitori L, Livi L, Marrazzo L, Pallotta S, Retico A, Sardi I, and Talamonti C
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- Humans, Child, Female, Male, Retrospective Studies, Adolescent, Child, Preschool, Craniospinal Irradiation methods, Craniospinal Irradiation adverse effects, Neurotoxicity Syndromes etiology, Neurotoxicity Syndromes diagnostic imaging, Machine Learning, Cluster Analysis, Radiomics, Medulloblastoma radiotherapy, Medulloblastoma diagnostic imaging, Cerebellar Neoplasms radiotherapy, Cerebellar Neoplasms diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis., Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering., Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively., Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma., (© 2024. The Author(s).) more...
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- 2024
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108. Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024.
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Bartolini L, Ricci S, Azzari C, Moriondo M, Nieddu F, L'Erario M, Ricci Z, Simonini G, Mortilla M, Indolfi G, Montagnani C, Chiappini E, Galli L, and Guerrini R
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- Humans, Italy epidemiology, Child, Preschool, Male, Female, Child, Infant, Brain Diseases epidemiology, Brain Diseases virology, Influenza, Human epidemiology, Influenza, Human diagnosis, Influenza, Human virology, Influenza A Virus, H1N1 Subtype isolation & purification, Disease Outbreaks
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A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination. more...
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- 2024
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109. Mycophenolate mofetil as induction and long-term maintenance therapy in childhood cerebral vasculitis: a case series.
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Pagnini I, Mortilla M, Gentile D, Maccora I, Abu-Rumeileh S, Limbucci N, Simonini G, and Rosati A
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- Humans, Immunosuppressive Agents therapeutic use, Cyclophosphamide, Mycophenolic Acid therapeutic use, Vasculitis, Central Nervous System drug therapy
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- 2023
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110. BIANCA-MS: An optimized tool for automated multiple sclerosis lesion segmentation.
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Gentile G, Jenkinson M, Griffanti L, Luchetti L, Leoncini M, Inderyas M, Mortilla M, Cortese R, De Stefano N, and Battaglini M
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- Humans, Magnetic Resonance Imaging methods, Algorithms, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, White Matter diagnostic imaging, White Matter pathology
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In this work we present BIANCA-MS, a novel tool for brain white matter lesion segmentation in multiple sclerosis (MS), able to generalize across both the wide spectrum of MRI acquisition protocols and the heterogeneity of manually labeled data. BIANCA-MS is based on the original version of BIANCA and implements two innovative elements: a harmonized setting, tested under different MRI protocols, which avoids the need to further tune algorithm parameters to each dataset; and a cleaning step developed to improve consistency in automated and manual segmentations, thus reducing unwanted variability in output segmentations and validation data. BIANCA-MS was tested on three datasets, acquired with different MRI protocols. First, we compared BIANCA-MS to other widely used tools. Second, we tested how BIANCA-MS performs in separate datasets. Finally, we evaluated BIANCA-MS performance on a pooled dataset where all MRI data were merged. We calculated the overlap using the DICE spatial similarity index (SI) as well as the number of false positive/negative clusters (nFPC/nFNC) in comparison to the manual masks processed with the cleaning step. BIANCA-MS clearly outperformed other available tools in both high- and low-resolution images and provided comparable performance across different scanning protocols, sets of modalities and image resolutions. BIANCA-MS performance on the pooled dataset (SI: 0.72 ± 0.25, nFPC: 13 ± 11, nFNC: 4 ± 8) were comparable to those achieved on each individual dataset (median across datasets SI: 0.72 ± 0.28, nFPC: 14 ± 11, nFNC: 4 ± 8). Our findings suggest that BIANCA-MS is a robust and accurate approach for automated MS lesion segmentation., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.) more...
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- 2023
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111. Continous somatosensory evoked potentials and brain injury in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia.
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Lori S, Bertini G, Bastianelli ME, Gabbanini S, Cossu C, Mortilla M, and Dani C
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- Evoked Potentials, Somatosensory, Female, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging methods, Male, Prospective Studies, Brain Injuries complications, Hypothermia complications, Hypothermia therapy, Hypothermia, Induced methods, Hypoxia-Ischemia, Brain complications, Hypoxia-Ischemia, Brain diagnostic imaging, Hypoxia-Ischemia, Brain therapy
- Abstract
Aim: To explore whether continuous somatosensory evoked potentials (SEPs) monitoring and video electroencephalograms (VEEG) accurately predict lesions observed on brain magnetic resonance imaging (MRI) in neonates with hypoxic-ischaemic encephalopathy (HIE) receiving therapeutic hypothermia., Method: This prospective study included 31 neonates (16 males, 15 females; mean [SD] gestational age 39 weeks [1.67]) who received therapeutic hypothermia for HIE. Therapeutic hypothermia was provided for 72 hours, with a target temperature of 33.0°C to 34.0°C and this was followed by a rewarming rate of approximately 0.5°C per hour, up to 36.5°C. SEPs and VEEG were evaluated simultaneously and continuously for 1 hour under normothermic conditions. MRI was carried out at a mean (SD) age of 6 (2) days., Results: Our results showed a statistically significant correlation between continuous SEP and MRI scores (r=0.37, p=0.03), but not between the VEEG and MRI scores (r=0.30, p=0.09). Receiver operating characteristic analysis confirmed that continuous SEPs were highly specific and sensitive at predicting MRI abnormalities, whereas the VEEG had high specificity but low sensitivity., Interpretation: Continuous monitoring of SEPs could provide early and important prognostic information in neonates with HIE., What This Paper Adds: Early continuous somatosensory evoked potential (SEP) monitoring is correlated with hypoxic-ischaemic encephalopathy (HIE) lesions. Video electroencephalograms (VEEGs) are associated with lesions diagnosed after magnetic resonance imaging. Both showed high specificity, but VEEGs did not show high sensitivity. Continuously monitoring SEPs provides important information about HIE., (© 2022 Mac Keith Press.) more...
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- 2022
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112. Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes.
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Provenzano A, La Barbera A, Scagnet M, Pagliazzi A, Traficante G, Pantaleo M, Tiberi L, Vergani D, Kurtas NE, Guarducci S, Bargiacchi S, Forzano G, Artuso R, Palazzo V, Kura A, Giordano F, di Feo D, Mortilla M, De Filippi C, Mattei G, Garavelli L, Giusti B, Genitori L, Zuffardi O, and Giglio S more...
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- Adolescent, Arnold-Chiari Malformation diagnostic imaging, Arnold-Chiari Malformation epidemiology, Child, Child, Preschool, Female, Humans, Infant, MAP Kinase Signaling System genetics, Magnetic Resonance Imaging, Male, Microcephaly genetics, Young Adult, Arnold-Chiari Malformation genetics, Chromatin Assembly and Disassembly genetics, Mutation, Missense, Exome Sequencing
- Abstract
Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3-5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees. more...
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- 2021
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113. Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome.
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Masnada S, Pichiecchio A, Formica M, Arrigoni F, Borrelli P, Accorsi P, Bonanni P, Borgatti R, Bernardina BD, Danieli A, Darra F, Deconinck N, De Giorgis V, Dulac O, Gataullina S, Giordano L, Guerrini R, La Briola F, Mastrangelo M, Montomoli M, Mortilla M, Osanni E, Parisi P, Perucca E, Pinelli L, Romaniello R, Severino M, Vigevano F, Vignoli A, Bahi-Buisson N, Cavallin M, Accogli A, Burgeois M, Capra V, Chaves-Vischer V, Chiapparini L, Colafati G, D'Arrigo S, Desguerre I, Doco-Fenzy M, d'Orsi G, Epitashvili N, Fazzi E, Ferretti A, Fiorini E, Fradin M, Fusco C, Granata T, Johannesen KM, Lebon S, Loget P, Moller RS, Montanaro D, Orcesi S, Quelin C, Rebessi E, Romeo A, Solazzi R, Spagnoli C, Uebler C, Zara F, Arzimanoglou A, and Veggiotti P more...
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- Adolescent, Adult, Brain abnormalities, Brain diagnostic imaging, Child, Child, Preschool, Drinking, Drug Resistant Epilepsy diagnostic imaging, Drug Resistant Epilepsy etiology, Eating, Electroencephalography, Female, Humans, Infant, Magnetic Resonance Imaging, Motor Skills, Retina diagnostic imaging, Retrospective Studies, Seizures diagnostic imaging, Seizures etiology, Seizures physiopathology, Treatment Outcome, Young Adult, Aicardi Syndrome diagnostic imaging, Basal Ganglia abnormalities
- Abstract
Objective: Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed., Methods: Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed., Results: Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported)., Conclusion: The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome., Classification of Evidence: This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes., (© 2020 American Academy of Neurology.) more...
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- 2021
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114. Gray matter atrophy cannot be fully explained by white matter damage in patients with MS.
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Zhang J, Giorgio A, Vinciguerra C, Stromillo ML, Battaglini M, Mortilla M, Tappa Brocci R, Portaccio E, Amato MP, and De Stefano N
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- Atrophy pathology, Brain diagnostic imaging, Brain pathology, Gray Matter diagnostic imaging, Gray Matter pathology, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, White Matter diagnostic imaging, White Matter pathology
- Abstract
Background: Source-based morphometry (SBM) was recently used for non-random "patterns" of gray matter (GM) atrophy or white matter (WM) microstructural damage., Objective: To assess whether and to what extent such patterns may be inter-related in MS., Methods: SBM was applied to images of GM concentration and fractional anisotropy (FA) in MS patients ( n = 41, median EDSS = 1) and normal controls (NC, n = 28). The same procedure was repeated on an independent and similar data set (39 MS patients and 13 NC)., Results: We found in MS patterns of GM atrophy and reduced FA ( p < 0.05, corrected). Deep GM atrophy was mostly (70%) explained by lesion load in projection tracts and lower FA in posterior corona radiata and thalamic radiation. By contrast, sensorimotor and posterior cortex atrophy was less (50%) dependent from WM damage. All patterns correlated with EDSS ( r from -0.33 to -0.56, p < 0.03) while the only cognition-related correlation was between posterior GM atrophy pattern and processing speed ( r = 0.45, p = 0.014). Reliability analysis showed similar results., Conclusion: In relatively early MS, we found a close link between deep GM atrophy pattern and WM damage while sensorimotor and posterior cortex patterns were partially independent from WM damage and perhaps related to primary mechanisms. Patterns were clinically relevant. more...
- Published
- 2021
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115. Changes in grey matter volume and functional connectivity in cluster headache versus migraine.
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Giorgio A, Lupi C, Zhang J, De Cesaris F, Alessandri M, Mortilla M, Federico A, Geppetti P, De Stefano N, and Benemei S
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- Adult, Brain physiopathology, Case-Control Studies, Cerebral Cortex physiopathology, Cognition physiology, Cohort Studies, Cross-Sectional Studies, Executive Function physiology, Female, Frontal Lobe physiopathology, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Nerve Net physiopathology, Cluster Headache physiopathology, Gray Matter physiopathology, Migraine Disorders physiopathology
- Abstract
Cluster headache (CH) shows a more severe clinical picture than migraine (Mig). We tested whether brain changes can explain such difference. Multimodal MRI was acquired in attack-free patients with CH (n = 12), Mig (n = 13) and in normal controls (NC, n = 13). We used FSL for MRI data analysis and nonparametric permutation testing for voxelwise analyses (p < 0.01, corrected). CH showed lower grey matter (GM) volume, compared to Mig and NC, in frontal cortex regions (inferior frontal gyrus and frontal pole [FP], respectively) and, only compared to Mig, in lateral occipital cortex (LOC). Functional connectivity (FC) of CH was higher than Mig and NC within working memory and executive control networks and, only compared to Mig, between cerebellar and auditory language comprehension networks. In the attack-free state, the CH brain seems to be characterized by: (i) GM volume decrease, compared to both Mig and NC, in pain modulation regions (FP) and, only with respect to Mig, in a region of visual processing modulation during pain and working memory (LOC); (ii) increased FC at short range compared to both Mig and NC and at long range only with respect to Mig, in key cognitive networks, likely due to maladaptation towards more severe pain experience. more...
- Published
- 2020
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116. Sine causa tetraparesis: A pilot study on its possible relationship with interferon signature analysis and Aicardi Goutières syndrome related genes analysis.
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Galli J, Gavazzi F, De Simone M, Giliani S, Garau J, Valente M, Vairo D, Cattalini M, Mortilla M, Andreoli L, Badolato R, Bianchi M, Carabellese N, Cereda C, Ferraro R, Facchetti F, Fredi M, Gualdi G, Lorenzi L, Meini A, Orcesi S, Tincani A, Zanola A, Rice G, and Fazzi E more...
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- Adolescent, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System genetics, Biomarkers, Brain diagnostic imaging, Child, Child, Preschool, Female, Humans, Interferon Type I blood, Interferon Type I genetics, Magnetic Resonance Imaging, Male, Nervous System Malformations diagnostic imaging, Nervous System Malformations genetics, Pilot Projects, Young Adult, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System diagnosis, Interferon Type I biosynthesis, Nervous System Malformations complications, Nervous System Malformations diagnosis, Paresis etiology
- Abstract
Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10% of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Goutières Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS. more...
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- 2018
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117. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.
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Giorgio A, Zhang J, Stromillo ML, Rossi F, Battaglini M, Nichelli L, Mortilla M, Portaccio E, Hakiki B, Amato MP, and De Stefano N
- Abstract
Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( n = 15) in comparison with age- and disability-matched AOMS patients ( n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term. more...
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- 2017
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118. Role of Whole-Body MR with DWIBS in child's Bartonellosis.
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Rossi E, Perrone A, Narese D, Cangelosi M, Sollai S, Semeraro A, Mortilla M, and Defilippi C
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- Animals, Bartonella henselae, Cats, Child, Humans, Male, Bartonella Infections diagnostic imaging, Cat-Scratch Disease diagnostic imaging, Diffusion Magnetic Resonance Imaging methods, Whole Body Imaging methods
- Abstract
Cat-scratch disease (CSD) is a zoonosis in children, result of infection by Bartonella henselae, a gram-negative bacillus. Infection is generally characterized by regional and self-limited lymphadenopathy after exposure to a scratch or bite from a cat. Rarely, B. henselae is cause of fever of unknown origin (FUO), with dissemination to various organs, most often involving the reticuloendothelial system (liver, spleen, bone marrow), mimicking an inflammatory rather than a lymphoproliferative disease. Whole-body Magnetic Resonance Imaging (WBMRI), in association with diffusion-weighted imaging (DWIBS), allows a comprehensive evaluation of pediatric patients, without the risks inherent to ionizing radiation. It is a rapid and sensitive method for detecting and monitoring multifocal lesions such as proliferative or inflammatory and infectious processes. We report a case of systemic CDS in an immunocompetent young boy with fever of unknown origin, without history of cat contact, investigated by WBMRI. more...
- Published
- 2016
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119. Agenesis of internal carotid artery associated with isolated growth hormone deficiency: a case report and literature review.
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Stagi S, Traficante G, Lapi E, Pantaleo M, Becciani S, Mortilla M, Seminara S, and de Martino M
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- Adolescent, Humans, Magnetic Resonance Imaging, Male, Prognosis, Carotid Artery, Internal pathology, Dwarfism, Pituitary complications, Human Growth Hormone deficiency
- Abstract
Background: Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency., Case Presentation: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes., Conclusion: To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder. more...
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- 2015
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120. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis.
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Sieni E, Barba C, Mortilla M, Savelli S, Grisotto L, Di Giacomo G, Romano K, Fonda C, Biggeri A, Guerrini R, and Aricò M
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- Adolescent, Adult, Area Under Curve, Child, Child, Preschool, Early Diagnosis, Electroencephalography, Evoked Potentials, Auditory, Evoked Potentials, Somatosensory, Female, Follow-Up Studies, Humans, Infant, Magnetic Resonance Imaging, Male, ROC Curve, Risk Factors, Sensitivity and Specificity, Young Adult, Histiocytosis, Langerhans-Cell diagnosis, Neurodegenerative Diseases diagnosis
- Abstract
Background: Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy., Methods: We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI) (group 1) or specific risk factors for (diabetes insipidus, craniofacial bone lesions), but no evidence of, neurodegenerative MRI changes (group 2). All patients underwent clinical, neurophysiological and MRI studies., Results: Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs), and five had abnormal brainstem auditory evoked potentials (BAEPs). MR spectroscopy (MRS) showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%), 100% (69.2%-100%), 100% (73.5%-100%), and 66.7% (38.4%-88.2%), respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient., Conclusion: A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future therapeutic trials. more...
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- 2015
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121. Ineffectiveness of tumor necrosis factor-alpha inhibition in association with bisphosphonates for the treatment of cherubism.
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Pagnini I, Simonini G, Mortilla M, Giani T, Pascoli L, and Cimaz R
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- Adalimumab, Antibodies, Monoclonal, Humanized, Cherubism diagnostic imaging, Child, Preschool, Female, Humans, Radiography, Treatment Failure, Alendronate therapeutic use, Antibodies, Monoclonal therapeutic use, Bone Density Conservation Agents therapeutic use, Cherubism drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Published
- 2011
122. Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study.
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Amato MP, Portaccio E, Goretti B, Zipoli V, Iudice A, Della Pina D, Malentacchi G, Sabatini S, Annunziata P, Falcini M, Mazzoni M, Mortilla M, Fonda C, and De Stefano N
- Subjects
- Adult, Cognition, Disease Progression, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Cognition Disorders diagnosis, Cognition Disorders etiology, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting pathology
- Abstract
Objective: To assess longitudinally cognitive functioning in relapsing-remitting multiple sclerosis (RRMS) patients and its relationship with clinical and MRI variables., Methods: Early RRMS patients and matched healthy controls were assessed in parallel in three testing sessions over 3 years, using the Rao's Brief Repeatable Battery of Neuropsychological Tests. Patients also underwent an MRI analysis of T2-weighted lesion volume (T2LV), number of gadolinium-enhanced lesions and whole brain atrophy. Forty-nine RRMS patients (mean age 36.9 ± 8.9 years; mean disease duration 2.9 ± 1.7 years, mean Expanded Disability Status Scale, 1.7 ± 0.7) and 56 healthy controls were recruited., Results: At baseline, cognitive impairment was detected in 15 patients (30.6%). After 3 years, cognitive functioning worsened in the 29.3% of patients, whereas Expanded Disability Status Scale progression was observed in only three patients. The most sensitive test to detect cognitive deterioration over time was the Symbol Digit Modalities Test (SDMT). Only the presence of moderate cognitive impairment at baseline predicted further cognitive deterioration (p = 0.03). Among MRI variables, T2LV showed a weak to moderate relationship with some cognitive tasks., Conclusions: Over a 3-year period cognitive deterioration can be expected in approximately one-third of MS patients with relatively short disease duration. The SDMT is particularly suitable for longitudinal assessment of MS-related cognitive changes. more...
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- 2010
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123. Familial hemophagocytic lymphohistiocytosis: clinical and neuroradiological findings and review of the literature.
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Decaminada N, Cappellini M, Mortilla M, Del Giudice E, Sieni E, Caselli D, Aricò M, and Fonda C
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- Adolescent, Diffusion Magnetic Resonance Imaging, Female, Follow-Up Studies, Humans, Lymphohistiocytosis, Hemophagocytic therapy, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Tomography, X-Ray Computed, Brain metabolism, Brain pathology, Lymphohistiocytosis, Hemophagocytic metabolism, Lymphohistiocytosis, Hemophagocytic pathology
- Abstract
Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare multisystem congenital disorder characterized by uncontrolled proliferation and infiltration of activated lymphocytes and histiocytes, secreting high amounts of inflammatory cytokines; this may affect multiple organs including liver, spleen, lymph nodes, bone marrow, and central nervous system (CNS; Janka, Eur J Pediatr 166:95-109, 1)., Objective: The objective of this study is to describe the characteristics of the encephalopathy and to correlate the neuroradiological findings with the clinical symptoms and the treatment response in a child with FHL type 3 studied by total body computed tomography and by brain magnetic resonance (MR) and MR spectroscopy., Results: VF, a 14-month-old female, developed a full-blown FHL, with facial nerve palsy as the only CNS complication. Brain MR imaging showed several focal areas of pathological signal in the subcortical and periventricular white matter, left thalamus, cerebellum, and brain stem. Proton MR spectroscopy also demonstrated no elevated peak of Cho, no lactate peak, and elevated glutamine/glutamate complex. Moreover, an elevated N-acetyl aspartate (NAA) peak was detected. The follow-up MR study after hematopoietic stem cells transplantation showed a dramatic reduction of the lesions and normalization of the metabolic pattern at spectroscopy., Conclusion: Brain lesions and metabolic alterations documented by MR and spectroscopy during active FHL reverted during disease control achieved by therapy. more...
- Published
- 2010
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124. Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.
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Andreucci E, Bianchi B, Carboni I, Lavoratti G, Mortilla M, Fonda C, Bigozzi M, Genuardi M, Giglio S, and Pela I
- Subjects
- Acidosis, Renal Tubular complications, Ear, Inner diagnostic imaging, Female, Hearing Loss, Sensorineural complications, Homozygote, Humans, Infant, Infant, Newborn, Male, Mutation, Proton-Translocating ATPases genetics, Radiography, Severity of Illness Index, Vacuolar Proton-Translocating ATPases genetics, Vestibular Aqueduct abnormalities, Vestibular Aqueduct diagnostic imaging, Acidosis, Renal Tubular genetics, Ear, Inner abnormalities, Genes, Recessive, Genetic Heterogeneity, Hearing Loss, Sensorineural genetics
- Abstract
A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined. more...
- Published
- 2009
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125. Communication of information to patients with inflammatory bowel disease: A European Collaborative Study in a multinational prospective inception cohort.
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Politi P, Bodini P, Mortilla MG, Beltrami M, Fornaciari G, Formisano D, Munkholm P, Riis L, Wolters F, Hoie O, Katsanos K, O'Morain C, Shuhaibar M, Lalli P, De Falco M, Pereira S, Freitas J, Odes S, and Stockbrügger RW more...
- Abstract
Background and Aims: Communication to patients of information about their disease has become increasingly important in modern medicine, and particularly with chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject is not adequately researched or understood., Methods: We studied the media and preferences for communication of information in a multi-national community-based inception cohort of European and Israeli patients with IBD and 10 years follow-up, using structured questionnaires categorizing demographics, disease status, current and preferred sources of information, use of electronic media, role of patients' associations, and satisfaction level., Results: The 917 patients completing the questionnaire were derived from northern (60%) and southern (40%) countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67% had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients designated the specialist as their primary source of information, 77% indicated satisfaction with their current information, and 65% reported not receiving information about medical treatment in the past year. Patient concerns were about new research into their illness (64%), medical treatments (58%), risks and complications (51%) and genetics (42%). Preferred sources of information were paper bulletin (76%), electronic media (30%) and international organization (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level and country impacted significantly on patients' choices., Conclusions: In providing health care information to patients with IBD their individual attitudes and preferences must be considered. There should be greater roles for IBD patients' associations and international IBD-research organizations, and an increasing use of electronic media. more...
- Published
- 2008
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126. Intracerebral atypical presentation of echinococcosis in a child.
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Sardi I, Sanzo M, Buccoliero AM, Mortilla M, de Martino M, and Genitori L
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- Brain Diseases pathology, Central Nervous System Helminthiasis pathology, Child, Echinococcosis pathology, Female, Humans, Magnetic Resonance Imaging, Brain Diseases diagnosis, Central Nervous System Helminthiasis diagnosis, Echinococcosis diagnosis
- Published
- 2008
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127. Cortical damage in brains of patients with adult-form of myotonic dystrophy type 1 and no or minimal MRI abnormalities.
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Giorgio A, Dotti MT, Battaglini M, Marino S, Mortilla M, Stromillo ML, Bramanti P, Orrico A, Federico A, and De Stefano N
- Subjects
- Adult, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Brain pathology, Myotonic Dystrophy pathology
- Abstract
Objective: To evaluate, by using quantitative MRI metrics, subtle cortical changes in brains of patients with the adult form of myotonic dystrophy type I (DM1) who showed no or minimal abnormalities on MRI., Background: DM1 is an autosomal dominant multisystem disorder caused by the expansion of CTG repeats in the myotonic dystrophy-protein kinase gene. Mild to severe involvement of the CNS can be part of the clinical features of the disease. Several MRI studies have demonstrated that both focal white matter (WM) lesions and diffuse grey matter atrophy can be found in the brains of DM1 patients. However, whether these two processes are related or may occur independently is not clear., Design/methods: Ten genetically-proven DM1 patients who showed no or minimal abnormalities on MRI underwent a new brain MRI examination to obtain computerized measures of total and regional brain volumes normalized to head size and regional measurements of the magnetization transfer ratio (MTr)., Results: Normalized brain volumes (NBV) were significantly (p < 0.0001) lower in DM1 subjects than in a group of age- and sex-matched normal controls. Normalized cortical volumes (NCV) also were lower (p = 0.003) in DM1 subjects than in normal controls, whereas normalized WM volumes were not different between the two groups (p = 0.3). In agreement with this, values of MTr in the neocortex (cortical-MTr) were significantly (p = 0.006) lower in DM1 patients than in normal controls and this difference was not found in the WM tissue (p = 0.8)., Conclusions: Neocortical damage seems to be evident in the absence of visible WM lesions suggesting that a neocortical pathology, unrelated to WM lesion formation, occurs in DM1 brains. more...
- Published
- 2006
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128. Neocortical volume decrease in relapsing-remitting multiple sclerosis with mild cognitive impairment.
- Author
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Portaccio E, Amato MP, Bartolozzi ML, Zipoli V, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, and De Stefano N
- Subjects
- Adult, Attention physiology, Case-Control Studies, Cognition Disorders etiology, Female, Humans, Magnetic Resonance Imaging methods, Male, Memory physiology, Middle Aged, Multiple Sclerosis, Relapsing-Remitting complications, Neuropsychological Tests statistics & numerical data, Statistics, Nonparametric, Verbal Learning physiology, Cognition Disorders pathology, Multiple Sclerosis, Relapsing-Remitting pathology, Neocortex pathology
- Abstract
The aim of the study was to assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting multiple sclerosis (RRMS). Conventional magnetic resonance was acquired in 41 RRMS patients and 16 demographically matched normal controls (NC). An automated analysis tool was used to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed through the Rao's Brief Repeatable Battery. We identified 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. Values of normalized cortical volumes (NCV) in the whole MS sample were lower than those in the NC group (p=0.01). MS-ci patients showed NCV values lower (p=0.02) than did both MS-cp patients and NC. Moreover, we found a positive correlation between NCV values and measures of verbal memory (r=0.51, p=0.02), verbal fluency (r=0.51, p=0.01) and attention/concentration (r=0.65, p<0.001) in MS-ci patients. Furthermore, NCV values were significantly decreased in patients who scored lower on a greater number of tests (r=-0.58, p<0.01) in the MS-ci group. Only MS-ci patients had cortical atrophy significantly correlated with a poorer neuropsychological performance. Grey matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease. more...
- Published
- 2006
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129. Proton magnetic resonance spectroscopy reveals central neuroaxonal impairment in systemic sclerosis.
- Author
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Bertinotti L, Mortilla M, Conforti ML, Colangelo N, Nacci F, Del Rosso A, Fonda C, Casale R, Matucci-Cerinic M, and Pignone A
- Subjects
- Adult, Aspartic Acid analogs & derivatives, Aspartic Acid analysis, Aspartic Acid metabolism, Axons physiology, Biomarkers analysis, Brain metabolism, Brain physiopathology, Choline analysis, Choline metabolism, Creatine analysis, Creatine metabolism, Female, Humans, Male, Middle Aged, Scleroderma, Diffuse metabolism, Scleroderma, Diffuse physiopathology, Scleroderma, Limited metabolism, Scleroderma, Limited physiopathology, Axons pathology, Brain pathology, Magnetic Resonance Imaging methods, Scleroderma, Diffuse diagnosis, Scleroderma, Limited diagnosis
- Abstract
Objective: . Involvement of the central nervous system (CNS) in systemic sclerosis (SSc) is rare. Proton magnetic resonance spectroscopy (1H-MRS) assesses in vivo cerebral metabolites. We investigated the biochemical modifications of the CNS in SSc., Methods: N-acetylaspartate/creatine ratio (NAA/Cr) and choline/creatine ratio (Cho/Cr) at right centrum semiovale (RCS) and at right basal ganglia (RBG) were evaluated by 1H-MRS in 12 patients with limited (lSSc) and 8 patients with diffuse SSc (dSSc) and 20 control subjects., Results: With 1H-MRS, a significant reduction of NAA/Cr ratio at RBG (p < 0.02) and at RCS (p < 0.002) was detected in SSc patients. Cho/Cr ratio was increased (p < 0.02) in the RCS, but not in RBG. In patients with lSSc, a significant reduction of NAA/Cr was detected in RCS but not in RBG., Conclusion: Evidence of neuroaxonal damage strongly suggests the existence of CNS involvement in SSc. more...
- Published
- 2006
130. Influence of apolipoprotein E epsilon4 genotype on brain tissue integrity in relapsing-remitting multiple sclerosis.
- Author
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De Stefano N, Bartolozzi ML, Nacmias B, Zipoli V, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, and Amato MP
- Subjects
- Adult, Apolipoprotein E4, Atrophy, Disability Evaluation, Female, Genetic Carrier Screening, Humans, Male, Multiple Sclerosis, Relapsing-Remitting diagnosis, Statistics as Topic, Alleles, Apolipoproteins E genetics, Brain pathology, Genotype, Image Enhancement, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting genetics
- Abstract
Background: Recent clinical and imaging studies have raised the hypothesis that patients with multiple sclerosis (MS) and the apolipoprotein E (ApoE) epsilon4 allele may have a more severe disease course than those without the ApoE epsilon4 allele. This seems to be related to more extensive tissue destruction and less efficient neuronal maintenance and repair in ApoE epsilon4 carriers., Objective: To evaluate the influence of different ApoE genotypes on brain tissue integrity in patients with relapsing-remitting MS (RRMS)., Design: We determined the ApoE genotype in 76 RRMS patients. Conventional T1-, T2-, and proton density-weighted magnetic resonance (MR) images were obtained for each patient and in a group of demographically matched healthy control subjects. On conventional T1-weighted MR images, an automated analysis tool was used to obtain total brain volumes normalized for head size (NBVs). Total brain lesion load was estimated on proton density- and T2-weighted MR images., Results: From the whole group of RRMS patients, we identified 18 with and 58 without the epsilon4 allele. Both patient groups were not significantly different in age, age of disease onset, clinical disability, and disease duration. Carriers of the epsilon4 allele showed significantly (P =.01) lower NBVs than controls and non-epsilon4 allele carriers. When a similar analysis was performed on only those patients with both very short disease duration and absence of clinical disability, NBV values were still significantly lower in RRMS patients with the epsilon4 allele than in those without it (P =.02) and in controls (P =.007). In contrast, RRMS patients with different ApoE genotypes did not show significant differences in values of total brain T2-weighted lesion volumes., Conclusions: The presence of significant NBV decreases only in the group of RRMS patients with the ApoE epsilon4 genotype provides new evidence that links ApoE epsilon4-related impaired mechanisms of cell repair and severe tissue destruction in MS. Results of the present study suggest that this negative influence of the ApoE epsilon4 genotype might be active from the earliest disease stages. more...
- Published
- 2004
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131. MR evidence of structural and metabolic changes in brains of patients with Werner's syndrome.
- Author
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De Stefano N, Dotti MT, Battisti C, Sicurelli F, Stromillo ML, Mortilla M, and Federico A
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- Adult, Female, Humans, Magnetic Resonance Spectroscopy, Male, Siblings, Werner Syndrome genetics, Brain pathology, Werner Syndrome pathology
- Abstract
Objective: To assess CNS abnormalities in patients with Werner's syndrome (WS) using MR metrics specific for tissue damage., Background: WS is a rare autosomal recessive disorder that causes premature aging. The CNS involvement in this disease is still debated., Methods: Two siblings who showed signs of neurological involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer (MT) imaging. Also, on conventional T1-weighted MR images, measurements of total brain volume were performed., Results: Conventional MR images of both WS patients did not show abnormalities on visual inspection. However, both WS patients showed significantly lower values of normalized total brain volume and MT ratio in the white matter than age-matched normal controls. Also, proton MRSI showed significantly lower values of central brain NAA/Cr in WS patients than in normal controls., Conclusions: Our findings suggest that, despite normal appearance on conventional MRI, diffuse structural and metabolic tissue damage can be demonstrated in WS brains by means of sensitive MR methods even in patients with moderate or subclinical CNS involvement. more...
- Published
- 2003
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132. Brain study using magnetic resonance imaging and proton MR spectroscopy in pediatric onset systemic lupus erythematosus.
- Author
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Mortilla M, Ermini M, Nistri M, Dal Pozzo G, and Falcini F
- Subjects
- Adolescent, Adult, Age of Onset, Anatomy, Cross-Sectional, Anti-Inflammatory Agents therapeutic use, Antirheumatic Agents therapeutic use, Child, Drug Therapy, Combination, Female, Glucocorticoids therapeutic use, Humans, Hydroxychloroquine therapeutic use, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic physiopathology, Magnetic Resonance Imaging instrumentation, Magnetic Resonance Spectroscopy instrumentation, Male, Severity of Illness Index, Steroids, Treatment Outcome, Brain pathology, Lupus Erythematosus, Systemic pathology, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy methods
- Abstract
Objective: The aim of the present study was to assess and monitor brain damage in patients with pediatric onset systemic lupus erythematosus (SLE) using non-invasive techniques such as magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS)., Methods: Twenty-four SLE patients, both symptomatic or asymptomatic for central nervous system (CNS) involvement, and 20 controls were examined. Each individual underwent a diagnostic MRI using a 1.5 T Philips ACS-NT scanner including transverse T2-weighted (T2W) spin echo, transverse FLuid Attenuated Inversion Recovery (FLAIR), and sagittal T2W turbo spin echo 5 mm slices. In addition, single voxel proton MR spectroscopy localized on the supraventricular region was performed in all patients and controls. Patients were re-examined after one year., Results: 75% of SLE patients had clinical CNS involvement; 46% showed abnormal MRI (3 of them, in the absence of neurologic signs); 4 SLE patients showed N-acetylaspartate/Creatine (NAA/Cr) ratios significantly lower than the controls. Among 5 SLE patients examined at the onset of the disease, 1 had MRI alterations and another showed a decrease of NAA/Cr values. Three patients with relapses showed a correlation between the course of the disease and the NAA/Cr ratios., Conclusion: MRI and H-MRS are non-invasive techniques that might be useful, in some cases, in detecting CNS involvement in SLE patients and monitoring the disease course and efficacy of pharmacological treatment. more...
- Published
- 2003
133. Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability.
- Author
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De Stefano N, Narayanan S, Francis SJ, Smith S, Mortilla M, Tartaglia MC, Bartolozzi ML, Guidi L, Federico A, and Arnold DL
- Subjects
- Adolescent, Adult, Brain pathology, Diffuse Axonal Injury pathology, Persons with Disabilities, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis physiopathology, Diffuse Axonal Injury etiology, Multiple Sclerosis complications
- Abstract
Background: Although in situ pathological studies and in vivo magnetic resonance (MR) investigations have shown that axonal injury can be significant in the early stages of multiple sclerosis (MS), diffuse axonal injury is generally considered a secondary event. Cerebral axonal damage can be specifically assessed in vivo by measuring levels of brain N-acetylaspartate (NAA, a specific index of axonal integrity detected by MR spectroscopy). Other new MR measurements such as magnetization transfer ratio (MTr) or computed estimation of brain volume can provide less specific indexes of tissue damage., Objective: To determine whether diffuse axonal and tissue injury is present in patients with definite MS who do not show clinically significant disability., Methods: We measured brain NAA levels (normalized to creatine [Cr]), MTr values, and cerebral volumes in patients with definite MS who had low T2-weighted MR imaging lesion volumes and no clinical disability, and also in age-matched healthy control subjects., Results: Values of central brain NAA/Cr and MTr in normal-appearing white matter were significantly lower in the MS patients than in controls (P<.001). In contrast, total brain volumes were not significantly different between these groups. Similar results were found for MS patients with early disease (duration, <3 years) and with a particularly low cerebral T2-weighted MR imaging lesion load (< or = 2 cm(3))., Conclusions: Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability. This suggests that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral demyelination. more...
- Published
- 2002
- Full Text
- View/download PDF
134. Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study.
- Author
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De Stefano N, Balestri P, Dotti MT, Grosso S, Mortilla M, Morgese G, and Federico A
- Subjects
- Adolescent, Adult, Creatine analysis, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Phosphocreatine analysis, Aspartic Acid analogs & derivatives, Aspartic Acid metabolism, Cysts pathology, Dementia, Vascular complications, Dementia, Vascular pathology, Magnetic Resonance Spectroscopy methods
- Abstract
Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cysts is a neurodegenerative disorder clinically characterized by megalencephaly with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent single-voxel proton MR spectroscopy studies have shown mild metabolic abnormalities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (1H-MRSI) study on 2 new, unrelated patients with this rare disorder. 1H-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneous decreases in all normally detected metabolites with significant widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemispheres. Metabolic abnormalities were milder in the frontal white matter and more severe in the posterior white matter. The 1H-MRSI pattern of the gray matter was normal in both patients. In one patient, a subsequent 1H-MRSI examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine in the white matter. We conclude that severe metabolic abnormalities can be found in the white matter of VML patients. This suggests that, despite the apparently mild clinical course, a severe neurodegenerative process may occur in the white matter of these patients. more...
- Published
- 2001
- Full Text
- View/download PDF
135. Quiz case of the month. Intramural hematoma in the caudal tract of the basilar artery with distal occlusion and a midsagittal ischemic lesion in the pons.
- Author
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Cellerini M, Nistri M, and Mortilla M
- Subjects
- Adult, Hematoma etiology, Humans, Male, Basilar Artery pathology, Hematoma diagnosis, Magnetic Resonance Imaging methods
- Published
- 2001
- Full Text
- View/download PDF
136. Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis.
- Author
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De Stefano N, Dotti MT, Mortilla M, and Federico A
- Subjects
- Adult, Aspartic Acid analysis, Aspartic Acid metabolism, Axons pathology, Brain metabolism, Cerebellum metabolism, Cerebellum pathology, Cerebral Ventricles metabolism, Cerebral Ventricles pathology, Choline analysis, Creatine analysis, Female, Humans, Lactic Acid analysis, Lactic Acid metabolism, Male, Middle Aged, Mitochondria metabolism, Predictive Value of Tests, Severity of Illness Index, Xanthomatosis, Cerebrotendinous metabolism, Aspartic Acid analogs & derivatives, Brain pathology, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Xanthomatosis, Cerebrotendinous diagnosis
- Abstract
Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to an inherited defect in the metabolic pathway of cholesterol. Early diagnosis of the disease is particularly important as patients benefit from therapy with chenodeoxycholic acid. Although the disease is clinically characterized by the concomitant presence of tendon xanthomas, juvenile cataracts and progressive neurological impairment, clinical features may vary greatly. Neuroradiological studies have suggested that the bilateral abnormality of the dentate nuclei could be typical of this disease. However, this finding has been seen inconsistently on conventional MRI. The dynamic of the CNS pathology in CTX is complex, and whether demyelination or axonopathy has primary importance in the pathogenesis of CTX pathology is not known. To clarify both neuroradiological and pathological issues, we performed combined brain MRI and spectroscopy examinations on 12 CTX patients. On conventional MRIs, bilateral hyperintensities of the dentate nuclei were clearly seen in nine out of 12 patients on T(2) -weighted MRIs, but were evident in all patients using a FLAIR sequence. On proton magnetic resonance (MR) spectroscopy, significant decreases in N: -acetylaspartate resonance intensities (P: <0.0001) and increases in lactate MR signals (P<0.05) were found in the group of CTX patients in large volumes of interest localized above the lateral brain ventricles and in the cerebellar hemispheres. Cerebral values of N -acetylaspartate resonance intensities showed a close correlation with patients' disability (Spearman rank correlation = -0.78, P<0.005). These results suggest that MR abnormalities in the dentate nuclei may be evident consistently in patients with CTX. Proton MR spectroscopy data demonstrated widespread axonal damage (as shown by the decrease in N -acetylaspartate) and diffuse brain mitochondrial dysfunction (as shown by the increase in brain parenchymal lactate) in patients with CTX. The close correlation seen between values of the putative axonal marker N-acetylaspartate and patients' disability scores suggests that proton MR spectroscopy can provide a useful measure of disease outcome in CTX. more...
- Published
- 2001
- Full Text
- View/download PDF
137. [Palliative intraluminal brachytherapy of tumors of the extrahepatic biliary tract. Experience with a new naso-biliary catheter].
- Author
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Bonetta A, Ricci E, Mortilla MG, Conigliaro R, Zingoni A, Bedogni G, and Armaroli L
- Subjects
- Catheterization instrumentation, Cholestasis, Extrahepatic etiology, Equipment Design, Humans, Palliative Care, Bile Duct Neoplasms complications, Bile Ducts, Extrahepatic, Brachytherapy instrumentation, Cholestasis, Extrahepatic radiotherapy
- Published
- 1996
138. Visual "disappearing phenomenon" can reliably predict the nonadenomatous nature of rectal and rectosigmoid diminutive polyps at endoscopy.
- Author
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Bertoni G, Sassatelli R, Conigliaro R, Nigrisoli E, Zanoni P, Pacchione D, Mortilla MG, and Bedogni G
- Subjects
- Adenomatous Polyps diagnosis, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Intestinal Polyps pathology, Male, Middle Aged, Prospective Studies, Rectal Neoplasms pathology, Sensitivity and Specificity, Sigmoid Neoplasms pathology, Colonoscopy, Intestinal Polyps diagnosis, Rectal Neoplasms diagnosis, Sigmoid Neoplasms diagnosis
- Abstract
Previous studies have failed to differentiate adenomatous from nonadenomatous diminutive polyps according to their gross macroscopic features at endoscopy. We prospectively evaluated the prevalence, distribution, and predictive value of a recently described morphologic feature-the "disappearing phenomenon"-in diminutive polyps of the distal 20 cm of the large bowel by studying 218 polyps in 90 consecutive patients. Disappearance was graded as complete, incomplete, or absent. Overall, complete disappearance was noted in 93 (43.1%) polyps, with a significantly higher prevalence in the middle and lower rectum (p < .05) and among smaller, paler, and smooth-surface polyps (p < .001). Incomplete disappearance was detected in both nonadenomas (23.1%) and adenomas (15.8%), but, more importantly, complete disappearance occurred in none of the 19 observed adenomas compared with 93 of 199 nonadenomas. Multiple logistic regression analysis revealed that disappearance was the strongest predictor (p < .001) of nonadenomatous histology among considered morphologic criteria. When complete disappearance was used to predict histologic type of diminutive polyps, its sensitivity was 100% and its specificity was 46.7%. In conclusion, the disappearing phenomenon represents a reliable visual marker for identifying nonadenomatous rectal and rectosigmoidal diminutive polyps at endoscopy. Diminutive polyps that disappear completely upon insufflation are invariably nonadenomatous and should not require endoscopic biopsy or removal. more...
- Published
- 1994
- Full Text
- View/download PDF
139. Assessment of genetic polymorphisms in DNA from formalin fixed neurological tissues.
- Author
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Mortilla M, Vaula G, and St George-Hyslop PH
- Subjects
- Alzheimer Disease genetics, Female, Formaldehyde, Humans, Male, Paraffin Embedding, Pedigree, Polymerase Chain Reaction, Repetitive Sequences, Nucleic Acid, Brain Chemistry, DNA genetics, Polymorphism, Genetic, Tissue Fixation
- Abstract
The ability to analyze the genotype of deceased affected members of pedigrees segregating inherited neurological diseases considerably augments the informativeness of such pedigrees. This information has direct application in attempts to isolate disease genes by positional cloning strategies, and for genetic counselling. We show that the genotype at polymorphic simple sequence repeat loci can be determined from genomic DNA isolated from 10 micron thick paraffin embedded, formalin fixed neurological tissues. The critical constraint on this method is the size of the template target bearing the simple sequence repeat, which should ideally be less than 165 base pairs. more...
- Published
- 1994
- Full Text
- View/download PDF
140. Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene.
- Author
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Karlinsky H, Vaula G, Haines JL, Ridgley J, Bergeron C, Mortilla M, Tupler RG, Percy ME, Robitaille Y, and Noldy NE
- Subjects
- Adult, Alzheimer Disease diagnosis, Alzheimer Disease pathology, Base Sequence, Brain pathology, Female, Humans, Middle Aged, Molecular Biology, Molecular Probes genetics, Molecular Sequence Data, Neuropsychological Tests, Phenotype, Prospective Studies, Retrospective Studies, Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Codon genetics, Mutation, Pedigree
- Abstract
We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families. more...
- Published
- 1992
- Full Text
- View/download PDF
141. Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases.
- Author
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Tanzi RE, Vaula G, Romano DM, Mortilla M, Huang TL, Tupler RG, Wasco W, Hyman BT, Haines JL, and Jenkins BJ
- Subjects
- Alzheimer Disease diagnosis, Base Sequence, DNA genetics, DNA Mutational Analysis, Humans, Isoleucine genetics, Male, Middle Aged, Molecular Sequence Data, Pedigree, Polymerase Chain Reaction, Recombination, Genetic, Valine genetics, Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Mutation
- Abstract
A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well-characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD-associated mutations in the beta A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val----Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD. more...
- Published
- 1992
142. Portal vein filling: a rare complication associated with ERCP for endoscopic biliary stent placement.
- Author
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Ricci E, Mortilla MG, Conigliaro R, Bertoni G, Bedogni G, and Chilovi F
- Subjects
- Aged, Cholestasis therapy, Extravasation of Diagnostic and Therapeutic Materials, Humans, Male, Sphincterotomy, Endoscopic, Cholangiopancreatography, Endoscopic Retrograde adverse effects, Portal Vein, Stents
- Published
- 1992
- Full Text
- View/download PDF
143. [Emergency endoscopy in children: experience of a digestive endoscopy department].
- Author
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Pacchione D, Mortilla MG, Ricci E, Bertoni G, Conigliaro R, Orsi P, Bedogni G, Lamborghini A, and Banchini G
- Subjects
- Adolescent, Child, Child, Preschool, Digestive System Diseases therapy, Emergencies, Humans, Infant, Infant, Newborn, Digestive System Diseases pathology, Endoscopy, Digestive System
- Abstract
Many changes and advances have been achieved in the last years, so that emergency endoscopy has now a definite role also in the diagnosis and treatment of diseases in childhood. In order to determinate main indications to endoscopic examination, and which are the most useful diagnostic and therapeutic measures that should be performed, we examined the records of 202 patients (aged 1 day-14 years) undergone emergency endoscopy from June 1979 to January 1990. Patients were referred to endoscopy because of foreign bodies or caustic ingestion, hematemesis, and in one patient a suspected intussusception. We didn't record any complication. Our study shows that emergency endoscopy has a definite role also in pediatric age and gives a diagnostic and therapeutic gain in the management of many diseases. more...
- Published
- 1992
144. [Treatment of perforation of the cervical esophagus during diagnostic endoscopy].
- Author
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Sinibaldi G, Piccinini G, Manzini L, and Mortilla MG
- Subjects
- Aged, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Drainage, Esophageal Perforation surgery, Esophageal Perforation therapy, Female, Humans, Male, Middle Aged, Endoscopy adverse effects, Esophageal Perforation etiology
- Abstract
Early diagnosis of esophageal perforation is critical. We believe that the treatment of each case must be individualized. The management of perforation in our series has been "conservative" in two cases, for small perforations; and "operative", suture closure and drainage, in the remainder, for a large perforation with contamination of the mediastinum. more...
- Published
- 1991
145. Nadolol for prevention of variceal rebleeding during the course of endoscopic injection sclerotherapy: a randomized pilot study.
- Author
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Bertoni G, Fornaciari G, Beltrami M, Conigliaro R, Grazia Mortilla M, Ricci E, Castagnetti E, Bedogni G, and Plancher AC
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Nadolol administration & dosage, Pilot Projects, Random Allocation, Recurrence, Esophageal and Gastric Varices therapy, Gastrointestinal Hemorrhage prevention & control, Nadolol therapeutic use, Sclerotherapy
- Published
- 1990
146. [Hexokinase in Alzheimer's disease].
- Author
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Mortilla M and Sorbi S
- Subjects
- Aged, Alzheimer Disease enzymology, Cells, Cultured, Chromosome Mapping, Fibroblasts enzymology, Humans, Italy, Middle Aged, Pedigree, Skin enzymology, Spectrophotometry, Alzheimer Disease genetics, Hexokinase analysis
- Abstract
Decreased hexokinase activity has been reported in brain, fibroblast, leukocytes and microvessels of patients with Alzheimer's disease. In this paper the results of an investigation on hexokinase activity in an Italian large pedigree are reported. The activity was comparable with that of the normal controls. These results suggest that Alzheimer's disease may be an heterogenic disorder. more...
- Published
- 1990
147. [Gastroesophageal reflux disease].
- Author
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Bedogni G, Ricci E, Bertoni G, Conigliaro R, Pedrazzoli C, and Mortilla MG
- Subjects
- Barrett Esophagus complications, Esophagoscopy, Humans, Gastroesophageal Reflux diagnosis, Gastroesophageal Reflux therapy
- Published
- 1987
148. Nasobiliary drainage following endoscopic sphincterotomy. A useful method of preventing and treating early complications.
- Author
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Ricci E, Conigliaro R, Bertoni G, Mortilla MG, Bedogni G, and Contini S
- Subjects
- Bile, Endoscopy, Humans, Intubation methods, Middle Aged, Retrospective Studies, Drainage methods, Postoperative Complications prevention & control, Sphincterotomy, Transduodenal
- Abstract
The authors analyze a retrospective study of 850 patients who underwent endoscopic sphincterotomy (ES). One group of patients (705) routinely had nasobiliary drainage following ES as a prophylactic measure to prevent complications, while 145 patients were not drained. Complications, mortality and the need for emergency surgery were compared in both groups. In the drained group, the complication rate was 2% vs 10.3% in the nondrained group (P less than 0.001), and mortality was 0.4% vs 2.7% (P = 0.03). Emergency surgery was required in 0.1% in the drained patients versus 3.4% in the nondrained group (P = 0.01). Based on these data within the limits of a retrospective study, the authors strongly support the routine use of nasobiliary drainage to prevent complications, which usually occur within the first 24 h, and also to facilitate the immediate treatment of the complications. This procedure is also highly recommended when ES is performed by inexperienced endoscopists and with a technically demanding ES, which is frequently followed by complications. more...
- Published
- 1987
- Full Text
- View/download PDF
149. Hereditary adenomatosis of the colon and rectum: clinical features of eight families from northern Italy.
- Author
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Ponz de Leon M, Sassatelli R, Zanghieri G, Sacchetti C, Roncucci L, Scalmati A, Bertoni G, Conigliaro R, Mortilla MG, and Rombaldi C
- Subjects
- Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli surgery, Adolescent, Adult, Child, Colon pathology, Female, Gene Frequency, Humans, Italy, Male, Middle Aged, Pedigree, Rectum pathology, Adenomatous Polyposis Coli pathology
- Abstract
Adenomatosis coli (or familial polyposis of the large bowel) and related syndromes are relatively rare diseases characterized by an autosomal dominant mode of inheritance. In these diseases, the entire colorectal mucosa is covered by hundreds (often innumerable) polyps of various dimensions. In addition, several extracolonic abnormalities have been reported. In the present study, we describe the clinical features of eight families from northern Italy fulfilling the diagnostic criteria of adenomatosis coli. Information was available on 123 unaffected and 30 affected family members. The most relevant findings of the study can be summarized as follows. 1) Gene frequency was calculated to be between 1:7,300 and 1:19,000. Segregation ratio in affected branches was 0.57, with a gene penetrance of nearly 60% and a male:female ratio of 1.73. 2) Extracolonic manifestations were present in all families and in 15 of 30 affected patients, the most frequent being cutaneous cysts and retinal lesions. No case fulfilling the classical criteria of Gardner syndrome was observed. 3) When the diagnosis of adenomatosis followed the appearance of symptoms, colorectal cancer had usually already developed, whereas no malignant changes were observed in individuals diagnosed in the asymptomatic stage. When colectomy with ileorectal anastomosis was the treatment of choice, polyps tended to recur in the rectal stump, and long-term endoscopic follow-up was necessary. In conclusion, adenomatosis coli may account for a definite proportion of colorectal neoplasms observed in the general population. Taking into consideration the genetic base of the disease, it follows that individuals at risk should be closely monitored for several years. Moreover, clinical investigations should not be limited to the large bowel, but should be extended to the skin, upper digestive tract, fundus oculi, bones, and probably other organs. more...
- Published
- 1989
150. Endoscopic sphincterotomy in Billroth II patients: an improved method using a diathermic needle as sphincterotome and a nasobiliary drain as guide.
- Author
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Ricci E, Bertoni G, Conigliaro R, Contini S, Mortilla MG, and Bedogni G
- Subjects
- Adult, Aged, Aged, 80 and over, Diathermy instrumentation, Drainage instrumentation, Female, Humans, Intubation, Gastrointestinal instrumentation, Male, Middle Aged, Needles, Gallstones surgery, Gastrectomy, Gastroenterostomy, Sphincterotomy, Transduodenal methods
- Published
- 1989
- Full Text
- View/download PDF
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