Neuroimaging characterization of multiple sclerosis lesions in pediatric patients: an exploratory radiomics approach.

Introduction: Multiple sclerosis (MS), a chronic inflammatory immune-mediated disease of the central nervous system (CNS), is a common condition in young adults, but it can also affect children. The aim of this study was to construct radiomic models of lesions based on magnetic resonance imaging (MRI, T2-weighted-Fluid-Attenuated Inversion Recovery), to understand the correlation between extracted radiomic features, brain and lesion volumetry, demographic, clinical and laboratorial data. Methods: The neuroimaging data extracted from eleven scans of pediatric MS patients were analyzed. A total of 60 radiomic features based on MR T2-FLAIR images were extracted and used to calculate gray level co-occurrence matrix (GLCM). The principal component analysis and ROC analysis were performed to select the radiomic features, respectively. The realized classification task by the logistic regression models was performed according to these radiomic features. Results: Ten most relevant features were selected from data extracted. The logistic regression applied to T2-FLAIR radiomic features revealed significant predictor for multiple sclerosis (MS) lesion detection. Only the variable "contrast" was statistically significant, indicating that only this variable played a significant role in the model. This approach enhances the classification of lesions from normal tissue. Discussion and conclusion: Our exploratory results suggest that the radiomic models based on MR imaging (T2-FLAIR) may have a potential contribution to characterization of brain tissues and classification of lesions in pediatric MS.

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. Methods: We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. Results: We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Discussion and conclusion: Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Systematic review and meta-analysis of the prevalence of coronavirus: One health approach for a global strategy.

Coronaviruses have been responsible for major epidemic crises in 2003 with SARS-CoV-1, in 2012 with MERS-CoV and in 2019 with SARS-CoV-2 (COVID-19), causing serious atypical pneumonia in humans. We intend, with this systematic analysis and meta-analysis, to clarify the prevalence of the various strains of coronavirus in different animal species. For this purpose, we carried out an electronic survey using Pubmed's Veterinary Science search tool to conduct a systematic assessment of published studies reporting the prevalence of different strains of coronavirus in different animal species between 2015 and 2020. We conducted different analysis to assess sensitivity, publication bias, and heterogeneity, using random effect. The final meta-analysis included 42 studies for systematic review and 29 in the meta-analysis. For the geographic regions with a prevalence greater than or equal to 0.20 (Forest plot overall; prevalence = 0.20, p < 0.01, Q = 10,476.22 and I2 = 100%), the most commonly detected viruses were: enteric coronavirus (ECoV), pigeon-dominant coronavirus, (PdCoV), Avian coronavirus M41, Avian coronavirus C46, Avian coronavirus A99, Avian coronavirus JMK, MERS-CoV, Bovine coronavirus, Ro-BatCoV GCCDC1, Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gamacoronavirus and human coronaviruses (HCoVs). The wide presence of different strains of coronavirus in different animal species on all continents demonstrates the great biodiversity and ubiquity of these viruses. The most recent epidemiological crises caused by coronavirus demonstrates our unpreparedness to anticipate and mitigate emerging risks, as well as the need to implement new epidemiological surveillance programs for viruses. Combined with the need to create advanced training courses in One Health, this is paramount in order to ensure greater effectiveness in fighting the next pandemics.

Inflammatory Activity and Treatment Response in Pediatric Compared to Adult Multiple Sclerosis: A Pilot, Retrospective and Observational Study of the First Year After Diagnosis.

INTRODUCTION: Pediatric-onset multiple sclerosis may contrast with adult-onset multiple sclerosis, in terms of disease activity. We aimed to determine differentiating features between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis, at diagnosis and after one year under disease modifying therapies, and analyse the attainment of the status of "No Evidence of Disease Activity" between groups. MATERIAL AND METHODS: We analyzed demographical, laboratory, clinical and imaging features of patients with relapsing-remitting multiple sclerosis diagnosed at our center, according to the McDonald's 2010 criteria, with ≥ 1 year under disease modifying therapies and with available magnetic resonance imaging scans at diagnosis and one year after disease modifying therapies initiation. Patients were paired according to gender and disease modifying therapies in use. "No Evidence of Disease Activity" status was assessed, and differences were studied. RESULTS: Fifteen pediatric-onset multiple sclerosis (aged ≥ 8 and < 18 years) and 15 adult-onset multiple sclerosis (≥ 18 and < 55 years) patients were recruited. We found a statistically significant difference in the number of T2 weighted image diffuse lesions/with poorly defined borders (p = 0.015). The mean expanded disability status scale score after one year under disease modifying therapies was lower in the pediatric-onset multiple sclerosis group (1.6 ± 0.8) compared to the adult-onset multiple sclerosis group (2.3 ± 0.8; p = 0.032). Nevertheless, no differences were found regarding the percentage of cases achieving "No Evidence of Disease Activity" in either group. DISCUSSION: Although there is an empirical impression about the difference in inflammatory activity between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis, it was not possible to corroborate it in our study. Nevertheless, this was an exploratory and retrospective analysis of a small sample of patients, identifying variables in which such differences appear to be most important. CONCLUSION: Extensive studies of children, adolescents and adults with multiple sclerosis will be needed to categorize the clinical and radiological differences that allow the identification of drug response biomarkers in the early stages of the disease.

Introdução: A esclerose múltipla de início em idade pediátrica pode contrastar com a esclerose múltipla de início na idade adulta, em termos de atividade da doença. Pretendemos determinar características diferenciadoras entre esclerose múltipla de início em idade pediátrica e esclerose múltipla de início na idade adulta ao diagnóstico e um ano após o início de terapêuticas modificadoras da doença e analisar o atingimento do estado de "Ausência de Evidência de Atividade de Doença". Material e Métodos: Analisámos as características demográficas, laboratoriais, clínicas e imagiológicas de doentes com esclerose múltipla surto-remissão diagnosticados no nosso centro, segundo os critérios de McDonald 2010, com ≥ 1 ano sob terapêuticas modificadoras de doença e com ressonâncias magnéticas disponíveis no diagnóstico e um ano após o início de terapêuticas modificadoras da doença. Os doentes foram emparelhados de acordo com o género e terapêuticas em uso. O estado de "Ausência de Evidência de Atividade de Doença" foi avaliado e as diferenças estudadas. Resultados: Quinze doentes com esclerose múltipla de início em idade pediátrica (≥ 8 e < 18 anos de idade) e 15 com esclerose múltipla de início na idade adulta (≥ 18 e < 55 anos de idade) foram recrutados para este estudo. Encontrámos uma diferença estatisticamente significativa no número de lesões difusas/com bordos mal definidos ponderadas em T2 (p = 0,015). A pontuação média da escala expandida de incapacidade após um ano sob a respetiva terapêutica modificadora de doença foi menor no grupo esclerose múltipla de início em idade pediátrica (1,6 ± 0,8) em comparação com o grupo esclerose múltipla de início na idade adulta (2,3 ± 0,8; p = 0,032). Ainda assim, não se encontraram diferenças relativamente à percentagem de casos alcançando "Ausência de Evidência de Atividade de Doença" em ambos os grupos. Discussão: Apesar de existir uma impressão empírica sobre uma diferença de atividade inflamatória entre a esclerose múltipla de início em idade pediátrica e a esclerose múltipla de início na idade adulta, não foi possível corroborá-la no nosso estudo. De qualquer modo, esta foi uma análise exploratória e retrospetiva de uma amostra pequena de doentes, em que identificámos as variáveis em que tais diferenças parecem ser mais importantes. Conclusão: Estudos alargados de crianças, adolescentes e adultos com esclerose múltipla serão necessários para categorizar as diferenças clínicas e radiológicas que permitam identificar biomarcadores de resposta a fármacos, em fases precoces da doença.

Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley Periodicals, Inc.