Intracranial vessel wall magnetic resonance imaging features of infectious vasculitis.

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. The infectious agent may directly infect the endothelium, causing vasculitis, or indirectly affect the vessel wall through an immunological mechanism. The clinical manifestations of these complications usually overlap with those of non-infectious vascular diseases, making diagnosis challenging. Intracranial vessel wall magnetic resonance imaging (VWI) enables the evaluation of the vessel wall and the diseases that affect it, providing diagnostic data beyond luminal changes and enabling the identification of inflammatory changes in cerebral vasculitis. This technique demonstrates concentric vessel wall thickening and gadolinium enhancement, associated or not with adjacent brain parenchymal enhancement, in patients with vasculitis of any origin. It permits the detection of early alterations, even before a stenosis occurs. In this article, we review the intracranial vessel wall imaging features of infectious vasculitis of bacterial, viral, and fungal etiologies.

A Deep Learning-based Model for Detecting Abnormalities on Brain MR Images for Triaging: Preliminary Results from a Multisite Experience.

PURPOSE: To develop a deep learning model for detecting brain abnormalities on MR images. MATERIALS AND METHODS: In this retrospective study, a deep learning approach using T2-weighted fluid-attenuated inversion recovery images was developed to classify brain MRI findings as "likely normal" or "likely abnormal." A convolutional neural network model was trained on a large, heterogeneous dataset collected from two different continents and covering a broad panel of pathologic conditions, including neoplasms, hemorrhages, infarcts, and others. Three datasets were used. Dataset A consisted of 2839 patients, dataset B consisted of 6442 patients, and dataset C consisted of 1489 patients and was only used for testing. Datasets A and B were split into training, validation, and test sets. A total of three models were trained: model A (using only dataset A), model B (using only dataset B), and model A + B (using training datasets from A and B). All three models were tested on subsets from dataset A, dataset B, and dataset C separately. The evaluation was performed by using annotations based on the images, as well as labels based on the radiology reports. RESULTS: Model A trained on dataset A from one institution and tested on dataset C from another institution reached an F1 score of 0.72 (95% CI: 0.70, 0.74) and an area under the receiver operating characteristic curve of 0.78 (95% CI: 0.75, 0.80) when compared with findings from the radiology reports. CONCLUSION: The model shows relatively good performance for differentiating between likely normal and likely abnormal brain examination findings by using data from different institutions.Keywords: MR-Imaging, Head/Neck, Computer Applications-General (Informatics), Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms© RSNA, 2021Supplemental material is available for this article.

Bone marrow burden score is not useful as a follow-up parameter in stable patients with type 1 Gaucher disease after 5 years of treatment.

INTRODUCTION: Gaucher disease (GD) is one of the most prevalent lysosomal disorders, with an estimated incidence of 1 in 40,000 live births worldwide. Skeletal involvement is one of the main features of GD, causing morbidity and impacting long-term quality of life in patients with type 1 GD. OBJECTIVES: To characterize bone marrow infiltration in patients with type 1 GD followed at the Gaucher Disease Referral Center of Porto Alegre, Brazil, and to assess whether the Bone Marrow Burden score (BMB) correlates with clinical or laboratory parameters. We also evaluated whether the BMB score is a suitable parameter for long-term follow-up of patients with type 1 GD. METHODS: All included patients underwent magnetic resonance imaging for BMB score calculation at baseline, 1 year, and every other year thereafter or as clinically indicated from 2012 to 2018. RESULTS: The BMB score tended to decrease during the first 5 years of treatment, at a rate of -1.08 points per year; after the 5-year mark, BMB tended to remain stable. CONCLUSIONS: The BMB score is useful for response monitoring in the first five years of treatment. We recommend that, after 5 years of treatment, MRI for BMB evaluation should only be performed in non-adherent patients or in those who develop symptoms of acute skeletal disease.

Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome.

Alopecia, neurologic defects, and endocrinopathy (ANE) syndrome is a rare ribosomopathy known to be caused by a p.(Leu351Pro) variant in the essential, conserved, nucleolar large ribosomal subunit (60S) assembly factor RBM28. We report the second family of ANE syndrome to date and a female pediatric ANE syndrome patient. The patient presented with alopecia, craniofacial malformations, hypoplastic pituitary, and hair and skin abnormalities. Unlike the previously reported patients with the p.(Leu351Pro) RBM28 variant, this ANE syndrome patient possesses biallelic precursor messenger RNA (pre-mRNA) splicing variants at the 5' splice sites of exon 5 (ΔE5) and exon 8 (ΔE8) of RBM28 (NM_018077.2:c.[541+1_541+2delinsA]; [946G > T]). In silico analyses and minigene splicing experiments in cells indicate that each splice variant specifically causes skipping of its respective mutant exon. Because the ΔE5 variant results in an in-frame 31 amino acid deletion (p.(Asp150_Lys180del)) in RBM28 while the ΔE8 variant leads to a premature stop codon in exon 9, we predicted that the ΔE5 variant would produce partially functional RBM28 but the ΔE8 variant would not produce functional protein. Using a yeast model, we demonstrate that the ΔE5 variant does indeed lead to reduced overall growth and large subunit ribosomal RNA (rRNA) production and pre-rRNA processing. In contrast, the ΔE8 variant is comparably null, implying that the partially functional ΔE5 RBM28 protein enables survival but precludes correct development. This discovery further defines the underlying molecular pathology of ANE syndrome to include genetic variants that cause aberrant splicing in RBM28 pre-mRNA and highlights the centrality of nucleolar processes in human genetic disease.

Determinants of cerebral radiological progression in Fabry disease.

BACKGROUND AND AIM: It is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. The aim of this study was to determine the effect of ERT and clinical characteristics on progression of WMLs and infarctions on MRI in patients with FD. METHODS: MRIs were assessed for WMLs (Fazekas scale), infarctions and basilar artery diameter (BAD). The effect of clinical characteristics (renal and cardiac involvement, cardiovascular risk factors, cardiac complications, BAD) and ERT on WML and infarction progression was evaluated using mixed models. RESULTS: One hundred forty-nine patients were included (median age: 39 years, 38% men, 79% classical phenotype). Median follow-up time was 7 years (range: 0-13 years) with a median number of MRIs per patient of 5 (range: 1-14), resulting in a total of 852 scans. Variables independently associated with WML and infarction progression were age, male sex and a classical phenotype. Progression of WMLs and infarctions was not affected by adding ERT to the model, neither for the whole group, nor for early treated patients. Progression was highly variable among patients which could not be explained by other known variables such as hypertension, cholesterol, atrial fibrillation and changes in kidney function, left ventricular mass or BAD. CONCLUSION: Progression of WMLs and cerebral infarctions in FD is mainly related to age, sex and phenotype. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible.

Depressive symptoms in Fabry disease: the importance of coping, subjective health perception and pain.

BACKGROUND: Despite the high prevalence of depressive symptoms in Fabry disease (FD), it is unclear which patient characteristics are important in relation to these symptoms. Additionally, the impact of coping styles in relation to depressive symptoms in FD has been unexplored. Determining the impact of different factors relating to depressive symptoms in FD can guide both prevention and treatment of these symptoms. METHODS: Depressive symptoms (Center for Epidemiologic Studies Depression scale (CESD)) and coping styles (Utrecht Coping List) were assessed in a Dutch FD cohort. Other potentially important variables were identified from FD literature and assessed in this cohort. Relations were evaluated using multiple linear models. RESULTS: Potentially important variables in FD literature were: pain, unemployment, health perception, being single, comorbidities and stroke. Employed coping styles were "avoidance and brooding", "positivity and problem solving" and "seeking social support". Thirty-one of the 81 FD patients (38%) had depressive symptoms. CESD-scores were lower in patients with better health perception and more "positivity and problem solving" and higher in patients with more pain and "avoidance and brooding". The best model explained 70% (95%CI: 54-76%) of observed variance of the CESD. CONCLUSIONS: Depressive symptoms in FD are related to pain, negative health perception and use of specific coping styles. Psychological interventions could be employed to alter coping behavior and alleviate depressive symptoms.

Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD.

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder.

Validation of a Smartphone Application in the Evaluation and Treatment of Acute Stroke in a Comprehensive Stroke Center.

Background and Purpose- The increasing demand and shortage of experts to evaluate and treat acute stroke patients has led to the development of remote communication tools to aid stroke management. We aimed to evaluate the JOIN App smartphone system-a low-cost tool for rapid clinical and neuroimaging data sharing to expedite decision-making in stroke. Methods- Consecutive acute ischemic stroke patients treated at a University Hospital in Brazil from December 2014 to December 2015 were evaluated. The analysis included all patients presenting with acute ischemic stroke who underwent initial evaluation by neurology residents followed by JOIN teleconsultation with a stroke neurologist on call for management decisions. An expert panel of stroke neurologists and neuroradiologists revised all cases using a standard Picture Archiving and Communication System imaging workstation within 24 hours and analyzed the decision made with remote assistance during the emergency setting. Results- A total of 720 stroke codes were evaluated with 442 acute ischemic stroke qualifying. Seventy-eight (18%) patients were treated with intravenous thrombolysis. The main reasons for tPA (tissue-type plasminogen activator) exclusion were symptom onset >4.5 hours (n=295; 67%) and hypodense middle cerebral artery territory area >1/3 (n=31; 7%). The agreement rates between Picture Archiving and Communication System versus JOIN-based thrombolysis decisions were 100% for the stroke (unblinded) and 99.3% for the neuroradiologist (blinded) experts. The use of the application resulted in a significant reduction in the door-to-needle times across the pre- versus postimplementation periods (median, 90 [interquartile range, 75-106] versus 63 [interquartile range, 61-117] minutes; P=0.03). The rates of 90-day excellent outcomes (modified Rankin Scale, 0-1) were 51.3%; 90-day mortality, 2.6%; and symptomatic intracranial hemorrhage, 3.8%. Conclusions- The JOIN smartphone system allows rapid sharing of clinical and imaging data to facilitate decisions for stroke treatment. The remote application-based decisions seem to be as accurate as the physical presence of stroke experts and might lead to faster times to treatment. This system represents an easily implementable low-cost telemedicine solution for centers that cannot afford the full-time presence of stroke specialists.

Predictors of objective cognitive impairment and subjective cognitive complaints in patients with Fabry disease.

This study investigates the relationship between objective cognitive impairment (OCI), subjective cognitive complaints and depressive symptoms in men and women with classical and non-classical Fabry disease (FD). Cognitive functioning was assessed using a neuropsychological test battery, subjective cognitive complaints using a structured interview and depressive symptoms using a depression scale (CESD). Eighty-one patients were included (mean age 44.5 ± 14.3, 35% men, 74% classical). Subjective cognitive complaints were reported by 64% of all patients. OCI was present in thirteen patients (16%), predominantly in men with classical FD. Thirty-one patients (38%) had a high score (≥16) on the CESD scale. Male sex (OR, 6.8; 95%CI, 1.6-39.8; p = 1.6 * 10-2) and stroke (OR, 6.4; 95% CI, 1.1-41.0; p = 3.7 * 10-2) were independently positively associated with OCI, and premorbid IQ (one IQ point increase: OR, 0.91; 95%CI, 0.82-0.98; p = 3.8 * 10-2) was independently negatively associated with OCI. The CESD-score (one point increase: OR, 1.07; 95% CI, 1.02-1.13; p = 3.3 * 10-3) and a history of depression (OR, 2.7; 95% CI, 1.1-7.3; p = 3.9 * 10-2) were independently positively associated with subjective cognitive complaints. OCI is present in 16% of FD patients, warranting referral for neuropsychological assessment. Nevertheless, subjective cognitive complaints are related to depressive symptoms, emphasizing the importance of recognition and treatment of the latter.

Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy: magnetic resonance imaging findings and neurological outcomes in a Brazilian cohort.

OBJECTIVE: To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country. STUDY DESIGN: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings. RESULTS: Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p < .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p < .001; p = .001; p = .001, and p = .011, respectively). CONCLUSIONS: Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.

Acute cerebellitis caused by herpes simplex virus

Case presentation of acute cerebellitis caused by herpes simplex virus.

Leigh Syndrome Due to mtDNA Pathogenic Variants

Abstract Leigh syndrome is a devastating neurodegenerative disease, typically manifesting in infancy or early childhood. Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions. It is genetically heterogeneous, causative mutations have been disclosed in mitochondrial DNA and nuclear genes involved in the process of energy production in the mitochondria .We investigated the whole mitochondrial DNA in three Brazilian patients with LS, based on their clinical and biochemical data, with the aim to identify the disease-causing mutations. In two of the patients, with complex I deficiency, a novel heteroplasmic variant m.4142G>T (p.R279L) in MT-ND1 and a recurrent homoplasmic mutation m.10197G>A (p.A47T) in MT-ND3 were identified. In the remaining patient, with complex IV deficiency, a de novo heteroplasmic variant in MT-CO1 m.6547T>C (p.L215P) was found. The molecular investigation in mitochondrial diseases have shifted their focus from mitochondrial DNA to nuclear DNA, however, mtDNA protein-coding genes are one of the important genetic causes of mitochondrial disorders for Leigh syndrome. This study expands the molecular and clinical spectrum associated with this disease.

Reproducibility of a quantitative system for assessing the quality of diagnostic ultrasound.

OBJECTIVE: To present a quantitative system for assessing the quality of ultrasound examinations-SQUALUS-and to determine its reproducibility, taking into consideration the images on file, as well as the consistency between the images obtained and the final report. MATERIALS AND METHODS: The system includes questions related to the number of images; the appropriateness of images in relation to the protocol established; focus adjustment; depth; gain; and appropriateness of the measurements for B-mode examinations. For Doppler examinations, the system includes questions related to the appropriateness of color images, the spectral analysis, and correction of the insonation angle. To assess the quality of the report, the system includes questions related to the consistency between the images obtained and the contents of the report. An overall numerical score was assigned by averaging the scores for image quality and for the contents of the report. Two independent examiners, each blinded to the evaluation of the other, assessed 30 different types of ultrasound examinations. RESULTS: There was statistically significant agreement between the two examiners for 8 of the 10 questions related to image quality. For the questions related to the quality of the reports, the interexaminer agreement was almost perfect. CONCLUSION: The proposed quantitative system for assessing the quality of ultrasound examinations is a reproducible tool that can be used in audits and accreditation programs.

Reproducibility of a quantitative system for assessing the quality of diagnostic ultrasound / Verificação da reprodutibilidade de um sistema quantitativo de avaliação da qualidade de exames de ultrassonografia diagnóstica

Abstract Objective: To present a quantitative system for assessing the quality of ultrasound examinations-SQUALUS-and to determine its reproducibility, taking into consideration the images on file, as well as the consistency between the images obtained and the final report. Materials and Methods: The system includes questions related to the number of images; the appropriateness of images in relation to the protocol established; focus adjustment; depth; gain; and appropriateness of the measurements for B-mode examinations. For Doppler examinations, the system includes questions related to the appropriateness of color images, the spectral analysis, and correction of the insonation angle. To assess the quality of the report, the system includes questions related to the consistency between the images obtained and the contents of the report. An overall numerical score was assigned by averaging the scores for image quality and for the contents of the report. Two independent examiners, each blinded to the evaluation of the other, assessed 30 different types of ultrasound examinations. Results: There was statistically significant agreement between the two examiners for 8 of the 10 questions related to image quality. For the questions related to the quality of the reports, the interexaminer agreement was almost perfect. Conclusion: The proposed quantitative system for assessing the quality of ultrasound examinations is a reproducible tool that can be used in audits and accreditation programs.

Resumo Objetivo: Apresentar e verificar a reprodutibilidade de um sistema quantitativo de avaliação da qualidade de exames de ultrassonografia (SQUALUS), levando em consideração as imagens documentadas e a coerência entre as imagens obtidas e o laudo final. Materiais e Métodos: Foram elaborados quesitos considerando o número de imagens, a adequação das imagens ao protocolo estabelecido, o ajuste do foco, a profundidade e ganho e a adequação das medidas. Para exames com Doppler também foram avaliadas a adequação das fotos coloridas, a análise espectral e a correção do ângulo. Para a qualidade do laudo foi considerada a coerência com as imagens documentadas e seu conteúdo. Um sistema numérico foi atribuído conferindo uma nota final à qualidade das imagens, ao conteúdo do laudo e à média das duas avaliações. Trinta exames de ultrassonografia de diferentes tipos foram avaliados por dois examinadores independentes, cegos à avaliação um do outro. Resultados: Os avaliadores apresentaram concordância estatisticamente significante em 8 de 10 quesitos para avaliação da qualidade da imagem. Na avaliação dos laudos, a concordância entre os avaliadores foi quase perfeita. Conclusão: O sistema quantitativo de avaliação da qualidade de exames ultrassonográficos proposta é uma ferramenta reprodutível que pode ser utilizada em auditorias e em programas de acreditação.

Surgical management of neurological manifestations of mucopolysaccharidosis disorders.

The mucopolysaccharidosis (MPS) disorders are ultra-rare lysosomal storage disorders associated with progressive accumulation of glycosaminoglycans (GAGs) in cells and tissues throughout the body. Clinical manifestations and progression rates vary widely across and within the different types of MPS. Neurological symptoms occur frequently, and may result directly from brain damage caused by infiltration of GAGs, or develop secondary to somatic manifestations such as spinal cord compression, hydrocephalus, and peripheral nerve entrapment. Management of secondary neurological manifestations often requires surgical correction of the underlying somatic cause. The present review discusses the surgical management of neurological disease in patients with MPS, including diagnostic imaging. Background information is derived from presentations and discussions during a meeting on the brain in MPS, attended by an international group of experts (April 28-30, 2016, Stockholm, Sweden), and additional literature searches.

Quantitative neuroimaging in mucopolysaccharidoses clinical trials.

The mucopolysaccharidosis (MPS) disorders are rare lysosomal storage disorders caused by mutations in lysosomal enzymes involved in glycosaminoglycan (GAG) degradation. The resulting intracellular accumulation of GAGs leads to widespread tissue and organ dysfunction. In addition to somatic signs and symptoms, patients with MPS can present with neurological manifestations such as cognitive decline, behavioral problems (e.g. hyperactivity and aggressiveness), sleep disturbances, and/or epilepsy. These are associated with significant abnormalities of the central nervous system (CNS), including white and gray matter lesions, brain atrophy, ventriculomegaly, and spinal cord compression. In order to effectively manage and develop therapies for MPS that target neurological disease, it is important to visualize and quantify these CNS abnormalities. This review describes optimal approaches for conducting magnetic resonance imaging assessments in multi-center clinical studies, and summarizes current knowledge from neuroimaging studies in MPS disorders. The content of the review is based on presentations and discussions on these topics that were held during a meeting of an international group of experts.

Correction to: Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses.

After publication of the article [1], it has been brought to our attention that the full funding acknowledgement is missing from the original article.