115 research outputs found
Diffusion Kurtosis Imaging of neonatal Spinal Cord in clinical routine
Diffusion kurtosis imaging (DKI) has undisputed advantages over the more classical diffusion magnetic resonance imaging (dMRI) as witnessed by the fast-increasing number of clinical applications and software packages widely adopted in brain imaging. However, in the neonatal setting, DKI is still largely underutilized, in particular in spinal cord (SC) imaging, because of its inherently demanding technological requirements. Due to its extreme sensitivity to non-Gaussian diffusion, DKI proves particularly suitable for detecting complex, subtle, fast microstructural changes occurring in this area at this early and critical stage of development, which are not identifiable with only DTI. Given the multiplicity of congenital anomalies of the spinal canal, their crucial effect on later developmental outcome, and the close interconnection between the SC region and the brain above, managing to apply such a method to the neonatal cohort becomes of utmost importance. This study will (i) mention current methodological challenges associated with the application of advanced dMRI methods, like DKI, in early infancy, (ii) illustrate the first semi-automated pipeline built on Spinal Cord Toolbox for handling the DKI data of neonatal SC, from acquisition setting to estimation of diffusion measures, through accurate adjustment of processing algorithms customized for adult SC, and (iii) present results of its application in a pilot clinical case study. With the proposed pipeline, we preliminarily show that DKI is more sensitive than DTI-related measures to alterations caused by brain white matter injuries in the underlying cervical SC
Further genotype-phenotype correlation emerging from two families with PLP1 exon 4 skipping
n/
Recommended from our members
Novel compound heterozygous pathogenic variants in nucleotide-binding protein like protein (NUBPL) cause leukoencephalopathy with multi-systemic involvement.
NUBPL (Nucleotide-binding protein like) protein encodes a member of the Mrp/NBP35 ATP-binding proteins family, deemed to be involved in mammalian complex I (CI) assembly process. Exome sequencing of a patient presenting with infantile-onset hepatopathy, renal tubular acidosis, developmental delay, short stature, leukoencephalopathy with minimal cerebellar involvement and multiple OXPHOS deficiencies revealed the presence of two novel pathogenic compound heterozygous variants in NUBPL (p.Phe242Leu/p.Leu104Pro). We investigated patient's and control immortalised fibroblasts and demonstrated that both the peripheral and the membrane arms of complex I are undetectable in mutant NUBPL cells, resulting in virtually absent CI holocomplex and loss of enzyme activity. In addition, complex III stability was moderately affected as well. Lentiviral-mediated expression of the wild-type NUBPL cDNA rescued both CI and CIII assembly defects, confirming the pathogenicity of the variants. In conclusion, this is the first report describing a complex multisystemic disorder due to NUBPL defect. In addition, we confirmed the role of NUBPL in Complex I assembly associated with secondary effect on Complex III stability and we demonstrated a defect of mtDNA-related translation which suggests a potential additional role of NUBPL in mtDNA expression
Diffusion Kurtosis Imaging of Neonatal Spinal Cord in Clinical Routine
ABSTRACT: Diffusion kurtosis imaging (DKI) has undisputed advantages over the more classical diffusionmagnetic resonance imaging (dMRI) as witnessed by the fast-increasing number of clinical applications and software packages widely adopted in brain imaging. However, in the neonatal setting, DKI is still largely underutilized, in particular in spinal cord (SC) imaging, because of its inherently demanding technological requirements. Due to its extreme sensitivity to non-Gaussian diffusion, DKI proves particularly suitable for detecting complex, subtle, fast microstructural changes occurring in this area at this early and critical stage of development, which are not identifiable with only DTI. Given the multiplicity of congenital anomalies of the spinal canal, their crucial effect on later developmental outcome, and the close interconnection between the SC region and the brain above, managing to apply such a method to the neonatal cohort becomes of utmost importance. This study will (i) mention current methodological challenges associated with the application of advanced dMRI methods, like DKI, in early infancy, (ii) illustrate the first semi-automated pipeline built on Spinal Cord Toolbox for handling the DKI data of neonatal SC, from acquisition setting to estimation of diffusion measures, through accurate adjustment of processing algorithms customized for adult SC, and (iii) present results of its application in a pilot clinical case study. With the proposed pipeline, we preliminarily show that DKI is more sensitive than DTI-related measures to alterations caused by brain white matter injuries in the underlying cervical SC
Vein of Galen aneurysmal malformation in newborns: a retrospective study to describe a paradigm of treatment and identify risk factors of adverse outcome in a referral center
BackgroundVein of Galen aneurysmal malformation (VGAM) is a rare cerebral vascular malformation associated with significant morbidity and mortality. Newborns with VGAM without adequate treatment may develop rapidly deteriorating high output heart failure (HOHF) and are at risk for severe neurological outcomes.ObjectiveTo describe the clinical course and management of newborns with VGAM, and identify which echocardiographic and neuroradiologic factors may be associated with severe heart failure at birth and adverse short term outcomes.MethodsThis is a single center retrospective cohort study including all consecutive newborns with VGAM admitted to Gaslini Children's Hospital between 2009 and 2022. We reviewed clinical data, intensive care support, fetal and neonatal cardiologic and neuroradiologic findings and we studied the association with severe HOHF, endovascular complications and death.ResultsOut of 40 newborns, 17 (42.5%) developed severe HOHF requiring early endovascular procedures. Medical treatment was focused on the main components of HOHF by providing inotropic support and peripheral vasodilation. Pulmonary vasodilators were avoided to reduce the negative effects of pulmonary overflow and prevent vascular remodeling. Reduction of the obligatory left to right shunt through the VGAM was possible only through endovascular treatment. Fetal cardiothoracic ratio was significantly associated with severe HOHF at birth and death. Cardiologic parameters of right ventricular overload, pulmonary hypertension and systemic steal were the leading findings associated with haemodynamic compromise at birth. The mediolateral diameter of the straight or falcine sinus at its shortest section (SS-MD), and arterial pseudofeeders were significantly associated with severe HOHF at birth in prenatal and postnatal assessments. None of the postnatal echocardiographic and MRI variables, nor a higher inotropic support were associated with major periprocedural complications or death. Mortality was due to palliation for congenital severe brain damage (4/40, 10%), or major periprocedural complications (3/40, 7.5%). None of the patients died due to HOHF and multiorgan failure. Overall survival at discharge was 82.5% (33/40).ConclusionsThe complexity of neonatal VGAM pathophysiology requires a multidisciplinary approach, specialized intensive care management, and early endovascular treatment to reduce mortality and optimize clinical outcomes. Cardiologic and neuroradiologic parameters are key to define risk stratification and treatment strategies
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience
n/
Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Purpose: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors.
Methods: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis.
Results: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage.
Conclusion: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.info:eu-repo/semantics/publishedVersio
Case report: Revascularization failure in NF1-related moyamoya syndrome after selumetinib: A possible pathophysiological correlation?
Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome caused by pathogenic variants in the NF1 gene, encoding a multidomain inhibitor of Ras activity. Thus, NF1 is considered a RASopathy and drugs targeting the RAS/mitogen-activated protein kinase (MAPK) pathway, such as the MAP kinase (MEK) 1/2 inhibitor Selumetinib, are promising therapeutic options to treat NF1-associated tumors, especially plexiform neurofibromas and optic way gliomas. However, surgical treatment is often required for NF1-related cerebrovascular manifestations, such as moyamoya syndrome (MMS). We report a case of an 8-year-old patient receiving Selumetinib at the dose of 25 mg/m2 orally 2 times a day as a treatment for many plexiform neurofibromas. He suffered from two close strokes and brain MRI revealed a severe cerebral vasculopathy consistent with MMS, with marked stenosis of both the internal carotid arteries. A two-step surgical revascularization procedure was performed, consisting of a direct by-pass with an encephalo-mio-synangiosis (EMS) followed by encephalo-duro-arterio-synangiosis (EDAS). Surprisingly, despite the surgical technical success, follow-up MRI revealed lack of the expected revascularization. Selumetinib is a powerful therapeutic option in the treatment of severe NF1-related tumors. However, our findings suggest that this drug may interfere with cerebral neovascularization in patients with MMS requiring surgical revascularization. This is supported by the crucial role of the Vascular-Endothelial Growth Factor (VEGF), whose signaling pathway involve MAPK, as promoter of the neovascularization. Our observations suggest to adopt an imaging surveillance strategy to prevent unfavorable surgical outcome in patients with NF1-associated MMS receiving Selumetinib, and that priority should be given to surgical revascularization
European recommendations on practices in pediatric neuroradiology: consensus document from the European Society of Neuroradiology (ESNR), European Society of Paediatric Radiology (ESPR) and European Union of Medical Specialists Division of Neuroradiology (UEMS)
Pediatric neuroradiology is a subspecialty within radiology, with possible pathways to train within the discipline from neuroradiology or pediatric radiology. Formalized pediatric neuroradiology training programs are not available in most European countries. We aimed to construct a European consensus document providing recommendations for the safe practice of pediatric neuroradiology. We particularly emphasize imaging techniques that should be available, optimal site conditions and facilities, recommended team requirements and specific indications and protocol modifications for each imaging modality employed for pediatric neuroradiology studies. The present document serves as guidance to the optimal setup and organization for carrying out pediatric neuroradiology diagnostic and interventional procedures. Clinical activities should always be carried out in full agreement with national provisions and regulations. Continued education of all parties involved is a requisite for preserving pediatric neuroradiology practice at a high level
- …