Model selection based algorithm in neonatal Chest EIT

This paper presents a new method for selecting a patient specific forward model to compensate for anatomical variations in electrical impedance tomography (EIT) monitoring of neonates. The method uses a combination of shape sensors and absolute reconstruction. It takes advantage of a probabilistic approach which automatically selects the best estimated forward model fit from pre-stored library models. Absolute/static image reconstruction is performed as the core of the posterior probability calculations. The validity and reliability of the algorithm in detecting a suitable model in the presence of measurement noise is studied with simulated and measured data from 11 patients. The paper also demonstrates the potential improvements on the clinical parameters extracted from EIT images by considering a unique case study with a neonate patient undergoing computed tomography imaging as clinical indication prior to EIT monitoring. Two well-known image reconstruction techniques, namely GREIT and tSVD, are implemented to create the final tidal images. The impacts of appropriate model selection on the clinical extracted parameters such as center of ventilation and silent spaces are investigated. The results show significant improvements to the final reconstructed images and more importantly to the clinical EIT parameters extracted from the images that are crucial for decision-making and further interventions

Model Selection Based Algorithm in Neonatal Chest EIT

This paper presents a new method for selecting a patient specific forward model to compensate for anatomical variations in electrical impedance tomography (EIT) monitoring of neonates. The method uses a combination of shape sensors and absolute reconstruction. It takes advantage of a probabilistic approach which automatically selects the best estimated forward model fit from pre-stored library models. Absolute/static image reconstruction is performed as the core of the posterior probability calculations. The validity and reliability of the algorithm in detecting a suitable model in the presence of measurement noise is studied with simulated and measured data from 11 patients

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) : characterisation of a novel cerebropulmonary disease

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.Peer reviewe

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Background. Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy.Methods. Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files.Results. Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts.Conclusions. Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.</div

Is brain MRI needed in diagnostic evaluation of mild intellectual disability?

Abstract Aim: The purpose of our study was to suggest an imaging strategy and guidelines for the selection of the children with mild intellectual disability (ID) for magnetic resonance imaging (MRI), to avoid unnecessary imaging. Methods: The brain MRIs and patient reports of 471 children were reviewed for the imaging findings and ID severity. The correlation between the clinical and brain MRI findings was analyzed in the 305 children with mild ID. Results: Thirty-eight (12.5%) of the children with mild ID had significant abnormal brain MRI findings. Thirty-five of these had other neurological symptoms or diseases in addition to ID, which were an indication for brain MRI. In the logistic regression analysis, seizures (in patients without an epilepsy diagnosis), epilepsy, movement disorders, dysmorphia, encephalitis, traumatic brain injury, and abnormal head size were statistically significant symptoms or comorbidities associated with abnormal MRI findings. Only three children (1.0%) with mild ID had a significant MRI finding without any other clinical symptoms or disease. Conclusion: Routine MRI in children with mild ID without specific neurological symptoms, dysmorphic features, or related diseases is not suggested for revealing an etiology of mild ID. Since children with ID usually need to be sedated for MRI, routine imaging in the diagnostic evaluation of mild ID should be carefully considered. Clinical examination, other symptoms, and related diseases should be carefully assessed to decide the need for MRI

Homozygous TAF1C variants are associated with a novel childhood-onset neurological phenotype

TATA-box binding protein associated factor, RNA polymerase I subunit C (TAF1C) is a component of selectivity factor 1 belonging to RNA polymerase I (Pol I) transcription machinery. We report two unrelated patients with homozygousTAF1Cmissense variants and an early onset neurological phenotype with severe global developmental delay. Clinical features included lack of speech and ambulation and epilepsy. MRI of the brain demonstrated widespread cerebral atrophy and frontal periventricular white matter hyperintensity. The phenotype resembled that of a previously described variant ofUBTF, which encodes another transcription factor of Pol I.TAF1Cvariants were located in two conserved amino acid positions and were predicted to be deleterious. In patient-derived fibroblasts,TAF1CmRNA and protein expression levels were substantially reduced compared with healthy controls. We propose that the variants impairingTAF1Cexpression are likely pathogenic and relate to a novel neurological disease. This study expands the disease spectrum related to Pol I transcription machinery, associating theTAF1Cmissense variants with a severe neurological phenotype for the first time.Peer reviewe

Favourable long-term recovery after decompressive craniectomy:the Northern Finland experience with a predominantly adolescent patient cohort

Abstract Purpose: Decompressive craniectomy (DC) is an effective treatment of intracranial hypertension. Correspondingly, the procedure is increasingly utilised worldwide. The number of patients rendered vegetative following surgery has been a concern—a matter especially important in children, due to long anticipated lifetime. Here, we report the long-term outcomes of all paediatric DC patients from an 11-year period in a tertiary-level centre that geographically serves half of Finland. Methods: We identified all patients younger than 18 years who underwent DC in the Oulu University Hospital between the years 2009 and 2019. Outcomes and clinicoradiological variables were extracted from the patient records. Results: Mean yearly prevalence of brain injury requiring DC was 1.34/100 000 children—twenty-four patients underwent DC during the study period and 21 (88%) survived. The median age of the patients was 16.0 years, and the median preoperative GCS was 5.0 (IQR 5.0). Fifteen patients (63%) had made a good recovery (Extended Glasgow Outcome Scale ≥ 7). Of the surviving patients, two (9.5%) had not returned to school. After traumatic brain injury (n = 20), the Rotterdam CT score (mean 3.0, range 1 to 5) was not associated with mortality, poor recovery or inability to continue school (p = 0.13, p = 0.41, p = 0.43, respectively). Absent basal cisterns were associated with mortality (p = 0.005), but not with poor recovery if the patient survived DC (p = 0.81). Hydrocephalus was associated with poor recovery and inability to continue school (p = 0.01 and p = 0.03, respectively). Conclusion: Most of our patients made a favourable recovery and were able to continue school. No late mortality was observed. Thus, even in clinically and radiologically severely brain-injured children, decompressive craniectomy appears to yield favourable outcomes

Preoperative measurements on MRI in Chiari 1 patients fail to predict outcome after decompressive surgery

Abstract Background: The purpose of our study was to research the parameters of magnetic resonance imaging (MRI) that would predict the outcome of surgery in patients with Chiari 1 malformation (CM1) and to evaluate changes in MRI parameters after surgery. Methods: Fifty-one patients (19 children, 13 adolescents, and 19 adults) operated on due to CM1 in Oulu University Hospital between 2004 and 2018 were evaluated. Seventeen parameters were measured from the preoperative MRI and 11 from the postoperative MRI. The correlations between the MRI parameters and the clinical variables before and after surgery were analyzed. Results: The majority (88.2%) of the patients had favorable surgical outcomes. Postoperatively, subjective symptoms improved in 88.6% of the patients and syringomyelia in 81.8%. The location of the cerebellar tonsils, when measured in relation to the C2 synchondrosis or the end plate, postoperatively moved cranially in 51.0% (n = 26), did not change in 27.4% (n = 14), and moved caudally in 21.6% (n = 11) of the patients. However, neither the location of the tonsils nor any other parameters measured from pre- or postoperative MRI correlated with the patients’ symptoms or surgical outcomes. Conclusions: No specific parameters on preoperative MRI evaluation were predictive of the outcome of surgery, emphasizing clinical examination in surgical decision-making. Furthermore, the postoperative MRI parameters did not correlate with the surgical outcomes. Thus, routine postoperative imaging is suggested only for patients with preoperatively diagnosed syringomyelia or worsening of symptoms

DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia:is there a causal relationship?

Abstract Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients