Improved prediction of postoperative paediatric cerebellar mutism syndrome using an artificial neural network

BACKGROUND: Postoperative paediatric cerebellar mutism syndrome (pCMS) is a common but severe complication which may arise following the resection of posterior fossa tumours in children. Two previous studies have aimed to preoperatively predict pCMS, with varying results. In this work, we examine the generalisation of these models and determine if pCMS can be predicted more accurately using an artificial neural network (ANN). METHODS: An overview of reviews was performed to identify risk factors for pCMS, and a retrospective dataset collected as per these defined risk factors from children undergoing resection of primary posterior fossa tumours. The ANN was trained on this dataset and its performance evaluated in comparison to logistic regression and other predictive indices via analysis of receiver operator characteristic curves. Area under the curve (AUC) and accuracy were calculated and compared using a Wilcoxon signed rank test, with p<0.05 considered statistically significant. RESULTS: 204 children were included, of whom 80 developed pCMS. The performance of the ANN (AUC 0.949; accuracy 90.9%) exceeded that of logistic regression (p<0.05) and both external models (p<0.001). CONCLUSION: Using an ANN, we show improved prediction of pCMS in comparison to previous models and conventional methods

Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study

BACKGROUND AND PURPOSE: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. MATERIALS AND METHODS: We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. RESULTS: A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). CONCLUSIONS: Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values

A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

BACKGROUND AND PURPOSE: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children. MATERIALS AND METHODS: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children's Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy. RESULTS: A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1-6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%-79%; specificity = 92%-99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors. CONCLUSIONS: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice

Novel <em>GFM2</em> variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits

Mitochondrial diseases are characterised by clinical, molecular and functional heterogeneity, reflecting their bi-genomic control. The nuclear gene GFM2 encodes mtEFG2, a protein with an essential role during the termination stage of mitochondrial translation. We present here two unrelated patients harbouring different and previously unreported compound heterozygous (c.569G&gt;A, p.(Arg190Gln); c.636delA, p.(Glu213Argfs*3)) and homozygous (c.275A&gt;C, p.(Tyr92Ser)) recessive variants in GFM2 identified by whole exome sequencing (WES) together with histochemical and biochemical findings to support the diagnoses of pathological GFM2 variants in each case. Both patients presented similarly in early childhood with global developmental delay, raised CSF lactate and abnormalities on cranial MRI. Sanger sequencing of familial samples confirmed the segregation of bi-allelic GFM2 variants with disease, while investigations into steady-state mitochondrial protein levels revealed respiratory chain subunit defects and loss of mtEFG2 protein in muscle. These data demonstrate the effects of defective mtEFG2 function, caused by previously unreported variants, confirming pathogenicity and expanding the clinical phenotypes associated with GFM2 variants

Development of Secondary Woodland in Oak Wood Pastures Reduces the Richness of Rare Epiphytic Lichens

Wooded pastures with ancient trees were formerly abundant throughout Europe, but during the last century, grazing has largely been abandoned often resulting in dense forests. Ancient trees constitute habitat for many declining and threatened species, but the effects of secondary woodland on the biodiversity associated with these trees are largely unknown. We tested for difference in species richness, occurrence, and abundance of a set of nationally and regionally red-listed epiphytic lichens between ancient oaks located in secondary woodland and ancient oaks located in open conditions. We refined the test of the effect of secondary woodland by also including other explanatory variables. Species occurrence and abundance were modelled jointly using overdispersed zero-inflated Poisson models. The richness of the red-listed lichens on ancient oaks in secondary woodland was half of that compared with oaks growing in open conditions. The species-level analyses revealed that this was mainly the result of lower occupancy of two of the study species. The tree-level abundance of one species was also lower in secondary woodland. Potential explanations for this pattern are that the study lichens are adapted to desiccating conditions enhancing their population persistence by low competition or that open, windy conditions enhance their colonisation rate. This means that the development of secondary woodland is a threat to red-listed epiphytic lichens. We therefore suggest that woody vegetation is cleared and grazing resumed in abandoned oak pastures. Importantly, this will also benefit the vitality of the oaks

Local Abundance Patterns of Noctuid Moths in Olive Orchards: Life-History Traits, Distribution Type and Habitat Interactions

Local species abundance is related to range size, habitat characteristics, distribution type, body size, and life-history variables. In general, habitat generalists and polyphagous species are more abundant in broad geographical areas. Underlying this, local abundance may be explained from the interactions between life-history traits, chorological pattern, and the local habitat characteristics. The relationship within taxa between life-history traits, distribution area, habitat characteristics, and local abundance of the noctuid moth (Lepidoptera: Noctuidae) assemblage in an olive orchard, one of the most important agro-ecosystems in the Mediterranean basin, was analyzed. A total of 66 species were detected over three years of year-round weekly samplings using the light-trap method. The life-history traits examined and the distribution type were found to be related to the habitat-species association, but none of the biological strategies defined from the association to the different habitats were linked with abundance. In contrast to general patterns, dispersal ability and number of generations per year explained differences in abundance. The relationships were positive, with opportunistic taxa that have high mobility and several generations being locally more abundant. In addition, when the effect of migrant species was removed, the distribution type explained abundance differences, with Mediterranean taxa (whose baricenter is closer to the studied area) being more abundant