Infection diagnosis in hydrocephalus CT images: a domain enriched attention learning approach.

Objective. Hydrocephalus is the leading indication for pediatric neurosurgical care worldwide. Identification of postinfectious hydrocephalus (PIH) verses non-postinfectious hydrocephalus, as well as the pathogen involved in PIH is crucial for developing an appropriate treatment plan. Accurate identification requires clinical diagnosis by neuroscientists and microbiological analysis, which are time-consuming and expensive. In this study, we develop a domain enriched AI method for computerized tomography (CT)-based infection diagnosis in hydrocephalic imagery. State-of-the-art (SOTA) convolutional neural network (CNN) approaches form an attractive neural engineering solution for addressing this problem as pathogen-specific features need discovery. Yet black-box deep networks often need unrealistic abundant training data and are not easily interpreted.Approach. In this paper, a novel brain attention regularizer is proposed, which encourages the CNN to put more focus inside brain regions in its feature extraction and decision making. Our approach is then extended to a hybrid 2D/3D network that mines inter-slice information. A new strategy of regularization is also designed for enabling collaboration between 2D and 3D branches.Main results. Our proposed method achieves SOTA results on a CURE Children's Hospital of Uganda dataset with an accuracy of 95.8% in hydrocephalus classification and 84% in pathogen classification. Statistical analysis is performed to demonstrate that our proposed methods obtain significant improvements over the existing SOTA alternatives.Significance. Such attention regularized learning has particularly pronounced benefits in regimes where training data may be limited, thereby enhancing generalizability. To the best of our knowledge, our findings are unique among early efforts in interpretable AI-based models for classification of hydrocephalus and underlying pathogen using CT scans.

Fatty filum terminale and low-lying conus medullaris in Gollop-Wolfgang complex: a case report and review of literature.

BACKGROUND/IMPORTANCE: Gollop-Wolfgang complex is a rare skeletal dysplasia with only 200 cases reported in the literature. This disorder is usually associated with several extraosseous anomalies. This report describes the first case of a fatty filum terminale and a low-lying conus medullaris in a patient with this complex. A review of the current literature of the Gollop-Wolfgang complex accompanies this case, highlighting the documented extraosseous anomalies seen in this complex. CLINICAL PRESENTATION: We report a case of an 18-month-old patient with Gollop-Wolfgang complex who underwent cord untethering with release of the filum terminale after extensive workup showed the presence of a dyssynergic bladder and radiological evaluation revealed a fatty filum terminale and low-lying conus medullaris. CONCLUSION: Gollop-Wolfgang complex is a skeletal dysplasia usually associated with several extra skeletal anomalies. Our report describes the first case of a fatty filum terminale and low-lying conus medullaris in this complex, as well as provides an overview of the documented anomalies seen in this disorder. A multidisciplinary approach is recommended when treating these infants in order to ensure that occult manifestations of the complex are not missed.

Preoperative risk and postoperative outcome from subdural fluid collections in African infants with postinfectious hydrocephalus.

OBJECTIVE: This study investigated the incidence of postoperative subdural collections in a cohort of African infants with postinfectious hydrocephalus. The authors sought to identify preoperative factors associated with increased risk of development of subdural collections and to characterize associations between subdural collections and postoperative outcomes. METHODS: The study was a post hoc analysis of a randomized controlled trial at a single center in Mbale, Uganda, involving infants (age < 180 days) with postinfectious hydrocephalus randomized to receive either an endoscopic third ventriculostomy plus choroid plexus cauterization or a ventriculoperitoneal shunt. Patients underwent assessment with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III; sometimes referred to as BSID-III) and CT scans preoperatively and then at 6, 12, and 24 months postoperatively. Volumes of brain, CSF, and subdural fluid were calculated, and z-scores from the median were determined from normative curves for CSF accumulation and brain growth. Linear and logistic regression models were used to characterize the association between preoperative CSF volume and the postoperative presence and size of subdural collection 6 and 12 months after surgery. Linear regression and smoothing spline ANOVA were used to describe the relationship between subdural fluid volume and cognitive scores. Causal mediation analysis distinguished between the direct and indirect effects of the presence of a subdural collection on cognitive scores. RESULTS: Subdural collections were more common in shunt-treated patients and those with larger preoperative CSF volumes. Subdural fluid volumes were linearly related to preoperative CSF volumes. In terms of outcomes, the Bayley-III cognitive score was linearly related to subdural fluid volume. The distribution of cognitive scores was significantly different for patients with and those without subdural collections from 11 to 24 months of age. The presence of a subdural collection was associated with lower cognitive scores and smaller brain volume 12 months after surgery. Causal mediation analysis demonstrated evidence supporting both a direct (76%) and indirect (24%) effect (through brain volume) of subdural collections on cognitive scores. CONCLUSIONS: Larger preoperative CSF volume and shunt surgery were found to be risk factors for postoperative subdural collection. The size and presence of a subdural collection were negatively associated with cognitive outcomes and brain volume 12 months after surgery. These results have suggested that preoperative CSF volumes could be used for risk stratification for treatment decision-making and that future clinical trials of alternative shunt technologies to reduce overdrainage should be considered.

Optimization of Neurite Tracing and Further Characterization of Human Monocyte-Derived-Neuronal-like Cells.

Deficits in neuronal structure are consistently associated with neurodevelopmental illnesses such as autism and schizophrenia. Nonetheless, the inability to access neurons from clinical patients has limited the study of early neurostructural changes directly in patients' cells. This obstacle has been circumvented by differentiating stem cells into neurons, although the most used methodologies are time consuming. Therefore, we recently developed a relatively rapid (~20 days) protocol for transdifferentiating human circulating monocytes into neuronal-like cells. These monocyte-derived-neuronal-like cells (MDNCs) express several genes and proteins considered neuronal markers, such as MAP-2 and PSD-95. In addition, these cells conduct electrical activity. We have also previously shown that the structure of MDNCs is comparable with that of human developing neurons (HDNs) after 5 days in culture. Moreover, the neurostructure of MDNCs responds similarly to that of HDNs when exposed to colchicine and dopamine. In this manuscript, we expanded our characterization of MDNCs to include the expression of 12 neuronal genes, including tau. Following, we compared three different tracing approaches (two semi-automated and one automated) that enable tracing using photographs of live cells. This comparison is imperative for determining which neurite tracing method is more efficient in extracting neurostructural data from MDNCs and thus allowing researchers to take advantage of the faster yield provided by these neuronal-like cells. Surprisingly, it was one of the semi-automated methods that was the fastest, consisting of tracing only the longest primary and the longest secondary neurite. This tracing technique also detected more structural deficits. The only automated method tested, Volocity, detected MDNCs but failed to trace the entire neuritic length. Other advantages and disadvantages of the three tracing approaches are also presented and discussed.

Normal childhood brain growth and a universal sex and anthropomorphic relationship to cerebrospinal fluid.

OBJECTIVE: The study of brain size and growth has a long and contentious history, yet normal brain volume development has yet to be fully described. In particular, the normal brain growth and cerebrospinal fluid (CSF) accumulation relationship is critical to characterize because it is impacted in numerous conditions of early childhood in which brain growth and fluid accumulation are affected, such as infection, hemorrhage, hydrocephalus, and a broad range of congenital disorders. The authors of this study aim to describe normal brain volume growth, particularly in the setting of CSF accumulation. METHODS: The authors analyzed 1067 magnetic resonance imaging scans from 505 healthy pediatric subjects from birth to age 18 years to quantify component and regional brain volumes. The volume trajectories were compared between the sexes and hemispheres using smoothing spline ANOVA. Population growth curves were developed using generalized additive models for location, scale, and shape. RESULTS: Brain volume peaked at 10-12 years of age. Males exhibited larger age-adjusted total brain volumes than females, and body size normalization procedures did not eliminate this difference. The ratio of brain to CSF volume, however, revealed a universal age-dependent relationship independent of sex or body size. CONCLUSIONS: These findings enable the application of normative growth curves in managing a broad range of childhood diseases in which cognitive development, brain growth, and fluid accumulation are interrelated.

Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial.

OBJECTIVE: Hydrocephalus in infants, particularly that with a postinfectious etiology, is a major public health burden in Sub-Saharan Africa. The authors of this study aimed to determine whether surgical treatment of infant postinfectious hydrocephalus in Uganda results in sustained, long-term brain growth and improved cognitive outcome. METHODS: The authors performed a trial at a single center in Mbale, Uganda, involving infants (age < 180 days old) with postinfectious hydrocephalus randomized to endoscopic third ventriculostomy plus choroid plexus cauterization (ETV+CPC; n = 51) or ventriculoperitoneal shunt (VPS; n = 49). After 2 years, they assessed developmental outcome with the Bayley Scales of Infant Development, Third Edition (BSID-III), and brain volume (raw and normalized for age and sex) with CT scans. RESULTS: Eighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms in terms of BSID-III cognitive score (p = 0.17) or brain volume (p = 0.36), so they were analyzed together. Raw brain volumes increased between baseline and 2 years (p < 0.001), but this increase occurred almost exclusively in the 1st year (p < 0.001). The fraction of patients with a normal brain volume increased from 15.2% at baseline to 50.0% at 1 year but then declined to 17.8% at 2 years. Substantial normalized brain volume loss was seen in 21.3% patients between baseline and year 2 and in 76.7% between years 1 and 2. The extent of brain growth in the 1st year was not associated with the extent of brain volume changes in the 2nd year. There were significant positive correlations between 2-year brain volume and all BSID-III scores and BSID-III changes from baseline. CONCLUSIONS: In Sub-Saharan Africa, even after successful surgical treatment of infant postinfectious hydrocephalus, early posttreatment brain growth stagnates in the 2nd year. While the reasons for this finding are unclear, it further emphasizes the importance of primary infection prevention and mitigation strategies along with optimizing the child's environment to maximize brain growth potential.

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

Normative human brain volume growth.

OBJECTIVE While there is a long history of interest in measuring brain growth, as of yet there is no definitive model for normative human brain volume growth. The goal of this study was to analyze a variety of candidate models for such growth and select the model that provides the most statistically applicable fit. The authors sought to optimize clinically applicable growth charts that would facilitate improved treatment and predictive management for conditions such as hydrocephalus. METHODS The Weibull, two-term power law, West ontogenic, and Gompertz models were chosen as potential models. Normative brain volume data were compiled from the NIH MRI repository, and the data were fit using a nonlinear least squares regression algorithm. Appropriate statistical measures were analyzed for each model, and the best model was characterized with prediction bound curves to provide percentile estimates for clinical use. RESULTS Each model curve fit and the corresponding statistics were presented and analyzed. The Weibull fit had the best statistical results for both males and females, while the two-term power law generated the worst scores. The statistical measures and goodness of fit parameters for each model were provided to assure reproducibility. CONCLUSIONS The authors identified the Weibull model as the most effective growth curve fit for both males and females. Clinically usable growth charts were developed and provided to facilitate further clinical study of brain volume growth in conditions such as hydrocephalus. The authors note that the homogenous population from which the normative MRI data were compiled limits the study. Gaining a better understanding of the dynamics that underlie childhood brain growth would yield more predictive growth curves and improved neurosurgical management of hydrocephalus.

Endoscopic Treatment versus Shunting for Infant Hydrocephalus in Uganda.

BACKGROUND: Postinfectious hydrocephalus in infants is a major health problem in sub-Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes. METHODS: We conducted a randomized trial to evaluate cognitive outcomes after ETV-CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID-3 motor and language scores, treatment failure (defined as treatment-related death or the need for repeat surgery), and brain volume measured on computed tomography. RESULTS: A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV-CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID-3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV-CPC and 2 for ventriculoperitoneal shunting; Hodges-Lehmann estimated difference, 0; 95% confidence interval [CI], -2 to 0; P=0.35). There was no significant difference between the ETV-CPC group and the ventriculoperitoneal-shunt group in BSID-3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, -2.4 and -2.1, respectively; estimated difference, 0.3; 95% CI, -0.3 to 1.0; P=0.12). CONCLUSIONS: This single-center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV-CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272 .).