BACKGROUND AND OBJECTIVES: Elevated intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been largely unexplored. The objectives of this study were to determine the frequency of increased ICP in MOGAD and its association with disease course and outcomes and to highlight cases requiring medical and/or surgical management of increased ICP. METHODS: In this retrospective, single-center cohort study, we examined the clinical and paraclinical data from the initial presentation and follow-up data of children diagnosed with MOGAD. In those with opening pressure (OP) measurements, univariate analyses were used to evaluate factors associated with increased ICP, which was defined as OP > 28 cm H2O. We also present a case series of patients with or without OP measurement who required medical and/or surgical management of increased ICP. RESULTS: Of 86 children with MOGAD, 43 (50.0%) had an OP recorded and 7 (8.1%) required ICP management. In those with OP recorded, the median (interquartile range) OP for the different MOGAD phenotypes were: 30.0 (22.8-41.6) (acute disseminated encephalomyelitis, ADEM), 20.5 (16.1-23.6) (optic neuritis), 17.0 (17.0-22.5) (myelitis), and 19.5 (16.5-29.3) (other) cm H20. Overall, 20.9% had increased ICP based on an OP > 28 cm H2O, of whom 77.8% presented with ADEM. In a subgroup analysis of those presenting with ADEM, those with an elevated ICP had longer hospital stay (p = 0.007) and neurologic disability (defined as modified Rankin Scale >1) (p = 0.049). In those with or without OP recorded, 7 (6 with ADEM, one with cerebral cortical encephalitis) required ICP-directed therapies. Findings on brain MRI in these 7 children revealed extensive disease burden with bilateral cerebral involvement and evidence of restricted diffusion. While neuropsychological data in this small subset revealed significant variability, all sustained identifiable deficits after discharge, including attention-deficit hyperactivity disorders and language and learning disorders. DISCUSSION: In pediatric MOGAD, increased OP and ADEM at initial presentation were associated with longer hospital stays and greater long-term morbidity. Although invasive ICP monitoring has not been specifically advocated in the management of MOGAD, it is important to recognize signs and symptoms of increased ICP in these patients and consider ICP monitoring and management strategies based on clinical and radiologic findings, especially in those presenting with ADEM and with OP > 28 cm H2O.

Recently, we showed that the addition of physiological concentrations of ascorbic acid, a tear antioxidant, to the OptiSafe™ macromolecular eye irritation test reduced the false-positive (FP) rate for chemicals that had reactive chemistries, leading to the formation of reactive oxygen species (ROS) and molecular crosslinking. The purpose of the current study was to 1) increase the number of chemicals tested to comprehensibly determine whether the antioxidant-associated reduction in OD is specific to FP chemicals associated with ROS chemistries and 2) determine whether the addition of antioxidants interferes with the detection of true positive (TP) and true negative (TN) ocular irritants. We report that when ascorbic acid is added to the test reagents, retesting of FP chemicals with reactive chemistries show significantly reduced OD values (P < 0.05). Importantly, ascorbic acid had no significant effect on the OD values of TP or TN chemicals regardless of chemical reactivity. These findings suggest that supplementation of ascorbic acid in alternative ocular irritation tests may help improve the detection of TN for those commonly misclassified reactive chemicals.

Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

Background

To determine whether restricted diffusion of the callosal splenium is specific for seizure activity in neonates.

Methods

We performed a retrospective chart review of 123 neonates who had a diagnosis of hypoxic ischemic encephalopathy (HIE) who underwent therapeutic cooling and had magnetic resonance imaging (MRI) within the first 10 days of life. The regions examined for injury include the callosal splenium, cortex, deep gray matter, and subcortical white matter. Neurodevelopmental outcomes were secondarily assessed using the Bayley Scales of Infant Development at 12 to 18 months of age and > 18 months of age. APGAR scores and pH, two important markers of hypoxia/ischemia and encephalopathy, were also analyzed in relation to these outcomes.

Results

Approximately 41% of the neonates had at least one abnormal region on brain MRI, and 21% had abnormal signal in the splenium. Clinical and/or electrographic seizures were documented in 32%. Changes in the splenium had a sensitivity of 54%, specificity of 94%, and positive predictive value of 81% for seizure presence. The presence of seizures and splenium lesion was associated poor developmental outcomes at 12 to 18 months of age. APGAR scores at 10 minutes, but not lowest pH was associated with splenial changes.

Conclusions

Restricted diffusion of the callosal splenium is specific for recent seizures in neonates with HIE. Seizures and splenial lesion represent risk factors for poor neurodevelopmental outcomes. Child neurologists and neonatologists should consider splenial signal abnormality in their assessment of neonates at risk for seizures and counsel families about likely outcomes accordingly.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a relatively new disease entity in the field of demyelinating disorders. Its first diagnostic criteria have recently been published. OBJECTIVES: We evaluated the positive predictive value (PPV) for MOG-IgG testing and report the clinical and radiologic features with respect to the recently published criteria. METHODS: A retrospective study was conducted at three centers in Dallas, Texas. Patients with positive MOG-IgG testing on cell-based assays at any time were included. Positive cases were reviewed by at least two neuroimmunologists for fulfillment of the criteria. RESULTS: We included 235 patients. The PPV of seropositivity at any time was 78.3% overall, 52.6% for low titer, and 90.1% for high titer. Children had a higher PPV than adults (93.9% versus 67.2%). Positive predictive value was 6.3% in those without a core clinical demyelinating attack. Children more often have the typical imaging features of MOGAD in optic neuritis than adults. CONCLUSIONS: We report a PPV of 78.3% for MOG-IgG testing using the 2023 MOGAD diagnostic criteria. Children had higher PPV and frequency of supporting imaging features. Careful consideration is necessary when assigning patients with no core demyelinating event and low titers a MOGAD diagnosis.

Neonatal diabetes mellitus (NDM) is a rare condition that presents with diabetes in the first few months of life. The treatment of NDM may differ depending on the genetic etiology, with numerous studies showing the benefit of sulfonylurea therapy in cases caused by mutations in KCNJ11 or ABCC8 Mutations in the insulin gene (INS) have also been identified as causes of NDM; these cases are generally best treated with insulin alone. We report a case of a female infant born small for gestational age (SGA) at late preterm diagnosed with NDM at 7 wk of life who was found by rapid whole-genome sequencing to harbor a novel de novo c.26C>G (p.Pro9Arg) variant in the INS gene. She presented with diabetic ketoacidosis, which responded to insulin therapy. She did not respond to empiric trial of sulfonylurea therapy early in her hospital course, and it was discontinued once a genetic diagnosis was made. Early genetic evaluation in patients presenting with NDM is essential to optimize therapeutic decision-making.

The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (¹³C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized ¹³C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized ¹³C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized ¹³C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized ¹³C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.