Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy.

OBJECTIVE: We analyzed long-term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy. METHODS: Forty-one children (25 males) with drug-resistant epilepsy had a baseline positron emission tomography (PET) scan at a median age of 4.7 years; the scans were repeated after a median of 4.3 years. Children with progressive neurological disorders or space-occupying lesion-related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2-deoxy-2(18 F)-fluoro-D-glucose-PET at baseline and follow-up was correlated with epilepsy variables and developmental outcome. RESULTS: On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow-up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow-up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow-up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline (r = .31, P = .05) and follow-up scans (r = .27, P = .09). SIGNIFICANCE: In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered.

Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.

BACKGROUND: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters. METHODS: Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples. RESULTS: Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005). CONCLUSIONS: We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

Use of Gonadotropin-Releasing Hormone for Intractable Seizures in a Girl with Precocious Puberty without Hypothalamic Hamartoma.

The use of gonadotropin-releasing hormone analogs has been reported in the treatment of gelastic seizures and precocious puberty associated with hypothalamic hamartomas, but not in other seizure types without hypothalamic hamartoma. We describe a 7.5 year-old girl whose seizures subsided after gonadotropin-releasing hormone analog implant, administered for precocious puberty.

Pediatric Resident Confidence in Assessing Neurological Cases: A Nationwide Survey.

BACKGROUND: A relative shortage of pediatric neurologists in proportion to estimated neurological disorders often results in general pediatricians evaluating and treating children with complex neurological conditions. Dedicated rotations in pediatric neurology are not mandated during medical school or pediatric residency. We evaluated the perceptions of a large cohort of pediatric residents and program directors (PDs) regarding child neurology training. METHODS: Using an online tool, surveys were sent to pediatric residents and pediatric and pediatric neurology PDs. RESULTS: Response rates were 41% from pediatric residency programs, yielding 538 resident responses; 31% from pediatric PDs; and 62% from pediatric neurology PDs. Only 27% of the surveyed residents reported completing a neurology rotation during residency, 89% of whom expressed a subjective improvement in confidence with neurological assessments. Factors affecting comfort with eliciting a neurological history included exposure to a neurology rotation during residency, year of training, duration of neurology rotation in medical school, and inpatient exposure to neurological patients, whereas those associated with examination additionally included program size and postresidency plans. Overall, 80% of surveyed residents, 78% of pediatric PDs, and 96% of pediatric neurology PDs acknowledged the potential value of a mandatory pediatric neurology rotation during residency. CONCLUSION: We suggest that a mandatory pediatric neurology rotation will boost the confidence of current and future pediatric trainees in assessing common neurological conditions of childhood.

Neurological Effects of COVID-19 in Children.

The COVID-19 pandemic has spread rapidly across the world in 2020, affecting both adults and, to a lesser extent, children. In this article, the authors describe the neurologic manifestations of COVID-19 in children, including the epidemiology, pathogenesis, clinical features, laboratory and imaging findings, and treatment options. The management of patients with concomitant neuroimmunologic disorders and drug interactions between medications used to treat COVID-19 and other neurologic disorders (especially immune-modifying drugs) is also discussed.

Refractory NMDA-receptor encephalitis in a teenager: A novel use of Bortezomib.

We report the case of a 14-year-old girl who was diagnosed with N-methyl-d-aspartate (NMDA)-receptor encephalitis, with severe features and autonomic instability, requiring intensive care unit admission. She had poor clinical response to the first-line therapies, she was then started on Rituximab and 6 cycles of Cytoxan infusion. She responded to Bortezomib therapy within 2 weeks of initiation, and with long-term sustenance of improvement in the long-term, also demonstrated by an improvement in NMDA titers . As far as we know, this is the first report of use of Bortezomib therapy in a child with refractory NMDA-receptor encephalitis.

Diagnosing Pseudotumor Cerebri: An Age-based Approach.

Investigators from Hillel-Yaffe, Carmel, and Bnai Zion Medical Centers in Israel studied the comparative clinical presentations and predisposing factors for idiopathic intracranial hypertension (IIH) across age groups.

Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and SCN1A Gene Variants.

Three children with drug-refractory epilepsy, normal magnetic resonance image (MRI), and a heterozygous SCN1A variant underwent 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) scanning between age 6 months and 1 year and then at age 3 years 6 months to 5 years 5 months. Regional FDG uptake values were compared to those measured in age- and gender-matched pseudo-controls. At baseline, the brain glucose metabolic pattern in the SCN1A group was similar to that of the pseudo-controls. At follow-up, robust decreases of normalized FDG uptake was found in bilateral frontal, parietal and temporal cortex, with milder decreases in occipital cortex. Children with epilepsy and an SCN1A variant have a normal pattern of cerebral glucose metabolism at around 1 year of age but develop bilateral cortical glucose hypometabolism by age 4 years, with maximal decreases in frontal, parietal, and temporal cortex. This metabolic pattern may be characteristic of epilepsy associated with SCN1A variants and may serve as a biomarker to monitor disease progression and response to treatments.