Perioperative Management of Children on Ketogenic Dietary Therapies.

Ketogenic diet therapy (KDT) is an effective treatment modality for children with drug-resistant epilepsy and certain other metabolic and neurologic disorders. With a resurgence of interest in KDT, pediatric anesthesiologists are increasingly encountering children on KDT for a variety of surgical and medical procedures. Maintenance of ketosis is critical throughout the perioperative period, and if not managed appropriately, these patients are at an increased risk of seizures. This review article provides an overview of the clinical indications, contraindications, proposed anticonvulsant mechanisms, initiation, and monitoring of children on KDTs. Recommendations for the perioperative anesthetic management of children on KDT are summarized. A comprehensive table listing the carbohydrate content of common anesthetic drugs is also included.

Mechanism of CREB recognition and coactivation by the CREB-regulated transcriptional coactivator CRTC2.

Basic leucine zipper (bZip) transcription factors regulate cellular gene expression in response to a variety of extracellular signals and nutrient cues. Although the bZip domain is widely known to play significant roles in DNA binding and dimerization, recent studies point to an additional role for this motif in the recruitment of the transcriptional apparatus. For example, the cAMP response element binding protein (CREB)-regulated transcriptional coactivator (CRTC) family of transcriptional coactivators has been proposed to promote the expression of calcium and cAMP responsive genes, by binding to the CREB bZip in response to extracellular signals. Here we show that the CREB-binding domain (CBD) of CRTC2 folds into a single isolated 28-residue helix that seems to be critical for its interaction with the CREB bZip. The interaction is of micromolar affinity on palindromic and variant half-site cAMP response elements (CREs). The CBD and CREB assemble on the CRE with 2:2:1 stoichiometry, consistent with the presence of one CRTC binding site on each CREB monomer. Indeed, the CBD helix and the solvent-exposed residues in the dimeric CREB bZip coiled-coil form an extended protein-protein interface. Because mutation of relevant bZip residues in this interface disrupts the CRTC interaction without affecting DNA binding, our results illustrate that distinct DNA binding and transactivation functions are encoded within the structural constraints of a canonical bZip domain.

Comparison of subdural grid and stereoelectroencephalography in a cohort of pediatric patients.

OBJECTIVE: To compare adverse events and outcomes between stereoelectroencephalography (SEEG) and subdural electrode (SDE) implantation in children. METHODS: This was a retrospective analysis of 108 patients who underwent intracranial monitoring with SEEG or SDE implantation at Children's Hospital Colorado between January 2011 and June 2019. RESULTS: There were 47 patients who underwent 53 SEEG implantations and 61 patients who underwent 64 SDE implantations, with an average age of 12.45 years (range: 1.22-19.96 years). Post-implantation imaging was performed in all SEEG implantations and 42 SDE implantations. 38 % and 88 % of SEEG and SDE implantations, respectively, had a hemorrhage of any kind (p < 0.01). Clinically significant hemorrhages did not differ between the two groups, though one death was reported in the SEEG group. No patient undergoing SEEG implantation received blood products compared to 20 % of SDE patients (p < 0.01). The rate of infection in SEEG patients was 4% compared to 33 % for SDE patients (p = 0.01). Resection was completed in 60 % of SEEG patients versus 93 % for SDE patients (p < 0.01). Rate of seizure response was not significantly different between the two groups, with 81 % and 71 % of SEEG and SDE patients, respectively, reaching Engel class I or II at 12 months (p = 0.76). SIGNIFICANCE: In pediatric patients at a single institution, SEEG is associated with less adverse effects overall yet similar rates of seizure freedom compared to SDE implantation. This includes significantly lower rates of asymptomatic hemorrhage, infection and need for blood transfusion associated with SEEG monitoring. There was no statistical difference in clinically significant hemorrhages between the two groups, although rare in both.

Ondansetron for Acute Migraine in the Pediatric Emergency Department.

BACKGROUND: Migraine patients are commonly encountered in the pediatric emergency departments. Much of the research on migraine treatment regimens involves antidopaminergic antiemetics such as prochlorperazine and metoclopramide. Despite a comparably more favorable side effect profile, no migraine treatment research has included ondansetron, a selective type three 5-hydroxytryptamine receptor antagonist. Our primary objective was to determine if treatment regimens including ondansetron were successful in reducing verbal pain scores. METHODS: We retrospectively reviewed patients with migraine aged seven to 18 years who visited the pediatric emergency departments over a four-year period. Charts were reviewed for initial and discharge pain scores, pediatric emergency department revisits, neurology consultation, and opioid administration. The primary outcome was treatment success, defined as reduction in the verbal pain score of 50% or more. Secondary outcomes included adverse effects, receiving non-evidence-based treatment defined as receiving an opioid, neurology consultation rate, and pediatric emergency department revisit rate within 48 hours. RESULTS: Ninety-eight encounters were included: 42 received ondansetron, 22 received an antidopaminergic, and 34 received no antiemetic. Thirty-eight patients (90%) in the ondansetron group (95% confidence interval 81 to 99) reached treatment success. Pediatric emergency department revisits, opioid administration, neurology consultation, and treatment success were similar among the ondansetron and antidopaminergic groups. CONCLUSION: Ondansetron may be a useful medication in the treatment regimen of migraine patients in the pediatric emergency department. Preliminary data suggest that ondansetron is comparable to antidopaminergic agents.