Elevated cerebrospinal fluid neuronal injury biomarkers within 24 hours of onset in infection-triggered acute encephalopathy compared to complex febrile seizures.

OBJECTIVE: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.

Efficacy and safety of buccal midazolam for seizures outside the hospital: Real-world clinical experience.

INTRODUCTION: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice. METHODS: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023. RESULTS: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age. CONCLUSIONS: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone.