痙攣重積型（二相性）急性脳症

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common pediatric acute encephalopathy characterized by biphasic seizures and development of a bright tree appearance (BTA) on diffusion-weighted MR imaging (DWI). Lesion extent and distribution have been linked to neurological prognosis, but the effects of lesion depth remained unclear. METHODS: We retrospectively analyzed 25 children with AESD onset between 1991 and 2022. Acute-phase magnetic resonance imaging (MRI) (4-14 days after onset) was evaluated using DWI. Lesions in 10 cerebral regions were classified by depth as BTA limited to the subcortical area (BTA-L) or BTA with extension into the deep white matter (BTA-E). Neurological outcomes included pediatric cerebral performance category scores and residual motor paralysis at ≥12 months. Associations between MRI findings and outcomes were analyzed using univariate logistic regression and receiver operating characteristic analyses. RESULTS: Thirteen patients had favorable outcomes, whereas 12 had unfavorable outcomes based on pediatric cerebral performance category scores. Bilateral temporal lobe involvement with BTA-L/E (odds ratio [OR], 16.8), bilateral frontal lobe involvement with BTA-E (OR, 10.0), and bilateral thalamus/basal ganglia lesions (OR, 12.0) showed significant associations with unfavorable outcomes. Residual motor paralysis was associated with lesion burden and distribution. Rolandic BTA-E showed an association with motor paralysis (OR, 90.0), even in unilateral cases. This study should be considered exploratory due to the small sample size and the lack of adjustment for multiple comparisons. CONCLUSIONS: Acute-phase MRI findings in AESD were associated with long-term neurological outcomes. Lesion distribution and deep white matter extension may serve as potential prognostic factors. Frontal BTA-E and Rolandic BTA-E were associated with cognitive impairment and motor paralysis, respectively.

Traumatic brain injury (TBI) in young children can rarely exhibit a biphasic clinical course with delayed neurological deterioration. We report a 2-year-old boy who fell from 50 cm and briefly lost consciousness with vomiting, initially found to have a right frontotemporoparietal acute subdural hematoma (SDH) with midline shift but no brain contusions. After transient stabilization, he developed new left-sided limb weakness and status epilepticus on day 3 post-injury. Follow-up diffusion-weighted magnetic resonance imaging (DWI) revealed a characteristic "bright tree" pattern of bilateral subcortical white matter diffusion restriction with corresponding decreased apparent diffusion coefficient (ADC) values. Electroencephalography showed generalized slowing with interictal focal epileptiform discharges. The patient was managed with antiepileptic therapy and supportive care. He demonstrated steady improvement and achieved near-complete neurological recovery by 9-month follow-up. This biphasic presentation-early trauma and late-onset seizures with diffusion restriction-is consistent with Traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD). Early recognition of TBIRD is crucial, as it resembles acute encephalopathy with biphasic seizures and late diffusion changes, and likely stems from secondary excitotoxic injury. Timely intervention in our case was associated with a favorable outcome, underscoring the importance of vigilant monitoring for delayed neurologic sequelae in pediatric TBI.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common form of acute infection-triggered encephalopathy in children. This study aimed to evaluate the safety and feasibility of remote ischaemic postconditioning (RIPoC) as an adjunct to therapeutic hypothermia in patients with AESD. METHODS: In this prospective, non-randomised study, patients treated in January 2021-July 2024 were compared with a historical control group treated in January 2017-December 2020. RIPoC (four cycles of 5-min inflation and 5-min deflation) was applied to the lower extremity at the initiation of therapeutic hypothermia. Adverse events were assessed between the RIPoC group (n = 15) and patients with therapeutic hypothermia in the control groups (n = 12). Neurological outcomes at 6-18 months post-onset were compared between the RIPoC group (n = 12) and patients with/without therapeutic hypothermia in the control groups (n = 13). Multivariate analyses were performed to identify predictors of favourable neurological outcomes. RESULTS: While the comparison of adverse events and neurological outcomes between groups did not show significant differences, multiple analysis suggested associations between a lower Tada score or RIPoC treatment and better outcomes. CONCLUSION: RIPoC combined with therapeutic hypothermia appears safe and feasible in patients with AESD. IMPACT: Remote ischaemic postconditioning (RIPoC) was safely combined with hypothermia in paediatric patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). No coagulation, hemodynamic complications, or adverse events were observed. Multiple linear regression analysis suggested associations between a lower Tada score or RIPoC treatment and better outcomes in patients with AESD. This is the first report to examine the feasibility and safety of the RIPoC in paediatric central nervous system disease not directly related to ischaemia-reperfusion injury. Findings support future randomised controlled studies to confirm RIPoC as a possible adjunctive neuroprotective therapy in paediatric brain injury, particularly AESD.

BACKGROUND: Exanthem subitum (ES), a benign febrile exanthematous disease, is caused by primary human betaherpesvirus 6B (HHV-6B) infection. It may cause neurological complications, including complex febrile seizures (cFS), acute encephalopathy with biphasic seizures, and late reduced diffusion (AESD). cFS resolves spontaneously; however, AESD can pose severe sequelae. We aimed to elucidate AESD pathogenesis using a proteomic analysis. METHODS: Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), serum and cerebrospinal fluid (CSF) protein profiles were compared between patients with AESD and those with cFS (n = 3 or 4 per group). Metascape was used for enrichment analysis, and the selected proteins were validated using a large sample via enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 698 proteins were identified across all serum and CSF samples using LC-MS/MS. Nineteen serum proteins were differentially expressed in AESD and cFS during the acute phase. The glycolytic pathway was upregulated in AESD. Myristoylated alanine-rich C kinase substrate (MARCKS) and Golgi membrane protein 1 (GOLM1) were selected for validation using ELISA. Both proteins were upregulated during the acute phase (n = 11) compared with the convalescent phase (n = 21) in AESD (MARCKS, P = .016; GOLM1, P < .001). MARCKS during the acute phase was also upregulated in AESD compared with that in uncomplicated ES (n = 15) (P = .015). In CSF, 38 proteins were differentially expressed between AESD and cFS during the acute phase. Cholesteryl ester transfer protein in the CSF of patients with AESD was upregulated; however, this could not be validated using ELISA. CONCLUSIONS: Glycolysis and MARCKS pathways might be involved in HHV-6B-associated AESD pathogenesis.