Eur J Pediatr. 2026 May 27;185(6):441. doi: 10.1007/s00431-026-07097-w.
ABSTRACT
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The primary objective was to assess the efficacy of pentoxifylline in terms of time taken for improvement in Glasgow coma scale (GCS) from baseline, in children with AES. The secondary objectives were adverse effects of pentoxifylline and frequency of sequelae among the survivors. This open-label randomized controlled trial (RCT) was conducted in a tertiary care teaching institution for 2 years (January 2022 to December 2023). Children aged 1 month to 14 years with a clinical diagnosis of AES were randomized to receive either standard treatment along with pentoxifylline or standard treatment alone. The data were recorded in case record forms. Forty-four children were randomized (median age, 77 months; male 72.7%). There was no significant difference in the time (median, IQR) taken for improvement of Glasgow coma scale (GCS) by 3 points or normalization between the pentoxifylline group [26 (19-50) hours] and control group [28 (16-52) hours] (p = 0.92). Other outcomes like requirement of mechanical ventilation, mortality, and sequalae were not significantly different between the two groups. The adverse event rate was also not different. Conclusion: Adjunctive pentoxifylline did not provide significant clinical benefit in children with AES, although it was safe and well tolerated. Larger, adequately powered multicenter trials with etiological stratification and biomarker integration are needed to identify potential subgroup benefits. What is Known: • Acute encephalitis syndrome (AES) is associated with high mortality and significant neurological sequelae, largely driven by host-mediated inflammatory responses. • No immunomodulatory adjunct therapy has yet shown proven benefit in pediatric AES. What is New: • Adjunctive pentoxifylline did not significantly improve neurological recovery or clinical outcomes in children with AES. • Pentoxifylline was safe and well tolerated, supporting further evaluation in larger, etiology-stratified trials.
PMID:42201544 | DOI:10.1007/s00431-026-07097-w
