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Can triple therapy improve survival in severe acute necrotising encephalopathy (ANE)?: a retrospective multicentre study in Malaysia

Objectives To examine the association of timing and types of immunotherapy with survival in children with acute necrotising encephalopathy (ANE) .

Methodology Retrospective review of clinical variables & outcomes (based on modified Rankin scale) in children diagnosed with ANE in 10 hospitals in Malaysia between February 2019 to January 2020.

Results The 27 children (12 males) were aged 0.7-14 (mean 4) years at diagnosis. Fever, seizures and encephalopathy were almost universal and extra-thalamic lesions were detected in all but one child (including 23 with brainstem lesions). 23/27 (85.2%) had ANE severity score of 5-9/9 (high risk). All received iv methylprednisolone (MTP); as monotherapy in two children, or in combination with intravenous immunoglobulins (IVIG) in 14; tocilizumab in 4; or IVIG and tocilizumab (ie triple therapy) in 7 children. Twenty (74%) children received first immunotherapy within 48 hours of admission. 9/27 (33.3%) died; of these 1/9 had monotherapy, 6/9 had MTP+IVIG & 2/9 had MTP+tocilizumab. All who received MTP+IVIG+tocilizumab (triple therapy) survived. Amongst survivors (3 lost to follow-up), 5/15 (33.3%) had severe, 4/15 (26.7%) had moderate and 6/15 (40%) had mild or no disabilities at 6 months follow-up. There was no significant association between timing of 1st immunotherapy from admission and survivors/non survivors or good/poor outcome at 6months.

Conclusion This study showed a trend towards better survival when severe ANE cases were treated with triple therapy. However, larger studies will be needed to determine the effect of this regime on the long term outcomes of ANE.
Keywords: ANE, clinical outcome, risk factors, Tocilizumab , immunotherapy