Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review

Background: Bilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic.

Methods: Systematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied.

Results: Data on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] female; 72 [44.4%] aged ≤18 years) from 103 articles were analyzed. DANE (62, 38.3%) was the commonest, followed by AE (56, 34.6%) and ADEM (27, 16.7%). The main clinical features were fever (100%), thrombocytopenia (79.0%), headache (57.8%), and seizures (43.7%). Patients with DANE had earlier neurological deterioration (3.5 [1 to 8] vs 5 [1 to 14] days in other encephalitis syndromes, P = 0.0127), seizures (54.2% vs 37.4%, P = 0.0471), higher cerebrospinal fluid (CSF) protein (0.92 [0.18 to 4.8] vs 0.73 [1 to 16] g/L, P = 0.0469), thalamic (100% vs 8.0%) and hemorrhagic brain lesions (73.3% vs 7.5%, P < 0.0001). CSF pleocytosis and positive CSF dengue IgM/viral polymerase chain reaction were reported in 66.7% and 78.6% with DANE. Mortality was 16.1% in DANE, and 40.6% of survivors had disability. High-risk ANE severity scores predicted poor outcomes (positive predictive value 64.3% [95% confidence interval 38.8% to 83.7%]).

Conclusion: DANE differs from other dengue encephalitis syndromes and is clinicoradiologically indistinguishable from sporadic ANE with sufficient evidence to be considered an ANE variant.