Acute necrotizing encephalopathy (ANE) is a feature of dengue virus encephalitis

Introduction Haemorrhagic thalamic lesions in dengue virus encephalitis resemble acute necrotizing encephalopathy (ANE), a severe febrile encephalopathy due to an innate immune response against respiratory viruses.

Methods Systematic review of paediatric and adult literature on dengue encephalitis was curated for clinical, laboratory, radiological and outcome data. ANE diagnostic criteria was applied. “Classic” ANE neuroimaging were bilateral thalamus + pons/cerebellum +/- cerebral white matter lesions, with haemorrhage. Forme fruste patterns were deemed ANE compatible. ANE severity scoring (ANE-ss) was applied and compared against outcomes.

Results Data on 127 patients (median age 21 (range 0.4-85 years)) were extracted from 81 articles; 53 (42%) were children ≤18 years. Predominant clinical features were fever (94%), thrombocytopenia (69%), seizures (46%) and abnormal motor signs (49%). ANE (in 46, 36%) was commonest followed by acute disseminated encephalomyelitis (18, 14%) and cortical grey matter encephalitis (17, 13%). Demographics, clinical features and CSF parameters were similar between ANE and other encephalitis syndromes. However, outcomes were poorer: 45% death/moderate-severe disability in ANE versus 13% in other encephalitis (p<0.01).

In ANE, median CSF white cells and protein was 12/mm3 (0-300) and 0.81 g/L (0.2-4.8) whilst 20 (43%) reported dengue IgM or PCR positivity in CSF. Classic ANE neuroimaging was noted in 26 (57%). ANE-ss mirrored outcome prediction in respiratory virus-related ANE: 78% with normal/mild disability outcomes in medium-risk patients whilst all deaths (100%) followed high-risk scores.

Conclusion Although clinico-radiologically identical to respiratory virus-related ANE, Dengue virus ANE is a distinct disorder with CNS viral invasion and an intrathecal adaptive immunobiology.
Keywords: acute necrotising encephalopathy, dengue, encephalitis