Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

Abstract

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

Acute necrotising encephalopathy in a child with H1N1 influenza infection: a clinicoradiological diagnosis and follow-up

“…A composite scoring system was devised for patients with ANEC by Wong et al 21 who observed a positive correlation between the MRI brain findings and clinical outcome. Follow-up imaging in survivors had shown significant regression of lesions with residual changes like cortical atrophy, cystic changes and haemosiderin deposition 12. Follow-up imaging in our patient had shown significant resolution of signal abnormalities with persistent cytotoxic oedema in the bilateral thalami and previous reports have rarely described persistent inflammation in the follow-up imaging, which might explain the incomplete recovery.…”

“…It is speculated that following a viral infection, there is an increase in the inflammatory mediators such as interleukin-1, interleukin-6 and tumour necrosis factor α 13. A cytokine storm following viral infection leading to systemic immune response could possibly explain the pathogenesis and clinical presentation in patients with ANEC 12 14. Although CSF PCR for H1N1 influenza was not performed in our case, a previous observation of rare isolation of the influenza virus from CSF has supported the hypothesis that ANEC reflects a cytokine storm mediated central nervous system injury 15.…”

Neurological Complications of Novel Influenza A (H1N1) pdm09 Infection: Report of Two Cases and a Systematic Review of the Literature

“…Other symptoms include fever, vomiting, and respiratory symptoms [11]. As mentioned before, it is generally considered to be a post-infectious disease secondary to immune mediated response which is triggered by the virus [12]. Although ANE may affect adults, most cases of ANE reported in the literature are usually children [13].…”

“…Neuroimaging usually demonstrates multifocal bilateral periventricular white matter, thalamic, brain stem, or cerebellar changes [16]. On pathology, affected areas of the brain are characterized by the presence of hemorrhages and necrosis [12]. ANE carries a bad prognosis and patients usually end up with either profound disability or death [17].…”

Acute necrotising encephalopathy of childhood: an uncommon cause of childhood encephalopathy with recognisable clinical and radiological features and genetic predisposition

“…There is an association with upper respiratory tract illnesses, particularly influenza A 2 3. It has significant morbidity and mortality 4 5. Evidence regarding optimal therapy is limited; however, early steroids and immunoglobulin is associated with improved outcome 5.…”