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.

Figure 1

Clinical course of acute necrotizing encephalopathy (ANE). Survivors of ANE go through three phases during the clinical course including prodromal stage, period of acute encephalopathy, and recovery stage. In the prodromal stage, the common symptoms include cough, vomiting, diarrhea, skin erythra mainly due to various viral infections. Soon after, the dysfunction of the brain gradually appeared during the acute encephalopathy stage, for example, disturbance of consciousness, seizures, focal deficits. If survived, patients of ANE would go through the third phase, so-called recovery stage, and most patients left with different neurological sequelae while a few could recover completely.

Figure 2

Dynamic changes of magnetic resonance imaging (MRI) of a patient with acute necrotizing encephalopathy (ANE). (a) was computerized tomography (CT) at onset; (b) and (c), (d) and (e), and (f) and (g) were, respectively, the T₁-weighted image (T₁WI), T₂WI, and fluid attenuated inversion recovery (FLAIR) image at onset which showed lesions on bilateral thalamus and brain stem (blue arrow); (h) and (i), (g) and (k), and (l) were, respectively, the T₁WI, T₂WI, and FLAIR imaging of follow-up which revealed disappearance of the brain stem lesions and impressive regression of the thalamic lesions, just left hemosiderin deposition (red arrow).

Figure 3

Diffusion MRI and susceptibility weighted imaging (SWI) findings of acute necrotizing encephalopathy (ANE). (a) was the schematic diagram of typical tricolor pattern corresponding to the thalamic lesions on (b) (a: center of thalamic lesions characterized by hemorrhage and necrosis; b: periphery of the central thalamic lesions characterized by cytotoxic edema; c: outside portions of the thalamic lesions suggesting vasogenic edema). (b) and (c), (d) and (e) were the apparent diffusion coefficient (ADC) and diffusion-weighted image (DWI), respectively, at onset which suggested the bilateral thalamus and brain stem lesions (blue arrow). (f) and (g), (h) and (i) were the ADC and DWI imaging of follow-up which revealed disappearance of the brain stem lesions and hemosiderin deposition on bilateral thalamus (red arrow). (j), (k), and (l) were the follow-up SWI images which showed hemosiderin deposition in the bilateral thalami and the cerebella (red arrow).