Acute haemorrhagic necrotizing encephalopathy and inflammatory demyelinating encephalopathy associated with COVID-19 in adults in Southern China

Abstract

Background: COVID-19 manifests with diverse systemic symptoms, including central nervous system involvement. Acute necrotizing encephalopathy (ANE), acute hemorrhagic leukoencephalitis (AHLE), and acute disseminated encephalomyelitis (ADEM) exhibit overlapping clinical features, creating diagnostic challenges. This study characterizes COVID-19-associated neuroinflammatory syndromes in patients without apparent respiratory symptoms.

Methods: We conducted a retrospective case series analysis of four patients with confirmed COVID-19 and acute neurological decline. Diagnostic evaluation included brain MRI, cerebrospinal fluid analysis, autoimmune/paraneoplastic antibody panels, and exclusion of alternative etiologies through microbiological/metabolic testing.

Results: Four cases were identified: two with ANE, one with ADEM, and one with AHLE. All patients tested SARS-CoV-2-positive by RT-PCR despite absent respiratory symptoms. Magnetic resonance imaging revealed characteristic patterns: Symmetric thalamic lesions in ANE (Cases 1-2), hemorrhagic lesions in basal ganglia and bilateral cerebellar hemispheres in AHLE (Case 3), widespread cortical and subcortical demyelination in ADEM (Case 4).

Conclusions: ANE, AHLE, and ADEM are critical neuroinflammatory complications of COVID-19 requiring urgent differentiation. It is imperative to maintain a high level of clinical suspicion when patients present with acute encephalopathy in the absence of respiratory symptoms, as this enables timely intervention.

Keywords: Acute disseminated encephalomyelitis; Acute hemorrhagic leukoencephalitis; Acute necrotizing encephalopathy; COVID-19; Coronavirus.

Fig. 1

Patient 1 Acute necrotizing encephalopathy in a 25-year-old girl presenting with fever and consciousness disturbance. Axial FLAIR (B and F) and (C and G) T2-weighted images show hyperintensities in the bilateral thalami, PONS, and bilateral cerebellar hemisphere. Axial T1-weighted image (A and E) reveals hyperintensities, suggesting haemorrhages in the thalami and pons. D and H SWI image demonstrating cerebral microbleeds in the bilateral thalami and bilateral cerebellar hemisphere

Fig. 2

Patient 2 Acute necrotizing encephalopathy in a 23-year-old male presenting with mental disorders. Axial T2-weighted (B and F) and T2 FLAIR (C and G) images show hyperintensities in the bilateral thalami and pons. Axial T1-weighted image (A and E) reveals hyperintensities, suggesting haemorrhages in the right thalami and pons. D and H SWI image demonstrating cerebral microbleeds in the right thalamus

Fig. 3

Patient 3 Encephalitis in a 35-year-old male presenting with fever, seizure and coma. Axial T1-weighted (A, E, I) and T2-weighted (B, F, J) images show abnormal signals in the basal ganglia region, corona radiata, bilateral frontal and temporal regions and pons. Axial diffusion-weighted image (C, G, K) reveals decreased diffusion (high signal intensity) in the same regions. SWI (D, H, L) images reveal dispersed microhaemorrhages in the above lesions that are predominantly located in the basal ganglia and bilateral cerebellar hemispheres

Fig. 4

Patient 4 with acute disseminated encephalomyelitis in a 52-year-old female. Axial T2 (A and E) and DWI (B and F) images show multifocal hyperintense lesions, the left cerebellar hemisphere and the right brachium of the pons. Axial postcontrast T1-weighted images (C and G) reveal mild contrast enhancement of the abnormalities. Sagittal T2-weighted image (D and H) shows patchy hyperintensity at the frontoparietal temporal lobe