Clinical Course of a Patient with Radiographically Described Acute Necrotizing Encephalopathy (ANE)

Editor:

We write in reference to a previously reported case of acute necrotizing encephalopathy (ANE) associated with acute SARS-COV-2 infection (1). A 58-year-old woman with hypertension presented with cough, fever, and altered mental status. She was somnolent but arousable, with bilateral ptosis and conjugate tonic downgaze. She initially was right hemiparetic, and over days became quadriplegic. SARS-CoV-2 RT-PCR testing was positive via nasopharyngeal swab. Initial cerebrospinal fluid (CSF) testing was unavailable. Later, SARS-CoV-2 RT-PCR was performed on the CSF and was negative.

Initial treatment was with 2 grams/kg of intravenous immunoglobulin in divided doses, without clinical improvement. High-dose steroids (IV methylprednisolone 1000 mg daily for a total of 5 days) were then given, followed by 40 mg prednisone for five days via percutaneous endoscopic gastrostomy tube. After supportive care, the patient demonstrated physical and cognitive improvement, with decreasing ophthalmoplegia, speaking in short answers, and participating with physical therapy. She was discharged to subacute rehabilitation.

The patient recovered considerably; four months after hospitalization, her sensory and motor examination were normal. There was residual psychomotor slowing. She was able to perform activities of daily living, although she was not yet driving. Modified Rankin Scale was 3. Repeat MRI brain without contrast showed residual T2 hyperintensities and hemosiderin deposition in the medial thalami; the former were significantly improved from previous. MRI T2 hyperintensities in the bilateral medial temporal lobes had resolved (Figure).

Figure:

Images in a 58-year-old woman with acute necrotizing encephalopathy (ANE) associated with acute SARS-COV-2 infection. Brain MRI without contrast 15 weeks after ANE onset. MRI demonstrates residual T2 FLAIR hyperintensity within the thalami (A, white arrow) with residual hemosiderin deposition indicated by hypointense signal intensity on susceptibilityweighted images (B, white arrow). C, Earlier T2 hyperintensities in the bilateral medial temporal lobes had resolved.

Several cases of COVID-19 associated ANE have now been reported (Table). Most show MRI abnormalities in the thalamus, putamen, hippocampus, medial temporal lobes, and amygdala, associated with illnesses (1-5). The brainstem, cerebellum, cerebral peduncles, and pons may also be involved. (2-5). The neuroinvasive mechanism of ANE is not known; there are two possible hypotheses, the immune-mediated neurotoxicity and neuronal retrograde dissemination (6). SARS-CoV and SARS-CoV-2 are similar in structure, and both can penetrate through the neuroepithelium of the olfactory nerve and olfactory bulb by an interaction between the viral spike" protein and host cell surface protein angiotensin-converting enzyme 2 (ACE2).

Table:

Case Report Summaries of COVID-19 associated ANE

In the brain, ACE2 is expressed in the brainstem, hypothalamus, motor cortex, and raphe nucleus (7). Immunotherapy has some role in the treatment of COVID-19 associated ANE, as described in the literature (1, 4,5).