Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid

Abstract

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

Figure. Timeline from symptoms to discharge and MRI scans illustrating anatomic location and alterations over time

(A) Timeline from symptom debut showing the neurologic status of the patient and the start and duration of the immunotherapies. The graph additionally illustrates the dynamics of inflammatory markers in plasma and CSF. The first and only positive PCR for SARS-CoV-2 in CSF was detected after 3 weeks indicated by red arrows. IVIG, IV immunoglobulin, PLEX, plasma exchange, GCS, Glasgow Coma Scale. (B) The top and middle rows show images from the first MRI scan at day 12, and the bottom row from the follow-up 1 week later. T2 turbo spin echo (B.a) and FLAIR (B.b) show symmetrically increased signal intensity in subinsular regions (surrounding the claustrum) and thalami (red arrow). The same areas had bright signal in trace images from diffusion-weighted images (b 1,000), indicating cytotoxic edema (B.c). Increased signal was also present on FLAIR images in the brain stem (asterisk, B.h) with suggested involvement of trigeminal nerves (without contrast enhancement, B.d). The olfactory tract had normal appearance (not shown). T1-weighted images show distinct signal decrease on the initial scan (B.e), with partial normalization on follow-up and small delineated malacias in the thalami (B.j). There was faint contrast enhancement initially (B.f), more evident on follow-up (boxes; B.k). Initial FLAIR images showed clear symmetrical involvement of medial temporal lobes, hippocampi, and cerebral peduncles (asterisks, B.g), as well as the pons (B.d, B.h). On follow-up, there was substantial decrease of signal changes in hippocampi and mesencephalon (B.l, B.m). Susceptibility-weighted images showed multiple small foci of presumed petechial hemorrhage in central thalami and subinsular regions (red arrows; B.i, B.n).