Encephalopathy in COVID-19 patients; viral, parainfectious, or both?

Abstract

We describe the clinical, laboratory and radiological features of 3 critically ill patients with COVID-19 who developed severe encephalopathy. The first patient did not regain consciousness when sedation was removed at the end of 2 weeks of intensive care. He had received treatment with convalescent plasma. His clinical examination was remarkable for intact brainstem reflexes, roving eye movements, later transient ocular flutter; and then what appeared to be slow ocular dipping. He had no coherent volitional response to the environment. The second patient recovered with measurable cognitive deficits after a prolonged period of encephalopathy. He had received combination treatment with interferon beta 1b and lopinavir/ritonavir. The third patient remained in persistent, severe agitated delirium and died 3 months into his illness. The MRI of the 3 patients showed multifocal abnormalities predominantly in the cerebral white matter, with varying involvement of the grey matter, brainstem and spinal cord. Case 1's MRI changes were consistent with acute disseminated encephalomyelitis. The patients also displayed blood markers, to varying degree, of autoimmunity and hypercoagulability. We were not able to convincingly show, from microbiological as well as immunological evaluation, if the effects of COVID-19 on these patients' nervous system were a direct consequence of the virus, proinflammatory-thrombotic state or a combination. Patient 1 responded partially to empirical, albeit delayed, therapy with intravenous immunoglobulins. Patient 2 recovered with no specific treatment. These cases illustrate the need to understand the full spectrum of encephalopathy associated with COVID-19 so as to better guide its management.

Keywords: Autoimmunity; COVID-19; Encephalitis; Parainfectious; SARS-CoV-2 virus.

Figs. 1–3

Fig. 1; case 1: Brain MRI done at day 34 and 44 of illness showing combination of white matter, brain stem and spinal cord changes suggestive of acute disseminated encephalomyelitis. Fig. 1a: Axial T2WI of the brain showing discrete hyperintense foci in the deep and subcortical white matter. Fig. 1b DWI and Fig. 1c: ADC, shows DWI hyperintensity of the lesions without restricted diffusion on the ADC maps. Fig. 1d: Axial T2WI showing subtle hyperintensity in the left side of the pons. Fig. 1e: Sagittal T2WI of the cervical spine with a small linear lesion on the right side of the spinal cord at C1 (white arrow). Fig. 1f: Follow-up MRI, axial T2WI showed no new white matter lesions, however, there is increase in the surrounding and background diffuse white matter hyperintensity. Fig. 2; case 2: Brain MRI done at day 114 deemed possible sequelae of hypoxia-ischaemia or inflammatory demyelination; corresponding to the contemporaneous neuropsychological assessment. Fig. 2a & b: Axial T2WI showing a) bilateral curivilinear high signal paralleling the ventricles and b) in the inferior frontal white matter (white arrows). Fig. 2c: Axial T1WI showing low signal in the white matter lesions (white arrows). Fig. 2d: Axial T2WI showing the discrete hyperintense lesions in the deep white matter on a background diffuse leuokoencephalopathy. Fig. 3; case 3: Brain MRI done at nine weeks of illness; the changes were attributable to para-infectious autoimmune coagulopathy and corresponding to his clinical state of sequential hemiplegia and persistent delirium. Fig. 3: Axial T2WI showing T2W hyperintensity in the right frontal and parietal deep and subcortical white matter; and evolved previous infarct in the left frontal and parietal lobes. There is cortical swelling and hyperintensity in the left parietotemporal region (arrow).

Fig. A

Timelines for cases 1, 2 and 3.