- This case series describes suspected white matter injury in six survivors of COVID-19 respiratory failure
- All patients exhibited altered mental status and neurologic symptoms between admission days 15 and 30
- On brain MRI, the patients exhibited relatively symmetric T2/FLAIR hyperintensity and restricted diffusion of the bilateral deep cerebral white matter, with relative sparing of the subcortical U-fibers and brain stem
- Neurologic symptoms in all six patients were first detected 14 to 23 days after the date of the PaO2 nadir, and the mean interval between the PaO2 nadir and MRI was 22 days; this is consistent with a delayed post-hypoxemic etiology of the leukoencephalopathy
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Emerging evidence suggests SARS-CoV-2, the virus that causes COVID-19, can affect the central nervous system. Initial neuroimaging findings in patients with COVID-19 include infarction, hemorrhage and encephalopathy; more recently (published in Radiology), leukoencephalopathy with intracranial microhemorrhages has been reported.
In AJNR: American Journal of Neuroradiology, Min Lang, MD, resident in Radiology, and Sandra P. Rincon, MD, staff neuroradiologist at the Department of Radiology, with Thabele Leslie-Mazwi, MD, director of Endovascular Stroke Services in the Department of Neurosurgery and Department of Neurology at Massachusetts General Hospital, and colleagues report on detailed brain MRI analysis of 42 patients with COVID-19, six patients of whom had findings suggestive of white matter injury, potentially a delayed sequela of profound hypoxia.
Background on the Cases
All six patients required intubation in the Mass General Emergency Department for hypoxic respiratory failure. Their average age was 64 (range, 60–76). All were without neurologic impairment at the time of presentation and none had a history of neurologic disease or were immunocompromised. One patient had undergone brain MRI a year before, which demonstrated minimal nonspecific white matter changes without other abnormalities.
All six patients were weaned off sedation between admission days 9 and 24 when their respiratory status improved, and two were successfully extubated. All patients subsequently exhibited altered mental status and neurologic symptoms between admission days 15 and 30.
The mean time to brain MRI was 26 days from admission. All patients exhibited relatively symmetric T2/FLAIR hyperintensity and restricted diffusion of the bilateral deep cerebral white matter, with relative sparing of the subcortical U-fibers and brain stem. Additional sites of white matter involvement were the:
- Corpus callosum in patient 2
- Middle cerebellar peduncles in patients 1, 2, 4, 5 and 6
- Corticospinal tracts in patients 2, 3 and 4
It has been postulated that prolonged or severe hypoxemia can lead to myelin sheath damage through dysfunction of the adenosine triphosphate–dependent enzymes responsible for myelin secretion and maintenance. Myelin secretion occurs every 19 to 22 days.
Three sets of findings in this study are suggestive of delayed post-hypoxemic leukoencephalopathy detected on brain MRI:
- Profound hypoxia documented in all six patients, who uniformly suffered severe COVID-19 manifestations
- Neurologic symptoms in all six patients first detected 14–23 days after the date of the lowest recorded PaO2, consistent with the timing of myelin sheath secretion
- MRI findings consistent with specific white matter involvement and relative sparing of gray matter. The mean interval between the PaO2 nadir and MRI was 22 days
Advice to Clinicians
The consequences of delayed post-hypoxic leukoencephalopathy can be severe, including chronic neurologic deficits and death. Health care professionals should be aware of the potential for a delayed leukoencephalopathy syndrome in patients with COVID-19 who display subacute neurologic deficits, even those whose respiratory status has improved. A low threshold to perform brain imaging on such patients is appropriate.
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