Leukoencephalopathy Related to Severe COVID-19 Has Clinical, Laboratory Correlates
Key findings
- This retrospective study involved 27 adults with PCR-confirmed COVID-19 who were admitted to the ICU and underwent brain MRI >24 hours later, of whom seven (26%) showed leukoencephalopathy with reduced diffusivity
- No baseline demographic or clinical characteristic differed significantly between the two groups except that body mass index was greater in the reduced diffusivity group (36 vs. 28 kg/m2, P<0.01)
- After ICU admission, the reduced diffusivity group had lower hemoglobin (8.1 vs. 10.2 g/dL, P<0.05), mildly higher serum sodium (147 vs. 139, P=0.04) and a lower estimated glomerular filtration rate (49 vs. 85 mL/min, P=0.06)
- A striking pattern of diffuse, confluent, predominantly symmetric supra- and infratentorial involvement with middle cerebellar peduncle lesions was seen in 86% of the reduced diffusivity group and only 5% of the control group (P<0.001)
- These findings overlap those of other conditions, such as delayed post hypoxic leukoencephalopathy and provide a basis for hypothesis testing in larger cohorts that may help determine the pathophysiology of severe COVID-19 encephalopathy
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Several groups have reported finding diffuse white matter abnormalities on brain MRI in patients with severe COVID-19. One such report, published in Radiology, described a series of patients with leukoencephalopathy, reduced diffusivity and microhemorrhages.
Otto Rapalino, MD, director of Brain Tumor Imaging in the Division of Neuroradiology, and Michael H. Lev, MD, director of Emergency Radiology and Emergency Neuroradiology at Massachusetts General Hospital; Shibani S. Mukerji, MD, PhD, associate director of the Neuro-Infectious Diseases Unit of the Department of Neurology; and colleagues have become the first to systematically analyze the clinical, imaging and laboratory correlates of COVID-19 leukoencephalopathy. They published their observations in the American Journal of Neuroradiology.
Study Methods
For the period February 1 to May 12, 2020, the researchers examined two overlapping databases maintained at Massachusetts General Hospital: adults with COVID-19 (N=7,146) and patients who had brain MRI studies (N=2,266). Of those, 27 adults with PCR-confirmed COVID-19 were admitted to the ICU and underwent brain MRI >24 hours later.
For purposes of this study, the MR images were reviewed by two neuroradiologists who were blinded to clinical and laboratory findings.
Cohort Characteristics
Seven of the 27 patients (26%) were identified as having leukoencephalopathy with reduced diffusivity. The other 20 did not and served as a control group.
There were no significant differences between the two groups with regard to age, sex, race/ethnicity, comorbidities, clinical data at the time of ICU admission or ICU treatment. However, body mass index was significantly higher in the group with reduced diffusivity (36 vs. 28 kg/m2, P<0.01).
ICU Clinical Data
In the reduced diffusivity group compared with the control group, there was a trend toward more frequent:
- Acute renal failure (100% vs. 45%, P=0.06)
- Acute renal dysfunction (estimated glomerular filtration rate, 49 vs. 85 mL/min; P=0.06)
The reduced diffusivity group showed two significant differences from the control group in average laboratory values within 24 hours before MRI:
- Hemoglobin (8.1 vs. 10.2 g/dL, P<0.05)
- Serum sodium (147 vs. 139 mmol/L, P=0.04)
Other organ system damage was not significantly different between groups, including cardiac events, acute liver failure, overt disseminated intravascular coagulation, ischemic bowel and frequency of septic shock.
Imaging
- The extent of bilateral supra- and infratentorial white matter abnormalities was significantly greater in the reduced diffusivity group
- Six patients in the reduced diffusivity group and one in the control group showed an unusual pattern of confluent supratentorial and middle cerebellar peduncular involvement (86% vs. 5%, P<0.001)
- Cerebellar white matter and brain stem lesions were significantly more common in the reduced-diffusivity group
- White matter lesions were more likely to have a predominantly symmetric pattern in the reduced diffusivity group (100% vs. 58%, P=0.06)
A Foundation for Future Research
The unusual pattern of white matter injury and the clinical and laboratory findings overlap those in several other conditions, including but not limited to delayed post hypoxic leukoencephalopathy, sepsis-related leukoencephalopathy and metabolic encephalopathies related to electrolyte disturbances.
This study provides a basis for hypothesis testing in larger cohorts that may help determine the pathophysiology of severe COVID-19 encephalopathy.
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