Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy.

BACKGROUND AND PURPOSE: Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology. MATERIALS AND METHODS: Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included. Seven (7/27, 26%) developed an unusual pattern of "leukoencephalopathy with reduced diffusivity" on diffusion-weighted MR imaging. The remaining patients did not exhibit this pattern. Clinical and laboratory indices, as well as neuroimaging findings, were compared between groups. RESULTS: The reduced-diffusivity group had a significantly higher body mass index (36 versus 28 kg/m2, P < .01). Patients with reduced diffusivity trended toward more frequent acute renal failure (7/7, 100% versus 9/20, 45%; P = .06) and lower estimated glomerular filtration rate values (49 versus 85 mL/min; P = .06) at the time of MRI. Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin levels (8.1 versus 10.2 g/dL, P < .05) and higher serum sodium levels (147 versus 139 mmol/L, P = .04) within 24 hours before MR imaging. The reduced-diffusivity group showed a striking and highly reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < .001). CONCLUSIONS: Our findings highlight notable correlations between severe COVID-19 leukoencephalopathy with reduced diffusivity and obesity, acute renal failure, mild hypernatremia, anemia, and an unusual brain MR imaging white matter lesion distribution pattern. Together, these observations may shed light on possible SARS-CoV-2 pathophysiologic mechanisms associated with leukoencephalopathy, including borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the known cytokine storm syndrome that accompanies severe COVID-19.

Brain MR Spectroscopic Findings in 3 Consecutive Patients with COVID-19: Preliminary Observations.

Brain multivoxel MR spectroscopic imaging was performed in 3 consecutive patients with coronavirus disease 2019 (COVID-19). These included 1 patient with COVID-19-associated necrotizing leukoencephalopathy, another patient who had a recent pulseless electrical activity cardiac arrest with subtle white matter changes, and a patient without frank encephalopathy or a recent severe hypoxic episode. The MR spectroscopic imaging findings were compared with those of 2 patients with white matter pathology not related to Severe Acute Respiratory Syndrome coronavirus 2 infection and a healthy control subject. The NAA reduction, choline elevation, and glutamate/glutamine elevation found in the patient with COVID-19-associated necrotizing leukoencephalopathy and, to a lesser degree, the patient with COVID-19 postcardiac arrest, follow a similar pattern as seen with the patient with delayed posthypoxic leukoencephalopathy. Lactate elevation was most pronounced in the patient with COVID-19 necrotizing leukoencephalopathy.

EEG functional connectivity is partially predicted by underlying white matter connectivity.

Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlying white matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales.