by Dr. Juliette Dufour
For July 2022, we have selected Rau A, Schroeter N, Blazhenets G, Dressing A, Walter L, Kellner E, Bormann T, Mast H, Wagner D, Urbach H, Weiller C, Meyer P, Reisert M, Hosp J, Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms. Brain, 2022, DOI: https://doi.org/10.1093/brain/awac045.
Recent neuropathological studies have revealed microstructural and inflammatory changes within brains of patients who died from COVID-19. Interestingly, neuropathological changes involved the white more than the grey matter. Unfortunately, in vivo, cerebral MRI-derived evidence of this inflammation is widely lacking.
Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcoming this discrepancy.
Our authors of the month conducted this monocentric prospective study including 20 patients and 35 healthy controls. COVID-19 patients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments (MoCA test; 22.4 ± 4.9), underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR).
Several results were revealed:
- A volume shift from the intra and extra-axonal space into the free water fraction (V-CSF) in the Covid patients’ brains. This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions.
- Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes.
- The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r =−0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12).
- Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response.
- In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase.
In summary, a redistribution with decreasing intra-axonal and extra-axonal volume fractions (V-intra and V-extra) and an increasing free water/CSF (V-CSF) fraction was observed, in line with vasogenic oedema. This diffuse process with maxima in the frontal and parietal white matter affected large parts of the supratentorial fibre tracts. Furthermore, these changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.