The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations. METHODS: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics. RESULTS: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis. CONCLUSIONS: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.

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MRI is an important diagnostic tool for evaluation of myelin content in multiple sclerosis and other CNS diseases, being especially relevant for studies investigating remyelinating pharmacotherapies. In this study we evaluated a new synthetic-MRI based myelin estimation in methylenetetrahydrofolate reductase deficiency as a treatable primary demyelinating disorder and compared this method with established diffusion tensor imaging in both methylenetetrahydrofolate reductase deficiency patients and healthy controls. This is the first synthetic-MRI-based in vivo evaluation of treatment-associated remyelination. 1.5Tesla synthetic-MRI and 3Tesla diffusion-MRI were obtained from three methylenetetrahydrofolate reductase deficiency patients at baseline and six months after therapy initiation, as well as from age-matched healthy controls (diffusion tensor imaging: n = 14, synthetic-MRI: n = 9). Global and regional synthetic-MRI parameters (myelin volume fraction, proton density, relaxation rates) were compared with diffusion metrics (fractional anisotropy, mean-/radial/-axial diffusivity) and related to healthy controls by calculating z-scores and z-deviation maps. Whole brain myelin [% of intracranial volume] of the index patient was reduced to 6% vs. 10% in healthy controls, which recovered to a nonetheless subnormal level of 6.6% following initiation of high dosage betaine. Radial diffusivity was higher at baseline compared to healthy controls (1.34 vs. 0.79 x10−3 mm2/s), recovering at follow-up (1.19 x10−3 mm2/s). The index patient`s lesion volume diminished by 58% under treatment. Regional analysis within lesion area and atlas-based regions revealed lower mean myelin volume fraction (12.7Baseline/14.71Follow-up%) and relaxation rates, higher proton density, as well as lower fractional anisotropy and higher radial diffusivity (1.08 x10−3Baseline/0.94 x10−3Follow-up) compared to healthy controls. The highest z-scores were observed for myelin volume fraction in the posterior thalamic radiation, with greater deviation from controls at baseline and reduced deviation at follow-up. Z-deviations of diffusion metrics were less pronounced for radial and mean diffusivity than for myelin volume fraction. Z-maps for myelin volume fraction of the index patient demonstrated high deviation within and beyond lesion areas, among others in the precentral and postcentral gyrus, as well as in the cerebellum, and partial remission of these alterations at follow up, while radial diffusivity demonstrated more widespread deviations in supra and infratentorial regions. Concordant changes of myelin volume fraction and radial diffusivity after treatment initiation, accompanied by dramatic clinical and paraclinical improvement, indicate the consistency of the methods, while myelin volume fraction seems to characterize remyelinated regions more specifically. Synthetic-MRI-based myelin volume fraction provides myelin estimation consistent with changes of diffusion metrics to monitor short-term myelin changes on individual patient level.