Modelling the Anatomic Distribution of Neurologic Events in Patients with COVID-19: A Systematic Review of MRI Findings

Parsons, Nick; Outsikas, Athanasia; Parish, Annie; Clohesy, Rebecca; D'Aprano, Fiore; Toomey, Fidel; Advani, Shailesh; Poudel, Govinda

doi:10.3174/ajnr.a7113

Cited by 34 publications

(39 citation statements)

References 35 publications

(50 reference statements)

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“…The presence of an association between systemic inflammation and white matter microstructure in the corpus callosum is coherent with studies describing cytokine-induced injury in the corpus callosum in critical illnesses, such as acute respiratory distress syndrome and COVID-19 (Cannac et al 2020), and a more frequent occurrence of white matter neurological events in this very same region in COVID-19 patients (Parsons et al 2020). Furthermore, the increased quotient albumin reported in the majority of our patients with available CSF analyses suggests a blood-brain barrier disruption associated with this systematic inflammation, which may explain the observed white matter microstructural changes.…”

Section: Discussionsupporting

confidence: 80%

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy

et al. 2021

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Encephalopathy is a neurological complication of COVID-19. The objective of this exploratory study is to investigate the link between systemic inflammation and brain microstructural changes (measured by diffusion-weighted imaging) in patients with COVID-19 encephalopathy. 20 patients with COVID-19 encephalopathy (age: 67.3 $$\pm$$ ± 10.0 years; 90% men) hospitalized in the Geneva University Hospitals for a SARS-CoV-2 infection between March and May 2020 were included in this retrospective cohort study. COVID-19 encephalopathy was diagnosed following a comprehensive neurobiological evaluation, excluding common causes of delirium, such as hypoxemic or metabolic encephalopathy. We investigated the correlation between systemic inflammation (measured by systemic C-reactive protein (CRP)) and brain microstructural changes in radiologically normal white matter (measured by apparent diffusion coefficient (ADC)) in nine spatially widespread regions of the white matter previously associated with delirium. Systemic inflammation (CRP = 60.8 ± 50.0 mg/L) was positively correlated with ADC values in the anterior corona radiata (p = 0.0089), genu of the corpus callosum (p = 0.0064) and external capsule (p = 0.0086) after adjusting for patients’ age. No statistically significant association between CRP and ADC was found in the other six white matter regions. Our findings indicate high risk of white matter abnormalities in COVID-19 encephalopathy patients with high peripheral inflammatory markers, suggesting aggressive imaging monitoring may be warranted in these patients. Future studies should clarify a possible specificity of the spatial patterns of CRP–white matter microstructure association in COVID-19 encephalopathy patients and disentangle the role of individual cytokines on brain inflammatory mechanisms.

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Section: Discussionsupporting

confidence: 80%

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy

et al. 2021

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“…Nevertheless, these mechanisms can be grouped into the direct effect of the viral infection and the indirect effect on mental health due to posttraumatic stress, social isolation, and economic factors, such as loss of employment. 69,70 Direct viral effects can be explained by several hypotheses, including persistent viremia due to immune fatigue and paresis, 71 relapse or reinfection, 72 hyperinflammatory immune response, cytokine-and hypoxia-induced injury, 73 and autoimmunity 74 as well as neurotropism using a transsynaptic spread mechanism, 5 resulting in hypoxic-or hemorrhagic-driven neuronal apoptosis. 75 Herein, widespread acute injury to cortical/ subcortical and white matter fiber bundles may affect brain function and impede distal brain connectivity, respectively, manifesting in common symptoms, such as those identified in this review.…”

Section: Discussionmentioning

confidence: 99%

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection

et al. 2021

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IMPORTANCE Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region. OBJECTIVE To estimate organ system-specific frequency and evolution of PASC. EVIDENCE REVIEW PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references.Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility.FINDINGS From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55. 0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders. CONCLUSIONS AND RELEVANCEIn this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low-and middleincome countries.

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“…The events were significantly associated with diffusion from the bilateral cerebellum in addition to the putamen. The study shows that transconnectom diffusion of pathology occurs via structural network connections of the cerebellum [14]. The vascular microhemorrhages are not uncommon etiology of cerebrovascular pathology in those with COVID-19.…”

mentioning

confidence: 77%

2 Years into the Pandemic: What Did We Learn About the COVID-19 and Cerebellum?

2022

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Highly contagious pandemic due to novel coronavirus SARS-CoV-2, COVID-19 has significantly affected humankind. At the onset of the pandemic, it was believed that it primarily affects the respiratory and hematological system, and has minimal influence on the human brain, even less so on the cerebellum. It was thought that the effects of a pandemic on cerebellar disorders would be the same as it would affect any other chronic neurological disease. It turned out that our understanding of the effects of COVID-19 on the cerebellar system was premature. Over the last 2 years, we appreciated many diverse and direct effects of COVID-19 on cerebellar function. SARS-CoV-2 affects the cerebellum via direct viral invasion, but even more so through its effects on immune, hematological, and metabolic pathways. Increasing evidence suggested the indirect effects of COVID-19 on preexisting chronic cerebellar disease due to lack of in-person care and social isolation. This editorial concisely summarizes critical literature on COVID-19 and the cerebellum published over the last 2 years.

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Modelling the Anatomic Distribution of Neurologic Events in Patients with COVID-19: A Systematic Review of MRI Findings

Cited by 34 publications

References 35 publications

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection

2 Years into the Pandemic: What Did We Learn About the COVID-19 and Cerebellum?

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