Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19.

Farhadian, Shelli; Glick, Laura; Vogels, Chantal B.F.; Thomas, Jared; Chiarella, Jennifer; Casanovas‐Massana, Arnau; Odio, Camila D.; Vijayakumar, Pavithra; Geng, Bertie; Fournier, John; Bermejo, Santos; Fauver, Joseph R.; Alpert, Tara; Turcotte, Cynthia; Steinle, Matthew; Paczkowski, Patrick; Cruz, Charles S. Dela; Wilen, Craig B.; Ko, Albert Icksang; Mackay, Sean; Grubaugh, Nathan D.; Spudich, Serena; Barakat, Lydia

doi:10.21203/rs.3.rs-28583/v1

Cited by 10 publications

(10 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Decline in, or loss of, consciousness was also reported in patients with right frontal ischaemia (Basi et al, 2020), right temporal haemorrhage (Sharifi-Razavi et al, 2020), lesions of the left midbrain (Fan et al, 2020) and of the left ventromedial prefrontal cortex (Muhammad et al, 2020), extensive right-sided (Fan et al, 2020) or left-sided lesions (Mohamed et al, 2020), diffuse WM lesions (McCuddy et al, 2020;Muccioli et al, 2020), diffuse cerebrovascular alterations (Pugin et al, 2020) and also in the absence of MRI abnormalities (Manganelli et al, 2020;Mohamud et al, 2020). Similarly, altered mental status was observed in patients with one lesion in the splenium (Sparr and Bieri, 2020), scattered WM lesions (Farhadian et al, 2020), and microbleeds (Fitsiori et al, 2020), in a case with haemorrhage in the right parieto-occipital territory (Franceschi et al, 2020), but in most cases alterations in mental state were not associated with any specific MRI finding (Radmanesh et al, 2020a,b).…”

Section: Cognitive Correlates Of Neuroimaging Findingsmentioning

confidence: 78%

“…However, some recurrent findings emerged from the studies focussing on encephalopathies. In particular, multiple papers reported WM lesions of variable aetiology, presentation, and location (Anand et al, 2020;Benameur et al, 2020;Farhadian et al, 2020;Hayashi et al, 2020;Jang et al, 2020;Nicholson et al, 2020) that have also been commonly observed in larger cohorts (Paterson et al, 2020;Radmanesh et al, 2020b). A considerable amount of older adults with COVID-19 examined with FDG-PET and arterial spin labelling MRI presented with hypoperfusion in bilateral frontal and temporal cortices (Delorme et al, 2020;Guedj et al, 2020;Helms et al, 2020a,b), while both hyperperfusion and hypoperfusion have been observed in the cerebellum (Delorme et al, 2020;Young et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…A non-enhancing abnormality in the right anterior-medial temporal lobe was noted by Benameur et al (2020). Atrophy and widespread periventricular and subcortical WM ischaemic lesions were found in a 78-year-old woman (Farhadian et al, 2020). Both studies investigated inflammatory changes compatible with encephalitis, by means of neuroimaging and cerebrospinal fluid (CSF) analysis, although the relationship with COVID-19 infection remained unclear.…”

Section: Multiple Findingsmentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Manca

Marco

Ince

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

Background: Other than its direct impact on cardiopulmonary health, Coronavirus Disease 2019 (COVID-19) infection affects additional body systems, especially in older adults. Several studies have reported acute neurological symptoms that present at onset or develop during hospitalisation, with associated neural injuries. Whilst the acute neurological phase is widely documented, the long-term consequences of COVID-19 infection on neurocognitive functioning remain unknown. Although an evidence-based framework describing the disease chronic phase is premature, it is important to lay the foundations for future data-driven models. This systematic review aimed at summarising the literature on neuroimaging and neuropathological findings in older over-60 patients with COVID-19 following a cognitive neuroscientific perspective, to clarify the most vulnerable brain areas and speculate on the possible cognitive consequences.Methods: PubMed and Web of Science databases were searched to identify relevant manuscripts published between 1st March 2020 and 31th December 2020. Outputs were screened and selected by two assessors. Relevant studies not detected by literature search were added manually.Results: Ninety studies, mainly single cases and case series, were included. Several neuroimaging and neuropathological findings in older patients with COVID-19 emerged from these studies, with cerebrovascular damage having a prominent role. Abnormalities (hyperintensities, hypoperfusion, inflammation, and cellular damage) were reported in most brain areas. The most consistent cross-aetiology findings were in white matter, brainstem and fronto-temporal areas. Viral DNA was detected mainly in olfactory, orbitofrontal and brainstem areas.Conclusion: Studies on COVID-19 related neural damage are rich and diverse, but limited to description of hospitalised patients with fatal outcome (i.e., in neuropathological studies) or severe symptoms (i.e., in neuroimaging studies). The damage seen in this population indicates acute and largely irreversible dysfunction to neural regions involved in major functional networks that support normal cognitive and behavioural functioning. It is still unknown whether the long-term impact of the virus will be limited to chronic evolution of acute events, whether sub-clinical pathological processes will be exacerbated or whether novel mechanisms will emerge. Based on current literature, future theoretical frameworks describing the long-term impact of COVID-19 infection on mental abilities will have to factor in major trends of aetiological and topographic heterogeneity.

show abstract

Section: Cognitive Correlates Of Neuroimaging Findingsmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Multiple Findingsmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Manca

Marco

Ince

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…SARS‐COV‐2 virus, in CSF, was demonstrated only in 2 patients. In the vast majority of COVID‐19 associated encephalopathy patients, CSF was reported normal 13‐54 (Table 1).…”

Section: Analysis Of Case Report and Case Seriesmentioning

confidence: 99%

“…Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of brain, that clinically manifests with encephalopathy and multifocal neurological signs. In ADEM, the cortical white matter brainstem, optic nerves, and spinal cord are variably affected and MRI demonstrates multifocal widespread T2/FLAIR hyperintense white matter lesions 29‐36 (Table 2).…”

Section: Neuroimagingmentioning

confidence: 99%

Encephalopathy in patients with COVID‐19: A review

Garg

Paliwal²,

Gupta

2020

Journal of Medical Virology

177

180

View full text Add to dashboard Cite

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019-associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.

show abstract

Infectious and immune-mediated central nervous system disease in 48 COVID-19 patients

Finsterer

Scorza

2021

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

Objectives to summarise and discuss current knowledge about SARS-CoV-2-associated infectious/immune-mediated central nervous system (CNS)-disease. Method literature review Results altogether 28 articles were found, which reported 48 patients with SARS-CoV-2-associated infectious/immune-mediated CNS-disease. Age ranged from 22 to 79y. There was male preponderance. There were 14 patients with infectious CNS-disease (meningitis (n=1), encephalitis (n=5), meningo-encephalitis (n=5), myelitis (n=3)), and 34 patients with parainfectious CNS-disease (encephalopathy (n=18), autoimmune encephalitis (n=11), acute, disseminated, encephalo-myelitis (n=3), acute, haemorrhagic, necrotizing encephalopathy (n=2)). The cerebrospinal fluid (CSF) was tested for SARS-CoV-2 in 40 patients and was positive for the virus in 4 patients with infectious CNS-disease but was negative for the virus in all patients with parainfectious CNS-disease. Immune-modulating treatment may be more effective than virostatics/antibiotics for SARS-CoV-2-associated infectious/parainfectious, non-vascular, non-hypoxic CNS-disease. In patients with autoimmune encephalitis plasmapheresis may be beneficial. Twenty-two patients recovered, 2 did not, and 6 patients died. Conclusions SARS-CoV-2 can cause infectious/immune-mediated CNS-disease. The CSF is positive for virus-RNA in only few patients with infectious CNS-disease but negative for virus-RNA in immune-mediated CNS-disease, suggesting an immune-mediated pathophysiological mechanism. The outcome of SARS-CoV-2-associated infectious/immune-mediated CNS-disease is favourable in the majority of cases but can be fatal in single cases.

show abstract

Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19.

Cited by 10 publications

References 8 publications

Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Encephalopathy in patients with COVID‐19: A review

Infectious and immune-mediated central nervous system disease in 48 COVID-19 patients

Contact Info

Product

Resources

About