key: cord-0903630-831bc8bd
authors: Espíndola, Otávio M.; Gomes, Yago C. P.; Lima, Marco Antonio S. D.; Leite, Ana Claudia C. B.; Araujo, Abelardo Q. C.; Silva, Marcus Tulius T.
title: Reply to “CSF Cytokine Profiles Do Not Reliably Delineate Encephalopathy and Inflammation in Neuro‐COVID”
date: 2021-08-24
journal: Ann Neurol
DOI: 10.1002/ana.26193
sha: ec175b513db2a50bd4591aff404e4def13b5c3cc
doc_id: 903630
cord_uid: 831bc8bd

nan

mm 3 . Their exclusion, however, did not alter the findings. Thus, CSF cytokine profiles were not influenced by serum contamination. Moreover, a correlation analysis showed that CSF and serum levels of cytokines were independent, except for CXCL10 in patients with encephalopathy (Table) , which was not altered as compared to controls. 2 Patients were organized by their primary neurological manifestation at the time of CSF collection. One patient was diagnosed with neuromyelitis optica, but antiaquaporin 4 was not tested. Patients with refractory headache presented normal brain magnetic resonance imaging (MRI), but 85% had CSF opening pressure > 200mmH 2 O, and half had idiopathic intracranial hypertension (>250mmH 2 O). 3 Seizures and abnormalities on electroencephalogram were considered for diagnosis of both encephalopathy and encephalitis. However, to avoid overlap between groups, encephalopathy was disregarded whenever signs of acute brain inflammation were present, including pleocytosis and/or brain MRI changes, which instead characterized encephalitis. Although headache may precede encephalopathy or IND, sequential onset between encephalopathy and IND can be ruled out in our study, because such conditions presented as first manifestations within 14 days from the onset of COVID-19. Therefore, CSF findings were unlikely to be associated with distinct stages of the same disease. Lastly, prospective analysis of patients would illuminate the dynamics of cytokines and biomarkers of inflammation. However, the study was conducted between April and June 2020, at the beginning Patients with COVID-19 and refractory headache, encephalopathy, and IND were evaluated for the dependency between serum and CSF levels of inflammatory cytokines previously assessed. 2 The analysis was performed with Spearman rank of correlation test for cytokines with detectable levels in paired CSF and serum in at least half of the individuals in each group. The analysis was carried out for IL-2, CXCL10, CCL2, and CXCL8. Spearman of the COVID-19 epidemic in Brazil, which complicated the establishment of a structured cohort. Nevertheless, cytokine profiles defined at early stages of neuro-COVID indicated that events triggering neuroinflammatory syndromes originated from within the central nervous system, 2 even when SARS-CoV-2 was not detected in the CSF. 1, 4 

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development

Inflammatory cytokine patterns associated with neurological diseases in coronavirus disease 2019

Isolated intracranial hypertension associated with COVID-19

Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid

We thank Drs Finsterer and Scorza for their questions regarding our study of CSF and serum cytokine profiles in neuro-COVID. We also thank Dr K. Nielsen-Saines for reading the manuscript.

Nothing to report.