Reader response: CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series
AnandKumar, Assistant Professor, Neurology, Banaras Hindu University, Institute of Medical Sciences (Varanasi, India)
NehaLall, Junior Resident, Radiotherapy & Radiation Medicine, Banaras Hindu University, Institute of Medical Sciences (Varanasi, India)
Submitted October 02, 2020
We read with interest the article by Edén et al.1 assessing the CSF biomarkers of intrathecal inflammation (CSF white blood cell counts, neopterin, β2-microglobulin [β2M] and immunoglobulin G-index), blood-brain-barrier [BBB] integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in COVID-19 patients with neurological symptoms. The results illustrate evidence of significant CSF inflammation with raised soluble markers without any cellular response; unlike other viral CNS infections. As far as intrathecal markers like neopterin and β2-microglobulin (β2M) are concerned, these are nonspecific and are produced by macrophages during activation of cell mediated immune response. These are often found significantly raised in various conditions like human immunodeficiency virus (HIV) infection,2 relapsing-remitting or chronic-progressive multiple sclerosis (RRMS),3 and in head trauma,4 putting forth questions about its value as a disease specific maker.
Neurofilament light chain protein (NfL) being a component of axonal and dendritic cytoskeleton, it is considered as a biomarker of axonal injury. It is raised in CSF in diseases like amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, head trauma, and Alzheimer’s disease making it a very low specific marker.5
Neuropathogenesis in COVID-19 is still unknown and is considered multifactorial. Systemic inflammation, hypoxemia, hypercoagulability, and some unidentifiable mechanisms may all contribute to specific neurological condition, and this warrants further study.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Edén A, Kanberg N, Gostner J, et al. CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series. Neurology 2020 Epub Oct 1.
Bogner JR, Junge-Hülsing B, Kronawitter U, Sadri I, Matuschke A, Goebel FD. Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches maximum levels early and late in the course of human immunodeficiency virus infection. Clin Investig 1992;70:665–669.
Ott M, Demisch L, Engelhardt W, Fischer PA. Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and beta 2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis. J Neurol 1993;241:108–114.
Lenzlinger PM, Hans VHJ, Joller-Jemelka HI, Trentz O, Morganti-Kossmann MC, Kossmann T. Markers for cell-mediated immune response are elevated in cerebrospinal fluid and serum after severe traumatic brain injury in humans. J Neurotrauma. 2001;18:479–489.
Peng L, Bi C, Xia D, Mao L, Qian H. Increased cerebrospinal fluid neurofilament light chain in central nervous system inflammatory demyelinating disease. Mult Scler Relat Disord 2019;30:123–128.
We read with interest the article by Edén et al.1 assessing the CSF biomarkers of intrathecal inflammation (CSF white blood cell counts, neopterin, β2-microglobulin [β2M] and immunoglobulin G-index), blood-brain-barrier [BBB] integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in COVID-19 patients with neurological symptoms. The results illustrate evidence of significant CSF inflammation with raised soluble markers without any cellular response; unlike other viral CNS infections. As far as intrathecal markers like neopterin and β2-microglobulin (β2M) are concerned, these are nonspecific and are produced by macrophages during activation of cell mediated immune response. These are often found significantly raised in various conditions like human immunodeficiency virus (HIV) infection,2 relapsing-remitting or chronic-progressive multiple sclerosis (RRMS),3 and in head trauma,4 putting forth questions about its value as a disease specific maker.
Neurofilament light chain protein (NfL) being a component of axonal and dendritic cytoskeleton, it is considered as a biomarker of axonal injury. It is raised in CSF in diseases like amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, head trauma, and Alzheimer’s disease making it a very low specific marker.5
Neuropathogenesis in COVID-19 is still unknown and is considered multifactorial. Systemic inflammation, hypoxemia, hypercoagulability, and some unidentifiable mechanisms may all contribute to specific neurological condition, and this warrants further study.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References