Cerebrospinal fluid markers of inflammation and brain injury in Lyme neuroborreliosis – a prospective follow-up study

• Published in: Clinical chemistry and laboratory medicine Vol. 60; no. 7; pp. 1124 - 1132
• Main Authors: Tjernberg, Ivar, Gyllemark, Paula, Zetterberg, Henrik, Blennow, Kaj, Ernerudh, Jan, Forsberg, Pia, Sjöwall, Johanna, Henningsson, Anna J.
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 27.06.2022; Walter De Gruyter & Company
• Subjects: Anesthesia; Antibiotics; biomarkers; Borreliosis; Brain; Brain injury; Central nervous system; Cerebrospinal fluid; CXCL13 protein; Diagnosis; Differential diagnosis; Glial fibrillary acidic protein; Head injuries; Inflammation; Lyme disease; Lyme neuroborreliosis; Markers; Myeloid cells; Neuronal-glial interactions; Neurosciences; Neurovetenskaper; pathogenesis; Patients; Proteins; Tau protein; Traumatic brain injury; pathogenesis; brain injury; Lyme neuroborreliosis; biomarkers; cerebrospinal fluid
• ISSN: 1434-6621; 1437-4331; 1437-4331
• DOI: 10.1515/cclm-2022-0097

The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies' guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p<0.001) and SAS (p≤0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.