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PubMed · 42556654

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Deborah K Erhart·Badrieh Fazeli·Franziska Bachhuber·Önder Soylu·Makbule Senel·Jan Lewerenz·Markus Otto·Steffen Halbgebauer·Hayrettin Tumani
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Abstract

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

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HumansGlial Fibrillary Acidic ProteinMaleFemaleBiomarkersNeurofilament ProteinsRetrospective StudiesAdultMiddle AgedCohort StudiesAdolescentMyelitisAgedYoung AdultMeningitisCranial Nerve DiseasesCerebrospinal fluidEncephalitisGlial fibrillary acidic proteinModified Rankin scaleNeurofilament light chainNeuroinfectious diseasesNeuroinfectious diseases of unknown pathogenJournal Article

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Deborah K Erhart, Badrieh Fazeli, Franziska Bachhuber, &#xd6;nder Soylu, Makbule Senel, Jan Lewerenz, Markus Otto, Steffen Halbgebauer, Hayrettin Tumani. 2026-08-05. Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.. https://doi.org/10.1016/j.nbd.2026.107565

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