Serum and CSF neurofilament light chain and glial fibrillary acidic protein levels in idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is a neurological disorder marked by increased intracranial pressure (ICP). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are established biomarkers of neuroaxonal degeneration and astroglial activation that typically show strong serum-cerebrospinal fluid (CSF) concordance. However, their behaviour in IIH and the influence of increased ICP on CSF-serum relationship remains poorly understood. The aim of this study was to investigate serum and CSF NfL and GFAP levels in IIH, examine their CSF-serum coupling, and assess associations with ophthalmological outcomes. In this prospective observational study, newly diagnosed people with IIH (pwIIH) underwent baseline serum and CSF sampling. NfL and GFAP levels were quantified using single-molecule array (Simoa→) technology, with age-, BMI-, and sex-adjustment. CSF-to-serum quotients (QNfL, QGFAP) and albumin-normalized indices were calculated. Outcome measures included: papilledema degree, visual acuity, perimetric mean deviation on automated perimetry, peripapillary retinal nerve fibre layer and macular ganglion cell layer thickness measured by optical coherence tomography, and arachnoid optic nerve sheath diameter measured by transbulbar sonography. Thirty pwIIH (mean age 34.1 [SD 10.0], 100.0% female, mean CSF opening pressure [OP] 34.1 cmCSF [3.9], median BMI 35.4 kg/m2 [IQR 32.7–40.8]) were included. We did not observe any relevant associations between fluid biomarkers and ophthalmological outcomes at any time point. Notably, CSF NfL and GFAP levels did not correlate with respective serum levels. In contrast, serum NfL and GFAP levels were inversely associated with CSF OP, and QNfL and QGFAP showed positive associations with CSF OP (QNfL: β = 9.28; 95% CI 2.82, 15.73; p = 0.007; QGFAP: β = 13.00; 95% CI 0.12, 25.88; p = 0.048). Neither NfL nor GFAP levels seem particularly promising as biomarkers for prediction of ophthalmological outcomes in IIH. However, the observed dissociation between serum and CSF biomarkers supports altered CSF dynamics, rather than neuroaxonal or astrocytic injury, as the dominant pathophysiological drivers in the active phase of IIH.