Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis.

Abstract

To compare CSF biomarkers' levels in patients suffering from anti-Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis to neurodegenerative [Alzheimer's disease (AD), Creutzfeldt-Jakob's disease (CJD)] and primary psychiatric (PSY) disorders. Patients with LGI1 encephalitis were retrospectively selected from the French Reference Centre database between 2010 and 2019 and enrolled if CSF was available for biomarkers analysis including total tau (T-tau), phosphorylated tau (P-tau), amyloid-beta Aβ1-42, and neurofilaments light chains (NfL). Samples sent for biomarker determination as part of routine practice, and formally diagnosed as AD, CJD, and PSY, were used as comparators. Twenty-four patients with LGI1 encephalitis were compared to 39 AD, 20 CJD and 20 PSY. No significant difference was observed in T-tau, P-tau, and Aβ1-42 levels between LGI1 encephalitis and PSY patients. T-Tau and P-Tau levels were significantly lower in LGI1 encephalitis (231 and 43ng/L) than in AD (621 and 90ng/L, p < 0.001) and CJD patients (4327 and 55ng/L, p < 0.001 and p < 0.01). NfL concentrations of LGI1 encephalitis (2039ng/L) were similar to AD (2,765ng/L) and significantly higher compared to PSY (1223ng/L, p < 0.005), but significantly lower than those of CJD (13,457ng/L, p < 0.001). Higher levels of NfL were observed in LGI1 encephalitis presenting with epilepsy (3855ng/L) compared to LGI1 without epilepsy (1490ng/L, p = 0.02). No correlation between CSF biomarkers' levels and clinical outcome could be drawn. LGI encephalitis patients showed higher NfL levels than PSY, comparable to AD, and even higher when presenting epilepsy suggesting axonal or synaptic damage linked to epileptic seizures.