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Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis



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 (Nf L). 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 43 ng/L) than in AD (621 and 90 ng/L, p < 0.001) and CJD patients (4327 and 55 ng/L, p < 0.001 and p < 0.01). Nf L concentrations of LGI1 encephalitis (2039 ng/L) were similar to AD (2,765 ng/L) and significantly higher compared to PSY (1223 ng/L, p < 0.005), but significantly lower than those of CJD (13,457 ng/L, p < 0.001). Higher levels of Nf L were observed in LGI1 encephalitis presenting with epilepsy (3855 ng/L) compared to LGI1 without epilepsy (1490 ng/L, p = 0.02). No correlation between CSF biomarkers’ levels and clinical outcome could be drawn.


LGI encephalitis patients showed higher Nf L levels than PSY, comparable to AD, and even higher when presenting epilepsy suggesting axonal or synaptic damage linked to epileptic seizures.

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Data availability

Data related to the current article are available from the corresponding authors on reasonable request.


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The authors acknowledge Hélène Boyer, PhD, for English language editing (Direction de la Recherche Clinique, Hospices Civils de Lyon) and Dr Aude Metzger, MD, PhD (Hospices Civils de Lyon), for providing statistical advice.


This work has been developped within the BETPSY project, which is supported by a public grant overseen by the French National Research Agency (ANR), as part of the second “Investissements d´Avenir” program (reference ANR-18-RHUS-0012). SM-C is supported by a research grant from Fundación Alfonso Martín Escudero (Spain).

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Correspondence to Virginie Desestret.

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The authors declare that there is no conflict of interest.

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Written consent was obtained from all patients and the present study (NCT-04001270) was approved by the institutional review board of the Université Claude Bernard Lyon 1 and Hospices Civils de Lyon. CSF samples were stored with authorization (declaration number DC-2008-304) of the Ministère de la Santé (French ministry of health).

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Lardeux, P., Fourier, A., Peter, E. et al. Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis. J Neurol 269, 377–388 (2022).

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  • LGI1 encephalitis
  • CSF biomarkers
  • Epilepsy
  • Neuronal damage