CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

Front Immunol. 2021 Dec 16:12:719432. doi: 10.3389/fimmu.2021.719432. eCollection 2021.

Abstract

Background and objectives: The two most common autoimmune encephalitides (AE), N-methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE.

Methods: Patients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease).

Results: A total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE.

Discussion: CSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted.

Keywords: LGI1 encephalitis; NMDAR encephalitis (NMDARE); autoimmune encephalitis (AE); biomarker; neurofilament light (NfL) chain; outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / cerebrospinal fluid
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / etiology
  • Biomarkers / cerebrospinal fluid
  • Child
  • Demyelinating Diseases / complications
  • Denmark
  • Encephalitis, Herpes Simplex / cerebrospinal fluid
  • Female
  • Follow-Up Studies
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukocytosis / etiology
  • Limbic Encephalitis / cerebrospinal fluid*
  • Limbic Encephalitis / etiology
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neurofilament Proteins / cerebrospinal fluid*
  • Paraneoplastic Syndromes, Nervous System / cerebrospinal fluid
  • Paraneoplastic Syndromes, Nervous System / etiology
  • Prognosis
  • Teratoma / complications
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Neurofilament Proteins
  • neurofilament protein L