Kappa index in the diagnostic work-up of autoimmune encephalitis

J Neurol Sci. 2024 Aug 15:463:123146. doi: 10.1016/j.jns.2024.123146. Epub 2024 Jul 18.

Abstract

Background: The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE.

Methods: Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied. CSF and serum kappa free light chains were determined using the Freelite assay (The Binding Site Group) and the turbidimetric Optilite analyzer.

Results: We identified 34 patients with "definite" AE (9 anti-NMDAR AE and 25 limbic AE) and nine patients with "possible" AE. Five patients (15%) with definite AE had pleocytosis and twelve (34%) showed CSF-restricted oligoclonal bands (OCB) at isoelectric focusing. The Kappa index was >6 in 29.4% and > 3 in 50% of the definite AE patients. It was elevated (>3) in 36.4% of patients with definite AE who resulted negative to OCB testing and was the only altered parameter suggestive of an ongoing inflammatory process in the CNS in three definite AE patients with otherwise normal CSF findings (i.e. normal cell count and protein levels, no OCBs). In the possible AE group, one patient had a Kappa index >3 in the absence of OCB.

Conclusions: The Kappa index could be useful, as a more sensitive marker of IS and as a supportive marker of neuroinflammation, in the diagnostic work-up of suspected AE.

Keywords: Autoimmune encephalitis; Cerebrospinal fluid; Free light chain; Kappa index; Oligoclonal bands.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / blood
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / cerebrospinal fluid
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnosis
  • Autoimmune Diseases of the Nervous System / blood
  • Autoimmune Diseases of the Nervous System / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / diagnosis
  • Autoimmune Diseases of the Nervous System / immunology
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Encephalitis* / blood
  • Encephalitis* / cerebrospinal fluid
  • Encephalitis* / diagnosis
  • Female
  • Hashimoto Disease / blood
  • Hashimoto Disease / cerebrospinal fluid
  • Hashimoto Disease / diagnosis
  • Humans
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin kappa-Chains / cerebrospinal fluid
  • Male
  • Middle Aged
  • Oligoclonal Bands / blood
  • Oligoclonal Bands / cerebrospinal fluid
  • Retrospective Studies
  • Young Adult

Substances

  • Biomarkers
  • Oligoclonal Bands
  • Immunoglobulin kappa-Chains

Supplementary concepts

  • Hashimoto's encephalitis