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Metabolic Brain Disease

, Volume 34, Issue 5, pp 1473–1485 | Cite as

Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis

  • V. FominykhEmail author
  • L. Brylev
  • V. Gaskin
  • R. Luzin
  • A. Yakovlev
  • I. Komoltsev
  • I. Belousova
  • A. Rosliakova
  • A. Guekht
  • N. Gulyaeva
Original Article

Abstract

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n = 24) as compared to multiple sclerosis (MS, n = 61) and control (n = 19) groups. Detailed clinical pictures of patients are presented. We focused on relevant cerebrospinal fluid (CSF) tests like protein levels, cytosis and oligoclonal bands, neuroinflammation indices (interleukin-6, soluble receptor of IL-6, neopterin, anti-ribosomal proteins antibodies) and markers of neurodegeneration (phosphorylated neurofilament heavy chain, pNfh). Elevated neopterin level was found in AE group as compared to the MS and control groups, while protein and pNfh were increased in both AE and MS groups. In the MS group, the cytosis and soluble receptor of IL-6 were higher as compared to the control group. Anti-ribosomal proteins antibodies were increased in a single patient with AE. High levels of protein were predictive of mortality in AE patients, while IL-6 and pNfh were elevated in severe AE patients. AE patients with paraneoplastic etiology demonstrated oligoclonal bands positivity. Taken together, our results suggest the neopterin as an additional marker of autoimmune brain inflammation. Though higher levels of protein, IL-6 and pNfh were found in patients with severe disease progression and death, prognostic values of these markers should be validated in larger cohorts of patients.

Keywords

Autoimmune encephalitis Multiple sclerosis Interleukin 6 Neopterin Neuroinflammation Neurodegeneration 

Abbreviations

ADEM

acute disseminated encephalomyelitis

AE

autoimmune encephalitis

ALS

amyotrophic lateral sclerosis

AMPA

ionotropic glutamate receptor

AQP4

aquaporin-4

CASPR2

contactin-associated protein-2

CNS

сentral nervous system

CSF

cerebrospinal fluid

EDSS

Kurtzke Expanded Disability Status Scale

GABA

gamma-aminobutyric acid

GAD

glutamic acid decarboxylase

Ig

immunoglobulin

IL-6

Interleukin-6

LGI1

Leucine-rich glioma-inactivated 1

MP

methylprednisolone

MRI

magnetic resonance imaging

MS

multiple sclerosis

NMDA

N-methyl-D-aspartate

NMOSD

neuromyelitisoptica spectrum disorders

Ogbs

oligoclonal bands

PLEX

plasmapheresis

pNfh

phosphorylated neurofilament heavy chain

sIL-6R

soluble Interleukin-6 Receptor

SLE

systemic lupus erythematosus

Notes

Acknowledgements

We thank all patients who participated in this study.

Funding source

Partially supported by Russian Academy of Sciences, Program Fundamental Bases of Physiological Adaptation Technologies.

Compliance with ethical standards

Conflict of interest

No conflict of interest.

Supplementary material

11011_2019_452_MOESM1_ESM.pdf (57 kb)
ESM 1 Correlation analysis of biochemical markers in AE patients (p < 0.05 for all correlation plots). (PDF 57 kb)
11011_2019_452_MOESM2_ESM.pdf (41 kb)
ESM 2 Correlation analysis of clinical characteristics and biochemical markers in MS patients (p < 0.05 for all correlation plots). (PDF 40 kb)
11011_2019_452_MOESM3_ESM.pdf (133 kb)
ESM 3 The induction of neopterin production in the brain (scheme). Pro-inflammatory cytokines (e.g. interferon gamma) induce the expression in neuronal cells of guanosine triphosphate-cyclohydrolase I converting guanosine triphosphate into 7,8-dehydroneopterin triphosphate, which, normally, is converted to 5,6,7,8-tetrahydrobiopterin (cofactor of monoaminoxidase involved in neurotransmitter generation). In conditions favoring oxidation and dephosphorylation in monocytic cells it is converted to neopterin. (PDF 133 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Higher Nervous Activity and NeurophysiologyMoscowRussia
  2. 2.Bujanov Moscow City Clinical HospitalMoscowRussia
  3. 3.Moscow Research and Clinical Center for Neuropsychiatry of the Healthcare Department of MoscowMoscowRussia
  4. 4.Research Center of NeurologyMoscowRussia
  5. 5.Pirogov Russian National Research Medical UniversityMoscowRussia

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