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.
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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
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We thank all patients who participated in this study.
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Partially supported by Russian Academy of Sciences, Program Fundamental Bases of Physiological Adaptation Technologies.
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ESM 1
Correlation analysis of biochemical markers in AE patients (p < 0.05 for all correlation plots). (PDF 57 kb)
ESM 2
Correlation analysis of clinical characteristics and biochemical markers in MS patients (p < 0.05 for all correlation plots). (PDF 40 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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Fominykh, V., Brylev, L., Gaskin, V. et al. Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis. Metab Brain Dis 34, 1473–1485 (2019). https://doi.org/10.1007/s11011-019-00452-x
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DOI: https://doi.org/10.1007/s11011-019-00452-x