Dataset Information

Cerebrospinal Fluid Findings in Patients With Autoimmune Encephalitis-A Systematic Analysis.

ABSTRACT: Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of different antineuronal antibodies. Recently, a clinical approach for diagnostic criteria for the suspected diagnosis of AIE as well as definitive AIE were proposed. These are intended to guide physicians when to order the antineuronal antibody testing and/or facilitate early diagnosis even prior to the availability of the specific disease-confirming test results to facilitate prompt treatment. These diagnostic criteria also include the results of basic cerebrospinal fluid (CSF) analysis. However, the different antibody-defined AIE subtypes might be highly distinct with regard to their immune pathophysiology, e.g., the pre-dominance of specific IgG subclasses, IgG1, or IgG4, or frequency of paraneoplastic compared to idiopathic origin. Thus, it is conceivable that the results of basic CSF analysis might also be very different. However, this has not been explored systematically. Here, we systematically reviewed the literature about the 10 most important AIE subtypes, AIE with antibodies against NMDA, AMPA, glycine, GABA_A, and GABA_B receptors as well as DPPX, CASPR2, LGI1, IgLON5, or glutamate decarboxylase (GAD), with respect to the reported basic CSF findings comprising CSF leukocyte count, total protein, and the presence of oligoclonal bands (OCB) restricted to the CSF as a sensitive measure for intrathecal IgG synthesis. Our results indicate that these basic CSF findings are profoundly different among the 10 different AIE subtypes. Whereas, AIEs with antibodies against NMDA, GABA_B, and AMPA receptors as well as DPPX show rather frequent inflammatory CSF changes, in AIEs with either CASPR2, LGI1, GABA_A, or glycine receptor antibodies CSF findings were mostly normal. Two subtypes, AIEs defined by either GAD, or IgLON5 antibodies, did not fit into this general pattern. In AIE with GAD antibodies, positive OCBs in the absence of other changes were typical, while the CSF in IgLON5 antibody-positive AIE was characterized by elevated protein.

SUBMITTER: Blinder T

PROVIDER: S-EPMC6670288 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cerebrospinal Fluid Findings in Patients With Autoimmune Encephalitis-A Systematic Analysis.

Blinder Tetyana T Lewerenz Jan J

Frontiers in neurology 20190725

Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of different antineuronal antibodies. Recently, a clinical approach for diagnostic criteria for the suspected diagnosis of AIE as well as definitive AIE were proposed. These are intended to guide physicians when to order the antineuronal antibody testing and/or facilitate early diagnosis even prior to the availability of the specific di ...[more]

PMID: 31404257

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Project description:Encephalitis mediated by autoantibodies against neuronal antigens and herpes simplex encephalitis (HSE) are seemingly separate causes of encephalopathy in adults. Autoimmune encephalitis (AE) is autoimmune in origin, and herpes simplex encephalitis is infectious. The purpose of this study was to examine the role of cerebrospinal fluid (CSF) exosomes from patients with antibody-positive AE and HSE. Towards this, exosomes were isolated from CSF from 13 patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, 11 patients with anti-gamma-aminobutyric acid-B (GABAB) receptor encephalitis, 9 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, and 12 control individuals negative of antibodies against neuronal autoantigens. There were ten miRNAs highly expressed in patients with anti-NMDAR encephalitis compared to those in control subjects. Eight miRNAs were found to be lower expressed in anti-NMDAR encephalitis CSF-derived exosomes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by AE differential expressed exosomic miRNAs demonstrated that AE-related exosomic miRNAs may participate as a feedback regulation in cancer development. In addition, the exosome concentration in CSF of 9 HSE patients was significantly higher compared to those from 9 HSV( -) patients. This observation was consistent with the results that exosome concentration was found to be higher in the animal model which was inoculated intranasally with HSV-1 compared to controls. Furthermore, western blot demonstrated that the subunits of NMDAR, GABABR, and AMPAR were detected highly expressed in exosomes derived from sera of HSV-1-treated animal model compared to controls. More importantly, exosomes isolated from CSF of HSE patients contained higher expression levels of two miRNAs encoded by HSV, miR-H2-3p, and miR-H4-3p compared to those from HSV( -) patients. In summary, HSV may trigger brain autoimmunity in HSE by presentation of surface autoantigens via exosomes.

Project description:In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

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Dataset Information

Cerebrospinal Fluid Findings in Patients With Autoimmune Encephalitis-A Systematic Analysis.

Publications

Cerebrospinal Fluid Findings in Patients With Autoimmune Encephalitis-A Systematic Analysis.

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