Immunoadsorption and plasma exchange-Efficient treatment options for neurological autoimmune diseases.

BACKGROUND: Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis. METHODS: In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases. RESULTS: A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE. CONCLUSIONS: In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group.

Diagnostics of paraneoplastic neurological syndromes.

This document presents the guidelines for onconeural antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on paraneoplastic neurological syndromes, indications and limits of onconeural antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of dysimmune peripheral neuropathies.

This document presents the guidelines for anti-ganglioside antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Main clinical information on dysimmune peripheral neuropathies, indications and limits of anti-ganglioside antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of myasthenic syndromes: detection of anti-AChR and anti-MuSK antibodies.

This paper presents the Italian guidelines for autoantibody testing in myasthenia gravis that have been developed following a consensus process built on questionnaire-based surveys, internet contacts and discussions during dedicated workshops of the sponsoring Italian Association of Neuroimmunology (AINI). Essential clinical information on myasthenic syndromes, indications and limits of antibody testing, instructions for result interpretation and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of anti-MAG antibody polyneuropathy.

This document presents the guidelines for anti-myelin-associated glycoprotein (MAG) antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses. The main clinical information on anti-MAG antibody polyneuropathy, indications and limits of anti-MAG antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD).

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Early Diagnosis of CNS Virus Infections from Neurological Autoimmune Diseases: A Cross-Sectional Study from China in ER Setting.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.

Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis.

Purpose: This study aimed to evaluate the features of corneal nerve with in vivo confocal microscopy (IVCM) among patients with non-neurological autoimmune (NNAI) diseases. Methods: We systematically searched PubMed, Web of Science, and Cochrane Central Register of Controlled Trials for studies published until May 2021. The weighted mean differences (WMDs) of corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), tortuosity, reflectivity, and beadings per 100 µm with a 95% CI between NNAI and control group were analyzed using a random-effects model. Results: The results showed 37 studies involving collective totals of 1,423 patients and 1,059 healthy controls were ultimately included in this meta-analysis. The pooled results manifested significantly decreased CNFL (WMD: -3.94, 95% CI: -4.77--3.12), CNFD (WMD: -6.62, 95% CI: -8.4--4.85), and CNBD (WMD: -9.89, 95% CI: -14--5.79) in NNAI patients. In addition, the NNAI group showed more tortuous corneal nerve (WMD: 1.19, 95% CI:0.57-1.81). The comparison between NNAI patients and healthy controls in beadings per 100 µm corneal nerve length was inconsistent. No significant difference was found in the corneal nerve fiber reflectivity between NNAI and the control group (WMD: -0.21, 95% CI: -0.65-0.24, P = 0.361). Conclusions: The parameters and morphology of corneal nerves observed by IVCM proved to be different in NNAI patients from healthy controls, suggesting that IVCM may be a non-invasive technique for identification and surveillance of NNAI diseases.

Identifying the culprits in neurological autoimmune diseases.

The target organ of neurological autoimmune diseases (NADs) is the central or peripheral nervous system. Multiple sclerosis (MS) is the most common NAD, whereas Guillain-Barré syndrome (GBS), myasthenia gravis (MG), and neuromyelitis optica (NMO) are less common NADs, but the incidence of these diseases has increased exponentially in the last few years. The identification of a specific culprit in NADs is challenging since a myriad of triggering factors interplay with each other to cause an autoimmune response. Among the factors that have been associated with NADs are genetic susceptibility, epigenetic mechanisms, and environmental factors such as infection, microbiota, vitamins, etc. This review focuses on the most studied culprits as well as the mechanisms used by these to trigger NADs.