Neuromyelitis Optica Patients Research Articles

Electrochemical Biosensing Strategy for Ultrasensitive Detection of Aquaporin-4 Antibody as Neuromyelitis Optica Autoimmune Disease Biomarker Using Aquaporin-4 Extracellular Loop

Neuromyelitis optica (NMO) is a severe and disabling neurodegenerative disorder of the central nervous system (CNS). Neuromyelitis optica-Immunoglobulin G (NMO-IgG) is a serum IgG autoantibody almost exclusively present in NMO patients, which helps to differentiate NMO from other CNS disorders. Developing standardized and user-friendly assays remains a significant challenge in making NMO-IgG testing widely available. Label-free methods are simpler and faster, without additional reagents and procedures. Here, we present a peptide-based label-free electrochemical biosensor for detecting aquaporin-4 antibodies (AQP4-Abs) using extracellular AQP4 to diagnose NMO disease via the DPV electrochemical method. We have developed a novel approach in which the E loop of extracellular AQP4 is bemployed to detect NMO. 3 phenylalanines (Phe) were annexed to the C terminal, and because phenylalanine has a benzene ring, it can have π-π interaction with the benzene ring of carbon nanotube (CNT). In the designated platform, instead of using functional groups with complex and multi-step processes for immobilizing on the electrode surface, we used Nickel-Metal−organic framework /CNT as a novel modifier for measuring AQP4 antibodies with a simple, cheap, and accessible synthesis method. The developed sensor can detect antibodies with detection limit and quantification of 6.2 and 10.0 pg ml−1, respectively (S/N = 3). Also, superb sensitivity of the biosensor was attained as 28.8 μA mL ng−1 cm−2, confirming that the sensor has great potential for clinical application as a diagnostic test.

Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates

This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methodologies, interrogating total RNA sequencing datasets from peripheral whole blood of treatment-naïve RRMS and NMO patients and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between NMO and RRMS patients, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors informed biological context and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Two small molecules identified, mitoxantrone and vorinostat, reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates, as their use in NMO patients and experimental autoimmune encephalomyelitis have been previously described. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA sequencing data enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding enhances detection of disease-specific signatures and possible therapeutic targets.

Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4-IgG-negative NMO patients. A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non-inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non-relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody-positive NMO patients compared to AQP4 antibody-negative patients. CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody-negative NMO patients.

Early involvement of peripherally derived monocytes in inflammation in an NMO-like mouse model

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the optic nerve and spinal cord within the central nervous system (CNS). Acute astrocyte injury caused by autoantibodies against aquaporin 4 (NMO-IgG) is a well-established key factor in the pathogenesis, ultimately leading to neuronal damage and patient disability. In addition to these humoral immune processes, numerous innate immune cells were found in the acute lesions of NMO patients. However, the origin and function of these innate immune cells remain unclear in NMO pathogenesis. Therefore, this study aims to analyze the origin and functions of these innate immune cells in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO. The expression of Tmem119 on Iba1 + cells in brain tissue disappeared immediately after the injection of NMO-IgG + human complement mixture, while the expression of P2ry12 remained well-maintained at 1 day after injection. Based on these observations, it was demonstrated that monocytes infiltrate the brain during the early stages of the pathological process and are closely associated with the inflammatory response through the expression of the proinflammatory cytokine IL-1β. Understanding the variations in the expression patterns of P2ry12, Tmem119, and other markers could be helpful in distinguishing between these cell types and further analyzing their functions. Therefore, this research may contribute to a better understanding of the mechanisms and potential treatments for NMO.

Dynamic changes in patient admission and their disabilities in multiple sclerosis and neuromyelitis optica: A Japanese nationwide administrative data study

BackgroundThe real-world data evidences how establishment of neuromyelitis optica (NMO) disease concept and development disease modifying therapy affect the patients with multiple sclerosis (MS) and NMO are lacking. The aim of this study is to clarify the diachronic trend of the severity and admissions of patients with MS and NMO. MethodsWe retrospectively investigated the trends in admissions, treatments, and disabilities in the patients with MS and NMO using the Japanese administrative data between 2012 and 2017. ResultsWe analyzed acute stage 9545 and 2035 admissions in each 6100 MS and 1555 NMO patients. The annual number of admission in MS significantly decreased in 6 years; however, those in NMO consistently increased. The patient proportion with lower disability was significantly increased in MS and NMO. These trends were especially observed in patients admitted to centralized hospitals with more active treatments, such as second-line disease modifying therapy for MS and plasmapheresis for NMO. Patients with NMO using DMT for MS diminished in 6 years. ConclusionA gradual improvement of disability in patients with MS and NMO was observed, probably due to advanced treatments, increased NMO awareness, and decreased misdiagnosis, which seems to be the key for better prognosis in MS and NMO.

Nationwide analysis of neuromyelitis optica in systemic lupus erythematosus and Sjogren's syndrome.

Neuromyelitis optica (NMO), also known as Devic's disease, is a rare inflammatory demyelinating disorder causing myelitis and optic neuritis. While there have been reports of systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS) occurring with NMO, a formal association is not established. We aimed to investigate the occurrence of NMO in SLE and SS patients and study the clinical characteristics and outcomes of NMO and SLE/SS hospitalizations utilizing the national inpatient sample (NIS) database. The NIS database from 2016 to 2019 was used to extract data. Adult hospitalizations with the principal or secondary diagnosis of NMO were included. We classified NMO patients with and without concomitant diagnosis of SLE or Sjogren's syndrome. We evaluated and compared the clinical characteristics and outcomes of NMO hospitalizations with and without SLE or Sjogren's syndrome. STATA17 was used for data analysis. We also calculated the odds ratio of NMO in SLE and Sjogren's syndrome. There were a total of 16,360 adult hospitalizations with the principal or secondary discharge diagnosis of NMO. Among all NMO hospitalizations, 1425 (8.71%) had the primary or secondary diagnosis of SLE or SS. The odds of NMO in SLE and Sjogren's syndrome were noted to be 12.29 and 5.56, respectively. NMO with SLE/SS group had higher proportion of females (89.82% vs 79%, P value < 0.001), African Americans (56.63% vs 38.28, P value < 0.001), and Asians (5.73% vs 3.25, P value 0.04). The Charlson comorbidity index was higher for NMO-SLE/SS overlap (2.44 vs 1.28, P value < 0.001). There was no significant difference in overall mortality rates of both groups (2.11% vs 1.2%, P value 0.197). There were significantly higher reported seizures (14.73% vs 6.05, P value < 0.001) and paraplegia (21.75% vs 13.93%, P value < 0.001) in NMO-SLE/SS patients. These patients also had a longer length of stay in comparison to the reference group (7 vs 5 days, P value < 0.001) as well as higher total charges. NMO patients had a 12-fold higher risk of SLE and 5-fold higher risk of Sjogren's disease when compared to general population. Patients with overlap of NMO and SLE or Sjogren's were predominantly women and were more likely to be African-American. Co-existence of these autoimmune disorders was associated with poor prognosis in terms of higher morbidity for patients and increased health care burden. Key Points • NMO is a rare autoimmune disease seen predominantly in women in the middle age group with low overall mortality. • SLE and Sjogren's have increased odds of NMO in comparison to general population. • NMO patients have high rates of several complications such as paraplegia, quadriplegia, seizures, blindness, sepsis, and respiratory failure with even higher rates of seizures and paraplegia in those with concomitant SLE or Sjogren's.

The Diagnostic Value of Neutrophil to Lymphocyte Ratio as an Effective Biomarker for Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis Optica (NMO) is a serious condition associated with inflammation. Early diagnosis and detection are critical for early intervention. In this systematic review, we investigate the role of the neutrophil to lymphocyte ratio (NLR) as an important biomarker for NMO. Ten studies were selected that were sufficiently high quality and then checked for quality. The studies were organized by English language and selective inclusion criteria. NLR was significantly increased in NMO patients compared to controls. The ratio was specifically proportional to severity of disease. More severe disease had a higher ratio. NLR offers a reliable and affordable method for early detection of disease severity. This can help guide appropriate treatment selection and monitor treatment response.

Investigation of sexual dysfunction and depression prevalence in neuromyelitis optica spectrum disorder.

To investigate the prevalence of sexual dysfunction (SD) and depression in patients with neuromyelitis optica (NMO), a demyelinating disorder of the central nervous system. A total of 110 NMO patients and 112 healthy individuals were included as a control group, and their SD was assessed using the Female Sexual Function Inventory (FSFI) and the International Index of Erectile Function (IIEF) for women and men, respectively. The FSFI categorizes female sexual dysfunction into six subscores, including libido, arousal, lubrication, orgasm, sexual satisfaction, and pain, while the IIEF categorizes male sexual dysfunction into five subscores, including sexual desire, erection, orgasm, intercourse satisfaction, and overall satisfaction. SD was prevalent among NMO patients, with 78% of female patients and 63.2% of male patients reporting SD in at least one subscore. The severity of the disease, as measured by the Expanded Disability Status Scale (EDSS), was found to be significantly correlated with SD in all subscores, while the duration of the disease was only correlated with the overall satisfaction subscore in men and the pain subscore in women. Furthermore, SD was found to be significantly correlated with depression in these patients. The study highlights the importance of addressing SD and depression in NMO patients, as they adversely affect the quality of life. The findings suggest that the physical aspects of SD are mostly affected by the severity of the disease, while psychological aspects are highly correlated with the chronicity of the disease.

RNA profiles to distinguish multiple sclerosis (MS) and neuromyelitis optica (NMO) in peripheral whole blood (S9.003)

RNA profiles to distinguish multiple sclerosis (MS) and neuromyelitis optica (NMO) in peripheral whole blood (S9.003)

Neuromyelitis Optica Spectrum Disorders: Clinical Perspectives, Molecular Mechanisms, and Treatments

Neuromyelitis optica (NMO) is a rare autoimmune inflammatory disorder affecting the central nervous system (CNS), specifically the optic nerve and the spinal cord, with severe clinical manifestations, including optic neuritis (ON) and transverse myelitis. Initially, NMO was wrongly understood as a condition related to multiple sclerosis (MS), due to a few similar clinical and radiological features, until the discovery of the AQP4 antibody (NMO-IgG/AQP4-ab). Various etiological factors, such as genetic-environmental factors, medication, low levels of vitamins, and others, contribute to the initiation of NMO pathogenesis. The autoantibodies against AQP4 target the AQP4 channel at the blood–brain barrier (BBB) of the astrocyte end feet, which leads to high permeability or leakage of the BBB that causes more influx of AQP4-antibodies into the cerebrospinal fluid (CSF) of NMO patients. The binding of AQP4-IgG onto the AQP4 extracellular epitopes initiates astrocyte damage through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Thus, a membrane attack complex is formed due to complement cascade activation; the membrane attack complex targets the AQP4 channels in the astrocytes, leading to astrocyte cell damage, demyelination of neurons and oligodendrocytes, and neuroinflammation. The treatment of NMOSD could improve relapse symptoms, restore neurological functions, and alleviate immunosuppression. Corticosteroids, apheresis therapies, immunosuppressive drugs, and B cell inactivating and complement cascade blocking agents have been used to treat NMOSD. This review intends to provide all possible recent studies related to molecular mechanisms, clinical perspectives, and treatment methodologies of the disease, particularly focusing on recent developments in clinical criteria and therapeutic formulations.

Comparison of OX40 expression in patients with multiple sclerosis and neuromyelitis optica as an approach to diagnosis

BackgroundPrevious studies have shown that CD134 (OX40) co-stimulation is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) models and the antigen is expressed within multiple sclerosis lesions in humans. OX40 (CD134) is thought to be a secondary co-stimulatory immune checkpoint molecule that is expressed by T cells. This study aimed to evaluate the mRNA expression of OX40 and its serum levels in the peripheral blood of patients with Multiple Sclerosis (MS) or Neuromyelitis Optica (NMO).MethodsPatients with MS (n = 60), NMO (n = 20), and 20 healthy subjects were recruited from Sina Hospital, Tehran, Iran. The diagnoses were confirmed by a specialist in clinical neurology. Peripheral venous blood was obtained from all subjects, and mRNA quantification of OX40 was conducted using real-time PCR. Serum samples were also obtained and the concentration of OX40 was determined using an enzyme-linked immunosorbent assay (ELISA).ResultsThere was a significant correlation between the mRNA expression and serum levels of OX40 and disability as assessed using the expanded disability status scale (EDSS) in the patients with MS, but not in the patients with NMO. Expression of OX40 mRNA was significantly higher in the peripheral blood of MS patients compared to healthy individuals and NMO patients (*P < 0.05). In addition, serum OX40 concentrations were also significantly higher in patients with MS patients compared with healthy subjects (9.08 ± 2.48 vs. 1.49 ± 0.54 ng/ml; P = 0.041).ConclusionsIt appears that an increased expression of OX40 may be associated with the hyperactivation of T cells in patients with MS, and this may play a role in the pathogenesis of the disease.

Monkeypox and Immunosuppressed Neurological Patients: What can we Advise Vaccination in Multiple Sclerosis and Neuromyelitis Optica Patients?

Monkeypox is a zoonotic viral disease that was identified in 1958 in research monkeys that came from Singapore. It is an orthopoxvirus that belongs to the Poxviridae family [1]. This viral infection was restricted to Africa but in the last year the cases started raising not only in Africa but in the rest of the world [1,2]. This is why it became a disease of interest; it is important to acknowledge its epidemiological behavior, risks and vaccines, especially in a world that was recently struck by COVID-19, challenging physicians in the way of treating and vaccinating their immunosuppressed patients.

Sera of Neuromyelitis Optica Patients Increase BID-Mediated Apoptosis in Astrocytes.

Neuromyelitis optica (NMO) is a rare disease usually presenting with bilateral or unilateral optic neuritis with simultaneous or sequential transverse myelitis. Autoantibodies directed against aquaporin-4 (AQP4-IgG) are found in most patients. They are believed to cross the blood–brain barrier, target astrocytes, activate complement, and eventually lead to astrocyte destruction, demyelination, and axonal damage. However, it is still not clear what the primary pathological event is. We hypothesize that the interaction of AQP4-IgG and astrocytes leads to DNA damage and apoptosis. We studied the effect of sera from seropositive NMO patients and healthy controls (HCs) on astrocytes’ immune gene expression and viability. We found that sera from seropositive NMO patients led to higher expression of apoptosis-related genes, including BH3-interacting domain death agonist (BID), which is the most significant differentiating gene (p < 0.0001), and triggered more apoptosis in astrocytes compared to sera from HCs. Furthermore, NMO sera increased DNA damage and led to a higher expression of immunological genes that interact with BID (TLR4 and NOD-1). Our findings suggest that sera of seropositive NMO patients might cause astrocytic DNA damage and apoptosis. It may be one of the mechanisms implicated in the primary pathological event in NMO and provide new avenues for therapeutic intervention.

Peptidylarginine Deiminase 2 Autoantibodies Are Linked to Less Severe Disease in Multiple Sclerosis and Post-treatment Lyme Disease.

BackgroundPeptidylarginine deiminase 2 (PAD2) mediates the post-translational conversion of arginine residues in proteins to citrullines and is highly expressed in the central nervous system (CNS). Dysregulated PAD2 activity has been implicated in the pathogenesis of several neurologic diseases, including multiple sclerosis (MS). In this study, we sought to define the cellular and regional expression of the gene encoding for PAD2 (i.e. PADI2) in the human CNS using publicly available datasets and evaluate whether anti-PAD2 antibodies were present in patients with various neurologic diseases.MethodsA total of 491 study participants were included in this study: 91 people with MS, 32 people with neuromyelitis optica (NMO), 281 people with post-treatment Lyme disease (PTLD), and 87 healthy controls. To measure PADI2 expression in the CNS from healthy individuals, publicly available tissue and single cell RNA sequencing data was analyzed. Anti-PAD2 antibodies were measured in the serum of study participants using anti-PAD2 ELISA. Clinical and demographic variables were compared according to anti-PAD2 antibody positivity for the MS and PTLD groups and correlations between anti-PAD2 levels and disease severity were examined.ResultsPADI2 expression was highest in oligodendrocytes (mean ± SD; 6.4 ± 2.2), followed closely by astrocytes (5.5 ± 2.6), microglia/macrophages (4.5 ± 3.5), and oligodendrocyte precursor cells (3.2 ± 3.3). There was an increased proportion of anti-PAD2 positivity in the MS (19.8%; p = 0.007) and PTLD groups (13.9%; p = 0.057) relative to the healthy controls (5.7%), and these antibodies were not detected in NMO patients. There was a modest inverse correlation between anti-PAD2 levels and disease severity in people with MS (τ = −0.145, p = 0.02), with levels being the highest in those with relapsing-remitting disease. Similarly, there was a modest inverse correlation between anti-PAD2 levels and neurocognitive score (τ = −0.10, p = 0.027) in people with PTLD, with difficulty focusing, memory changes, fatigue, and difficulty finding words contributing most strongly to the effect.ConclusionPADI2 expression was observed in diverse regions and cells of the CNS, and anti-PAD2 autoantibodies were associated with less severe symptoms in subsets of patients with MS and PTLD. These data suggest that anti-PAD2 antibodies may attenuate inflammation in diseases of different etiologies, which are united by high PADI2 expression in the target tissue.

HLA-genotyping by next-generation-sequencing reveals shared and unique HLA alleles in two patients with coexisting neuromyelitis optica spectrum disorder and thymectomized myasthenia gravis: Immunological implications for mutual aetiopathogenesis?

The exact immunopathogenesis, genetic mechanisms and triggering factors underlying myasthenia gravis (MG) and neuromyelitis optica (NMO) remain unknown and the coexistence may underline an aetiopathogenetic link be- tween these two diseases. We report the cases of two thymectomized patients with acetylcholine receptor (AChR) antibody (Ab)-positive MG who eventually developed AQP4-NMO. Next-Generation Sequencing (NGS) analysis showed that patient-1 had two HLA alleles previously associated with MG, mainly HLA-A*01:01:01 and HLA-DRB1*03:01, present in a haplotype in Caucasian MG patients (HLA-A1-B8-DR3-DQ2). Patient-2, expressed HLA-C*07:01:01, a well characterized MG risk factor and HLA-DQB1*05:02:01, previously described both in MG and NMO patients. Finally, we observed two common alleles in patient 1 and 2, HLA-DQA1*05:01:01 and HLA-DPB1*04:02:01. We believe that this study provides clinical evidence of the role of specific HLA alleles in rare forms of combined human peripheral and CNS autoimmunity, a fact that enhances the aim towards tailor-made therapeutic decision making.

Magnetic Resonance Image in Monitor and Diagnosis of Patients with Neuromyelitis Optica.

This study was aimed to investigate the craniocerebral magnetic resonance imaging (MRI) measurement and clinical characteristics of patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). 50 patients with NMO (NMO group) and 50 patients with MS (MS group) were studied. The clinical manifestations, brain injury morphology, MRI signal characteristics, brain distribution characteristics, and related laboratory tests (serum aquaporin 4 [AQP4] antibody) were statistically analyzed. The results showed that the analysis of clinical manifestations of patients revealed that optic neuritis (37 cases) was the most common disease in NMO patients, and myelitis (16 cases) was more common in MS patients than NMO patients. There were significant differences in gender ratio, abnormal expression of brain MR1, positive serum AQP4-IgG, and other immune diseases and symptoms between the two groups (P < 0.05). When the lesions measured by MRI were located in the white matter area of the cerebral hemisphere, the image showed blurred edges and a relatively symmetrical distribution. When the lesions measured by MRI were located around the medulla oblongata, the lesions mainly involved the central gray matter and white matter of the spinal cord, with patchy and line-like long T1 and long T2 signals. Moreover, in the late stage of recurrence of spinal cord disease, severe spinal cord atrophy may occur. In conclusion, craniocerebral MRI measurement in NMO patients can provide more basis for the diagnosis and differential diagnosis of the disease, so as to improve the diagnostic level of NMO.

A new form of axonal pathology in a spinal model of neuromyelitis optica.

Neuromyelitis optica is a chronic neuroinflammatory disease, which primarily targets astrocytes and often results in severe axon injury of unknown mechanism. Neuromyelitis optica patients harbour autoantibodies against the astrocytic water channel protein, aquaporin-4 (AQP4-IgG), which induce complement-mediated astrocyte lysis and subsequent axon damage.Using spinal in vivo imaging in a mouse model of such astrocytopathic lesions, we explored the mechanism underlying neuromyelitis optica-related axon injury.Many axons showed a swift and morphologically distinct ‘pearls-on-string’ transformation also readily detectable in human neuromyelitis optica lesions, which especially affected small calibre axons independently of myelination. Functional imaging revealed that calcium homeostasis was initially preserved in this ‘acute axonal beading’ state, ruling out disruption of the axonal membrane, which sets this form of axon injury apart from previously described forms of traumatic and inflammatory axon damage. Morphological, pharmacological and genetic analyses showed that AQP4-IgG-induced axon injury involved osmotic stress and ionic overload, but does not appear to use canonical pathways of Wallerian-like degeneration. Subcellular analysis demonstrated remodelling of the axonal cytoskeleton in beaded axons, especially local loss of microtubules. Treatment with the microtubule stabilizer epothilone, a putative therapy approach for traumatic and degenerative axonopathies, prevented axonal beading, while destabilizing microtubules sensitized axons for beading.Our results reveal a distinct form of immune-mediated axon pathology in neuromyelitis optica that mechanistically differs from known cascades of post-traumatic and inflammatory axon loss, and suggest a new strategy for neuroprotection in neuromyelitis optica and related diseases.

Effective connectivity within the corticothalamic circuit in the neuromyelitis optica patients: A comparative study using resting-state fMRI

Neuromyelitis Optica, which is known as NMO, is a demyelination syndrome and inflammatory condition of the central nervous system that affects the optic nerves. Since structural imaging approaches cannot adequately describe the brain disorders in patients with NMO, functional magnetic resonance imaging (fMRI) can be used. Resting-state fMRI was performed on 25 healthy subjects and 26 NMO patients. After preprocessing the data, the time series belonging to the regions of the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precuneus (PRE), thalamus (THA), and middle temporal gyrus (MTG) were extracted as components of the corticothalamic circuit. The obtained time series were statistically analyzed as the input of dynamic causal modeling (DCM) in order to evaluate the effective connectivity within the corticothalamic circuit. The statistical analyses showed that the mean of effective connectivity power was significantly higher in the healthy subjects than in the NMO patients. For the healthy subjects, there was no significant difference in effective connectivity power between the two groups of males and females at the significance level of 0.05. In the NMO patients, there was a significant difference between the effective connectivity levels of the male and female groups only for IFG → MFG, in which it was greater in males than in females. The results of our studies showed that resting-state fMRI could exhibit the difference between healthy and NMO subjects.

Serum levels of interleukin-6 and Vitamin D at the onset of multiple sclerosis and neuromyelitis optica: A pilot study.

Interleukin-6 (IL-6) is an important mediator in the acute phase of inflammatory diseases such as neuromyelitis optica (NMO) and multiple sclerosis (MS). The level of IL-6 is higher in cerebrospinal fluid and serum of NMO patients compare to MS. Vitamin D has a regulatory effect on IL-6, so it may have a negative correlation with IL-6 in the acute phase of these diseases. This study was performed to evaluate the serum levels of IL-6 and Vitamin D in NMO and MS patients at the onset of disease to find differences that may help in early diagnosis. This case-control study was done on patients with the first episode of optic neuritis, transverse myelitis, and area postrema syndrome who were referred to Kashani MS Center in Isfahan, Iran, between January 2018 and January 2020. The serum levels of Vitamin D and IL-6 were assessed using enzyme-linked immunosorbent assay in blood sample taken at the time of first presentation in patients who had a definitive diagnosis of NMO and MS during subsequent workup. During a 2-year follow-up, definitive diagnosis of NMO was given in 25 cases, and they were compared with 25 cases that were randomly selected from patients with definite MS. Nineteen patients in the NMO group and 21 patients in the MS group were female. The mean age of patients in the NMO and MS groups was 29.64 ± 1.47 and 30.20 ± 1.42, respectively (P = 0.46). The mean of serum level of Vitamin D was 24.88 ± 15.2 in NMO patients and 21.56 ± 18.7 in MS patients without significant difference (P = 0.48). The mean of IL-6 was 30.1 ± 22.62 in the NMO group and 23.35 ± 18.8 in the MS group without significant difference (P = 0.28). The serum levels of Vitamin D were insufficient in both groups. No correlation between Vitamin D and IL-6 levels was found in our study (P > 0.05). Our results showed that serum IL-6 levels were higher at the onset of NMO disease compared with MS. The serum levels of Vitamin D were low in both groups and there was no association between serum levels of Vitamin D and IL-6 in either group. Future studies with large sample size are needed to confirm these findings.

Prevalence and Direct Costs of Patients with Neuromyelitis Optica: Data from Campania Region in Southern Italy

Aim: The study aimed to estimate the prevalence and direct costs of neuromyelitis optica (NMO) patients in Campania, Italy. Materials &amp; methods: We retrospectively evaluated 53 NMO patients (mean age: 50.9 ± 16.5 years; 34% men) from the Campania Region administrative databases identified through disease exemption codes in 2018 and analyzed the incidence of NMO among the Campania region population and the disease-related cost. Results: The prevalence of NMO was 0.91 per 100,000 individuals. The average regional cost per NMO patient was 10,836.2 euros. The highest cost was related to drugs (60.6%), followed by hospitalizations (32.7%), diagnostics (4.8%) and laboratory tests (1.0%). Conclusion: NMO is an extremely rare disease with an annual disease-related cost of 0.005% of public health expenditure.