NMOSD Patients Research Articles

Novel insights into pathophysiology and therapeutic possibilities reveal further differences between AQP4-IgG- and MOG-IgG-associated diseases.

This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies. Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune diseases of the central nervous system (CNS). Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to differences in clinical response of anti-CD20 therapy remains to be analyzed. Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19 + B cells), and satralizumab (anti-IL-6R blocking IL-6 actions). New insights into pathological mechanisms and therapeutic responses argue to consider NMOSD with AQP4-IgG and MOGAD as separate disease entities.

The 2015 IPND Criteria Increases the Yield in Diagnosis of Neuromyelitis Optica Spectrum Disorder in Thai Patients Compared to the 2006 Diagnostic Criteria

BackgroundThe 2015 International Panel for Neuromyelitis Optica (NMO) Diagnosis (IPND) criteria was revised using systematic literature reviews and consensus from the experts. It facilitates NMOSD diagnosis and is applicable in an Asian population. ObjectiveTo compare the utility of the 2015 IPND criteria and the 2006 NMO diagnostic criteria for the diagnosis of NMO/SD. MethodsWe retrospectively reviewed the electronic medical records 5 of patients with NMOSD who attended Multiple Sclerosis and Related Disorders Clinic between January 2010 and December 2016. Two independent investigators applied the 2006 revised diagnostic criteria for NMO in patients who fulfilled the 2015 IPND criteria. ResultsOf all 70 cases who had an NMOSD diagnosis according to 2015 criteria, 56 cases (80.0%) were positive for aquaporin-4 immunoglobulin (AQP4-IgG). Nineteen patients (27.1%) fulfilled the 2006 NMO diagnostic criteria. The 2015 IPND criteria identified 51 more NMOSD cases, increasing the diagnostic yield by 268%, compared to the 2006 criteria. The median time from onset to diagnosis by using the 2015 IPND criteria was shorter than those identified by the 2006 criteria (128 vs. 547 days, p=0.002). The 2015 IPND also provides for lesser attacks occurring before achieving diagnosis (1.7 vs. 2.7, p<0.001). In the absence of known AQP4-IgG serostatus, the 2015 criteria still indicated NMOSD patients by a 124% increase in detection rate (p<0.001); however, time to diagnosis was not statistically significant between the two criteria (258 vs. 604 days, p=0.081). ConclusionsCompared to the 2006 criteria, the 2015 IPND criteria increased diagnostic yield for NMOSD regardless of AQP4-IgG status and shortened the time from onset to diagnosis in patients with NMOSD with known AQP4-IgG serostatus.

Altered resting-state functional connectivity density in patients with neuromyelitis optica-spectrum disorders

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, demyelinating disorder, accompanied by abnormal spontaneous activity of the brain and impairment of the retina and optic nerve. Functional connectivity density (FCD) map, a graph theory method, was applied to explore the functional connectivity alterations of brian in NMOSD patients and investigate the alterations of FCD to the structural and microvascular changes around the optic nerve head (ONH). MethodsNineteen NMOSD patients and 22 healthy controls (HCs) were included in our study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scans of the brain, and ophthalmological examinations included optical coherence tomographic angiography (OCT-A) imaging, visual acuity (VA), and intraocular pressure (IOP). The long- and short-range FCD was calculated by the fMRI graph theory method and two-sample t-tests were performed to compare the discrepancy of FCD between NMOSD and HCs. OCT-A imaging was used to obtain the structure (peripapillary retinal nerve fiber layer, pRNFL) and microvessels (radial peripapillary capillary, RPC) details around the ONH. The association between the long- and short-range FCD values with the structural and microvascular variation around the ONH were evaluated using Spearman's correlation. ResultsSignificantly decreased (corrected p < 0.05) long-range FCD was seen in the right superior parietal gyrus (SPG) in patients with NMOSD when compared to HCs. Increased long-range FCD was seen in the right fusiform gyrus (FFG), left orbital part of superior frontal orbital gyrus (ORBsup) and left anterior cingulum and paracingulate gyri (ACG) in NMOSD patients (corrected p < 0.05). The regions with reduced short-range FCD in NMOSD were the left angular gyrus (ANG) and right SPG (corrected p < 0.05). Increased short-range FCD was shown (corrected p < 0.05) in the right FFG of NMOSD. The pRNFL thickness and RPC density in all participants were negatively correlated with the long-range FCD values in the right FFG, left ORBsup, and left ACG as well as short-range FCD values in the right FFG, besides, both were positively correlated with the long-range FCD values in the right SPG and short-range FCD values in the left ANG and right SPG (p < 0.05). ConclusionOur study demonstrates that patients with NMOSD have widespread brain dysfunction after optic neuritis attacks which shows as impairment of widespread spatial distribution in long- and short-range FCD. Structural and microvascular changes around the ONH are associated with neural changes in the brain.

Dorsal midbrain involvement in MRI as a core clinical manifestation for NMOSD diagnosis

BackgroundFew data are available on the prevalence of midbrain lesions among NMOSD patients. The study aimed to address the frequency of midbrain lesions, especially dorsal midbrain involvement, among a group of NMOSD patients. MethodsThe medical records of 108 NMOSD patients were reviewed, who were registered at the Al-Zahra MS Clinic, Isfahan, Iran. The patients´ information including sex, age, first recorded chief complaint, and midbrain lesion presence in the first brain MRI was collected. ResultsOut of the 108 NMOSD patients, eight had midbrain lesions in their first brain MRI (7.4%). Of these patients, 50% were male and 50% were female, with the mean age being 35.25 ± 12.17 years. The most frequent first chief complaints included diplopia due to incomplete third nerve palsy and vertigo. The brain MRIs of the patients showed symmetric dorsal midbrain involvement in all the patients, and enhancement was discovered in only one of the brain MRIs. ConclusionAmong the patients, 7.4% presented midbrain involvement at onset. Therefore, midbrain lesions should also be considered as a possible core clinical manifestation in the NMOSD diagnostic criteria.

Serum albumin level is associated with the severity of neurological dysfunction of NMOSD patients

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system. Serum albumin (SA) has antioxidant, immunomodulatory and anti-inflammatory effects. However, the roles of SA in NMOSD have not been studied. The current study aimed to clarify the association of SA with disease severity and prognosis in NMOSD patients. MethodsSerum levels of albumin were measured by Bromcresol Green method. Serum level measurements of interleukins were performed using enzyme-linked immunoassay (ELISA) method. ResultsOf all the 130 NMOSD patients, 96 patients were in the acute phase while 34 patients were in the remission phase of disease at the time of sampling. SA concentration was significantly correlated with EDSS score in patients in the acute phase but not in remission phase (r = - 0.388, p < 0.001 and r = - 0.467, p = 0.809, respectively). Logistic analysis revealed that SA was the only significant factor to predict severe NMOSD (EDSS 8.0–9.5) OR = 0.698, 95%CI 0.563–0.865, p = 0.001) after adjustment of other confounding factors. Furthermore, SA was negatively correlated with the serum level of IL-33 (r = -0.438, p = 0.016) in the acute phase of NMOSD patients. ConclusionThe current study found that low level of SA was an independent indicator of more severe neurological deficit in patients in acute phase of NMOSD. SA concentration was negatively correlated with the serum level of IL-33 in the acute phase of the disease, which implies that SA might participate in the immunopathology of NMOSD partly through its interaction with IL-33.

Characterization of T cells in NMOSD patients - an emerging role for T cells in disease pathogenesis (4017)

Characterization of T cells in NMOSD patients - an emerging role for T cells in disease pathogenesis (4017)

Brain magnetic resonance imaging features in multiple sclerosis and neuromyelitis optica spectrum disorders patients with or without aquaporin-4 antibody in a Latin American population

IntroductionThere is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients. MethodsWe retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included. ResultsWe included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p<0.001, CT = p<0.001, PBVL p = 0.01). ConclusionDifferent MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI.

Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS Registry (RelevarEM)

RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort. A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6years. In NMOSD, the mean age was 40 ± 7years, female sex 78.7%, mean disease duration 5 ± 3.5years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p< 0.001 between groups). In NMOSD, the CCI was 0 in 64% while ≥ 1 was in 36%. The MS/NMOSD ratio found was 21/1. This is the first analysis of the longitudinal Argentinean registry of MS and NMOSD describing and comparing conditions that contributes to provide reliable real-world data in the country.

A Study of HBM9161 in NMOSD Patients

A Study of HBM9161 in NMOSD Patients

The Comparison of VEP Parameters in NMOSD and MS Patients with Acute Optic Neuritis

The Comparison of VEP Parameters in NMOSD and MS Patients with Acute Optic Neuritis

NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) and MS are the most common autoimmune inflammatory demyelinating diseases of the CNS. However, the mechanisms of pathogenesis are still unclear. nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), an important protein of the innate immune system that is activated by mitochondrial DNA (mtDNA), has been reported to be associated with various autoimmune disorders. ObjectiveTo assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1β, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors. Methods28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1β, IL-6 and IL-17 were measured by ELISA. CSF extracellular mtDNA was measured by qPCR. The severity of clinical presentation was evaluated by EDSS score. ResultsCSF levels of NLRP3, mtDNA, IL-1β, IL-6 and IL-17 were higher in NMOSD patients than in controls. Elevated CSF NLRP3, mtDNA and IL-6 were found in MS patients compared with controls. CSF NLRP3 and IL-6 levels were significantly higher in NMOSD patients than in MS patients. The EDSS scores of NMOSD patients during relapse were positively correlated with CSF NLRP3 and mtDNA. ConclusionOur findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.

Cognitive functions in Egyptian neuromyelitis optica spectrum disorder.

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, characterized by optic neuritis and longitudinally extensive transverse myelitis. Magnetic resonance imaging abnormalities may be observed in various brain regions of NMOSD patients. Only a few studies have addressed the cognitive functions in NMOSD, but none among Egyptian patients. ObjectiveTo investigate cognitive performance in a cohort of 20 Egyptian patients with NMOSD. DesignObservational, prospective study. PatientsWe studied 20 Egyptian patients with NMOSD and compared them with 18 healthy Egyptian controls matched for age, sex, and educational level. Main Outcome MeasureWe applied an Arabic translation of MOCA and BICAMSTests for Multiple Sclerosis. ResultsCognitive performance was significantly worse in the NMOSD group than in healthy controls for CVLT (P = 0.0099), SDMT (P = 0.0112), BVSMT (P = 0.019) and BICAMS in total (P = 0.0014). Patients with a later disease onset performed worse in MOCA and BVSMT. ConclusionsThis study confirms the concept of cognitive involvement in NMOSD among Egyptian patients. Information processing speed was the function most commonly impaired.

Efficacy of different rituximab therapeutic strategies in patients with neuromyelitis optica spectrum disorders

ObjectiveTo evaluate disease activity according to rituximab (RTX) induction and maintenance regimens in a multicenter real-life dataset of NMOSD patients. MethodsThis is an observational-retrospective multicentre study including patients with NMOSD treated with RTX in 21 Italian and 1 Swiss centers. Demographics, relapse rate and adverse events over the follow-up were summarized taking into account induction strategy (two-1 g infusions at a 15-day interval (IND-A) vs. 375 mg/m2/week infusions for one month (IND-B)) and maintenance therapy (regimen A (M-A) with fixed time-points infusions vs. regimen B (M-B) based on cytofluorimetric driven reinfusion regimens, the least further subdivided according to CD19+ B cells (M-B1) or CD27+ memory B cells (M-B2) monitoring). Results131 subjects were enrolled, 127 patients completed the induction regimen and 119 patients had at least one follow-up visit and were included in the outcome analysis. Median follow-up was 1.7 years (range 0.1–11.6). Annualized relapse rate (ARR) was 1.7 in the year before RTX start and decreased to 0.19 during the follow-up. Both ARR and Time to first relapse (TTFR) analysis showed a trend toward an increased disease activity for IND-B and M-A. No patients with MT-B2 experienced relapses during the follow-up. Number of relapses in the year before RTX initiation and having received a previous treatment were significantly associated with higher ARR and reduced TTFR in the multivariate analysis. InterpretationWe confirm RTX efficacy in NMOSD patients. Use of specific induction and maintenance protocols is warranted in order to foster RTX efficacy and to reduce costs and side effects.

Effectiveness of rituximab in reducing relapse among Filipino neuromyelitis optica patients

Neuromyelitis optica (NMO) is an autoimmune disease with a relapsing progressive course, which result to disability. Recent evidence points to repeated treatment with Rituximab as effective in reducing relapse rates. Currently, there is no local data regarding the effectiveness of Rituximab in adult Filipino patients. A retrospective cohort study of Filipino patients diagnosed with NMOSD and treated with at least 1 Rituximab infusion and a minimum of 6 months follow-up from August 2013 until September 2018 in a private tertiary hospital was done through records review. Patients who were lost to follow-up for 2 years were excluded. The primary outcome was the effectiveness of rituximab, defined based on the comparison of Annualized Relapse Rate (ARR) before and after Rituximab infusion. Seroconversion of anti-aquaporin 4 antibody and the safety profile of Rituximab were secondary outcomes. Among 23 qualified patients, 21 (91.3%) were female. The mean age of the participants was 46.1 years old.The number of patients relapse-free during rituximab treatment was 69.5%. The mean annualized relapse rate (ARR) pre- Rituximab was 16.9 compared to 2.4 in an international study while the mean ARR post-Rituximab was 1.6 compared to 0.1 (p-value of 0.001).There was 1 patient who was initially seropositive then later converted to seronegative at the last follow-up. No adverse effects were reported. Rituximab was effective in reducing relapse rates among Filipino NMOSD patients with no reported adverse effects.

Radiological characteristics of neuromyelitis optica spectrum disorder in Kuwait: A tertiary neurology centre experience

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disorder of the central nervous system that was previously thought to be a subtype of multiple sclerosis (MS). We describe radiological characteristics of a case series of NMOSD patients from the largest tertiary neurology centre in Kuwait. MethodsThis is a case series study of NMOSD patients who were seen at the Multiple Sclerosis clinic, Ibn Sina Hospital from January 2017 to January 2019. We describe their magnetic resonance imaging (MRI) characteristics. ResultsOur study identified 32 patients who fulfilled the 2015 international NMOSD diagnostic criteria. Twenty-six females and 6 males were identified of whom 22 patients tested positive for AQP4 antibodies in the serum while 10 were seronegative. The mean age was 35.4 and mean age at onset was 28.5 years with an average disease duration of 7 years. There was a strong female predominance with a ratio of 4.3:1. We identified MRI features of the cohort and compared it with those reported in other worldwide studies. InterpretationThis is the first study from Kuwait describing the radiological characteristics of NMOSD. We highlighted the similarities and differences of our cohort from other worldwide cohorts reported in the literature.

Long-term outcome and prognosis in patients with neuromyelitis optica spectrum disorder from Serbia

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) most commonly, although not exclusively, targets optic nerves and spinal cord. Untreated, early and severe disability is common. We evaluated the long-term outcome in NMOSD patients diagnosed according to the 2015 criteria. MethodsWe retrospectively analyzed 74 patients from the hospital-based NMOSD cohort at the Clinic of Neurology, Belgrade, Serbia, who fulfilled the 2015 NMOSD criteria. We identified patients based on 2015 criteria; 51.4% of whom would not have fulfilled 2006 criteria. Median follow-up was 6.9 years. Aquaporin-4 (AQP4) IgG was tested in all patients using a cell-based indirect immunofluorescence assay. The level of neurological disability was assessed by the Expanded Disability Status Scale (EDSS) score, and by Opticospinal Impairment Scale (OSIS), visual acuity (VA) and motor function subscores. ResultsThe disease course was monophasic in 17.6% patients and relapsing in the remainder; none developed progressive disease. AQP4-IgG was detected in 89.2% of patients. 45 of 74 patients were treated with immunosuppressants, 40 with azathioprine, 3 with mycophenolate mofetil, 1 with cyclophosphamide, 1 with mitoxantrone, and 2 patients with rituximab. The median intervals from onset to EDSS 4.0, 6.0 and 7.0 were 6.5 years, 11.9, and 22.0 years, respectively. Higher baseline EDSS was associated with risk of attaining EDSS 4.0, 6.0 and 7.0; a shorter first inter-attack interval for reaching EDSS 4.0 and 6.0; longer time to the start of treatment for reaching EDSS 7.0. Worse visual acuity at the disease onset predicted faster assignment of OSIS VA = 6 and VA = 8. Severe visual deficit (OSIS VA 6) was reached earlier after optic neuritis (median time, 10.0 years) or combined opticospinal onset (median time, 11.4 years) than after myelitis onset (median time, 18.0 years) (p = 0.002). ConclusionOur results support the benefits of early diagnosis and treatment of NMOSD, especially in persons with severe optic and spinal disability at onset.

The imbalance between regulatory and memory B cells accompanied by an increased number of circulating T-follicular helper cells in MOG–antibody-associated demyelination

ObjectiveTo explore the alteration of T and B lymphocyte subsets proportions in myelin oligodendrocyte glycoprotein (MOG)-antibody-associated demyelination. Methods19 MOG-antibody-positive, 25 AQP4-antibody-positive and 25 double-negative NMOSD patients in the acute phase of the diseases were included in the study, as well as 29 healthy controls. The frequencies of different lymphocyte subsets, including CD19+CD27+ memory B cells, CD19+CD24hiCD38hi, and CD19+CD5+CD1dhi regulatory B cells, IFN-γexpressing B cells, IL-10 expressing B cells and CD4+CXCR5+ICOS+T-follicular helper cells (TFH) were measured via flow cytometry and compared among the four groups. ResultsThe frequencies of CD19+CD24hiCD38hi, CD19+CD5+CD1dhi regulatory B cells as well as the IL-10 expressing B cells were significantly lower in the MOG-antibody-associated demyelination compared to the healthy controls, whereas the frequencies of CD19+CD27+ memory B cells were significantly higher in the MOG-antibody-positive group. The frequencies of TFH were significantly higher in the MOG-antibody-positive group as compared to the healthy controls. No significant difference was detected in the above mentioned lymphocytic profile between the MOG-antibody-positive and the AQP4-antibody-positive groups. ConclusionsThe immuno-regulatory functions of B cells were significantly impaired whereas TFH cells were markedly increased in the acute phase of MOG-antibody-associated demyelination. Despite having distinct clinical features, MOG-antibody-associated demyelination shared a similar lymphocytic profile with AQP4-antibody-positive NMOSD in the acute relapse phase.

The mediating effect of health-related hardiness on the degree of physical disability and perceived stress in Chinese female patients with neuromyelitis optica spectrum disorder

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a rare and chronic disease of the central nervous system. The characteristics and main symptoms of recurrent NMOSD lead to an increase in psychological stress and accelerate a decline in the patients’ quality of life. The incidence of NMOSD in the Chinese population is much higher than that for other countries and the majority of NMOSD patients are female. In general, there are sex differences in the perception and management of stress, with females experiencing higher levels of perceived stress than males. Thus, we should be concerned about the psychological issues experienced by Chinese female NMOSD patients. Health-related hardness is a psychological adjustment factor that could affect perceptions of illness that impact on NMOSD patients. The objective of this study was to evaluate the mediating role of health-related hardiness on physical disability and perceived stress in Chinese NMOSD female patients. MethodsParticipants were 68 females patients with NMOSD treated at the Department of Neurology, Huashan Hospital, Fudan University, China, between March and September 2018. Patients were evaluated for their degree of physical disability, perceived stress, and health-related hardiness. Measures included the Expanded Disability Status Scale (EDSS), Perceived Stress Scale (PSS), and Health-related Hardiness Scale (HRHS). Pearson's correlation analyses and stepwise multiple linear regression analysis were used. ResultsFindings indicated a positive correlation between the PSS and EDSS (r = 0.735, P < 0.001) and a negative correlation between the PSS and HRHS total score (r = −0.441, P < 0.001). After adjusting for the confounding factors, the EDSS was found to have a positive predictive effect on the PSS (β = 2.743, P = 0.000), and the HRHS was found to have a negative predictive effect on the PSS (β = −0.152, P = 0.04). Mediation analysis showed a direct effect of the EDSS on the PSS, and as a mediating variable for health-related hardiness (α = −1.928, b = −0.152, c = 2.743, c’ = 2.481), which was statistically significant (P < 0.05). The mediating effect of health-related hardiness accounted for 10.68% of the total effect. ConclusionsAs a mediating variable, health-related hardiness indirectly affected perceived stress caused by physical disability and improved health-related hardiness. This was beneficial in reducing psychological stress and promoting mental health in NMOSD female patients.

The clinical value of complement proteins in differentiating AQP4-IgG-positive from MOG-IgG-positive neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) refers to a range of autoimmune inflammatory demyelinating diseases affecting the optic nerves, spinal cord, and periependymal regions of the brain. Classical NMOSD is characterized by the presentation of autoantibodies against the water channel aquaporin-4 (AQP4). However, a subset of patients fulfilling the clinical criteria for NMOSD is negative for AQP4-IgG but positive for autoantibodies against myelin oligodendrocyte glycoprotein (MOG); these patients are associated with different clinical manifestations and pathogenesis. MethodsPatients who received a first diagnosis of NMOSD were reviewed retrospectively between April 2015 and December 2018. Patients were classified according to the presence of AQP4-IgG and MOG-IgG in serum and/or cerebrospinal fluid. Clinical characteristics, magnetic resonance imaging findings, disease severity, and serum C3 and C4 levels at the first episode were compared between the groups. ResultsThe NMOSD patients with AQP4-IgG and MOG-IgG demonstrated specific, differential clinical features. The AQP4-IgG group featured more women, the presentation of transverse myelitis attacks and simultaneous occurrence of optic neuritis and transverse myelitis were more common, and intrathecal synthesis was more evident. The MOG-IgG group featured younger patients, more acute disseminated encephalomyelitis (ADEM) or ADEM-like attacks, more frequent cerebrospinal fluid pleocytosis, and a better overall outcome. C3 levels were significantly lower in AQP4-IgG-positive patients and higher in MOG-IgG-positive patients relative to healthy controls. C4 levels were significantly lower in the AQP4-IgG-positive NMOSD group when compared to both MOG-IgG-positive patients and controls. C3 and C4 were then combined in a receiver operating characteristic model. The area under the curve of the model was calculated to differentiate the AQP4-IgG-positive group from the MOG-IgG-positive group was 0.787, which was considered moderately predictive. ConclusionThe combination of C3 and C4 could assist in the differential diagnosis of AQP4-IgG-positive NMOSD from MOG-IgG-positive NMOSD.

Disease course, progression and activity of neuromyelitis optica (NMOSD) in patients who were treated with Rituximab, 6 and 12 months after receiving the first dose of drug, in Isfahan city

IntroductionNeuromyelitis optica spectrum disease (NMOSD) is a chronic inflammatory and usually relapsing demyelinating disease which mainly involves optic nerve and spinal cord and also other parts of the central nervous system. Rituximab has been used for some neurological disorders with a probable autoimmune basis. Early and aggressive immunosuppression therapy is necessary to prevent clinical relapses and permanent disability in NMOSD. Rituximab, a monoclonal antibody against B cells, has been found effective in several recent studies. The objective of this study is to evaluate the clinical efficacy of Rituximab as a newly introduced treatment to NMOSD in Iran. Methods and MaterialsThis is an observational cohort study carried out,on 56 patients who have been diagnosed with NMOSD. The patients’ information registered in Kashani Hospital MS clinic. They received the first dose of Rituximab for approximately 6 months before the beginning of study. In the first session, every patient was interviewed and examined based on necessary information for the study. Follow up visits were done as needed in a period of 12 months after the first dose. Patient's age, sex, age of onset, presenting symptom, annual relapse rate, acute attacks, EDSS (primary, 6 and 12 months) were recorded. Comparative aims achieved by within group analysis before and after treatment. AntiAQP4 antibody had been checked before the start of study. patients divided into two groups based on the antibody test results for subgroup analysis. Data were analyzed using the IBM SPSS23 - United States software. Results56 known cases of NMOSD including 17.85% male and 82.15% female were under study. The Mean disease duration was 87.60±59.65 months and mean duration of treatment was 19.56±8.26.The mean EDSS score was primarily 4.83±1.87 and after treatment it decreased significantly (p-value<0.001) to 3.38±1.57 and 2.87±1.63 (6 months and 12 months later).There was a statistical difference between the annual mean relapse rate before and after treatment (p<0.001). The above mentioned index decreased from 1.43±1.107–0.147±0.27. Also, the mean number of attacks in one year before and after treatment were 1.97±0.57 and 0.28±0.45 with significant statistical difference (p<0.001).In the patients with positive anti AQP4 antibody,the mean EDSS decreased from 4.94±1.83–3.52±1.27 and 2.92±1.54. Annual mean relapse rate also decreased significantly from 1.35±0.85–0.10±0.19. Mean number of attacks in one year before and after treatment were 2.05±0.75–0.27±0.46 (p<0.001) respectively. ConclusionIn the current study, we found that Rituximab can significantly improve disability state and also can markedly reduce relapse rate in NMOSD patients.