Neuromyelitis Optica Research Articles

Targeting cytokine networks in neuroinflammatory diseases.

In neuroinflammatory diseases, systemic (blood-borne) leukocytes invade the central nervous system (CNS) and lead to tissue damage. A causal relationship between neuroinflammatory diseases and dysregulated cytokine networks is well established across several preclinical models. Cytokine dysregulation is also observed as an inadvertent effect of cancer immunotherapy, where it often leads to neuroinflammation. Neuroinflammatory diseases can be separated into those in which a pathogen is at the centre of the immune response and those of largely unknown aetiology. Here, we discuss the pathophysiology, cytokine networks and therapeutic landscape of 'sterile' neuroinflammatory diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), neurosarcoidosis and immune effector cell-associated neurotoxicity syndrome (ICANS) triggered by cancer immunotherapy. Despite successes in targeting cytokine networks in preclinical models of neuroinflammation, the clinical translation of targeting cytokines and their receptors has shown mixed and often paradoxical responses.

Effects of long-term magnesium L-threonate supplementation on neuroinflammation, demyelination and blood–brain barrier integrity in mice with neuromyelitis optica spectrum disorder

In clinical practice, we found cerebrospinal fluid magnesium concentration significantly lower in neuromyelitis optica spectrum disorder (NMOSD) patients compared to controls with non-autoimmune encephalitis neurological diseases. To investigate the effects and potential mechanisms of long-term magnesium supplementation on neuroinflammation, demyelination, and blood–brain barrier (BBB) integrity in NMOSD, we used two models: (1) NMOSD mouse model, which was induced by intraperitoneal injection of purified NMO-IgG to experimental autoimmune encephalomyelitis (EAE) mice, and (2) cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). In the NMOSD mouse model, Magnesium L-threonate (MgT) pretreatment alleviated NMO-IgG–induced effects, including AQP4 loss, leukocyte infiltration, astrocyte and microglia activation, demyelination, decreased tight junction (TJ) protein expression, and neurological deficits. In vitro, MgT pretreatment ameliorated NMO-IgG induced damage to TJ protein expression in a (transient receptor potential melastatin 7) TRPM7-dependent manner. Magnesium supplementation shows potential protective effects against NMOSD, suggesting it may be a novel therapeutic approach for this condition. The beneficial effects appear to be mediated through preservation of blood–brain barrier integrity and reduction of neuroinflammation and demyelination.

Role of clinicoradiological correlation in evaluation of various demyelinating disorders: A Systematic review

Background: There are mainly three types of white matter disorders resulting from defective myelination (dysmyelinating), destruction of myelin (demyelination) and decreased myelination (hypomyelinating). Each of these disorders require MRI and specific imaging for diagnosis. However, diagnosis of white matter disorders cannot solely rely on imaging. Objective: In this review we aim to correlate clinical presentation, history, laboratory investigations, and imaging as a tool rather than diagnostic modality to highlight the importance of clinical and radiological collaboration to diagnose the exact disease process. We would specifically discuss variants of multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis Optica spectrum disorder, progressive multifocal leuckoencephalothy, and osmotic demyelination syndrome. This study also includes specific signs of different demyelination white matter disorders on MRI which are characteristic of that disease process. However, we also highlight what clinical correlation and investigations may further aid to confirm the diagnosis, prognosis and extent of disease progression. Methods: In this review article we used Prisma guidelines we extracted studies where there was evidence of better patient outcome in terms of clinicoradiological collaboration in diagnosing various demyelinating white matter disorders. Results: We found that timely diagnosis and better patient outcomes can be achieved if clinicians also take in accord their own clinical judgement and based on that order relevant radiological investigations resulting better clinician to clinician communication, judicious use of hospital resources and overall better outcome in disease process. Conclusion: Our study concludes that solid clinical judgement, laboratory investigations along with radiological features of disease process would enhance clinical outcomes in terms of timely diagnosis, specific treatment and tracking disease prognosis.

Abnormal dynamic features of spontaneous brain activity and their concordance in neuromyelitis optica spectrum disorder related optic neuritis: A resting-state fMRI study

ObjectiveCharacterizing the neuropathological features of neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) is crucial for understanding its mechanisms. Given the important role of dynamic features in the brain’s functional architecture, we aim to investigate the dynamic features of spontaneous brain activity and their concordance using resting-state functional magnetic resonance imaging (rs-fMRI) in NMOSD-ON. MethodsFourteen NMOSD-ON patients and 21 healthy controls (HCs) underwent rs-fMRI and ophthalmological examinations. Five dynamic indices depicting different aspects of functional characteristics were calculated using a sliding window method based on rs-fMRI data. Kendall’s coefficient was utilized to measure concordance among these indices at each time point. The differences of dynamic features between two groups were evaluated using two-sample t-tests, with correlations explored between altered dynamics and clinical parameters. ResultsCompared to HCs, NMOSD-ON patients exhibited significant decreases in dynamic regional homogeneity (dReHo) and dynamic degree centrality (dDC) in visual regions, including bilateral cuneus, lingual gyrus, calcarine sulcus, and occipital gyrus. Conversely, increases were observed in left insula, left thalamus, and bilateral caudate. The concordance of NMOSD-ON patients was significantly lower than HCs. The dReHo of right cuneus negatively correlated with mean deviation of visual field (r = -0.591, p = 0.026) and the dReHo of left cuneus negatively correlated with disease duration (r = -0.588, p = 0.030). ConclusionThe evidence suggests that regional dynamic functional alterations involving vision, emotional processing, and cognitive control may provide a new understanding of brain changes in the progression of NMOSD-ON.

Progress in the study of the correlation between dyslipidemia and demyelinating diseases of the nervous system

Demyelinating disorders of the nervous system constitute a broad spectrum of neurological conditions characterized by the depletion of myelin sheaths accompanied by inflammatory cell infiltration, manifesting in either the central or peripheral nervous system. The former primarily encompasses conditions such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), while the latter is exemplified predominantly by Guillain-Barre syndrome (GBS). Recent investigations have revealed that dyslipidemia may be related to the occurrence and development of neurological demyelination, but there are fewer analyses and summaries of related advances in China. Consequently, this review aims to comprehensively outline advancements in research concerning the correlation between dyslipidemia and neurological demyelinating disordersand discusses in depth the interrelationship between dyslipidemia and neurological demyelinating diseases, so as to provide reference for the prevention and treatment of neurological demyelinating diseases.

Recurrence-Independent Progressive Inner-Retinal Thinning After Optic Neuritis: A Longitudinal Study.

Longitudinal changes in the inner retina in patients with optic neuritis (ON) may be helpful in monitoring patients and determining maintenance treatment. The aim of this study was to investigate longitudinal changes in the inner retina after subsiding of acute demyelinating ON and to identify the factors associated with such changes. In this multicenter retrospective observational study, we reviewed the medical records of 77 patients with ON, including 23 with neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4)-immunoglobulin G (IgG) (AQP4 group), 23 with myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOG group), 18 with multiple sclerosis (MS group), and 13 with idiopathic ON (iON group). We measured the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) using optical coherence tomography (OCT) at baseline and at follow-up examinations (mean follow-up duration, 29.6 ± 8.6 months; mean number of OCT, 4.2 ± 1.2) in the absence of ON recurrence. The estimated rate of pRNFL thinning in the AQP4, MOG, MS, and iON groups was 0.66 (95% confidence interval, 0.35-0.97), 0.35 (0.04-0.66), 0.53 (0.16-0.90), and 0.25 (-0.18 to 0.68) μm/year, respectively, indicating that, in the iON group in contrast to the other groups, there was no significant decrease of pRNFL thickness. Among the AQP4, MOG, and MS groups, there was no significant difference in the rate of pRNFL thinning (P = 0.560). The rate of mGCIPL thinning in the AQP4 and MOG groups was 0.25 (0.04-0.46) μm/year and 0.38 (0.23-0.53) μm/year, respectively. Meanwhile, the rate of mGCIPL change in the MS and iON groups was 0.04 (-0.12 to 0.19) and 0.00 (-0.17 to 0.16) μm/year, respectively, which indicates that there was no significant mGCIPL thinning in the latter 2 groups. Between the AQP4 and MOG groups, meanwhile, the rate of mGCIPL change did not significantly differ (P = 0.295). Age older than 40 years was associated with significant progression of mGCIPL thinning (P = 0.005). We noted inner retina thinning progression independent of relapse activity in AQP4-ON, MOG-ON, and MS-ON. Because subclinical neuroaxonal damage continues to be incurred after an acute attack of ON subsides despite suppression of new attacks, long-term follow-up and neuroprotection should be considered to be integral to the treatment of patients with ON.

Heterogenous relapse and efficacy endpoint definitions for neuromyelitis optica spectrum disorder studies: A systematic review

BackgroundOver the last years, multiple studies have been dedicated to evaluate the efficacy of different treatment options for Neuromyelitis Optica Spectrum Disorder (NMOSD). However, there is a wide variety of endpoints employed across these studies. Our goal is to conduct a systematic review describing the endpoints utilized in studies related to NMOSD. MethodsMedline, Embase, and Cochrane were searched from inception to May 2023, to identify studies analyzing treatment options in patients with NMOSD. We collected data on baseline study characteristics and all efficacy outcomes available. ResultsWe included 127 studies and identified approximately 40 different efficacy endpoints, categorized into 1) relapse, 2) disability, 3) visual acuity, and 4) surrogate outcomes. Most studies were retrospective (54.3 %) and aimed at attack prevention (81.4 %). The most common relapse-related outcomes were annualized relapse rate (73.2 %), followed by relapse rate (50.4 %), and relapse-free rate (36.2 %). The relapse definition also varied widely among studies, with only 73 (57.4 %) studies explicitly addressing the definition used. The most common disability outcome was the Expanded Disability Scale (97.6 %), followed by the Modified Rankin Scale (7.9 %). Visual Acuity Score was employed in 14.2 % of studies, followed by Visual Evoked Potentials (6.3 %). Imaging was the most common surrogate (20.5 %), followed by the fraction of B cells (18.1 %). ConclusionPublications were heterogeneous in measuring efficacy, with different use of endpoints and relapse definitions. Standardization across studies would improve data analysis and application in clinical practice.

Spectrum of Auto-antibodies in NMO and MOG Associated CNS Demyelination- The SANMAD Study

This observational study explored coexisting organ-specific and non-organ-specific autoantibodies in Neuromyelitis optica spectrum disorder(NMOSD) and Myelin oligodendrocyte glycoprotein-IgG-1(MOG-IgG1) associated central nervous system demyelination(MOGAD) in a South Asian cohort from March 2017–2023. Of the 250 cases, 148 were MOGAD(82pediatric) and 102 were NMOSD(15 pediatric). 17.6 % tested positive for ≥1 antibody, with NMOSD showing a higher positivity rate (25.5 %) than MOGAD(12.2 %,p = 0.011). Double antibody positivity occurred more in NMOSD (5.9 %vs.MOGAD,1.4 %,p = 0.045). Three NMOSD cases had Sjogren syndrome with higher Anti-Ro-52 prevalence(12.7 %vs.4.1 %,p = 0.014). NMOSD patients with ≥1 antibody positivity had more constitutional symptoms (45.5 %vs.23.1 %,p = 0.045). Significant associations were found between NMOSD and female gender, having ≥1 antibody-positive status, and testing positive for Anti-Ro-52 and SS-A antibodies (p < 0.05).

Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.

Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1β: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (β = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: β = -0.020, P = 7.203 × 10-5; right: β = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: β = -0.030, P = 2.175 × 10-8; right: β = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (β = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases

Pro-inflammatory autoantigen-specific CD4+ T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional exvivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced. Instead, exhaustion-associated co-inhibitory receptors were expressed together with FOXP3, the canonical regulatory Tcell (Treg) transcription factor. Auto-Th cells responded invitro to checkpoint inhibition and provided potent B cell help. Cells with the same exhaustion-like (ThEx) phenotype were identified in soluble liver antigen (SLA)-antibody-autoimmune hepatitis and BP180-antibody-positive bullous pemphigoid, AIDs of the liver and skin, respectively. While originally described in cancer and chronic infection, our data point to Tcell exhaustion as a common mechanism of adaptation to chronic (self-)stimulation across AID types and link exhausted CD4+ Tcells to humoral autoimmune responses, with implications for therapeutic targeting.

B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity.

This post hoc analysis of the randomized, placebo-controlled N-MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B-cell subsets and aquaporin-4 immunoglobulin G (AQP4-lgG) titers and attacks. Among participants receiving placebo, CD20+ and CD27+ B-cell counts were modestly increased from the pre-attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre-attack visit (p = 0.016) and from baseline to attack (p = 0.009). With inebilizumab treatment, B-cell subset counts decreased and did not increase with attacks. No difference in change of AQP4-IgG titers from baseline to time of attack was observed.

MOG CNS Autoimmunity and MOGAD.

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. MOG-specific T cells are required in MOG EAE, and while anti-MOG Abs can exacerbate EAE and CNS demyelination, those Abs are neither necessary nor sufficient to cause EAE. Knowledge regarding the spectrum of MOGAD clinical and radiologic presentations is advancing rapidly, yet our grasp of MOGAD pathogenesis is incomplete. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis.

Changes in the incidence of optic neuritis before and after COVID-19: A nationwide study 2017-2022

PurposeTo determine the risk of optic neuritis (ON) during non-pharmaceutical interventions (NPI), vaccination and infection phase of coronavirus disease-19 (COVID-19) in comparison to pre-outbreak levels in pediatric and adult populations in South Korea. DesignA nationwide, population-based, retrospective study. ParticipantsSouth Korean individuals with a primary diagnosis of ON between January 2017 and December 2022. MethodsThe Korean Health Insurance Review and Assessment database was queried for new diagnoses of ON between January 2017 and December 2022. Data were divided into 4 periods: pre-COVID-19 (2017-2019), NPI (2020), nationwide vaccination (2021) and nationwide infection (2022). The risk of ON development for each period was calculated and compared to pre-COVID-19 levels with 95% confidence intervals (CI) reported. Main outcome measuresIncidence rate ratio (IRR) of ON for each period. ResultsA total of 7,216 patients (52.7 % females) were included in the study, with 3,770 patients diagnosed with ON pre-COVID-19 (2017-2019), 1,193 patients during NPI, 1,135 patients during the vaccination and 1,118 patients during the infection phases. The annual incidence of ON during NPI (IRR 0.92 (95% CI 0.85-1.00), P=0.043), vaccination (IRR 0.88 (95% CI 0.81-0.95), P=0.001) and infection (IRR 0.86 (95% CI 0.80-0.93), P<0.001) phases significantly decreased compared to pre-COVID-19 levels when adjusted for age and sex. The proportions of diagnosis with multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM) among patients who developed ON significantly increased in 2021 in comparison to the pre-outbreak levels (9.87% vs. 5.81%; P=0.0002). ConclusionsThe risks of ON development during NPI, vaccination and infection phases of COVID-19 did not increase in comparison to the pre-outbreak levels in general population. However, COVID-19 vaccination may be associated with increased risks of ON associated with diseases such as ADEM, MS and NMOSD.

Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD.

In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.

Investigation of health care use and a possible prodrome before the first attack in NMOSD and MOGAD

Background: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. Methods: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. Results: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25–1.73; aRR: 1.67; 95% CI: 1.19–2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. Conclusion: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.

Neuromyelitis Optica Spectrum Disorder: A Case Report

Neuromyelitis optica spectrum disorder also known as Devic's disease is an autoimmune condition where the body produces antibodies against Aquaporin-4 in the astrocytes. This affects the brain and spinal cord leading to numerous manifestations like paralysis, transverse myelitis, and optic neuritis. MRI and aquaporin-4 antibody (AQP4-IgG) are crucial for its diagnosis. Treatment of the acute stage involves plasma exchange and intravenous steroids. Steroids and immune modulators can do long-term management. This case highlights a 40-year-old woman who manifested a wide range of neurological symptoms, including paralysis and eyesight loss. She had blood testing, radiology, and a clinical evaluation to diagnose her condition. Neuromyelitis optica spectrum disorder was diagnosed in light of the investigations. This instance emphasizes the need for careful examination and consideration of any paralysis. To prevent patients from experiencing psychological, financial, or physical challenges, treating physicians should be vigilant for any findings related to conditions like neuromyelitis optica spectrum disorder.

Clinical spectrum of demyelinating disease of central nervous system and frequency of anti AQP4 and anti MOG among them: one-year single-center retrospective study

Background: Inflammatory demyelinating diseases of the central nervous system (CNS) are autoimmune conditions leading to significant neurological disability in adults. Recent classifications include myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) which pose diagnostic challenges due to overlapping clinical and radiological features. This study aimed to assess the clinical spectrum among adults and children diagnosed with CNS demyelinating diseases and to find the proportion of MOG and/or aquaporin-4 (AQP4) autoantibodies amongst them. Methods: This single-center, retrospective study examined 20 patients diagnosed with CNS demyelinating disorders between March, 2023 and February, 2024. Data pertaining to demographics, disease types, CSF analysis, MRI findings, treatment modalities, and serological profiles for anti-AQP4 and anti-MOG antibodies were collected from hospital records and evaluated. Results: Among 20 patients [median age, 34 years (IQR, 18.75); males (n=10) and females (n=10)], acute transverse myelitis (TM) was the most common demyelinating disorder at onset (60%) followed by optic neuritis (ON) (20%). CSF analysis found elevated protein levels in 53% and pleocytosis in 33% of patients. MRI findings revealed longitudinal extensive involvement in 52% of patients, predominantly affecting the cervical and dorsal spine. Serological testing identified 15% positive for anti-AQP4 and 10% for anti-MOG antibodies. MOG+ patients were significantly younger than AQP4+ patients (mean age 16.5 vs. 36.66 years, p=0.016). Both MOG+ patients were male, with 50% presenting with acute TM and 50% with acute disseminated encephalomyelitis. Among AQP4+ patients, the male-to-female ratio was 1:2, with 66.66% presenting with acute TM and 33.33% with ON. Conclusion: CNS demyelinating disorders primarily affect younger individuals, with TM as the most common initial disorder and extensive spinal involvement in cervical and dorsal regions. Serological testing identified three patients with anti-AQP4 and two with anti-MOG antibodies, providing valuable insights into the clinical spectrum of these disorders through cell-based assays.

Cognitive performance in patients with neuromyelitis optica: clinical and imaging characteristics

This study aimed to identify the prevalence, clinical and radiographic characteristics, and risk factors for cognitive dysfunction in patients with Neuromyelitis optica spectrum disorder (NMOSD). Eighty-three participants who were diagnosed with NMOSD were recruited. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). The mean age of the patients was 47.78 ± 13.14 years, with an average of 12.05 ± 4.62 years of formal education. The majority (54%) exhibited cognitive impairment, defined by a MoCA score < 25 (mean: 22.96 ± 3.82). Disease severity (evaluated by the Expanded Disability Status Scale) and lower formal education levels were associated with cognitive impairment (p = 0.011 and < 0.001, respectively). The annualized relapse rate, disease duration, and AQP4 antibody status were not associated with cognitive impairment. Interestingly, informant-reported cognitive decline was associated with poorer cognitive performance (p = 0.027). Radiographic findings of lesion location and severity were associated with MoCA-assessed cognitive performance, particularly for lesions in the right parietal lobes (p = 0.023). Hippocampal atrophy was negatively correlated with FAB scores. In conclusion, approximately half of the Thai patients with NMOSD exhibited cognitive impairment, which was associated with age, formal education level, disease severity, relative perception, and specific radiological findings. Further studies incorporating comprehensive neuropsychological tests and subjective cognitive complaints are warranted.

Patterns of cerebral damage in multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders-major differences revealed by non-conventional imaging.

Multiple sclerosis and aquaporin-4 antibody neuromyelitis optica spectrum disorders are distinct autoimmune CNS disorders with overlapping clinical features but differing pathology. Multiple sclerosis is primarily a demyelinating disease with the presence of widespread axonal damage, while neuromyelitis optica spectrum disorders is characterized by astrocyte injury with secondary demyelination. Diagnosis is typically based on lesion characteristics observed on standard MRI imaging and antibody testing but can be challenging in patients with in-between clinical presentations. Non-conventional MRI techniques can provide valuable diagnostic information by measuring disease processes at the microstructural level. We used non-conventional MRI to measure markers of axonal loss in specific white matter tracts in multiple sclerosis and neuromyelitis optica spectrum disorders, depending on their relationship with focal lesions. Patients with relapsing-remitting multiple sclerosis (n = 20), aquaporin-4 antibody-associated neuromyelitis optica spectrum disorders (n = 20) and healthy controls (n = 20) underwent a 3T brain MRI, including T1-, T2- and diffusion-weighted sequences, quantitative susceptibility mapping and phase-sensitive inversion recovery sequence. Tractometry was used to differentiate tract fibres traversing through white matter lesions from those that did not. Neurite density index was assessed using neurite orientation dispersion and density imaging model. Cortical damage was evaluated using T1 relaxation rates. Cortical lesions and paramagnetic rim lesions were identified using phase-sensitive inversion recovery and quantitative susceptibility mapping. In tracts traversing lesions, only one out of 50 tracts showed a decreased neurite density index in multiple sclerosis compared with neuromyelitis optica spectrum disorders. Among 50 tracts not traversing lesions, six showed reduced neurite density in multiple sclerosis (including three in the cerebellum and brainstem) compared to neuromyelitis optica spectrum disorders. In multiple sclerosis, reduced neurite density was found in the majority of fibres traversing (40/50) and not traversing (37/50) white matter lesions when compared to healthy controls. A negative correlation between neurite density in lesion-free fibres and cortical lesions, but not paramagnetic rim lesions, was observed in multiple sclerosis (39/50 tracts). In neuromyelitis optica spectrum disorders compared to healthy controls, decreased neurite density was observed in a subset of fibres traversing white matter lesions, but not in lesion-free fibres. In conclusion, we identified significant differences between multiple sclerosis and neuromyelitis optica spectrum disorders corresponding to their distinct pathologies. Specifically, in multiple sclerosis, neurite density reduction was widespread across fibres, regardless of their relationship to white matter lesions, while in neuromyelitis optica spectrum disorders, this reduction was limited to fibres passing through white matter lesions. Further studies are needed to evaluate the discriminatory potential of neurite density measures in white matter tracts for differentiating multiple sclerosis from neuromyelitis optica spectrum disorders.