Neuromyelitis Optica Spectrum Disorder in Latin America: State-of-the-Art and Current Challenges.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system characterized by severe attacks of optic neuritis, myelitis, and/or area postrema. Advances in understanding the pathophysiology of NMOSD have led to improved diagnostic and therapeutic approaches. There has been a notable increase in research efforts worldwide, including in Latin America (LATAM). In recent years, LATAM has witnessed a surge in research on NMOSD, resulting in a growing body of evidence on various aspects such as epidemiology, clinical manifestations, paraclinical features (including AQP4-IgG [Aquaporin-4-immunoglobulin G] and imaging), acute and long-term treatment strategies, as well as accessibility to diagnostic tests. This narrative review aims to present the most relevant findings from different NMOSD cohorts in LATAM, providing a comprehensive overview of the current understanding of the disease in the region, while considering its unique characteristics and challenges. LATAM-focused evidence is crucial for adding valuable information to the international dataset and is therefore summarized in this review.

[Anti-MOG associated disease]. / Maladie du spectre des anticorps anti-MOG.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD) is an autoimmune disease responsible for demyelination of the central nervous system that can occur in adults or children. Overlapping phenotypes between MOGAD, multiple sclerosis (MS) and neuromyelitis optica spectrum disease (NMOSD) have been described. The diagnostic criteria for MOGAD were proposed by a panel of international experts and published in 2023. Defining clinical, biological and imaging characteristics specific to this entity helps to improve diagnostic specificity. In this article, we present the clinical characteristics suggestive of MOGAD and discuss the importance of the antibody detection method and therapeutic management.

La maladie du spectre des anticorps anti-MOG (glycoprotéine de myéline oligodendrocytaire) (myelin oligodendrocyte glycoprotein antibody-associated disease, MOGAD) est une maladie autoimmune responsable d'une démyélinisation du système nerveux central pouvant survenir chez les adultes ou les enfants. Des phénotypes de chevauchement entre MOGAD, sclérose en plaques et maladie du spectre de la neuromyélite optique ont été décrits. Les critères diagnostiques de MOGAD ont été proposés par un panel d'experts internationaux et publiés en 2023. Ils permettent de définir des caractéristiques cliniques, biologiques et d'imagerie propres à cette entité, afin d'améliorer la spécificité diagnostique. Nous présentons dans cet article les caractéristiques cliniques en faveur de MOGAD, discutons de l'importance de la méthode de détection des anticorps et terminons par une mise au point sur la prise en charge thérapeutique.

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Mortality of the Danish Nationwide AQP4 Antibody-Seropositive Neuromyelitis Optica Spectrum Disorder Patient Cohort.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population. METHODS: We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death. RESULTS: Of 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02). DISCUSSION: AQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.

Nausea and Vomiting as Initial Manifestations of Pediatric NMOSD.

Intractable nausea and vomiting are commonly attributed to gastrointestinal (GI) conditions but can sometimes be a symptom of an underlying central nervous system disease. One potentially overlooked neurologic cause of intractable nausea and vomiting that is refractory to antiemetics is area postrema syndrome (APS). APS is a condition characterized by lesions of the dorsal caudal medulla and is considered a core clinical feature of neuromyelitis optica spectrum disorder (NMOSD). APS is present in up to 30% of patients ultimately diagnosed with NMOSD and can be the first presenting symptom of NMOSD in 12% of patients, as our case illustrates. Importantly, APS is highly responsive to immunotherapy. We present the case of a 14-year-old female with a history of migraines who presented to the emergency department multiple times for persistent nausea, vomiting, and hiccups. Multiple GI diagnoses were considered until she developed additional neurologic symptoms that prompted further workup and revealed the final diagnosis of NMOSD-APS. We posit that NMOSD-APS should be considered in the differential diagnosis for patients with intractable nausea and vomiting, especially in patients with a negative GI workup result and poor response to antiemetics.

AQP4-DARPin1: A Chimeric Antigen Based on Scaffold Protein DARPin for Efficient Detection of AQP4-IgG in NMOSD.

AQP4-IgG is an autoantibody associated with neuromyelitis optica spectroscopic disorder (NMOSD), a central nervous system inflammatory disease that requires early diagnosis and treatment. We designed two fusion proteins, AQP4-DARPin1 and AQP4-DARPin2, comprising the complete antigenic epitopes of aquaporin-4 (AQP4) and the constant region of the scaffold protein DARPin. These fusion proteins were expressed and purified from Escherichia coli and coated on microplates to develop an efficient method for detecting AQP4-IgG. Molecular dynamics simulation revealed that the fusion of AQP4 extracellular epitopes with DARPin did not alter the main structure of DARPin. The purified AQP4-DARPins bound recombinant antibody rAb-53 (AQP4-IgG) with affinities of 135 and 285 nM, respectively. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation demonstrated that AQP4-DARPin1 specifically recognized AQP4-IgG in the NMOSD patient serum. AQP4-DARPin1 as a coated antigen showed higher ELISA signal and end point dilution ratio than full-length AQP4. Our AQP4-DARPin1-coated AQP4-IgG ELISA had 100% specificity and 90% sensitivity. These results indicate that AQP4-DARPin1, compared to existing detection strategies that use full-length or extracellular loop peptides of AQP4, provides a new and more effective approach to the ELISA detection of NMOSD.

Cell-Based Assay to Detect the Autoantibody Serostatus in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).

Cell-based assay (CBA) is an immunofluorescence assay that is extensively used for the confirmatory diagnosis of inflammatory demyelinating diseases of the central nervous system, like neuromyelitis optica spectrum disorder (NMOSD). Detecting the type of autoantibody present in the sera of the patients is the primary goal. CBA is the most sensitive and recommended detection method among all similar tools. Briefly, serum autoantibody is screened by transfecting specific cells seeded on cover glasses with full-length specific antigen fused with green fluorescent protein (GFP), followed by treating them with the patient serum used here as the source of primary antibody. The autoantibody-treated cells are further labeled with a rhodamine-conjugated secondary antibody. The co-localization of GFP and rhodamine is visualized by confocal microscopy, and the intensity of fluorescence is evaluated to determine the presence of autoantibody. A detailed protocol to screen antibodies against AQP4 and MOG in human sera using this method is described.

Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4.48×102 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.

Seizures in inflammatory demyelinating disorders of the central nervous system.

BACKGROUND: Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may be associated with acute symptomatic seizures and chronic epilepsy as well. The clinical features of the seizures and/or accompanying epilepsy seen in each disease group may vary. In this study, we aimed to contribute to the existing literature by describing the clinical features of seizures and epilepsy in our demyelinating patient population. METHODS: We retrospectively analyzed patients who were followed up in our tertiary referral center neurology demyelinating diseases outpatient clinic between 2019 and 2024. Patients who had at least one seizure before, simultaneously, or after the diagnosis of demyelinating disease were included in the study. RESULTS: Among 1735 patients with MS, 40 had experienced at least one epileptic seizure (2.3 %). Thirty patients (1.7 %) had seizures that could not be explained by another factor than MS. When secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) were compared, the interval between MS-epilepsy diagnosis was longer and seizure recurrence was more in SPMS. However, the prognosis of epilepsy was good in both subtypes. There were 21 patients followed up with antibody-positive neuromyelitis optica spectrum disorder. No patient had a seizure during the follow-up. We identified 56 patients who fulfilled the criteria for MOGAD with high antibody titers. Seizures were observed in three of them (5.4 %). All of them had status epilepticus either at the onset or during the course of the disease. CONCLUSION: Even rare, seizures constitute one of the important clinical features of the inflammatory demyelinating disorders of the central nervous system. The pathophysiologic mechanism underlying seizures in MS is still not clear. Seizures may occur through different mechanisms in patients where seizures are the initial symptom or a sign of relapse and those that occur spontaneously during the progressive course of the disease. Prevalence of status epilepticus was common in MOGAD patients. Given the rarity of the seizures in CNS demyelinating disorders, it is difficult the define clinical and pathophysiological characteristics of accompanying seizures and epilepsy. Future studies conducted on large patient groups will contribute to the existing literature.

A study of referral bias in NMOSD and MOGAD cohorts.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare disorders often seen in highly specialized services or tertiary centres. We aimed to assess if cohort characteristics depend on the origin of the referral catchment areas serviced by our centre (i.e. local, regional or national). METHODS: Retrospective cohort study using a national referral service database including local (Oxfordshire), regional (Oxfordshire and neighbouring counties), and national patients. We included patients with the diagnosis of NMOSD, seronegative NMOSD or MOGAD, followed at the Oxford Neuromyelitis Optica Service. RESULTS: We included 720 patients (331 with MOGAD, 333 with aquaporin-4 antibody (AQP4)-NMOSD, and 56 with seronegative NMOSD. The distribution of diagnoses was similar across referral cohorts. There were no significant differences in the proportion of pediatric onset patients, sex, or onset phenotype; more White AQP4-NMOSD patients were present in the local than in the national cohort (81 % vs 52 %). Despite no differences in follow-up time, more relapsing MOGAD disease was present in the national than in the local cohort (42.9 % vs. 24 %, p = 0.029). CONCLUSION: This is the first study assessing the impact of potential referral bias in cohorts of NMOSD or MOGAD. The racial difference in the AQP4-NMOSD cohorts likely reflects the variation in the population demographics rather than a referral bias. The over representation of relapsing MOGAD patients in the national cohort probably is a true referral bias and highlights the need to analyze incident cohorts when describing disease course and prognosis. It seems reasonable therefore to compare MOGAD and NMOSD patients seen withing specialised centres to general neurology services, provided both use similar antibody assays.

Brain and spinal cord atrophy in NMOSD and MOGAD: Current evidence and future perspectives.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe form of inflammation of the central nervous system (CNS) including acute myelitis, optic neuritis and brain syndrome. Currently, the classification of NMOSD relies on serologic testing, distinguishing between seropositive or seronegative anti-aquaporin-4 antibody (AQP4) status. However, the situation has recently grown more intricate with the identification of patients exhibiting the NMOSD phenotype and myelin oligodendrocyte glycoprotein antibodies (MOGAD). NMOSD is primarily recognized as a relapsing disorder; MOGAD can manifest with either a monophasic or relapsing course. Significant symptomatic inflammatory CNS injuries with stability in clinical findings outside the acute phase are reported in both diseases. Nevertheless, recent studies have proposed the existence of a subclinical pathological process, revealing longitudinal changes in brain and spinal cord atrophy. Within this context, we summarise key studies investigating brain and spinal cord measurements in adult NMOSD and MOGAD. We also explore their relationship with clinical aspects, highlight differences from multiple sclerosis (MS), and address future challenges. This exploration is crucial for determining the presence of chronic damage processes, enabling the customization of therapeutic interventions irrespective of the acute phase of the disease.

Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

Multi-registry analysis of patients with multiple sclerosis and neuromyelitis optica to improve capture of demographic data and compare visual outcomes.

IMPORTANCE: The American Academy of Neurology Axon Registry® provides real-world data for patients with multiple sclerosis and neuro-myelitis optica. However, some data are incomplete (e.g. demographics) and some relevant outcomes are not systematically captured in neurology documentation (e.g. visual acuity). The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) contains demographic and visual function data that may complement Axon Registry-derived data to enhance understanding of real-world visual outcomes in neurological disease. OBJECTIVE: To combine Axon Registry and IRIS Registry data to reduce missingness of demographic information and characterize visual outcomes in patients with multiple sclerosis and neuro-myelitis optica. DESIGN: Cross-sectional study. SETTING: Outpatient neurology and ophthalmology clinical practices. PARTICIPANTS: Patients participating in both registries between January 1, 2014 through December 10, 2021 were included if they had repeat ICD-9/10 codes for with multiple sclerosis or neuro-myelitis optica in the Axon registry. EXPOSURE: Diagnosis (multiple sclerosis or neuro-myelitis optica). MAIN OUTCOME AND MEASURE: Age, sex, race and ethnicity were assessed in the individual registries and classified as conflicting, missing, or not missing in the combined data set. The IRIS Registry contributed visual acuity data. RESULTS: Among 60,316 patients with multiple sclerosis and 1,068 patients with neuro-myelitis optica in the Axon Registry, 14,085 and 252 had temporal overlap in the IRIS Registry. Combining data reduced missing or conflicting data for race and ethnicity by 15-19 % (absolute reduction, all p ≤ 0.0005), but not age (p = 1.0) or gender (p = 0.08). 10,907 patients with MS and 142 with NMO had visual acuity data in the IRIS Registry. Visual acuity averaged between eyes was worse in patients with NMO after adjusting for age and gender (0.17 logMAR, 95 %CI 0.12,0.21, p < 0.0005). CONCLUSION AND RELEVANCE: Using data from two registries reduced missing data for race and ethnicity and enabled examination of outcomes captured in the IRIS Registry for conditions that are diagnosed more frequently in the Axon Registry, demonstrating the utility of a multi-registry analysis.

Clinical features and prognosis of Tibetan patients with neuromyelitis optica spectrum disorder are different from those of Han Chinese patients.

We compared the prognosis of Tibetan and Han Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). The Expanded Disability Status Scale (EDSS) score at each attack, response to immunosuppressive therapy, risk of first relapse, severe attack, visual disability, motor disability, and total risk of disability were compared between Tibetan and Han Chinese patients. Tibetan patients showed higher EDSS during acute attacks. Annualized relapse rate did not differ between groups. Risk of severe attack, visual disability, and total risk of disability were higher in Tibetan patients. Tibetan patients with NMOSD have a higher risk of poor prognosis than Han Chinese patients.

The critical role of magnetic resonance imaging in the diagnosis of transverse myelitis: a case report.

INTRODUCTION: Transverse Myelitis is a rare inflammatory disorder of the spinal cord, characterized by the inflammation of the myelin sheath covering nerve fibers. Although rare, Transverse Myelitis holds significant clinical importance due to its potential life-altering consequences. The case report provides insight into the clinical presentation of Transverse Myelitis and the importance of Magnetic Resonance Imaging in confirming Transverse Myelitis. CASE PRESENTATION: A 27-year-old Nigerian female presented to a hospital facility after 2 months onset of paraplegia, urinary, and fecal incontinence. She was diagnosed with Acute Transverse Myelitis with Magnetic Resonance Imaging, a lacking imaging modality in Nigeria. On presentation, it was important to rule out spinal cord compression, a close differential to her presentation. Despite her late arrival at the facility, early diagnosis and prompt initiation of treatment with high-dose intravenous steroids and physiotherapy improved her quality of life. DISCUSSION: This case report reveals the poor health-seeking behavior in developing countries and the need for imaging modalities like Magnetic Resonance Imaging for improved diagnoses of rare neurological conditions such as Transverse Myelitis. The lack of healthcare infrastructure has led to clinical misdiagnosis, patient mismanagement, and underrepresentation of data in the country, underscoring the critical role of diagnostic tools for improved patient care pre-treatment and post-treatment. Additionally, follow-up of these patients is important to prevent the long-term sequelae of Transverse Myelitis like Neuromyelitis Optica or Multiple Sclerosis.

'I Thought It Was My Diabetes': An Acute Presentation of Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated neuroinflammatory disease of the central nervous system. Patients typically present with sensory deficits, weakness, and incontinence. This is a case of a 43-year-old female with diabetes mellitus admitted for acute onset leg weakness and stool incontinence. Spinal MRI imaging revealed transverse myelitis, and her lab work was significant for an anti-aquaporin 4 (AQP4) antibody titer of 1:2,560. Initial treatment consisted of a high-dose steroid taper and plasmapheresis. This unique case illustrates the importance in recognizing delayed presentations of rare neuroinflammatory conditions previously assumed to be a sequela of diabetic neuropathy.

Systemic Connective Tissue Disease and Neuromyelitis Optica Spectrum Disorder Coexistence: A Systematic Review and Meta-Analysis.

BACKGROUND: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. METHODS: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. RESULTS: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. CONCLUSIONS: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

Therapeutic plasma exchange for neuromyelitis optica attacks: Evidence and challenges from a real-world cohort from Brazil.

Therapeutic plasma exchange (TPE) can improve disability recovery after neuromyelitis optica spectrum disease (NMOSD) attacks, but its effectiveness and safety in Latin-American patients with access barriers and diverse ethnicity is underexplored. We carried out a retrospective cohort study with NMOSD patients that underwent TPE. 84 NMOSD attacks in 68 patients were evaluated. Despite a median 25-day delay from symptom onset to TPE, 65,5% of patients showed significant improvement. Adverse events occurred in 39% of patients, usually transitory and with no fatalities.

Susceptibility-weighted image features in AQP4-negative-NMOSD versus MS.

OBJECTIVE: To characterize the susceptibility-weighted image (SWI) features including paramagnetic rim and nodular lesions with signal intensity changes and central vein sign (CVS) associated with aquaporin 4 (AQP4)-immunoglobulin G (IgG)-negative neuromyelitis optica spectrum disorder (NMOSD), and explore whether they can be used as potential imaging biomarkers for differentiating multiple sclerosis (MS) from this disorder. METHODS: We prospectively recruited NMOSD with AQP4-IgG-negative (AQP4- NMOSD) and IgG-positive (AQP4+ NMOSD), and MS subjects from the Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE) project (NCT0410683) between 2019 and 2021. The SWI features including paramagnetic rim and nodular lesions with signal intensity changes and CVS were analyzed and compared among groups, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for distinguishing MS from AQP4- NMOSD. RESULTS: We enrolled a total of 160 consecutive patients (22 AQP4- NMOSD, 65 AQP4+ NMOSD, and 73 MS). We observed paramagnetic rim lesion (0/120 lesions, 0 %) and nodular (1/120, 1 %) lesions with hypointense signals on SWI in the AQP4- NMOSD group. These characteristics were similar to those recorded from AQP4+ NMOSD patients (rim: 0/369 lesions, 0 %, P = 1.000; nodular: 10/369 lesions, 2.7 %, P = 1.000), but differed significantly from those observed in the MS group (rim: 162/1665 lesions, 9.7 %, P<0.001; nodular: 392/1665 lesions, 23.5 %, P < 0.001). AQP4- NMOSD patients had fewer average CVS+ rate (12 %) than MS patients (46 %, p<0.001), similar to AQP4+ NMOSD (13 %, p = 1.000). The SWI imaging features denoting lesions with paramagnetic rim or nodular hypointense SWI signals showed 90.4 % sensitivity, 95.5 % specificity, 98.5 % PPV, and 75 % NPV, and the criteria with≥3 CVS lesions showed sensitivity of 91.8 %, specificity of 90.9 %%, PPV of 97.1 %, and NPV of 76.9 % in distinguishing MS from AQP4- NMOSD. DISCUSSION: The SWI imaging features including lesions with paramagnetic rim or nodular hypointense SWI signals and 3 CVS lesions carries useful information in distinguishing MS from AQP4- NMOSD.