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.

Exploring resting-state EEG oscillations in patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVE: Quantitative resting-state electroencephalography (rs-EEG) is a convenient method for characterizing the functional impairments and adaptations of the brain that has been shown to be valuable for assessing many neurological and psychiatric disorders, especially in monitoring disease status and assisting neuromodulation treatment. However, it has not yet been explored in patients with neuromyelitis optica spectrum disorder (NMOSD). This study aimed to investigate the rs-EEG features of NMOSD patients and explore the rs-EEG features related to disease characteristics and complications (such as anxiety, depression, and fatigue). METHODS: A total of 32 NMOSD patients and 20 healthy controls (HCs) were recruited; their demographic and disease information were collected, and their anxiety, depression, and fatigue symptoms were evaluated. The rs-EEG power spectra of all the participants were obtained. After excluding the participants with low-quality rs-EEG data during processing, statistical analysis was conducted based on the clinical information and rs-EEG data of 29 patients and 19 HCs. The rs-EEG power (the mean spectral energy (MSE) of absolute power and relative power in all frequency bands, as well as the specific power for all electrode sites) of NMOSD patients and HCs was compared. Furthermore, correlation analyses were performed between rs-EEG power and other variables for NMOSD patients (including the disease characteristics and complications). RESULTS: The distribution of the rs-EEG power spectra in NMOSD patients was similar to that in HCs. The dominant alpha-peaks shifted significantly towards a lower frequency for patients when compared to HCs. The delta and theta power was significantly increased in the NMOSD group compared to that in the HC group. The alpha oscillation power was found to be significantly negatively associated with the degree of anxiety (reflected by the anxiety subscore of hospital anxiety and depression scale (HADS)) and the degree of depression (reflected by the depression subscore of HADS). The gamma oscillation power was revealed to be significantly positively correlated with the fatigue severity scale (FSS) score, while further analysis indicated that the electrode sites of almost the whole brain region showing correlations with fatigue. Regarding the disease variables, no statistically significant rs-EEG features were related to the main disease features in NMOSD patients. CONCLUSION: The results of this study suggest that the rs-EEG power spectra of NMOSD patients show increased slow oscillations and are potential biomarkers of widespread white matter microstructural damage in NMOSD. Moreover, this study revealed the rs-EEG features associated with anxiety, depression, and fatigue in NMOSD patients, which might help in the evaluation of these complications and the development of neuromodulation treatment. Quantitative rs-EEG analysis may play an important role in the management of NMOSD patients, and future studies are warranted to more comprehensively understand its application value.

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.

Retinal structural and microvascular deterioration independent of optic neuritis in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders: An optical coherence tomography angiography study.

PURPOSE: To assess the retinal structural and microvascular change in aquaporin-4 antibody (AQP4) positive neuromyelitis optica spectrum disorder (NMOSD) patients and the correlation with clinical features. METHODS: A cross-sectional study was performed with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal structure and microvascular parameters in AQP4 positive NMOSD patients. RESULTS: Sixty-two NMOSD patients (44 eyes with ON, NMOSD+ON; 77 eyes without ON, NMOSD-ON) and 62 healthy controls (HC, 124 eyes) were included. BCVA was worse in NMOSD patients compared to HC (p<0.001). Peripapillary retinal nerve fiber layer (pRNFL, p<0.001) and ganglion cell complex (GCC, p<0.001) was thinner in NMOSD+ON eyes compared to NMOSD-ON eyes and HC. Compared to HC, pRNFL (p = 0.002) and GCC (p = 0.001) was thinner in NMOSD-ON eyes. The vessel density (VD) in superficial capillary plexus (SCP, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.002) and radial peripapillary capillary (RPC, NMOSD+ON vs HC p<0.001, NMOSD-ON vs HC p = 0.001) were also lower in NMOSD patients than HC independent of the history of ON. ON frequency and BCVA were correlated with the thickness of pRNFL and GCC, and VD in SCP and RPC (all p<0.001). EDSS was correlated with thickness of GCC (p = 0.008), and VD in SCP (p = 0.013), DCP (p<0.001) and RPC (p = 0.009). CONCLUSIONS: Subclinical degradation of retinal structure and microvasculature was found in NMOSD patients before the occurrence of ON, and was correlated with clinical disability. Retinal parameter might be a tool to estimate the disease progression and investigate the pathogenesis of NMOSD.

The Etiology and Outcome of Area Postrema Syndrome in Childhood: Two Cases and a Literature Review.

BACKGROUND: Area postrema syndrome (APS), a rare childhood condition, manifests as intractable nausea and hiccups. APS has high diagnostic significance in neuromyelitis optica syndrome spectrum disorders (NMOSD) and can be the initial presentation of other critical diseases, including brainstem glioma. METHODS: We described two representative cases of unrelated Japanese patients with APS. An etiologic evaluation, including a detailed intracranial neuroradiological examination and autoantibodies assessment, was performed. We also reviewed the literature focusing on the prognosis of pediatric APS symptoms. RESULTS: A 14-year-old girl with aquaporin-4 antibody-positive NMOSD showed a good prognosis with immunotherapy, whereas another nine-year-old girl with irresectable medullary low-grade glioma had persistent symptoms for more than 10 years. All reported children aged >12 years were diagnosed with NMOSD, and patients aged <13 years showed heterogeneous etiologies. CONCLUSIONS: Distinctive time courses and neuroimaging features were key clinical findings for the diagnostic and therapeutic processes in these patients. This literature review highlights the wide spectrum and prognosis of pediatric-onset APS.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD. METHODS: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses. RESULTS: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall. DISCUSSION: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Thyroid hormone dysfunction in MOGAD and other demyelinating diseases.

BACKGROUND: Thyroid hormones play a critical role in both neuronal and glial cell functions. Multiple sclerosis (MS) has increased co-occurrence with autoimmune thyroid diseases, and recent studies have suggested a potential link between neuromyelitis optica spectrum disorder (NMOSD) and thyroid hormones. However, no previous studies have examined the relationship between thyroid hormones and myelin oligodendrocyte glycoprotein-associated demyelination (MOGAD). METHODS: We investigated the role of thyroid hormones in central nervous system (CNS) autoimmune demyelinating diseases in 26 MOGAD patients, 52 NMOSD patients, 167 patients with MS, and 16 patients with other noninflammatory neurological disorders. Thyroid hormone levels and clinical data (Expanded Disability Status Scale [EDSS]) were analyzed. Volumetric brain information was determined in brain magnetic resonance imaging (MRI) using the MDbrain platform. RESULTS: MOGAD patients had significantly higher levels of free triiodothyronine (FT3) compared to NMOSD patients. No correlation was found between FT3 levels and disease severity or brain volume. Thyroid-stimulating hormone (TSH) levels did not differ significantly between the groups, but in NMOSD patients, higher TSH levels were associated with lower disability scores and increased brain volume. No significant differences in free thyroxine (FT4) levels were observed between the different groups, however, FT4 levels were significantly higher in relapsing versus monophasic MOGAD patients and increased FT4 levels were associated with a higher EDSS and lower brain volume in NMOSD patients. CONCLUSION: Our findings highlight the potential involvement of thyroid hormones specifically in MOGAD patients and other demyelinating CNS disorders. Understanding the role of thyroid hormones in relapsing vs monophasic MOGAD patients and in comparison to other demyelinating disorder could lead to the development of therapeutic interventions. Further studies are needed to explore the precise mechanisms and potential interventions targeting the thyroid axis as a treatment strategy.

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

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

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

[Pregnancy-associated neuromyelitis optical spectrum disorder combined with primary Sjögren's syndrome: A critical illness case report].

Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.

Relationship of immune cells with disability and cognitive impairment in patients with neuromyelitis optica spectrum disorder.

OBJECTIVE: This study aimed to investigate the relationship between common clinical immune indicators, disability degree, and cognitive impairment in patients with neuromyelitis optica spectrum disorder (NMOSD). PATIENTS AND METHODS: We retrospectively analyzed lymphocyte subsets and routine parameters in the peripheral blood of 55 patients with NMOSD. We assessed the degree of disability using the Extended Disability Status Scale (EDSS). The Montreal Cognitive Assessment (MoCA) scores were used to assess cognitive function. In addition, we also determined the cytokine levels in 33 patients with NMOSD. The relationships of these immunological indicators with disability and cognitive impairment were assessed using correlation and multiple linear regression analyses. RESULTS: The results of the multiple linear regression analysis suggested that for patients with NMOSD, the neutrophil-lymphocyte ratio (NLR) (ß=0.072, p=0.034) and number of attacks (ß=0.131, p=0.03) were positively correlated with EDSS scores, whereas the number of attacks was positively correlated with MoCA scores. In addition, we also collected cytokine levels in 33 of these patients. The results of the study showed a positive correlation between IL-10 and EDSS scores and a negative correlation between IL-6 and MoCA scores. CONCLUSIONS: Our results show that these immune cells and cytokines are, to some extent, associated with the degree of disability and cognitive impairment in patients with NMOSD. Closely monitoring these indicators may allow detecting changes in patients' disease courses and predicting the severity of their disease. In clinical practice, this may facilitate early intervention and appropriate treatment decisions, which may improve the management of patient prognosis.

Neuromyelitis optica spectrum disorder with herpes simplex viral infection presenting with syndrome of inappropriate antidiuretic hormone: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease that causes lesions in areas with abundant aquaporin-4 (AQP4) channels, including the hypothalamus. Hypothalamic lesions can disrupt antidiuretic hormone regulation, resulting in hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH). Various factors can trigger NMOSD, including viral infections. We report the case of a young female patient who presented with hyponatremia due to SIADH and was found to have bilateral hypothalamic lesions along with positive serum herpes simplex virus immunoglobulin M. PATIENT CONCERNS: An 18-year old female patient presented with fever and nausea that had persisted for 5 days. Three days after hospitalization, the patient complained of blurred vision, hiccups, and excessive daytime sleepiness. DIAGNOSIS: The patient hyponatremia was attributed to SIADH. Magnetic resonance imaging revealed bilateral lesions in the hypothalamus, and serum laboratory tests were positive for herpes simplex virus immunoglobulin M. On the 15th day of admission, the anti-AQP4 antibody test result was positive, leading to the diagnosis of NMOSD. INTERVENTIONS: On the initial suspicion of herpes encephalitis, treatment with acyclovir was initiated. However, upon the confirmation of after anti-AQP4 antibody, the patient was additionally treated with a high-dose intravenous steroid for 5 days. OUTCOMES: The patient fever, nausea, visual disturbances, and other complaints improved within 1 week of initiating steroid treatment. LESSONS: In young patients presenting with hyponatremia and suspected SIADH accompanied by neurological abnormalities, it is crucial to differentiate central nervous system diseases, including NMOSD, which can involve lesions in AQP4-abundant areas, such as the hypothalamus.

Neuromyelitis Optica: Pathogenesis Overlap with Other Autoimmune Diseases.

PURPOSE OF REVIEW: Neuromyelitis optica (NMO) is an auto-immune disease essentially depicted by optic neuritis and transverse myelitis. Per se, NMO was initially believed to be a sub-type of multiple sclerosis with typical demyelinating cerebral lesions and optic nerve inflammation. More recently, corroborating lignes of evidence have strengthened the concept of the spectrum of diseases associated with NMO and more specifically with the role of anti-aquaporin-4 antibodies in the pathogenesis of disease. RECENT FINDINGS: In this article, we review the recent pathogenic findings in NMO and more interestingly the newly discovered role of anti-aquaporin-4 antibodies as key players in triggering cerebral lesions. The concept of spectrum of diseases associated with NMO is also discussed. These recent findings have paved in the further understanding of the pathogenesis underlying NMO and new treatments are currently being developed targeting anti-aquaporin-4 antibodies.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder in a paraneoplastic context.

OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.

Neuromyelitis Optica spectrum disorders in Argentina: A hospital-based study.

BACKGROUND: Neuromyelitis Optica spectrum disorder (NMOSD) is an antibody-mediated autoimmune disease of the CNS, which especially affects the optic nerves and spinal cord. There is little known in Latin America (LATAM) about NMOSD, and few reports have been published in the literature so far. We aimed to describe an NMOSD study in a single center from Argentina. METHODS: A retrospective cross sectional study was carried out in a single reference center in the city of Buenos Aires, Argentina. Data were collected from January 2000 through December 2021 using medical records from patients attending Ramos Mejia Hospital in Buenos Aires, Argentina. Here we describe the clinical, laboratory, MRI, disability course, and treatment of 92 NMOSD patients. RESULTS: Mean age at the onset of symptoms was 31 years (range 2-68) with a female/male ratio of 4.8:1. 71.7 % had an early onset before the age of 50 years old, 8.7 % had a late onset of the disease and 19.6 % had an onset at pediatric age. The first symptom of NMOSD was optic neuritis in 47.8 % of the patients, followed by transverse myelitis, 33.7 % and area postrema syndrome, 5.4 %. 96.7 % of patients relapsed at least once during the follow-up period. The mean of the expanded disability status scale (EDSS) was 4.0 (range 2-8). 34,8 % had one or more associated autoimmune diseases. 78,6 % had a positive result for AQP4-IgG. The ratio of male to female was 1:8.4 vs.1:1.2 in the seropositive group vs. the seronegative. CSF results showed OCB type 2 in 6.3 %. The brain MRI did not show brain lesions in 71,7 % of the patients. 17 % presented spinal cord lesions with less than 3 vertebral segments. All patients received treatment with immunosuppressive drugs. Rituximab and azathioprine were the most used. CONCLUSIONS: This is the largest hospital-based study in an Argentina cross-sectional study of patients with NMOSD. Recurrent disease, early age at onset, female prevalence in AQP4-IgG+ patients, and the difficulty to assess new treatments, are the highlight features in our study of patients. Further Argentinian and LATAM studies will provide more information.

Factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorders.

OBJECTIVE: To investigate the factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorder (NMOSD) and provide evidence for disease monitoring and clinical intervention. METHODS: Eighty-four patients with NMOSD at Xuanwu Hospital Capital Medical University were enrolled in this retrospective study. Before treatment, blood was collected from all patients, and their expanded disability status scores were assessed. RESULTS: Of the 84 patients assessed, 66 (78.57%) had an expanded disability status scale score < 7, and 18 (21.43%) had scores ≥ 7. The univariate analysis showed that the total bilirubin (TBil), cerebrospinal fluid albumin (CSF ALB), cerebrospinal fluid immunoglobulin G (CSF IgG), QALB, and QIgG levels in the group with scores ≥ 7 were significantly different from those with scores < 7 (P < 0.05). In addition, Spearman's correlation analysis showed a significant correlation between ALB and expanded disability status scores in patients with NMOSD (P < 0.05), and the multivariate logistic regression analysis showed that TBil was an independent factor influencing the degree of disability in patients with NMOSD (P < 0.05). The receiver operating characteristic curve was constructed using TBil values; the area under the curve of TBil was 0.729 (P < 0.01), and the best cut-off value was 11.015 g/L. Its sensitivity in predicting the severity of disability in NMOSD patients was 51.5% while its specificity was 88.9%. CONCLUSION: TBil is an independent factor that influences the severity of disability in patients with NMOSD. In addition, ALB is closely related to NMOSD severity, and some factors associated with the BBB are significantly increased in severely disabled NMOSD patients.

Structural disconnection is associated with disability in the neuromyelitis optica spectrum disorder.

OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. Accumulating evidence suggests there is a distinct pattern of brain lesions characteristic of NMOSD, and brain MRI has potential prognostic implications. However, the question of how the brain lesions in NMOSD are associated with its distinct clinical course remains incompletely understood. Here, we aimed to investigate the association between neurological impairment and brain lesions via brain structural disconnection. METHODS: Twenty patients were diagnosed with NMOSD according to the 2015 International Panel for NMO Diagnosis criteria. The white matter lesions were manually drawn section by section. Whole-brain structural disconnection was estimated, and connectome-based predictive modeling (CPM) was used to estimate the patient's Expanded Disability Status Scale score (EDSS) from their disconnection severity matrix. Furthermore, correlational tractography was performed to assess the fractional anisotropy (FA) and axial diffusivity (AD) of white matter fibers, which negatively correlated with the EDSS score. RESULTS: CPM successfully predicted the EDSS using the disconnection severity matrix (r = 0.506, p = 0.028; q2 = 0.274). Among the important edges in the prediction process, the majority of edges connected the motor to the frontoparietal network. Correlational tractography identified a decreased FA and AD value according to EDSS scores in periependymal white matter tracts. DISCUSSION: Structural disconnection-based predictive modeling and local connectome analysis showed that frontoparietal and periependymal white matter disconnection is predictive and associated with the EDSS score of NMOSD patients.

Impact of the autonomic dysfunction on the quality of life in people with NMOSD and MS: An international cross-sectional study.

BACKGROUND: A substantial autonomic nervous system (ANS) dysfunction has been described in multiple sclerosis (MS) and recently, also in neuromyelitis optica spectrum disorder (NMOSD). The prevalence of ANS symptoms contributes to the chronic symptom burden in both diseases. The aim of our study was to assess ANS dysfunction in people with (pw) NMOSD and MS, using the Composite Autonomic Symptom Score-31 (COMPASS-31), and additionally, to evaluate if ANS dysfunction have impact on the quality of life of these patients. METHODS: We conducted cross-sectional study at three national referral neurological clinics in Serbia, Croatia, and Montenegro. A total of 180 consecutive subjects, 80 pwNMOSD and 100 pwMS, followed-up at these clinics, were enrolled in the study. Subjects included in the study completed: the validated versions of the COMPASS-31 and the Multiple Sclerosis Quality of Life-54 (MSQoL-54), and the Beck Depression Inventory (BDI). RESULTS: This study demonstrated that the total COMPASS-31 score > 0.0, implicating the presence of ANS dysfunction, was detected in almost all NMOSD and MS study participants tested (80/80, and 97/100, respectively). Our findings showed that autonomic symptom burden was statistically significantly correlated with decreased quality of life, in both NMOSD and MS cohorts. The independent predictors of the better quality of life in pwNMOSD were lower autonomic burden, particularly the absence of the orthostatic intolerance (p = 0.005), along with lower EDSS and BDI score (p ≤ 0.001). Similarly, in pwMS, independent predictors were EDSS, BDI, orthostatic intolerance, and the total COMPASS-31 (p ≤ 0.001). CONCLUSION: Our study demonstrated that a significant proportion of persons with both NMOSD and MS have considerable dysautonomic symptom burden which is correlated with the decreased quality of life. Further investigations are warranted in order to optimize treatment interventions in MS and NMOSD.

The prevalence of depression, anxiety, and sleep disturbances in patients with neuromyelitis optica spectrum disorders (NMOSD): A systematic review and meta-analysis.

OBJECTIVE: To estimate pooled prevalence of depression, anxiety, and sleep disturbances in neuromyelitis optica spectrum disorders (NMOSD) cases. METHODS: Electronic database of PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Web of Science ware systematically searched to identify relevant studies published not later than June 10, 2022. Specifically, original articles that reported the prevalence of depression, anxiety and sleep disturbances were selected. All pooled prevalence and 95 % confidence intervals (CIs) were calculated using a random-effects model. Publication bias was examined using funnel plots, and sensitivity analysis was used to explore the stability of the pooled results. RESULTS: A total of 31 studies involving 4213 participants were included in this review. The pooled prevalence of depression was 40 % (95 % CI: 32-49 %), the pooled prevalence of anxiety was 45 % (95 % CI: 24-66 %), and the pooled prevalence of sleeping disturbances was 55 % (95 % CI: 46-64 %). The depression and anxiety prevalence estimates varied based on different screening tools. CONCLUSIONS: There is a high prevalence of depression, anxiety, and sleep disturbances among NMOSD. These findings underscore the importance of regular monitoring of psychological status in NMOSD as well as the need for preventive approaches, early diagnosis, and intervention to improve medical and psychosocial outcomes.

Therapy challenges for NMOSD in a patient with HIV.

Neuromyelitis optica spectrum disorder (NMOSD) in people living with HIV (PLWH) is rare and its management can be difficult. Here we report a case of an HIV patient with bilateral vision loss, who was diagnosed with AQP4-IgG-positive NMOSD in 2020 during the COVID-19 pandemic. Rituximab treatment was initiated after attack therapy with corticosteroids and plasma exchange. NMOSD and HIV disease remained stable, but SARS-CoV-2 immune response after repeated vaccinations was insufficient. After switching immunotherapy due to the lack of vaccination response to satralizumab, peripheral B cells reoccurred and a humoral immune response was observed after reapplication of SARS-CoV-2 vaccination. This case illustrates the challenges associated with the treatment of NMOSD in PLWH.