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Neuromyelitis optica is an autoimmune disease with nonspecific onset, with symptoms that may be similar and confused with multiple sclerosis. Devic's disease (neuromyelitis optica) mainly manifests as optic neuritis and concomitant myelitis. The patient's first manifestation of Devic's disease was reported in April 2020. Two months later the patient was admitted to the neurology ward where serological analysis, MRI and other diagnostics were performed, leading to an initial diagnosis of transverse myelitis. After another two months, significant deterioration of vision in the right eye occurred. The presence of AQP4-Ab and differential diagnostics performed established the diagnosis of neuromyelitis optica. The patient was treated with rituximab and plasmapheresis. Despite effective immunosuppressive treatment quadriplegia persists, and the patient moves using a wheelchair. This report presents features of rare astrocytopathy, which is underdiagnosed due to its similarity to multiple sclerosis. This work aims to remind us which symptoms suggest the proper diagnosis of neuromyelitis optica. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The association of neuromyelitis optica concurrently with two other autoimmune diseases is rare. Neuromyelitis optica should be taken into consideration when evaluating the symptoms of the patient as a differential diagnostic aspect. [ABSTRACT FROM AUTHOR]

Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis. Case presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells. Conclusions: Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity. [ABSTRACT FROM AUTHOR]

BackgroundThe expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.Case presentationHere, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells.ConclusionsFatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.

The chronic inflammatory condition known as multiple sclerosis (MS) causes inflammation and demyelination in the central nervous system (CNS). The activation of multiple cell types, including the CNS's resident immune cells called microglia, is a component of the immunological response in MS. Recently, the triggering receptor expressed on myeloid cells (TREM) family has emerged as a crucial player in modulating microglial function and subsequent neuroinflammation. Understanding the role of TREM receptors in MS pathogenesis could provide insightful information on how to develop new therapeutic approaches. The TREM family consists of several receptors, including TREM-1 and TREM-2, which can be expressed on both immune cells, such as myeloid cells and microglia, and non-immune cells. These receptors interact with their respective ligands and regulate signaling pathways, ultimately leading to the control of microglial activation and inflammatory reactions. TREM-2, in particular, has garnered significant interest because of its connection with MS and other neurodegenerative diseases. The activation of microglia through TREM receptors in MS is thought to influence the equilibrium between helpful and detrimental inflammatory responses. TREM receptors can promote the phagocytosis of myelin debris and remove apoptotic cells, thus contributing to tissue repair and regeneration. However, excessive or dysregulated activation of microglia mediated by TREM receptors can lead to the release of pro-inflammatory cytokines and neurotoxic factors, exacerbating neuroinflammation and neurodegeneration in MS. The emerging role of the TREM family in demyelinating diseases highlights the importance of microglia in disease pathogenesis. Understanding the mechanisms by which TREM receptors modulate microglial function can provide valuable insights into the development of targeted therapies for these disorders. By selectively targeting TREM receptors, it may be possible to harness their beneficial effects on tissue repair while dampening their detrimental pro-inflammatory responses. Further research is warranted to elucidate the precise signaling pathways and ligand interactions involved in TREM-mediated microglial activation, which could uncover novel therapeutic avenues for treating MS and other neuroinflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorder (NMOSD) often leads to disability and exerts a heavy toll on the work and life of affected female patients. This study aimed to analyze the current employment situation and economic burden as well as the risk factors for unemployment in female patients with NMSOD. Methods: We compared the following unemployment- and employment-related aspects in with NSMOD, which were investigated using questionnaires: the specific impact of NMOSD on work, medical expenses, and factors affecting unemployment. Results: We enrolled 351 female patients with NMOSD. More than half (54.1%, 190/351) of participants reported that the disease led to unemployment. The unemployment group was significantly older (46.9 ± 12.1 years vs. 39.3 ± 9.4 years, P = 0.000), had a higher annual recurrence rate (ARR) (0.6 [inter quartile range [IQR]:0.4-0.9] vs. 0.5 [IQR: 0.3-0.8], P = 0.141), and a higher severe disability rate (44.2% vs. 11.2%, P = 0.000) than the employment group. Moreover, unemployed patients had lower education levels. The factors influencing unemployment included low education (junior middle-school or below), age, higher ARR, and severe disability (odds ratio [OR] = 6.943, P = 0.000; OR = 1.034, P = 0.010; OR = 1.778, P = 0.038; and OR = 4.972, P = 0.000, respectively). Medication and hospitalization costs constituted the principal economic burdens. Conclusion: The heavy financial burden, employment difficulties, and high unemployment rate are the most prominent concerns of female patients with NMOSD who require more social support and concern. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorders (NMOSDs) are degenerative diseases frequently associated with severe recurrences and high risk of progressive disability. In this report, we describe an unusual case of a patient with the coexistence between NMOSD and mixed connective tissue disease (MCTD)., Case Description: A 58-year-old Caucasian man was admitted to the Emergency Department (ED) with low back pain and walking inability. He had an unsteady gait, paraesthesia of the lower limbs and pain in the left lumbar area of the spine. He previously manifested repeated episodes of Raynaud's phenomenon. The neurological examination revealed pyramidal signs with asymmetric and progressive paraparesis associated with hypoesthesia and bladder dysfunction. A spine magnetic resonance imaging (MRI) revealed the presence of a long extensive cervico-dorsal myelitis. Among laboratory analyses, serum immunometric examinations came back positive for anti-RNP (272 U/mL) and anti-SSA (20 U/mL) antibodies, whereas a recombinant immunofluorescence assay revealed the presence of immunoglobulin G (IgG) antibodies against AQP4. Consequently, he was treated with high-doses of corticosteroids, with progressive resolution of symptoms. To date, his last cervico-dorsal spine MRI showed negative results., Conclusions: Only a few anecdotal cases of the coexistence between NMOSD and MCTD have so far been described, and many clinical aspects of this association are not yet fully known. Missed diagnosis of rheumatologic or neurologic diseases may lead to treatment delay and, potentially, irreversible disability. Closer collaboration between neurologists and rheumatologists is needed for the early diagnosis of both diseases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-48/coif). The authors have no conflicts of interest to declare., (2025 AME Publishing Company. All rights reserved.)

Abstract Neuromyelitis optica (NMO) was long considered a clinical variant of multiple sclerosis (MS). However, the discovery of a novel and pathogenic anti-astrocytic serum autoantibody targeting aquaporin-4 (termed NMO-IgG or AQP4-Ab), the most abundant water channel protein in the central nervous system, led to the recognition of NMO as a distinct disease entity in its own right and generated strong and persisting interest in the condition. NMO is now studied as a prototypic autoimmune disorder, which differs from MS in terms of immunopathogenesis, clinicoradiological presentation, optimum treatment, and prognosis. While the history of classic MS has been extensively studied, relatively little is known about the history of NMO. In Part 1 of this series we focused on the late 19th century, when the term ‘neuromyelitis optica’ was first coined, traced the term’s origins and followed its meandering evolution throughout the 20th and into the 21st century. Here, in Part 2, we demonstrate that the peculiar concurrence of acute optic nerve and spinal cord affliction characteristic for NMO caught the attention of physicians much earlier than previously thought by re-presenting a number of very early cases of possible NMO that date back to the late 18th and early 19th century. In addition, we comprehensively discuss the pioneering concept of ‘spinal amaurosis’, which was introduced into the medical literature by ophthalmologists in the first half of the 19th century.

Neuromyelitis optica ((NMO), Devic's syndrome) is an immune-mediated inflammatory demyelinating disease characterized by transverse myelitis and optic neuritis. Determination of the level of antibodies to aquaporin 4 (NMO-IgG) is presently one of the key methods for the diagnosis and assessment of the activity of ONM, which allows this disease to be differentiated from multiple sclerosis and other demyelinating CNS lesions. ONM can occur not only as an independent disease, but also as a syndrome in different systemic diseases, such as: systemic lupus erythematosus (SLE), antineutrophilic cytoplasmic antibody-associated vasculitides, Sjögren's disease, etc. (up to 50–70%). In such situations, the clinician is always confronted with a question as whether the patient can have two rare autoimmune diseases or develop ONM as a systemic manifestation of rheumatic disease.The paper describes a clinical case of a young female patient with SLE concurrent with a CNS lesion, the manifestations of which corresponded to ONM. The patient had focal changes in the substance of the brain and spinal cord, as evidenced by magnetic resonance imaging, as well as high NMO-IgG titers. The development of ONM worsens SLE prognosis and requires active immunosuppressive therapy. The patient received three plasmapheresis sessions, ultrahigh-dose glucocorticoid and cyclophosphamide therapy, followed by replacement with azathioprine, causing a stable clinical and laboratory disease remission to be achieved.

Devic's Optic neuromyelitis (OND) is a very rare disease defined as a central nervous system (CNS) inflammation resulting in optic neuritis and/or myelitis. The discovery of a highly specific serum autoantibody biomarker for the diagnosis has triggered a great interest in conducting further research into this disease. The association of OND with Tuberculosis (TB) is even rarer and could be an entirely random conjunction. To our knowledge, we reported the first case of Neuromyelitis Optica associated with pulmonary TB in Tunisia.

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Background: Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs). Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correlation with cognitive performance. Methods: We acquired RS fMRI from 25 NMOSD patients and 30 healthy controls (HC). Patients underwent an extensive neuropsychological evaluation. Between-group RS FC comparisons and correlations with cognitive performance were assessed on the main cognitive RS networks identified by independent component analysis. Results: NMOSD patients showed higher RS FC versus HC in the precuneus of the default mode network (DMN) and right working memory network (WMN), as well as in several frontoparietal regions of the salience network (SN) and bilateral WMNs. Reduced frontal RS FC in NMOSD versus HC was detected in the left WMN. Increased RS FC in the DMN and right WMN was correlated with better cognitive performance, while decreased RS FC in the left WMN was associated with worse cognitive performance. Conclusion: Cognitive-network reorganization occurs in NMOSD. Clinico-imaging correlations suggest an adaptive role of increased RS FC. Conversely, reduced RS FC seems to be a maladaptive mechanism associated with a worse cognitive performance. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) was long considered a clinical variant of multiple sclerosis (MS). However, the discovery of a novel and pathogenic anti-astrocytic serum autoantibody targeting aquaporin-4 (termed NMO-IgG or AQP4-Ab), the most abundant water channel protein in the central nervous system, led to the recognition of NMO as a distinct disease entity in its own right and generated strong and persisting interest in the condition. NMO is now studied as a prototypic autoimmune disorder, which differs from MS in terms of immunopathogenesis, clinicoradiological presentation, optimum treatment, and prognosis. While the history of classic MS has been extensively studied, relatively little is known about the history of NMO. In Part 1 of this series we focused on the late 19th century, when the term 'neuromyelitis optica' was first coined, traced the term's origins and followed its meandering evolution throughout the 20th and into the 21st century. Here, in Part 2, we demonstrate that the peculiar concurrence of acute optic nerve and spinal cord affliction characteristic for NMO caught the attention of physicians much earlier than previously thought by re-presenting a number of very early cases of possible NMO that date back to the late 18th and early 19th century. In addition, we comprehensively discuss the pioneering concept of 'spinal amaurosis', which was introduced into the medical literature by ophthalmologists in the first half of the 19th century. [ABSTRACT FROM AUTHOR]

Introduction/background: Devic's syndrome is a rare autoimmune disorder that occurs when the body's immune system damages and mistakenly attacks the optic nerves and the spinal cord, leading to numerous neurological. Symptoms, such as inflammation, weakness, numbness, and vision problems. Rituximab has mainly been utilized as an immunosuppressive therapy for patients with Devic's syndrome. Although evidence has shown that rituximab is efficient and well tolerated in treating patients with Devic's syndrome, there is the possibility of rituximab exacerbating severe psoriasis and psoriatic arthritis flare., Case Presentation: In this paper, we describe a case of a 58-year-old female with Devic's syndrome, blindness, and neurological involvement who responded exceptionally well to rituximab. However, she developed a severe flare of psoriatic arthritis. After withdrawing from the use of rituximab, her psoriatic arthritis symptoms had resolved. However, she did have another episode of blindness, and rituximab was started once again. Although her vision improved, her psoriatic arthritis symptoms had reoccurred. The patient was switched to eculizumab and ustekinumab, which controlled both her psoriatic arthritis and Devic's syndrome., Conclusion: Very few reports have identified rituximab to induce a flare-up of psoriatic arthritis, raising uncertainty regarding its potential effects on psoriatic symptoms. The precise mechanism underlying the exacerbation of psoriatic arthritis by rituximab remains uncertain. This case report highlights that rituximab can worsen psoriasis and psoriatic arthritis, and that the complexities of Devic's syndrome may require medication adjustments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

An 87-year-old man presented with a 2-day history of painful bilateral visual loss. On examination, exophthalmos, lid edema, chemosis, and optic disc edema, on the left side only, were found. Visual acuity was 4/10 OD and no light perception OS. Magnetic resonance imaging (MRI) revealed bilateral optic neuritis and a diffuse and severe infiltration of the intra- and extraconal fat on the left. Laboratory testing was negative except for serum myelin oligodendrocyte glycoprotein (MOG) antibodies. This presentation adds a new variant to the MOG-associated disease spectrum. Testing for MOG antibodies should be considered in patients presenting with diffuse orbital inflammation and optic neuritis. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory diseases of the central nervous system that predominately affect women. Some of these patients are of childbearing age at NMOSD onset. This study reviews, on the one hand, the role NMOSD play in fertility, pregnancy complications and pregnancy outcome, and on the other, the effect of pregnancy on NMOSD disease course and treatment options available during pregnancy. Animal studies show lower fertility rates in NMOSD; however, investigations into fertility in NMOSD patients are lacking. Pregnancies in NMOSD patients are associated with increased disease activity and more severe disability postpartum. Some studies found higher risks of pregnancy complications, e.g., miscarriages and preeclampsia. Acute relapses during pregnancy can be treated with methylprednisolone and/or plasma exchange/immunoadsorption. A decision to either stop or continue immunosuppressive therapy with azathioprine or rituximab during pregnancy should be evaluated carefully and factor in the patient’s history of disease activity. To this end, involving neuroimmunological specialist centers in the treatment and care of pregnant NMOSD patients is recommended, particularly in specific situations like pregnancy. [ABSTRACT FROM AUTHOR]

Devic's disease or neuromyelitis optica (NMO) is an autoimmune, inflammatory and demyelinating pathology of the central nervous system that affects the optic nerve and the spinal cord. Diagnosis confirmed by imaging, magnetic resonance (MR) and the presence of the anti-aquaporin 4 antibody (anti-AQP4). We describe two cases of patients with mixed connective tissue disease (MCTD) and Devic's disease, who had anti-AQP4 positive and areas with neuroaxis MR abnormalities, showing this rare association. [ABSTRACT FROM AUTHOR]

Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient′s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

Background Few studies have evaluated patient perspectives on neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD). Objective Describe patient-reported clinical and treatment experience in NMOSD and compare disease characteristics of NMOSD with those of multiple sclerosis (MS). Methods This retrospective, observational study included 522 members with NMO or NMOSD (hereafter collectively referred to as NMOSD) from PatientsLikeMe (PLM), an online patient community. Data describing member demographics, symptoms, and treatments were collected, analysed descriptively, and compared with data from PLM members with MS. Results Fatigue, pain, and stiffness/spasticity were each rated as moderate to severe by more than half of NMOSD members, and 59% reported that their health limited the type of work or other activities they could perform all or most of the time. Overall, symptom severity and disability levels were comparable between NMOSD and MS members; however, NMOSD members were more likely than MS members to attribute disability to vision-related symptoms and were less likely to report moderate to severe cognitive and emotional symptoms, including brain fog, depressed or anxious mood, and emotional lability. Conclusion This analysis underscores the challenges of living with fatigue, pain, stiffness/spasticity, and visual difficulties, prevalent NMOSD symptoms among members of the PLM community. [ABSTRACT FROM AUTHOR]

Objective: To draw attention to ophthalmic neuromyelitis in the pediatric environment, even though its presentation is rare in this age group, we must take cognizance of its symptoms, diagnosis and treatment, because despite being a chronic disease and a poor prognosis, identified with rapid demonstration improvement of the acute and chronic clinic of the patient, improving their quality of life significantly. Method: Medical record review and literature review. Result: A 4-year-old patient with non-classical symptomatology of Optic Neuromyelitis evolved with significant clinical improvement after the diagnosis and acute treatment of the disease was started, but it should be continued with immunosuppressants in an indeterminate period of time. Conclusion: Optic neuromyelitis is an inflammatory disorder of the central nervous system characterized by severe demyelination of the optic nerves and spinal cord associated with serum IgG antibody aquaporin-4. Treatment with high doses of steroids and immunosuppressants has shown to improve the symptomatological and quality of life outcome of these patients. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus(SLE) which is generally related to central or peripheral nervous system abnormality is a complex and multisystem involving disease. Neurological involvement in SLE is known as bad prognostic criteria and considered as the major cause of mortality. 27 year old female patient was admitted to our clinic with the clinical pictures of recurrent cerebral venous thrombosis and myelitis accompanying to optic nerve involvement. While she has been evaluated for the etiology she was diagnosed as systemic lupus erythematosus because of establishment of the antibodies ANA ve Anti SS-A. Her response to endoxan and steroid treatment was good.In this paper we aimed to emphasize the significances of consideration of the diagnosis of SLE and immediate and appropriate immunosupressive treatment in patients applying in the clinical pictures of cerebral venous thrombosis and myelitis with optic nerve involvement eventhough they do not have the cardinal symptoms of the disease

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system that has been thought to be a severe subtype of multiple sclerosis for a long time. The discovery of aquaporin-4 (AQP4) antibody as a highly specific marker responsible for the pathogenesis of NMO, not only has made a revolutionary pace in establishing a serologic distinction between the two diseases, but it has also classified NMO as an antibody-mediated disorder. Similarly, myasthenia gravis (MG) is a well-known antibody-mediated disorder. In this report, we describe the case of a middle-aged female patient who experienced definite MG with an unclear clinical picture of chronic demyelinating disease that initially reflected the diagnosis of MS, but further imaging and paraclinical workup (e.g. positive AQP4 antibody test) revealed NMO. The coexistence of NMO and MG is previously described. However, this is the first case with NMO symptoms preceding the onset of MG. Of note, the development of MG occurred after a 2-year period of interferon β-1b (IFN β-1b) administration. This calls the question to mind of whether in our case MG is induced by the administration of interferon, instead of an original pathogenic link between MG and NMO. In other words, immunomodulatory treatments can slip the immunity towards T-helper II predominant pathways that can trigger MG. However, if we assume that such an explanation (i.e. increased susceptibility to autoantibody-mediated disorders) is true, our case can be considered the first case of NMO who developed MG following IFN β-1b treatment.

OBJECTIVES: Neuromyelitis optica (Devic’s syndrome) is an uncommon but severe form of demyelinating disease. This syndrome is characterized by acute or relapsing inflammatory demyelination restricted to the optic nerves and spinal cord. We present a patient with monophacic Devic’s syndrome according to Dean Wingerchuk and et al. diagnostic criteria (2006). MATERIAL-METHODS: A 26-year-old woman was admitted in our hospital with acute visual lost and tetraplegia. There were demyelination in MRI that involved cervicomeduller junction to thoracal 5 level and bilateral optic nerves. The cerebrospinal fluid included mild pleocytosis and raised protein level. Oligoclonal band was absent. In the blood examinations, immunological and enfectious markers was negative. RESULTS: The patient had been treated with corticosteroid, plasma exchange and intravenous immunglobuline respectively. CONCLUSION: The clinic was less recovery and stable for 6 years

Background: Neuromyelitis optica spectrum disease (NMOSD) is a severe autoimmune demyelinating disorder of the central nervous system that throughout epidemiological data, it has not been completely determined. The aim of this study was to assess characteristics of NMOSD patients in Isfahan as one of the most prevalent cities for multiple sclerosis in Iran. Materials and Methods: Forty-five patients diagnosed as neuromyelitis optica (NMO) disease through 5 years enrolled in this study. Demographics and characteristics of disease such as Expanded Disability Status Scale (EDSS) score, disease duration, clinical symptoms, laboratory data, and magnetic resonance imaging findings (including T1, T2, and flair protocols) were recorded. NMO-immunoglobulin G serology assay was done 0 in all of the patients by ELISA test. Results: Female to male ratio was 5.4:1. The mean age of disease onset was 29.8 ± 11.2 years. NMO antibody was positive in 24.4% of patients. The presenting symptoms were optic neuritis (55.5%), transverse myelitis (40%), and brainstem symptoms (4.5%). The interval between the first and second attack was 19.28 ± 31.27 months (range: 1 month to 17 years). The mean EDSS score of the patients was 2.8 ± 2.25. Frequency of long-extending cervical plaque was higher among men than women (85.7% vs. 57.9%). Conclusion: Based on this study, the mean age of NMOSD onset among Isfahan population was considerably lower than other studies, and there was higher frequency of long-extending cervical lesion among male patients which needs more consideration in further studies. [ABSTRACT FROM AUTHOR]

Rituximab (RTX) efficacy in NMO is suggested by several case series. No consensus exists on optimal dosing strategies. At present the treatment schedules more frequently used are 375 mg/m2/week iv for 4 weeks (RTX-A) and 1000 mg iv twice, 2 weeks apart (RTX-B). Aim of this study is to confirm RTX efficacy and safety in the treatment of NMO and to evaluate whether a most favourable dosage regimen exists. Data on RTX-treated NMO patients were collected from 13 Italian Hospitals. 73 patients (64 F), were enlisted. RTX-A was administered in 42/73 patients, RTX-B in 31/73. Median follow-up was 27 months (range 7-106). Mean relapse rate in the previous year before RTX start was 2.2 ± 1.3 for RTX-A and 2.3 ± 1.2 for RTX-B. ARR in the first year of treatment was 0.8 ± 0.9 for RTX-A and 0.2 ± 0.4 for RTX-B, in the second year of treatment was 0.9 ± 1.5 for RTX-A and 0.4 ± 0.8 for RTX-B patients ( p = 0.001 for the first year, ns (0.09) for the second year). RTX-B was more effective in delaying the occurrence of a relapse (HR 2.2 (95 % IC 1.08-4.53) p = 0.02). Adverse events were described in 19/73 patients (mainly urinary tract and respiratory infections, and infusion reactions). Two deaths were reported in severely disabled patients. Though with the limitations of an observational study, our data support RTX efficacy in NMO and suggest that high dose pulses might be more effective than a more fractioned dose. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD), previously known as Devic's syndrome, are a group of inflammatory disorders of the central nervous system (CNS) characterized by severe, immune-mediated demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord typically associated with a disease-specific serum NMO-IgG antibody that selectively binds aquaporin-4 (AQP4). The classic and best-defined features of NMOSD include acute attacks of bilateral or rapidly sequential optic neuritis (leading to visual loss) or transverse myelitis (often causing limb weakness and bladder dysfunction) or both with a typically relapsing course. The diagnosis of NMO/NMOSD requires a consistent history and examination with typical clinical presentations, findings on spinal cord neuroimaging with MRI, cerebrospinal fluid analysis along with determination of AQP4-IgG serum autoantibody status, and exclusion of other disorders. Two major advances in this field has been the development of diagnostic criteria and treatment recommendations. Consensus diagnostic criteria have been established and were recently revised and published in 2015, enhancing the ability to make a diagnosis and appropriately evaluate these disorders. Expert recommendations and uncontrolled trials form the basis of treatment guidelines. All patients with suspected NMOSD should be treated for acute attacks as soon as possible with high-dose intravenous methylprednisolone −1 gram daily for three to five consecutive days and in some cases, plasma exchange should be used. It is recommended that every patient with NMOSD be started on an immunosuppressive agent, such as, azathioprine, methotrexate, or mycophenolate and in some cases, rituximab, soon after the acute attack and usually be treated for about 5 years after the attack. These advances have helped improve the prognosis and outcome in these disorders. [ABSTRACT FROM AUTHOR]

Objective Neuromyelitis optica (NMO) is a rare antibody-mediated CNS disease characterised by disabling relapses leading to high morbidity and mortality. Understanding relapse activity and severity is important for treatment decisions and clinical trial design. We assessed (1) whether clinical and demographic factors associate with different relapse rates and (2) the relative impact of immunosuppressive treatments on relapse rates and on attack-related residual disability. Methods Clinical, demographic and treatment data were prospectively collected from 79 consecutive aquaporin 4 antibody positive patients seen in the nationally commissioned Oxford NMO service. The influence of clinical features on annualised relapse rates (using multiple regression) and the effect of immunosuppression on relapse-associated residual disability for transverse myelitis and optic neuritis attacks (using a mixed effect model) were analysed. Results The mean annualised relapse rate was 0.93. Relapse rates were significantly higher in Afro-Caribbeans, children and in those of shorter disease duration. Relapse rates reduced on treatment (from 0.87 to 0.42). Delay to first treatment did not influence eventual on-treatment relapse rate. Immunosuppressive treatment significantly reduced the residual disability from ON ( p <0.01), and TM ( p =0.029) attacks. Conclusions Relapse rates in NMO are influenced by multiple factors, including age, ethnicity and disease duration. Current immunosuppressive treatments reduce but do not abolish relapses, however, they appear to additionally lessen the chronic disabling effect of a relapse. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica or Devic’s syndrome is a rare autoimmune disorder which is characterized by inflammatory demyelination of the optic nerves and the spinal cord. Clinically, it causes visual loss in one or both eyes, and numbness or paralysis of the arms and legs. Although tonic spasm is the most frequent movement disorder occuring in MS, it has not been definetely described clinical entity for Devic’s syndrome. We hereby describe a case of Devic’s syndrome with tonic spasms treated with levetiracetam as a new approach and discussed the results of the treatment. A 52-year-old woman with Devic’s syndrome with the complaint of painful tonic spasms primarily affecting the abdomen was given levetiracetam therapy. Levetiracetam therapy resulted in a good response in our patient. Levetiracetam can be a new choice for the treatment of painful tonic spasm with Devic’s syndrome. However, more detailed studies are necessary to investigate efficacy of levetiracetam.

[english] Introduction: Neuromyelitis optica (NMO) is a severe demyelinating syndrome characterized by optic neuritis (ON) and acute myelitis. The NMO spectrum is actually recognized to typically evolve as a relapsing disorder that also includes patients with atypical unilateral ON and those with index events of ON and myelitis occurring weeks or even years apart (Jarius/Wildemann 2013). NMO was previously assumed to be a variant of multiple sclerosis (MS), but the discovery of aquaporin-4 antibodies in patients with neuromyelitis optica has led to this view being revised (Mandler 2006, Barnett/Sutton 2012, Wingerchuk et al. 2007). The cause of the condition is still unknown, but it has been shown that the antibodies bind selectively to a water channel expressed mainly on astrocytes at the blood-brain-barrier, which has an important role in the regulation of brain volume and ion homeostasis. However, there are some patients with NMO that are antibodies negative. The diagnosis is made on the basis of case history, clinical examination, magnetic resonance imaging (MRI) of the brain and spinal cord, analysis of cerebrospinal fluid (CSF), visual evoked potentials and a blood test with analysis of aquaporin-4 antibodies (Barnett/Sutton 2012, Wingerchuk et al. 2007, Thornton et al. 2011). This suggests that periodical revisions of established concepts and diagnostic criteria are necessary.Purpose: The authors describe an extremely rare case of neuromyelitis optica and the aim of this paper is to call attention for the cases of NMO whith NMO-IgG negative.Methods: The selected method is a case report.Results: To date the patient showed partial recovery of left eye acuity and improvement of muscle strength of upper and lower limbs and does not show recurrence of the disease.Conclusion: NMO has a distinct clinical, imaging and immunopathological features sufficient to distinguish it from MS. This distinction is essential, because the treatment and the prognosis is different.

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low ( p = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher ( p = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) is rare in Finland. To identify rare genetic variants contributing to NMO risk we performed whole exome, HLA and regulatory region sequencing in all ascertained cases during 2005–2013 (n = 5) in a Southern Finnish population of 1.6 million. There were no rare variant shared by all patients. Four missense variants were shared by two patients in C3ORF20 , PDZD2 , C5ORF47 and ZNF606 . Another PDZD2 variant was found in a third patient. In the non-coding sequence two predictably functional rare variants were shared by two patients. Our results do not support a homogeneous genetic etiology of NMO in Finland. [ABSTRACT FROM AUTHOR]

A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG). [ABSTRACT FROM AUTHOR]

Background: It is unclear why AQP4-IgG primarily causes central nervous system lesions by activating complement, but generally spares peripheral AQP4-expressing organs. Objectives: To determine whether peripheral AQP4-expressing cells are protected from complement-mediated damage by expressing complement regulators. Methods: Human tissue and cultured human cells were immunostained for aquaporin-4 (AQP4), CD46, CD55 and CD59. We also determined the vulnerability to AQP4-IgG and complement-mediated damage of astrocytes cultured alone or co-cultured with endothelial cells. Results: In normal brain, astrocyte end-feet express AQP4, but are devoid of CD46, CD55 and CD59. Immunoreactivity for CD46, CD55 and CD59 is not increased in or around neuromyelitis optica lesions. In kidney AQP4 is co-expressed with CD46 and CD55, in stomach AQP4 is co-expressed with CD46 and in skeletal muscle AQP4 is co-expressed with CD46. Astrocytes cultured alone co-express AQP4 and CD59 but, in astrocyte-endothelial co-cultures, AQP4 is found in cell processes devoid of CD59. Astrocytes co-cultured with endothelial cells are more vulnerable to AQP4-IgG and complement-mediated lysis than astrocytes cultured alone. Conclusions: Complement regulators protect peripheral organs, but not the central nervous system, from AQP4-IgG and complement-mediated damage. Our findings may explain why neuromyelitis optica primarily damages the central nervous system, but spares peripheral organs. [ABSTRACT FROM AUTHOR]

Background Treatment options for neuromyelitis optica (NMO) are currently based on small retrospective case series and open label studies, ranging from 10 to 103 patients. Objective To compare the efficacy and tolerability of azathioprine, cyclophosphamide, mycophenolate, and rituximab in patients with neuromyelitis optica. Methods This is a retrospective chart review and telephone follow-up study of 71 patients with NMO or NMO spectrum disorder, 54 of whom were treated with the study drugs. We compared adverse events, annualized relapse rates and expanded disability status scales before and after treatment. Results The median ARR decreased from 1.17 to 0.25 on rituximab (P < 0.01), 0.92 to 0.56 on azathioprine (P = 0.475), 1.06 to 0.39 on mycophenolate (P < 0.05) and 1.30 to 0.92 on cyclophosphamide (P = 0.746). When compared directly to azathioprine, rituximab significantly reduced relapse rates (P = 0.021). The median EDSS decreased from 7 to 5 on rituximab (P < 0.01) and 7 to 6 on azathioprine (P < 0.01), and did not change significantly on mycophenolate (4 to 5; P = 0.463) or cyclophosphamide (6.5 to 6.5; P = 0.881). Twenty-five percent of patients noted adverse events on rituximab, 36% on azathioprine, 36% on mycophenolate, and 80% on cyclophosphamide. Conclusion Rituximab significantly reduces relapse rates and improves disability while maintaining comparable tolerability to other immunosuppressive treatments for NMO. [ABSTRACT FROM AUTHOR]

• Long-term safety of satralizumab in NMOSD was evaluated in SAkuraSky & SAkuraStar. • The safety profile of satralizumab was comparable between the DB and OST periods. • Rates of adverse events in the OST were comparable with the DB periods. • Overall, rates of infections and serious infections did not increase over time. • The favorable safety profile of satralizumab was sustained with long-term treatment. This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD). SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods. In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1–7.0) in SAkuraSky and 4.0 years (range 0.1–6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies. The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed. ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar). [ABSTRACT FROM AUTHOR]

The extreme variability of clinical and MRI findings in the suspicion of Devic's disease always requires the detection of specific antibodies (AQP4).MRI scans were performed with a high-field MRI scanner (1.5T General Electric Signa Horizon): the MRI protocol of the brain employed axial DP, T2, T1, FLAIR and DWI weighted images (wi) and coronal T2-wi. After intravenous administration of contrast medium axial and sagittal T1-weighted images of the brain were repeated. The spine protocol employed after contrast medium included sagittal T2-wi, T2-wi with fat suppression and T1-wi.In May 2004, a 64-year-old healthy Caucasian woman began to suffer loss of motor and thermal sensitivity in the left lower limb. MRI showed non-specific areas of abnormal signal intensity on the deep left frontal and right frontoparietal white matter with no pathological enhancement after contrast medium and a small intramedullary area of altered signal at metameric level C2-C4 with a diagnosis of post-viral transverse myelitis. The patient had two similar episodes years later so the neurologist decided to search for circulating IgG AQP4 with the definitive diagnosis of neuromyelitis optica.In this case, compared to a clinical presentation of atypical deficit neurological involvement, the neuroradiological results of a progressive diffuse involvement of the white matter were atypical. [ABSTRACT FROM AUTHOR]

While the history of classical multiple sclerosis has been extensively studied, only little is known about the early history of neuromyelitis optica (Devic's syndrome). Here we discuss a forgotten report by Edward Octavius Hocken (1820-1845) published in The Lancet in 1841. Hocken's report is important from a historic point of view for two reasons. Firstly, apart from a French language report by Antoine Portal, no earlier case of spinal cord inflammation and amaurosis is known. Secondly and much more importantly, Hocken, who upon his untimely death at the age of just 25 years was honoured by his contemporaries as a 'precocious talent' of 'very early reputation', in that article propagated the novel concept of 'spinal amaurosis', i.e. the concept of acute amaurosis and spinal cord disease being pathogenetically connected. Hocken's ideas predate Devic and Gault's seminal works on 'neuromyelitis optica' by more than 50 years. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the effectiveness and adverse drug reactions of beta-interferon (IFN-β) treatment in Thai patients with demyelinating diseases. It says that the data of Thai patients with MS, neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSDs) who participated the MS Clinic were retrospectively reviewed. Results show that IFN-β treatment was effective to reduce both annualized relapse rates (ARR) and disability progression in MS patients.

The discovery of a novel serum autoantibody (termed NMO-IgG or AQP4-Ab) in a subset of patients in 2004 has revived interest in neuromyelitis optica (NMO). While the history of classical multiple sclerosis has been extensively studied, only little is known about the history of NMO. In the present article, we provide a comprehensive review of the early history of this rare but intriguing syndrome. We trace the origins of the concept of NMO in the 19th century medical literature and follow its evolution throughout the 20th and into the 21st century. Finally, we discuss recent proposals to revise the concept of NMO and explain why there is indeed a need for a more systematic and descriptive nomenclature. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system with exacerbations involving the optic nerves, spinal cord, or both. This study explores the utility of maintenance plasma exchange (mTPE) as a therapy in patients with relapsing, corticosteroid-refractory, NMO. This retrospective case series presents data on patients who were diagnosed with NMO using currently accepted criteria. These patients were refractory to high-dose corticosteroids and received mTPE. Seven patients met the criteria for NMO diagnosis and all were positive for antibodies against aquaporin-4. Over a mean of 7.1 years (range, 2-16), these patients received between 21 and 154 TPE treatments (mean, 76). Although treated with mTPE, five out of the seven patients improved by more than one point on the Expanded Disability Status Scale. Interruption in mTPE in five patients resulted in clinical worsening. When mTPE was restarted in three out of the five patients who experienced a cessation of mTPE, these patients either stabilized or improved. The two patients who did not restart the mTPE protocol died. Patients treated with mTPE also experienced a reduction in the number of NMO exacerbations. Finally, stabilization of the retinal nerve fiber layer thickness was observed while on mTPE. In this preliminary study, mTPE appeared safe and may bring about improvement in disability and sustained stabilization of the clinical course in patients with steroid-refractory relapsing forms of NMO. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]