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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]

Background: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren’s syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation.Objectives: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms.Methods: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4.Results: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69).Conclusion: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) is an inflammatory/demyelinating disorder predominantly affecting the optic nerves and spinal cord. Recent findings showed an underlying humoral abnormality in NMO, characterized by a serum antibody against aquaporin-4 (Aqp-4-Ab). In this study, we evaluated the Aqp-4-Ab status among Turkish patients with NMO to determine the clinical and prognostic relevance. Serum samples from 35 consecutive patients with NMO followed at a single center and diagnosed according to the 2006 revised criteria, were evaluated for Aqp-4-Ab. All samples were obtained during a relapse prior to any immunosuppressive treatment. Aqp-4-Ab was positive in 21/35 (60%) patients. Among these cases, 11 had an EDSS of 6.0 or more, whereas only two patients in the seronegative group had such severe disability ( p < 0.05). Overall, seropositive cases had a mean EDSS score of 5.1 ± 2.2 compared with 3.5 ± 1.7 in seronegative cases ( p < 0.01). There were trends towards female predominance in seropositive cases and a monophasic course predominance in seronegative cases. Disease duration, age at onset, number of attacks and time to definite NMO did not differ between groups. Our findings in this single-center cohort suggest that the presence of Aqp-4-Ab might have a prognostic significance indicating a more severe disease course. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate anti-aquaporin-4 (AQP-4) water channel antibodies, affecting cerebrospinal fluid (CSF) secretion and absorption, in idiopathic intracranial hypertension (IIH) patients.Methods: Patients fulfilling the modified Dandy’s diagnostic criteria for IIH were included and their clinical features and CSF findings were reviewed. Their serum samples and control groups were investigated by immunofluorescence and a cell-based assay for anti-AQP-4 antibodies and by immunohistochemistry for IgG binding patterns.Results: Twenty-nine patients diagnosed with IIH were investigated. We could not detect any anti-AQP-4 antibodies in our series. However, we identified different serum IgG binding patterns in 11 IIH patients.Conclusion: There is only one report investigating the anti-AQP4 antibodies in IIH. Our study with a larger sample confirmed the results of this report and indicated that AQP4 antibodies did not have a primary role in IIH pathogenesis, but provided some support for the contribution of inflammatory mechanisms in IIH. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Antibodies to aquaporin-4 (AQP4-Ab) are found in 60–80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord. Objective: To assess the frequency of AQP4-Ab in patients with optic neuritis (ON), and to investigate the prognostic implications of AQP4-Ab seropositivity in such patients. Patients and methods: AQP4-Ab serum levels were determined in 224 individuals from Austria, Denmark, France, Germany, Italy, and Turkey using a newly developed fluorescence immunoprecipitation assay employing recombinant human AQP4. Results: AQP4-Ab were detectable in 8/139 (5.8%) patients with acute monosymptomatic optic neuritis (AMON) and in 10/17 (58.8%) patients with established NMO and a last relapse of acute ON (NMO/ON), but not in 32 patients with multiple sclerosis or in 36 healthy controls. At last examination, 4/8 (50%) seropositive AMON patients had met the criteria for NMO but 0/128 seronegative AMON patients. Disease severity differed significantly between seropositive and seronegative AMON. Complete bilateral or unilateral blindness occurred in six AQP4-Ab positive patients, but only in one AQP4-Ab negative patient. AQP4-Ab levels did not vary between seropositive AMON and NMO/ON and did not correlate with disease severity. Female gender, a relapsing course, and concomitant autoimmunity were associated with AQP4-Ab seropositive status and risk of developing NMO. Conclusion: AQP4-Ab is relatively rare among patients with AMON, but if present it predicts a high rate of conversion to NMO within one year. [ABSTRACT FROM AUTHOR]

Abstract: Background: Seronegative NMO is highly prevalent in non-Western countries implying the presence of as yet unknown antibodies (Ab). We investigated potential novel Ab in aquaporin-4 Ab (AQP-4-Ab) positive and negative NMO patients. Methods: Sera of 20 NMO patients were examined for AQP-4, myelin oligodendrocyte glycoprotein (MOG) and glycine receptor (GlyR) Ab by cell-based assays. Results: AQP-4-Ab was identified in 10 NMO patients, MOG-Ab was detected only in one AQP-4-Ab positive patient and GlyR-Ab was detected in two AQP-4-Ab negative patients. GlyR-Ab positive patients displayed simultaneous optic neuritis and transverse myelitis attacks and relatively low disability, whereas MOG and AQP-4-Ab double positive patient had a significantly increased disability. Conclusion: This study showed for the first time the presence of GlyR-Ab in Turkish NMO patients. In contrast with previous reports, MOG Ab does not appear to be a distinctive marker for Turkish AQP-4-Ab negative NMO patients. [Copyright &y& Elsevier]