Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren's syndrome: a systematic review of individual patient data.

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.

Prasad CB ，Kopp CR ，Naidu G ，Sharma V ，Misra DP ，Agarwal V ，Sharma A ... -  《-》

MOG-IgG is rare in AQP4-IgG seronegative NMO phenotype in Brazil.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease most frequently characterized by a neuromyelitis optica (NMO) phenotype, comprising both simultaneous or sequential optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Symptoms of brainstem, diencephalic and cerebral involvement may also occur. While most NMOSD patients test positive for serum aquaporin-4 (AQP4) antibodies, some seronegative patients test positive for oligodendrocyte glycoprotein-IgG (MOG-IgG). Early identification of seropositive MOG-IgG seropositive patients among those with AQP4-IgG seronegative NMO phenotype may impact disease treatment and outcome. To determine the frequency of MOG-IgG in patients with AQP4-IgG seronegative NMO phenotype at a single reference center in Brazil and to analyze factors influencing their identification. A retrospective review of medical records of patients who presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4 antibodies was conducted in a single center in Brazil. Patients were tested for serum AQP4 antibodies and retrospectively for MOG-IgG using cell-based assays. In addition to demographic, clinical, and imaging data, information on time intervals between disease onset and MOG-IgG testing, as well as the most recent relapse to MOG-IgG testing, was collected. Out of 118 patients tested for MOG-IgG, 28 (23.7 %) presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4-IgG. Three (10.7 %) of them tested positive for MOG-IgG serostatus. All were females and had a median age of 26 (11-34) years at disease presentation. The median disease duration was 11.2 yrs. Two patients had a relapsing course. Optic neuritis, myelitis, and brainstem syndrome were the most common presenting symptoms. The median annualized relapse rate was 0.25, and the median EDSS score at the most recent visit was 2.0 (1.5-5.0). There were 25 double seronegative patients, 21 (84 %) of whom were female and non-Caucasian; the median age at disease onset was 30 years (2-60), and the median EDSS at most recent visit was 4.0 (0 - 8.0). The study identified MOG-IgG antibodies in 10.7 % of a cohort with AQP4-IgG seronegative NMO phenotype. Immunosuppressive treatment and long intervals between disease attacks and antibody testing may have impacted the frequency of MOG-IgG seropositivity. As MOG-IgG testing is crucial for diagnosing MOGAD in AQP4-IgG seronegative NMO phenotype, we highlight the need for broader and timely testing to improve diagnostic accuracy in resource-limited settings.

Pedrosa DA ，Fernandes GBP ，Talim N ，Welter EAR ，Marques AG ，Christo PP ，Ponsá T ，Araújo C ，Queiroz AC ，Rocha ACH ，Fialho G ，Moreira M ，Marques RF ，Lana-Peixoto MA ... -  《-》

The real-world impact of biologics for NMOSD: A retrospective single-center study compared with natural course and conventional treatments in Japanese.

Neuromyelitis optica spectrum disorder (NMOSD), a central nervous system inflammatory disease associated with aquaporin-4 immunoglobulin G (AQP4-IgG), is conventionally treated with oral steroids and immunosuppressants (IS) in Japan. Several biologics which show great efficacy in the clinical trials have been developed recently. However, studies on their efficacy, especially those comparing them with conventional treatments in real-world situations are lacking. Here, we conducted a single-center retrospective cohort study in Japan comparing the efficacy of biologics, over conventional drugs, in treating AQP4-IgG-positive NMOSD. We extracted the medical history of patients with AQP4-IgG-positive NMOSD who visited the Tohoku University Hospital between 2000 and 2023, from the hospital patient database. All patients were diagnosed according to the international consensus diagnostic criteria for NMOSD 2015. We then classified the disease duration of each patient into four periods based on their prescription history as: no-treatment, prednisolone monotherapy (PSL-mono), immunosuppressants (IS) treatment, and biologics (Bio) treatment. Subsequently, the efficacy of Bio treatment, over the conventional treatment, in alleviating AQP4-IgG-positive NMOSD was estimated. We used univariate Poisson regression analysis to compare the annualized relapse rate (ARR), log-rank test for the first attack, and the hazard ratios (HR)-calculated using multivariate Andersen-Gill model for recurrent attacks-of the Bio and conventional treatment period groups. The safety of each treatment period group was assessed by comparing infection and mortality rates. A total of 109 patients (92 % females) met the eligibility criteria of the study. We could extract a total of 1,283 patient years with 289 NMOSD attacks from their medical history data. The mean ARR of no-treatment group was 0.60. Most of the Bio group initially received combined treatments with PSL or IS. The mean ARR of the Bio group was 0.01 [95 % confidence interval (CI): 0.002 to 0.08], which was significantly lower than the PSL-mono group (0.16, 95 % CI: 0.13 to 0.19, p = 0.03) and the IS group (0.17, 95 % CI: 0.13 to 0.22, p = 0.02). In the survival analysis, the Bio group showed a significantly prolonged attack-free period than the other groups, suggesting its potential in reducing 79 % of relapses in the no-treatment group, 33 % in the PSL-mono group, and 31 % in the IS group during the two years. The multivariate analysis using Andersen-Gill model showed that the Bio group had significantly lower HR (log HR -2.75, 95 % CI: -4.71 to -0.8, p = 0.006), relative to the PSL-mono group. Importantly, the patients needed significantly lower PSL (median 5 mg/day) during the Bio group treatment period than in the PSL-mono group treatment period (median 10 mg/day). Further, the concomitant use of IS could be stopped safely in all patients who were on Bio treatment. All treatment period groups showed similar safety profiles. In patients with AQP4-IgG-positive NMOSD, biologics demonstrated more efficacy than conventional PSL and/or IS treatment, without increasing infection and mortality rates.

Yamazaki N ，Misu T ，Matsumoto Y ，Takai Y ，Namatame C ，Ono H ，Kaneko K ，Nishiyama S ，Kuroda H ，Takahashi T ，Nakashima I ，Fujihara K ，Aoki M ... -  《-》

Quantitative Contribution of Clinical Attacks to Residual Disability in Patients With AQP4-Antibody Neuromyelitis Optica Spectrum Disorder.

Chen B ，Francis A ，Cooper SA ，Dobson R ，Hacohen Y ，Halfpenny C ，Hemingway C ，Hobart JC ，O'Sullivan E ，Rashid W ，Martin RJ ，Williams V ，Ramdas S ，Geraldes R ，Leite MIS ，Palace J ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》