The significantly increased relapse rate and numerous cases of NMOSD onset after pregnancy suggest that delivery adversely affects the course of NMOSD. Prospective studies are needed to confirm our findings.

Objective:To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). Methods:The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively.Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. Conclusions:Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed. Neurology ® 2012;78:1601-1607 GLOSSARY Ab ϭ antibodies; AChR-Ab ϭ acetylcholine receptor antibody; AChR-MG ϭ acetylcholine receptor antibody-mediated myasthenia gravis; AQP4-Ab ϭ aquaporin-4 antibody; AQP4-NMOSD ϭ aquaporin-4 antibody-mediated neuromyelitis optica spectrum disorder; IgG ϭ immunoglobulin G; IS ϭ immunosuppressive; LETM ϭ longitudinally extensive transverse myelitis; MG ϭ myasthenia gravis; NMO ϭ neuromyelitis optica; NMOSD ϭ neuromyelitis optica spectrum disorder; OCB ϭ oligoclonal bands; ON ϭ optic neuritis; SLE ϭ systemic lupus erythematosus; VGKC ϭ voltage-gated potassium channel.Neuromyelitis optica (NMO) is a recurrent inflammatory and demyelinating CNS disorder that affects predominantly the optic nerve and spinal cord.

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and $1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1. , respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor.Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing. Neurology ® 2016;86:79-87 GLOSSARY AQP4 5 aquaporin-4; ARR 5 annualized relapse rate; CI 5 confidence interval; IgG 5 immunoglobulin G; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; ON 5 optic neuritis; OR 5 odds ratio.Neuromyelitis optica spectrum disorder (NMOSD) is a severe recurrent antibody-mediated inflammatory disorder of the CNS, mainly characterized by optic neuritis (ON) and longitudinally extensive transverse myelitis, 1 but also affecting other areas in the CNS (e.g., brainstem and hypothalamus). The presence of immunoglobulin G (IgG) that binds to aquaporin-4 (AQP4), 2,3 known to be key in the pathogenic process of this disorder, distinguishes NMOSD from other CNS inflammatory disorders.1 NMOSD is up to 8 times more prevalent in women, 4 many of whom have active disease during childbearing years. [5][6][7] Recently, experimental and clinical reports have demonstrated the presence of AQP4 in human and animal placenta, and have linked AQP4-mediated placental inflammation to fetal death. [8][9][10] It is clear that the annualized relapse rate (ARR) of NMOSD is significantly increased in the 0-to 3-month postpartum period, 11-13 but there is a lack of information on the influence of NMOSD on the course of pregnancy.We investigated the effect of NMOSD on miscarriage and preeclampsia rates using multivariate logistic regre...

Background Primary Sjögren Syndrome (pSS) is an autoimmune disorder characterized by a chronic lymphocytic and plasmacellular infiltration of exocrine glands and extraglandular features including both peripheral nervous system and central nervous system involvement. However, the diagnosis of pSS with neurologic involvement is sometimes difficult and specially central nervous system manifestations have been rarely described. Objectives To perform an observational retrospective cross-sectional case–control study to evaluate prevalence, clinical patterns and outcomes of neurological involvement in a cohort of pSS patients followed up in a single centre. Methods A total of 91 pSS patients (88 females, 3 male) with a mean age 47,6 years, diagnosed according to the 2002 criteria proposed by the American–European Consensus Group, were evaluated for neurological involvement after exclusion of secondary causes. Demographic, clinical, immunological data were compared between patients with and without neurological involvement. Neuroimaging data and peripheral nerve conduction study with quantitative sensory testing were also analysed. Results Neurological involvement was detected in 24 (26, 4%) patients (all females). The mean age at disease onset and neurological onset were 41,8 and 47,9 years, respectively. Neurologic involvement frequently preceded the diagnosis of pSS in 10 (42%) patients. Fifty (n=12) patients had peripheral system involvement (PNS), 46% (n=11) patients had CNS disorders and 4% (n=1) patients had both PNS and CNS involvement. In patients with PNS involvement, pure sensory neuropathy (small fiber neuropathy confirmed by quantitative sensory testing and sural neuropathy) occurred most frequently (n=5), followed by cranial nerve involvement affecting trigeminal, facial, or trochlear nerves (n=4). Multiple mononeuropathy (n=1), sensorimotor polyneuropathy (n=1), autonomic neuropathy (n=1) and myasthenia gravis (n=1), were also observed. In patients with CNS disorders, headache with MRI abnormalities compatible with inflammatory disease (n=3) occurred most frequently. Spinal cord involvement (n=2), seizures (n=2), motor and sensory deficit (n=2), movement disorders (n=2), aseptic meningitis (n=1) were the other manifestations observed. Cognitive dysfunction was observed in 3 of these patients. Headache was reported in nine patients other than the three mentioned above. The Raynaud’s phenomenon was more common in these patients (p=0, 04).The frequency of constitutional symptoms (such as fever and fatigue) and lung involvement was significantly higher (p<0,05) in pSS with neurological involvement than in pSS without neurological involvement and the articular symptoms were significantly less frequent (p<0,05) in pSS with neurological involvement. There was no statisticalsignificance in other factors parameters between the two groups. The neurologic outcome was good in 58% (n=14) patients. Conclusions Our results showed that neurological complications were present in 26, 4% of all patients with pSS. In other...

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1∗15 (OR = 2.17) and HLA-DRB1∗03 (OR = 1.81) alleles with MS, HLA-DRB1∗03 with SLE (OR = 2.49), HLA-DRB1∗01 (OR = 1.79) and HLA-DRB1∗04 (OR = 2.81) with RA, HLA-DRB1∗07 with Ps + PsA (OR = 1.79), HLA-DRB1∗01 (OR = 2.28) and HLA-DRB1∗08 (OR = 3.01) with SSc, and HLA-DRB1∗03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1∗13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1∗13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1∗13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1∗13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.