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      A Systematic Review of Peripheral and Central Nervous System Involvement of Rheumatoid Arthritis, Systemic Lupus Erythematosus, Primary Sjögren's Syndrome, and Associated Immunological Profiles

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          Abstract

          Both central (CNS) and peripheral nervous system (PNS) complications are frequent and varied in connective tissue diseases. A systematic review was conducted between 1989 and 2014 in the databases Medline, Scopus, and Cochrane Library using the search terms, peripheral and central nervous complications and immunological profiles, to identify studies in specific connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. A total of 675 references were identified, of which 118 were selected for detailed analysis and 22 were included in the final review with a total of 2338 participants. Our search focused only on studies upon connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome associated with seroimmunological data. The reported prevalence of CNS involvement ranges from 9 to 92% across the reported studies. However, the association between CNS and PNS manifestations and seroimmunological profiles remains controversial. Τo date, no laboratory test has been shown as pathognomonic neither for CNS nor for PNS involvement.

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          The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes.

          To develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE). An international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests. Case definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed. The American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.
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            Neuromyelitis optica and non organ-specific autoimmunity.

            Neuromyelitis optica (NMO) is often associated with other clinical or serological markers of non-organ-specific autoimmunity. To evaluate the relationship between NMO spectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sjögren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion. Retrospective blinded serological survey. Mayo Clinic College of Medicine, Rochester, and Centre Hospitalier Régional Universitaire de Lille. Group 1 included 153 US patients with NMOSDs (78 with NMO and 75 with longitudinally extensive transverse myelitis) and 33 control subjects with SS/SLE. Group 2 included 30 French patients with SS/SLE, 14 with NMOSDs (6 with NMO, 6 with longitudinally extensive transverse myelitis, and 2 with recurrent optic neuritis), 16 without NMOSDs, and 4 with NMO without SS/SLE. For group 1, NMO-IgG was detected in 66.7%, antinuclear antibodies in 43.8%, and Sjögren syndrome A (SSA) antibodies in 15.7% of patients with NMO and longitudinally extensive transverse myelitis. Five NMO-IgG-seropositive patients with NMOSDs had coexisting SLE, SS, or both. Antinuclear antibodies and SSA antibodies were more frequent in NMO-IgG-seropositive patients than in NMO-IgG-seronegative patients (P= .001). For group 2, NMO-IgG was detected in 5 of 14 patients (35.7%) with NMOSDs and SS/SLE and in 2 of 4 patients (50.0%) with NMO without SS/SLE (P= .59). We detected NMO-IgG only in patients with NMOSDs and not in 49 controls with SS/SLE but without optic neuritis or myelitis from the 2 cohorts (P= .01). Neuromyelitis optica spectrum disorders with seropositive findings for NMO-IgG occurring with SS/SLE or non-organ-specific autoantibodies is an indication of coexisting NMO rather than a vasculopathic or other complication of SS/SLE.
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              Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients.

              Neurologic involvement occurs in approximately 20% of patients with primary Sjögren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS. Copyright 2004 Lippincott Williams & Wilkins
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                Author and article information

                Journal
                Int J Chronic Dis
                Int J Chronic Dis
                IJCD
                International Journal of Chronic Diseases
                Hindawi Publishing Corporation
                2356-6981
                2314-5749
                2015
                25 November 2015
                : 2015
                : 910352
                Affiliations
                1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece
                Author notes
                *Anastasia Bougea: annita139@ 123456yahoo.gr

                Academic Editor: Gabriel J. Tobón

                Article
                10.1155/2015/910352
                4673346
                ac0d86c2-b10e-4910-9786-2e9539cca21d
                Copyright © 2015 Anastasia Bougea et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 June 2015
                : 21 October 2015
                : 29 October 2015
                Categories
                Review Article

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