Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

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 Sjogren'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

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production

Behcet's Disease

Neurologic involvement in Beh double dagger et's disease (BD) is seen in about 5% to 10% of all BD patients. Clinical and imaging data suggest that neurologic involvement in BD presents in two major forms. The first, central nervous system (CNS) parenchymal involvement with a predilection to brainstem-diencephalic regions, is seen in the majority of patients with neuro-BD (NBD). The second form is cerebral venous sinus thrombosis (CVST), which is seen in up to 20% of cases. BD is very rare in children, but when it does occur, the patterns are reversed: most children with NBD present with CVST. Other syndromes such as spinal cord involvement, arterial CNS involvement, optic neuritis, aseptic meningitis, and peripheral neuropathies may be seen, but are rare. Venous sinus thrombosis in BD has a significantly better neurologic prognosis than parenchymal CNS involvement. There is no Class I evidence regarding treatment of parenchymal CNS involvement or CVST in BD. Current treatment applications are based largely on expert opinion; none are evidence-based. Acute parenchymal CNS involvement should be treated with high-dose intravenous methylprednisolone (IVMP), 1 g per day, for 5 to 10 days, followed by either a prolonged oral taper or intermittent IVMP pulses with a low oral dose between the pulses, over 6 months. After treatment of the acute attack, long-term maintenance with immunosuppressive agents should be considered in patients with parenchymal CNS involvement, as this form may follow a relapsing or secondary progressive course and may result in significant physical and cognitive deficits leading to severe neurologic disability. A number of randomized controlled studies have tested treatments for systemic manifestations of BD. Colchicine was found to be effective for mucocutaneous symptoms, thalidomide was found to be effective in erythema nodosum-like skin lesions, azathioprine and cyclosporine were shown to be effective in BD uveitis, and cyclophosphamide was shown to be effective for major vascular involvement. More recently, interferon alfa and anti-TNF agents were also shown to be effective in BD uveitis. Although randomized controlled studies have not been performed in NBD, the most widely used long-term therapeutic agent is azathioprine. Recent observations suggest that the addition and long-term use of azathioprine in NBD could be associated with a more favorable course. A growing number of case reports in recent years suggest that anti-TNF agents may be an effective alternative in NBD, but current experience with these agents is limited. CVST in BD is also treated with steroids. The addition to glucocorticoids of anticoagulation, including short-term fractionated heparin, is controversial, as these patients have a higher probability of harboring pulmonary or other aneurysms, which may be associated with an increased risk of bleeding. Long-term oral anticoagulation is unnecessary. Interestingly, the prognosis of CVST due to BD seems to be much more favorable than the prognosis of CVST due to other causes, with much less tendency for venous infarcts and seizures. However, as recurrences may occur, long-term treatment with azathioprine is recommended

Autoimmune Diseases Associated with Epilepsy

Involvement of the central nervous system (CNS) during the course of systemic autoimmune diseases is not rare. Connective tissue disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Behcet's disease; granulomatous disorders such as sarcoidosis, granulomatous angitis; autoimmune bowel disorders such as inflammatory bowel and Celiac diseases; thyroid disorders such as Hashimoto and Graves diseases are best examples of the autoimmune diseases in this category. Epileptic seizures may be observed in patients with and without any obvious lesions in these disorders. In this review, we will summarize patterns of neurological involvement in systemic autoimmune diseases associated with epilepsy

Behcet's Disease and Nervous System Involvement

Management of neuro-Behcet's disease can be divided into two stages: treatment of acute attacks and prevention of relapses. Treatment of acute attacks is accomplished by high-dose intravenous corticosteroids followed by maintenance treatment with oral steroids for 6-12 months depending on the type and severity of the neurological involvement. Relapses can be prevented by using immunosuppressants. Oral immunosuppressants such as azathioprine and mycophenolate are the most widely utilized agents for this purpose. Patients who are refractory or who cannot tolerate these medications can be managed by cyclophosphamide, interferon alpha, or anti-TNF-alpha monoclonal antibodies such as infliximab, etanercept, and adalimumab. Recent reports showed that newer agents such as tocilizumab, canakinumab, and anakinra, which exert their biological activity through IL-1 and IL-6 pathways, are also promising treatment alternatives for progressive or relapsing patients

Autoimmune Diseases Associated with Epilepsy

WOS: 000370637700009Involvement of the central nervous system (CNS) during the course of systemic autoimmune diseases is not rare. Connective tissue disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Behcet's disease; granulomatous disorders such as sarcoidosis, granulomatous angitis; autoimmune bowel disorders such as inflammatory bowel and Celiac diseases; thyroid disorders such as Hashimoto and Graves diseases are best examples of the autoimmune diseases in this category. Epileptic seizures may be observed in patients with and without any obvious lesions in these disorders. In this review, we will summarize patterns of neurological involvement in systemic autoimmune diseases associated with epilepsy

Neuromyelitisoptica spectrum disorders: the evaluation of 66 patients followed by Istanbul Bilim University, Department of Neurology

Conference of the Pan-Asian-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (PACTRIMS) -- NOV 13-15, 2019 -- Singapore, SINGAPOREWOS: 000556862300090[No abstract available]Pan Asian Comm Treatment & Res Multiple Sclerosi

Multiple sclerosis-like clinical and magnetic resonance imaging findings in human immunodeficiency virus positive-case

Objective: Neurologic complications may develop during the course of acquired immunodeficiency syndrome. Differential diagnosis of the chronic progressive myelopathy related to human immunodeficiency virus must include multiple sclerosis

Cerebral Venous Thrombosis in the Mediterranean Area in Adults. Role of Behcet's Disease as an Underlying Cause

Cerebral venous and dural sinus thrombosis (CVT) is a rare condition with a wide spectrum of clinical presentations. The epidemiology of the disease has evolved considerably during the recent decades with increasing oral contraceptive use in young and middle-aged women. CVT has various causes including genetic and acquired prothrombotic disorders and it usually has a favorable outcome with a low rate of thrombotic recurrence and mortality. Geographical and ethnic variations between populations may result in different distribution of CVT etiologies leading to different pathophysiological mechanisms and clinical presentations. In CVT series reported mostly from the Americas and the western European countries Behcet's disease (BD) is not reported as a common cause of CVT. However it can be discerned as a frequent cause of CVT in BD series. Due to the high prevalence of BD in the southeast Mediterranean region BD is a frequent cause of CVT in the area. Discerning characteristics of patients with BD and CVT have been reported previously and these might be helpful in guiding diagnosis and treatment of CVT especially in this part of the world