neuro-Behcet's Disease Research Articles

B Cells Specific CpG Induces High IL-10 and IL-6 Expression In Vitro in Neuro-Behçet's Disease.

Remitting-RelapsingMultiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuroinflammatory disorders leading to neurological damage. Herein, we investigated in these patients the IL-10-producing cells during the early stages of these disorders. Cellular and molecular investigations were carried out on treatment naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that CSF-B cells from NBD patients, but not RRMS, are the major source of intrathecal IL-10 as compared to T-CD4 cells. Moreover, we showed a lower expression of TGF-β and IL35, in the CSF cells of NBD patients as compared to the control group. Specific in vitro CpG stimulation of peripheral blood B cells from NBD patients resulted in a concomitant early mRNA expression of IL6 and IL10 but was limited to IL10 for RRMS patients. Furthermore, mRNA expression of IL-6 and IL-10 receptors was assessed and intriguingly IL6ST receptor subunit was significantly lower in NBD CSF, but not RRMS while IL10RB was increased in both. Deciphering the role of increased IL-10-producing B cells and IL10RB despite relapsing disease as well as the discordant expression of IL6 and IL6ST may pave the way for a better understanding of the pathophysiology of these neuro-inflammatory disorders.

Cerebrovascular changes in neuro-Behcet's disease and neuropsychiatric lupus by transcranial Doppler ultrasonography and magnetic resonance imaging

IntroductionTranscranial Doppler ultrasonography (TCD) is a technique that allows measurement of blood flow from the basal intracerebral vessels. It is relatively inexpensive, non-invasive, can be performed at the bedside, and allows monitoring in acute emergency settings and for prolonged periods with a high temporal resolution, making it ideal for studying the haemodynamics within the intracranial arteries in neuro-Behcet's disease (NBD) and neuro-psychiatric lupus (NPSLE). Our aim was to assess the cerebral haemodynamic patterns in patients with NBD and NPSLE using TCD, while brain lesions were examined using magnetic resonance imaging (MRI). Material and methodsCase–control prospective study of 30 neuro-Behcet's disease patients, 25 neuro-psychiatric lupus patients and 26 healthy age-matched volunteers. All patients and healthy controls were examined by TCD. Only the groups of patients underwent cranial magnetic resonance imaging (MRI). ResultsTranscranial Doppler (TCD) values for middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA) in NBD, NPSLE and control groups were measured. The results showed that there was a significant decrease in mean blood flow velocities in all the arteries examined in NBD and NPSLE patients. There was also a significant increase in the pulsatile index of PCA, VA and BA between NBD and NPSLE patients. The same results were obtained when comparing NBD versus controls. However, there was no significant difference between the NPSLE patients and the control group. The MRI lesions described were parenchymal lesions in 14 patients (46.7%), and vascular lesions in 4 patients (13.3%). Vascular lesions co-existed with parenchymal lesions (mixed lesion). Parenchymal lesions were in white matter (40%), thalamus (26.7%), brain stem (26.7%) and cerebellum (20%). While, in NPSLE, 23 patients were normal (92%) and only two patients had a vascular lesion (8%). ConclusionThere was a significant decrease in mean blood flow and a significant increase in the pulsatile index among both NBD and NPSLE patients, according to the TCD values.

Neuro-Behcet disease in a Nigerian man- a case report.

Neuro-Behcet disease in a Nigerian man- a case report.

Elevated levels of IL-32 in cerebrospinal fluid of neuro-Behcet disease: Correlation with NLRP3 inflammasome

Interleukin-32 (IL-32) is a pro-inflammatory cytokine that induces other cytokines involved in inflammation, including tumour necrosis factor (TNF)-α, IL-6 and IL-1β. The objective of this study was to evaluate IL-32, NLRP3 inflammasome, IL-1β, IL-6, IL-17A, TNF-a, IL-10 and IL-37 in cerebrospinal fluid (CSF) and paired serum samples of patients with neuro-Behcet disease (NBD) by ELISA, RT-PCR and Western blotting analysis. A receiver operating characteristic (ROC) curve was employed to explore of the predictive value of IL-32 levels. IL-32, IL-1β, IL-6, IL-17 and TNF-α, were highly expressed in CSF of NBD and multiple sclerosis (MS) patients contrasting with their low levels in patients with noninflammatory neurological diseases (NIND) and Headache attributed to BD (HaBD). IL-32 and NLRP3 inflammasome in NBD, correlate significantly with CRP and ESR. IL-32 should be studied further as potential BD biomarker of inflammation in NBD.

Primary Headache in Behçet's and Neuro-Behçet's Disease.

Behçet's disease (BD) is a multisystem vasculitis, which can involve the central nervous system, the gastrointestinal tract, the blood vessels, the joints, and the lungs. Neurological involvement is about 5%, but the headache is common in these patients. This study aimed to investigate whether differences exist in the onset and types of primary headaches between patients with BD without neurological involvement (BWoNI) and patients with neurological involvement, that is, neuro-Behçet's disease (NBD). A total of 136 consecutive BD patients (98 BWoNI and 38 NBD) were evaluated and compared. Primary headaches beginning before and after the onset of BD were found in 27.6 and 48.1% of BWoNI patients, respectively, and in 10.5 and 34.2% of NBD patients, respectively. The start of primary headaches was more frequent after then before the onset of BD in each group and overall. The primary headache types were similar in both BWoNI and NBD patients. The primary headache starts more frequently after then before the onset of BD, and characteristics of primary headaches were similar in both BWoNI and NBD patients.

Cerebrospinal fluid level of neurofilament light chain is associated with increased disease activity in neuro-Behçet's disease.

Clinical exacerbations characterized with neurological symptoms are observed in around 10% of Behçet's disease (BD) patients and may culminate in severe disability. Although certain immunological factors have been associated with disease activity in neuro-Behçet's disease (NBD), biomarkers for monitoring the clinical outcome of NBD have not been properly investigated. Levels of neurofilament light chain (NFL), homeobox protein Hox-B3 (HoxB3), and YKL-40 were measured in cerebrospinal fluid (CSF) samples of 23 parenchymal (n = 16) and nonparenchymal (n = 7) NBD patients obtained during NBD attacks by ELISA. Parameters of clinical progression and outcome were assessed for an average follow-up period of 3.9 ± 1.3 years. Parenchymal NBD patients showed elevated CSF levels of NFL, HoxB3, and YKL-40 as compared to nonparenchymal patients. NBD patients showing an increase in modified Rankin score (mRS) values during follow-up had significantly higher CSF NFL levels. Patients with relatively lower CSF NFL levels (<1000 ng/L) did not develop attacks or cognitive impairment interfering with daily life activities during follow-up. NFL levels correlated with disease duration and mRS at the last follow-up visit, while HoxB3 levels correlated with a number of attacks during follow-up. CSF level of NFL appears to predict the prospective somatic and cognitive disability in NBD patients and may thus be potentially used as a biomarker of clinical outcome in this disease.

Lesion distribution pattern of parenchymal Neuro-Behçet's disease using probability mapping

Background and PurposeBehçet's disease (BD) is an inflammatory disorder with multisystemic involvement. The most disabling aspect of BD is Neuro-Behçet's disease (NBD). In NBD, parenchymal lesions tend to occur in the mesodiencephalic region and brainstem, as reported in large series of NBD. Our study aimed to generate probability maps of parenchymal lesions to compare patient subgroups with different clinical and laboratory features. MethodWe included 66 non-standardized acute relapse MRIs of 55 patients with parenchymal NBD (p-NBD). We used T2-weighted axial images to digitalize the lesions using the CAD software. Boundaries of lesions were determined as polygons and converted into high-definition raster datasets. Then, digitalized lesion maps were transferred into the ICBM-152 brain template to perform spatial analyses. Finally, we created subtraction maps to compare the patient subgroups. ResultsWe used a total of 66 MRIs of 55 patients to generate the probability maps. The most frequently affected parenchymal structures were the rostral pons, mesencephalon, and diencephalic region. Interestingly, the brainstem was more commonly affected in females than males (p<0.01). In the late-onset disease, lesions were localized in the corticospinal tracts and caudal brainstem (p<0.01). Progressive disease and severe disability at the end of the follow-up period were associated with corticospinal tract lesions during relapses (p<0.01). Patients with positive pathergy tests were more likely to present right hemisphere involvement (p<0.01). Additionally, cyclosporine-induced lesions tend to be in atypical locations such as hemispheric white matter. ConclusionsIn the published studies, lesions in NBD were localized according to coarse anatomical regions. Our study uses visual maps to offer accurate lesion localizations using non-standardized brain MRIs, allowing comparisons across different NBD subgroups. By using this technique, we investigated the relationship of the clinical and laboratory features with the lesion locations. We found that the late age of onset was associated with a poor prognosis. Additionally, corticospinal lesions may predict severe and progressive disease course, requiring aggressive treatment. Interestingly, females had more brainstem lesions and lesion lateralization might be influenced by the pathergy test status.

Neuro-Behçet Disease, Neuro-Sweet Disease, and Spectrum Disorders.

Behçet disease and its related disorder, Sweet disease, are multifactorial disorders whose susceptibility loci have been identified in the genes of various immunological factors aside from human leukocyte antigens. The neurological involvement of these diseases, including encephalitis, myelitis, and meningitis, referred to as neuro-Behçet disease (NBD) and neuro-Sweet disease (NSD) respectively, is sometimes difficult to diagnose, especially when the characteristic mucocutaneous symptoms do not precede neurological symptoms or when characteristics of both diseases are present in a single patient. NBD and NSD constitute a spectrum of diseases that are differentiated according to the combination of risk factors, including the genetic background. Encephalitis, myelitis, and meningitis similar to NBD or NSD can be diagnosed as spectrum disorders, even if the characteristic mucocutaneous symptoms fail to be detected. Understanding these conditions as a disease spectrum may help elucidate the disease pathogenesis and assist in the development of therapeutic agents.

The Cerebrospinal Fluid Presentations of Neuro-Bechet Disease, a Way to Know ‎the Etiopathogenesis and Improve Armamentarium‎.

Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17 pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as TNF and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.

Myocardial involvement in Behçet’s disease may be higher in patients with Neuro-Behçet’s disease: a speckle tracking echocardiographic study

Background Behcet’s disease (BD) may present with life threating complications including neurological and cardiovascular involvement. Neuro-Behcet’s disease (NBD) is one of the most important causes of morbidity and mortality in patients with BD. The aim of the present study is to investigate whether patients with NBD are different than BD patients with other manifestations in terms of subclinical myocardial dysfunction. Methods Forty patients with NBD (23 female, mean age: 42.4 ± 9.4 years), 40 patients with BD (9 female, mean age: 39.7 ± 9.0 years) and 40 controls (20 male, mean age: 41.8 ± 6.5 years) were consecutively included in the study. All subjects underwent a transthoracic echocardiography for evaluation of left ventricular (LV) and atrial (LA) functions with two-dimensional (2D) speckle tracking echocardiography (STE). Results Baseline characteristics, clinical data, LV dimensions, systolic and diastolic functions were all in normal range among the groups. LV global longitudinal strain (LV-GLS) was significantly lower in patients with NBD and BD patients without neurologic involvement compared to controls. LA conduit strain was significantly lower in patients with NBD compared to controls. Patients with both parenchymal NBD and vascular NBD manifestations had significantly lower LV-GLS and LA conduit strain compared to controls. Linear regression analysis demonstrated that among cardiovascular risk factors only presence of NBD was the independent predictor of LV-GLS. Conclusions BD is associated with impaired LV and LA functions. LV-GLS and LA conduit strains of the patients with NBD were lower. NBD was an independent predictor of LV-GLS, suggesting a link between neurological manifestations and cardiac dysfunction in BD patients.

Evaluation of diagnostic performance of haematological parameters in Behçet's disease.

Behçet's Disease (BD) is a polygenic and chronic autoinflammatory multisystemic vasculitis disease characterised by mucocutaneous, musculoskeletal, neurological, gastrointestinal and ophthalmologic lesions. There has been no specific test or serum marker to measure and determine the diagnosis and severity of BD. The study aimed to investigate the diagnostic performance of haematological parameters as MLR (monocyte to lymphocyte ratio), NLR (neutrophil to lymphocyte ratio), PLR (platelet to lymphocyte ratio), MPV (mean platelet volume), MPVPR (mean platelet volume to platelet ratio), LMR (lymphocyte to monocyte ratio), LPM (lymphocyte and platelet multiplication), WLP (lymphocyte and leukocyte multiplication), RDW (red blood cell distribution width) and PCT (plateletcrit) in BD and compare these with disease activity and clinical findings. A total of 266 participants (49 healthy control and 217 BD patients) were recruited from the rheumatology department in a single-centre as a case-control study. The laboratory data were obtained from the electronic registration database. BD Activity scores (BDCAF/Behcet's Disease Current Activity Form) were calculated. Laboratory findings of BD patients and healthy controls were compared and evaluated. RDW, Platelet, PCT, NLR and PLR values were significantly higher in patient group than in the healthy controls. However, haemoglobin, MPVPR and LMR were significantly lower in the patient group which compared with the healthy controls. LPM in BD with genital ulcers, WLP in BD with genital ulcers and arthritis, MPR in BD with uveitis, RDW in BD with thrombosis and neuro-Behçet's disease (NBD), PLR in NBD were observed to be higher. However, LMR in NBD and MPV in BD with thrombosis were lower than those without. There was a positive correlation between BDCAF score and RDW, and NLR. Haemoglobin, RDW, Platelet, PCT, NLR, LMR, PLR and MPVPR were statistically significant predictors for BD. RDW, PCT and NLR are the most valuable predictors for BD.

Cerebrovascular changes in neuro-Behcet's disease and neuropsychiatric lupus by transcranial Doppler ultrasonography and magnetic resonance imaging

IntroductionTranscranial Doppler ultrasonography (TCD) is a technique that allows measurement of blood flow from the basal intracerebral vessels. It is relatively inexpensive, non-invasive, can be performed at the bedside, and allows monitoring in acute emergency settings and for prolonged periods with a high temporal resolution, making it ideal for studying the haemodynamics within the intracranial arteries in neuro-Behcet's disease (NBD) and neuro-psychiatric lupus (NPSLE). Our aim was to assess the cerebral haemodynamic patterns in patients with NBD and NPSLE using TCD, while brain lesions were examined using magnetic resonance imaging (MRI). Material and methodsCase–control prospective study of 30 neuro-Behcet's disease patients, 25 neuro-psychiatric lupus patients and 26 healthy age-matched volunteers. All patients and healthy controls were examined by TCD. Only the groups of patients underwent cranial magnetic resonance imaging (MRI). ResultsTranscranial Doppler (TCD) values for middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA) in NBD, NPSLE and control groups were measured. The results showed that there was a significant decrease in mean blood flow velocities in all the arteries examined in NBD and NPSLE patients. There was also a significant increase in the pulsatile index of PCA, VA and BA between NBD and NPSLE patients. The same results were obtained when comparing NBD versus controls. However, there was no significant difference between the NPSLE patients and the control group. The MRI lesions described were parenchymal lesions in 14 patients (46.7%), and vascular lesions in 4 patients (13.3%). Vascular lesions co-existed with parenchymal lesions (mixed lesion). Parenchymal lesions were in white matter (40%), thalamus (26.7%), brain stem (26.7%) and cerebellum (20%). While, in NPSLE, 23 patients were normal (92%) and only two patients had a vascular lesion (8%). ConclusionThere was a significant decrease in mean blood flow and a significant increase in the pulsatile index among both NBD and NPSLE patients, according to the TCD values.

Infliximab for reversible dementia in acute onset of neuro-Behçet's disease: A case report and cytokine analysis

We describe a 49-year-old female patient with neuro-Behçet's disease (NBD) with acute onset of fever and symptoms of dementia. High-dose glucocorticoid was partially effective for cognitive impairment, and infliximab, an anti-TNF-α antibody, gradually improved the symptoms. An analysis of cytokines showed that IP-10 in the cerebrospinal fluid was higher than that in the peripheral blood, and both decreased after treatment. This is the first known case of NBD wherein the patient with acute onset of dementia responded to a treatment with infliximab. In glucocorticoid-resistant patients, it is important to consider the introduction of infliximab to prevent irreversible brain dysfunction.

Acute Neuro-Behçet's Disease

Neuro-Behçet's disease accounts for 10-20% cases of Behçet's disease, and patients manifest neurological symptoms due to parenchymal inflammation in the central nervous system. Neuro-Behçet's disease is classified into two types (acute and chronic progressive) based on clinical symptoms and therapeutic responsiveness. This review aimed to summarize the acute type of neuro-Behçet's disease according to the guidelines of the Japanese Behçet's Disease Research Committee.

Chronic Progressive Neuro-Behçet's Disease

Neuro-Behçet's disease (NB) is classified into acute and chronic progressive types. Acute NB occurs as acute meningoencephalitis with focal lesions, presenting with high-intensity areas on T2-weighted images or flat images on magnetic resonance imaging (MRI). Chronic progressive NB is characterized by intractable, slowly progressive dementia and ataxia with progressive brain stem atrophy on MRI. The most important feature of chronic progressive NB is persistent elevation of cerebrospinal fluid (CSF) IL-6 levels. The progression rate of the brain stem atrophy has been shown to be closely correlated with integrated CSF IL-6. For the correct diagnosis of acute or chronic progressive NB, it is mandatory to confirm the diagnosis of Behçet's disease. Regarding treatment, all of corticosteroids, cyclophosphamide, and azathioprine are ineffective to treat chronic progressive NB. Low-dose methotrexate (MTX) is effective in decreasing CSF IL-6 levels without promoting the progression of neuropsychological manifestations. Infliximab has a beneficial effect in patients with inadequate response to MTX. Recently, clinical guidelines were established for the management of acute NB and chronic progressive NB, which is helpful for routine clinical practice.

Isolated myelitis in a patient with Behcet's disease during golimumab therapy

Tumor necrosis factor-alpha (TNF-α) inhibitors are increasingly used for various autoimmune diseases. Demyelinating events in the CNS, including myelitis, are reportedly associated with TNF-α inhibitor exposure. Behcet's disease rarely involves the spinal cord. A 51-year-old Japanese woman presented with back pain, leg weakness, and numbness during golimumab administration, a TNF-α inhibitor, for Behcet's disease. Magnetic resonance imaging revealed multifocal myelitis in the cervical and thoracic spinal cords. Discontinuation of golimumab and steroid therapy were effective and the symptoms have not relapsed. Although it is possible that the patient's myelitis was part of the symptoms of neuro-Behcet's disease, we believe that golimumab likely played a role in the myelitis development.

Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease.

Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.

Neuro-Behcet Disease and Ocular Inflammation: A Case Report and Literature Review

ABSTRACT Purpose: To describe a case of panuveitis with occlusive vasculitis leading to the diagnosis of neuro-Behcet disease (NBD) and discuss the relationship between uveitis and NBD. Methods: Case report with a literature review of ocular inflammation in NBD. Results: A 26-year-old woman with a seven-month history of recurrent cerebral venous sinus thromboses (CVST) and right-sided hemiparalysis secondary to rhombencephalitis presented with bilateral panuveitis and occlusive retinal vasculitis. Systemic evaluations were negative for hypercoagulability and infection. Although HLA-51 negative, the diagnosis was consistent with NBD. Conclusion: NBD is a rare subset of BD with a limited number of studies and patients. However, uveitis is more common in adults with parenchymal disease; may predate the development of neurological symptoms. The most common locations of ocular inflammation were posterior and panuveitis. MRI/V of the brain can identify enhancing lesions in the rhombencephalon or CVST in patients with uveitis with neurological findings.

Quality of life in neuro-Behçet's disease: a cross-sectional study.

Behçet's disease (BD) is a multisystemic perivasculitis with recurrent oral aphthous ulcers, genital ulcers, and eye involvement which was first described in 1937. Neurological involvement in BD patients is referred to as neuro-Behçet's disease (NBD). Studies have shown that BD worsens quality of life. However, there is no study that conducts a head-to-head comparison of quality of life between NBD patients and healthy controls. Forty patients with NBD and 39 age-sex-matched healthy control subjects were included in this study. Sociodemographic data of all participants were recorded; SF-36 was used to assess quality of life. NBD patients had significantly lower SF-36 scores of physical functioning, physical difficulty, bodily pain, and general health perception compared with healthy controls. However, there was no significant difference between the groups according to the SF-36 scores of role limitation due to emotional problems, mental health, vitality, and social functioning. There was no significant difference between parenchymal and non-parenchymal NBD groups according to SF-36, Beck's Depression Inventory, and Beck's Anxiety Inventory scores. Patients with cerebellar system involvement had significantly lower physical and social functioning scores compared with those who did not. Patients with brain stem involvement were found to have higher role limitation due to emotional problems, vitality, social functioning, physical pain, and general health perception scores compared with those without brain stem findings. NBD negatively affects many aspects of the quality of life.

Recommendations for the Management of Neuro-Behçet's Disease by the Japanese National Research Committee for Behçet's Disease.

Objective Brain parenchymal involvement in Behçet's disease (BD) (neuro-Behçet's disease, NB) can be classified into acute type (ANB) and chronic progressive type (CPNB) based on differences in the clinical course and responses to corticosteroid treatment. The present study developed evidence-based recommendations for the management of NB. Methods The task force of the research subcommittee consisted of seven board-certified rheumatologists (one was also a board-certified neurologist) and three board-certified neurologists. First, several clinical questions (CQs) were established. A systematic literature search was performed by The Japan Medical Library Association in order to develop recommendations. The final recommendations for each CQ developed from three blind Delphi rounds, for which the rate of agreement scores [range 1(strongly disagree)-5(strongly agree)] was determined through voting by the task force. Results A flow chart of the algorithm was established for the management of ANB and CPNB. Thirteen recommendations were developed for NB (general 1, ANB 7, CPNB 5). The strength of each recommendation was established based on the evidence level as well as the rate of agreement. Conclusion The recommendations generated in this study are based on the results of uncontrolled evidence from open trials, retrospective cohort studies and expert opinions, due to the lack of randomized clinical trials. Nevertheless, these recommendations can be used for international studies, although verification by further properly designed controlled clinical trials is required.