neuro-Behçet's Disease Patients Research Articles

Myelin basic protein and index for neuro-Behçet's disease

Neuro-Behçet's disease (NBD) contributes to poor prognosis in BD patients which lacks reliable laboratory biomarkers in assessing intrathecal injury. This study aimed to determine the diagnostic value of myelin basic protein (MBP), an indicator of central nervous system (CNS) myelin damage, in NBD patients and disease controls. Paired samples of cerebrospinal fluid (CSF) and serum MBP were measured using ELISA, while IgG and Alb were routinely examined before the MBP index was developed. CSF and serum MBP in NBD were significantly higher than in NIND, which could distinguish NBD from NIND with a specificity exceeding 90%, moreover, they could also be excellent discriminators for acute NBD and chronic progressive ones. We found positive linkage between MBP index and IgG index. Serial MBP monitoring confirmed serum MBP's sensitive response to disease recurrences and drug effects, whereas MBP index suggests relapses prior to clinical symptoms. MBP has high diagnostic yield for NBD with demyelination and identifies CNS pathogenic processes before imaging or clinical diagnosis.

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.

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.

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.

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.

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.

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.

Serum Immunoglobulin G of Neuro-Behçet's Disease Patients Reduce Cerebral Expression Levels of Survival Pathway Factors

Objective: Anti-neuronal antibodies are found in sera of neuro-Behçet's disease (NBD) patients. In this study, our aim was to analyze the potential mechanisms by which NBD immunoglobulin (Ig) Gs affect neuronal dysfunction. Materials and Methods: Purified IgGs obtained from pooled sera of six each NBD patients and healthy controls (HCs) were administered to Sprague Dawley rats through intraventricular injection. Control rats received phosphate-buffered saline (PBS) only. Locomotor activity was assessed by open field test on days 0, 10, and 25. Cerebral expression levels of intracellular pathway factors associated with cell survival and viability were measured by real-time polymerase chain reaction. Results: Rats treated with NBD IgG exhibited reduced motor activity. On day 25, the mean number of crossings was 44 ± 7, 90 ± 12, and 93 ± 5 and the mean number of rearings was 18 ± 7, 34 ± 5, and 35 ± 6 for NBD IgG, HC IgG, and PBS groups, respectively (P &lt; 0.001). Relative expression levels of Akt-1 (0.4 ± 0.2, 1.0 ± 0.3, and 0.9 ± 0.6; P = 0.004), DJ-1 (0.6 ± 0.2, 1.0 ± 0.6, and 0.9 ± 0.5; P = 0.047), mouse double mininute-2 (0.5 ± 0.3, 0.9 ± 0.2, and 1.0 ± 0.2; P = 0.002), and mechanistic target of rapamycin (0.4 ± 0.2, 0.8 ± 0.4, and 0.9 ± 0.6; P = 0.006) were significantly lower in NBD-IgG group than HC IgG and PBS groups. By contrast, the expression levels of factors associated with apoptosis (caspase 3, mitochondrial carrier homolog 1, and B-cell lymphoma-2) were comparable among different treatment arms. Conclusion: Our results suggest that at least a fraction of NBD IgG interacts with neuronal surface antigens and subsequently decreases neuronal viability through Akt pathway inhibition. By contrast, NBD IgG does not appear to activate neuronal apoptosis. Further identification of the binding sites of serum IgG ıs required.

Apparent diffusion coefficient characteristics of parenchymal neuro-Behçet's disease.

To evaluate apparent diffusion coefficient (ADC) characteristic of parenchymal neuro-Behçet's disease (NBD). We retrospectively reviewed cranial magnetic resonance imaging (MRI) examinations of NBD patients with acute or chronic parenchymal lesions. ADC measurements of the lesions and contralateral normal brain parenchyma were performed by a consensus of two radiologists. To compare the ADC value of the chronic and acute lesions, relative ADC values (rADC) were calculated. The ratio of the lesions' ADC to contralateral normal brain parenchyma ADC yielded a rADC value of the lesions. Contrast enhancement patterns and the locations of the lesions were also noted. A total of 24 NBD patients with 45 parenchymal lesions, 25 acute, and 20 chronic, were enrolled in the study. A significant difference was observed between the mean ADC value of the acute lesions (1074.48±138.31m/s) and the mean ADC value of the contralateral normal brain parenchyma (841.20±142.96m/s; P<0.0001). A significant difference was observed between the mean ADC value of the chronic lesions (1069.95±143.95m/s) and the mean ADC value of the contralateral normal brain parenchyma (793.90±96.71m/s; P<0.0001). No significant difference was observed between the mean rADC (1.35±0.20) and the mean rADC value of the chronic lesions (1.29±0.15; P=0.22). ADC measurements might provide substantial information about the histopathological aspect of parenchymal NBD lesions.

Olfactory Dysfunction Associated With Neuro-Behçet Disease.

Neurologic involvement associated with Behçet disease (BD) is defined as a different entity: Neuro-Behçet disease (NBD). Behçet disease presents with olfactory dysfunction. It is not known whether this is the consequence of mucosal involvement or neurologic involvement. The aim of this study was to investigate whether olfactory dysfunction was further aggravated as the result of neurologic involvement. Sixteen patients diagnosed with NBD and 16 healthy control patients with similar demographic characteristics were recruited as the healthy control group. Expanded Disability Status Scale (EDSS) scoring was used for quantification of neurological disability. All diagnoses were confirmed and categorized with magnetic resonance imaging studies in all patients individually: parenchymal or nonparenchymal. A well-established test of orthonasal olfaction developed at the CCCRC was used. Correlation analysis was carried out. The mean CCCRC score of NBD patients was 4.60 out of 7, and this group was diagnosed to be moderately hyposmic, whereas the average score of the control group was 6.5; the difference was significant (P < 0.0001). CCCRC scores of NBD patients were significantly lower compared both healthy control patients and those of BD patients reported in the literature. Mean EDSS score of NBD patients was 1.75 ± 1.0 out of 10 (0-no neurologic disability and 10-worst neurologic disability). Magnetic resonance imaging of NBD patients revealed 4 nonparenchymal and 12 parenchymal patients. Neuro-Behçet disease patients with parenchymal involvement presented with (worse) EDSS scores. Mean olfactory CCCRC score of this group was 4.38 whereas the average olfactory score of the vascular group was 5.25 out 7. Average EDSS score of vascular group was 0.75, much better compared to higher average neurologic disability score of 2.08 for the parenchymal group. Significant correlation existed between the duration of NBD and both olfactory and neurologic dysfunction scores. Neuro-Behçet disease present with aggravated olfactory dysfunction compared to BD. Neurologic involvement-especially parenchymal involvement-seems to deteriorate the olfactory dysfunction. Duration of disease is correlated with this severity of dysfunction.

Impact of Neuro-Behçet Disease Immunoglobulin G on Neuronal Apoptosis.

Parenchymal neuro-Behçet disease (NBD) is encountered in 5%-15% of Behçet disease (BD) patients and is characterized by inflammation of the brainstem and diencephalon structures. Neuronal apoptosis has been shown to participate in neuronal cell loss. Anti-neuronal antibodies have been identified in NBD patients. However, the pathogenic properties of these antibodies have not been studied. To delineate the potential pathogenic activity of serum antibodies on neurons, pooled sera from seven NBD patients and seven healthy controls were divided into purified immunoglobulin G (IgG) and IgG-depleted serum fractions, and each fraction was administered to cultured SH-SY5Y neuroblastoma cells. Cell death was evaluated with a toxicity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Moreover, expression levels of several apoptosis markers were evaluated with real time polymerase chain reaction (PCR). Administration of NBD IgG to cultured SH-SY5Y cells induced significantly increased cell death and apoptosis compared with other treatments. NBD IgG also enhanced the mRNA expression levels of major apoptosis and cell survival pathway factors. Our results suggest that IgGs isolated from the sera of NBD patients have a neurotoxic activity that is presumably mediated by apoptotic mechanisms.

Effects of in vivo and in vitro administration of neuro-Behcet’s disease IgG

Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n=10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.

Tumefactive Neuro-Behcet’s Disease: A Case Report and Review of the Literature

Aim: Behcet's disease is a multi-systemic autoimmune disease, characterized with recurrent oral-genital ulcers and uveitis. Neuro-Behcet's disease (NBD) may rarely cause tumour like brain lesions. Methods: Here we present a case of forty-two-year-old Turkish male with tumour like brain lesion whose tissue biopsy result was compatible with necrotic inflammation, perivascular polymorphonuclear leukocytes (PMNL), lymphocytes and other inflammatory cells infiltration. Bacterial and fungal blood cultures were negative. The patient was diagnosed with NBD and was treated with intravenous methylprednisolone 1000 mg/day for 5 days. His neurologic examination improved significantly with the treatment. We evaluated histopathological properties of all biopsy proven cases reported so far in the literature including our case. Results: When tumour-like lesions were seen in patients who had Behcet's disease in past medical history, NBD should be considered for preventing unnecessary brain operation. Seventy-three percent of all biopsy proven tumefactive NBD cases had inflammatory cell infiltration in the tumour like lesion area. Conclusion: After excluding infectious aetiology, high dose IV methylprednisolone should be begun as soon as possible in spite of mass effect that is compatible with tumour in brain magnetic resonance imaging (MRI); the good response to steroid supports to the diagnosis of tumefactive NBD. Although most tumefactive NBD patients have inflammatory infiltration in biopsy material why some cases do not have any inflammatory cell infiltration in acute lesion area needs to be clarified in further research.

Characteristics of Neuro-Behcet disease: six cases case report and literature review

Six patients with Neuro-Behcet disease (NBD) were admitted in Beijing Hospital from 2000 to 2014, during the same period 344 NBD cases were reported in the literature. The clinical data of 350 Chinese NBD patients, including the symptoms, signs, laboratory tests, imaging, treatment and prognosis were retrospectively analyzed. The average onset age was 36.7 years old. The average interval time from Behcet disease (BD) to NBD was 5.6 years. NBD often occurred in male, the male/female ratio was 1.94∶1. The most common manifestations were oral ulcer 94.9% (277/292), followed by genital ulcer 69.1% (215/311) and fever 42.1%(131/311). The most common symptoms in neurology were limb weakness (36.9%, 129/350), headache (34.0%, 119/350) and sensory disturbance (21.1%, 74/350), followed by bulbar symptoms (11.4%, 40/350), pyramidal sign was most often (27.1%, 95/350). The central neurology system (CNS) was the major target of NBD, parenchymal CNS was affected most (88.0%, 308/350), non-parenchymal CNS was affected less (5.7%, 20/350), peripheral neurology system (PNS) was rarely affected (6.9%, 24/350). Steroids were the first-line drug for NBD, if it failed, immunosuppressive agents or biologic agents could be used. The most NBD patients had single episodes, 32.0% (49/153) had relapses with remission, 7.7% (27/350) had adverse prognosis. Analysis showed that NBD should be paid more attention. Key words: Behcet syndorme; Diseases attributes

Retinal nerve fiber layer structure abnormalities in patients with Neuro-Behcet's disease.

Our aim was the evaluation of retinal nerve fiber layer (RNFL) and central macular thickness (CMT) in patients with Neuro-Behcet's disease (NBD) and to compare the results with healthy control subjects. We recruited 50 eyes of 25 patients with NBD and 42 eyes of 21 age-matched healthy control subjects. Patients and control subjects underwent a thorough ophthalmic examination, including retinal nerve fiber layer and macular thickness measurements by optical coherence tomography. No significant difference was found between groups for age, sex, intra-ocular pressure and central corneal thickness measurements. The average RNFL in patients with NBD was significantly lower than that of healthy controls (86.92 ± 18.36 μm vs. 99.74 ± 8.73 μm; p = 0.00). There was significant thinning of the RNFL in three of four quadrants of the peripapillary area, superior (107.22 ± 30.91 μm vs. 125.57 ± 20.97 μm; p = 0.00), inferior (110.36 ± 25.57 μm vs. 132.19 ± 12.71 μm; p = 0.00) and nasal (68.84 ± 18.47 μm vs. 74.98 ± 11.42 μm; p = 0.05), in patients with NBD. Average CMT was significantly lower in NBD patients than in control subjects (244.06 ± 26.25 μm vs. 261.69 ± 25.71 μm; p = 0.00). There are significant differences in average RNFL and CMT between the two groups. RNFL and CMT thicknesses are reduced in patients with NBD compared with the healthy controls.

Neuro‐behçet's disease in South Korea: clinical characteristics and treatment response

Neuro-behçet's disease (NBD) is a rare complication of Behçet's disease (BD) but is still important due to its morbidity and mortality. In this study, we sought to identify the characteristics of NBD by examining the clinical characteristics, and whether there were differences in the clinical characteristics or the treatment between relapsed and non-relapsed groups. We retrospectively reviewed the medical history of all patients diagnosed with BD at the Asan Medical Center in South Korea from January 1996 to May 2012. NBD was defined as neurological symptoms and compatible abnormalities identified by magnetic resononance imaging. Among 624 BD patients, 22 were diagnosed with NBD. The common initial neurological symptoms were headache, gait disturbance and dysarthria. The common involved sites were the diencephalon, including internal capsule, the thalamus and basal ganglia, followed by the brainstem. An increased signal intensity on T2-weighted images was the most common finding. All patients had an improved disease state after steroid treatment, regardless of combined treatment with cyclophosphamide. However, eight patients experienced a disease recurrence at 7.3 ± 5.1 months after treatment. There were no significant differences in treatment patterns between the relapsed group and the non-relapsed group. NBD may present with various neurologic manifestations with multifocal diencephalon and brainstem involvement. Most NBD patients had a good clinical outcome after steroid treatment, with or without a cytotoxic agent, but showed a pattern of relapse-remission. Therefore, careful long-term follow-up is needed in most cases of NBD.

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease

Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation.

Characteristics of neurological manifestations of Behçet's disease: A retrospective monocentric study in Tunisia

ObjectiveThe aim of the present study was to analyze demographic, clinical and genetic features of Behçet's disease patients with neurological involvement through a monocentric study of a homogenous group of hospitalized patients observed in the same department and to compare them with those of other ethnic and geographic groups. MethodsFour hundred and thirty Behçet's disease (BD) patients were retrospectively studied. Diagnosis of BD was made according to the international study group for Behçet's disease criteria. Patients with neurological findings suggestive of involvement of the nervous system by BD were further studied according to clinical examination, laboratory tests and neuroradiological investigations. ResultsNeurological involvement was observed in 121 patients (28.1%). The mean age at neuro-Behçet's disease (NBD) onset was 29.7 years. Average disease duration of BD before neurological manifestations onset was 6.4 years. Male to female ratio was 1.8. Of the 121 NBD patients, parenchymal involvement occurred in 74 patients (61%). Among them 26 (21.4%) presented with brainstem involvement, 24 (19.8%) with hemispheric involvement and 2 (1.6%) with spinal cord involvement. Non-parenchymal NBD occurred in 47 patients (39%). Involvement of the main vascular structures (Vasculo-NBD) was the most common non-parenchymal NBD lesion found in 35 patients (28.9%) consisting of cerebral vein thrombosis (CVT) in 24 cases and cerebral arterial thrombosis in 11 cases. Forty-nine (40.5%) patients with NBD have been followed-up for a median of 3 years (range 1–19 years). Forty-one of them recovered well without significant residual disability, 5 patients made no improvement and are left with severe neurological impairments and 3 died. Male gender and CNS parenchymal lesions occurrence were significantly associated with a poorer prognosis. ConclusionClinical and epidemiological features of NBD are various. In our Tunisian cohort of NBD patients the main characteristic features were male predominance, a relatively high prevalence of CVT, a low prevalence of intra-cranial hypertension and a significant lower frequency of HLA-B51 haplotype.

Cognitive impairment in Brazilian patients with Behçet's disease occurs independently of neurologic manifestation

Neuro-Behçet's disease (NBD) presents cognitive and behavioral symptoms possibly explained by secondary dysfunction of frontal and temporal cortices due to subcortical damage, as NBD commonly involves the brainstem and basal ganglia. Nonetheless, there are reports of cognitive impairment in patients without neurological manifestations. ObjectiveTo evaluate cognitive function in Behçet's disease (BD) patients with and without neurological manifestations and to analyze clinical variables associated with cognitive deficits. MethodsThis is a cross-sectional study that compared healthy controls, BD patients without neurological manifestations and NBD patients. Each group comprised 24 participants. All participants underwent neuropsychological evaluation, Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) application and brain MRI. Cumulative prednisone dose, years of education, and presence of white-matter lesions in brain MRI were recorded. Results41.6% of BD and 41.6% of NBD patients showed impaired language and executive function, whereas visual memory was impaired only in NBD patients. Multiple logistic regression revealed that anxiety (OR 1.09 95% CI 1.03–1.16, p=0.003) and lower educational level (OR 0.62 95% CI 0.48–0.80, p<0.0001) were independently associated with cognitive impairment. ConclusionCognitive impairment occurs frequently in patients with BD independently of neurological manifestation. Low educational level and anxiety are risk factors for cognitive impairment in BD.