neuro-Behcet's Disease Research Articles

Evaluation of Sleep Disorders and Polisomnographic Findings in Behcet and Neurobehcet Disease (P06.219)

Evaluation of Sleep Disorders and Polisomnographic Findings in Behcet and Neurobehcet Disease (P06.219)

Infliximab Treatment in Neuro-Behcet Disease Unresponsive to Immunosuppressive Treatments: Clinical Assessment of Eleven Patients (P01.055)

Infliximab Treatment in Neuro-Behcet Disease Unresponsive to Immunosuppressive Treatments: Clinical Assessment of Eleven Patients (P01.055)

Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

Neuro-Behçet’s disease (NBD) involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension); thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD); the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1). We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases). In 19/53 patients (36%), neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine). Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our review and personal experience, a delayed diagnosis, and the consequently delayed immunosuppressive treatment, may favour permanent sequelae, in particular, optic atrophy.

Cognitive Impairment in Neuro-Behcet's Disease and Multiple Sclerosis: A Comparative Study

Both multiple sclerosis (MS) and neuro-Behcet's disease (NBD) can cause a cognitive dysfunction mainly involving the executive functions. We conducted this study to clarify the probable differential cognitive/behavioral profiles of MS and NBD. Twenty consecutive cases with parenchymal NBD (13 male, seven female), and 20 cases with MS (five male, 15 female) were evaluated. Both groups had a thorough neurological examination; an evaluation for Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Beck's Depression Scale; and a detailed neuropsychological evaluation masked to the diagnosis. Among the two groups, male/female ratio differed significantly while other demographic and clinical features were not different. In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe “frontal”-executive dysfunction than MS patients.

Encephalitis syndrome: Look for autoimmune causes

Background: Encephalitis with lymphocytic-normal glucose CSF profile usually is caused by viral infections. Search for viruses is, however, successful in only half of the cases. It has been increasingly recognized that encephalitis can also be due to autoimmune causes. We attempted to identify patients presenting with immune encephalitis syndrome. We also tried to determine whether there were specific clinical patterns that might help identify such patients. Methods: Patients with encephalitis admitted between January 2011 and January 2012 were examined for evidence of viral infections [CSF-PCR for herpesviruses 1-6, Japanese encephalitis (JEV) and dengue viruses and enteroviruses; serology for dengue and JEV]. Autoimmune panel consisted of NMDA, AMPA, GABA, CASPR-2 and LGI-1 and 14 paraneoplastic antibodies. They were determined by indirect immunofluorescence (IIF) assay in sera. Results: There were 84 patients with an encephalitis presentation. Thirty-four patients (40.5%) had no etiologies identified. Twenty-six (31%) were associated with infections. These were 8 with herpes simplex virus, 4 varicella-zoster virus, 3 JEV, 3 Epstein-Barr virus, 3 fungal infection, 2 Mycobacterium tuberculosis, 1 dengue, 1 rabies and 1 with dual infection with herpes simplex and dengue. Initially misdiagnosed subjects were 8 patients (9.5%) with fever who had cerebral venous thrombosis (1), subarachnoid hemorrhage (1), metabolic encephalopathy (2), and cerebral infarction (4). There were 16 febrile encephalitis patients with immune disorders (19%). These were Neurobehcet's disease (1), neuropsychiatric-lupus erythematosus (2), multiple sclerosis (1) and neuromyelitis optica (1), anti- ANNA-2 (4), anti-NMDA (3), anti-AMPA2 (1), anti-GABA (1), anti-VGKC (1) and anti-NMDA coexisting with ANNA-2 (1). Ages ranged in the immune group were between 3 and 90 (2 <15 years old). Presenting symptoms were fever, altered consciousness, behavioral changes or psychosis and seizures. Facial dyskinesia was evident in one anti-NMDA receptor encephalitis patient. Conclusion: Immune encephalitis is not rare and can occur in all age groups. Diagnosis in most such cases cannot be made based on clinical grounds alone. In cases where there is no definitive diagnosis, antibody assays should be ordered to identify possible autoimmune diseases that require specific treatment.

White Matter Lesions in Behcet's Disease: Neuro-Behcet's Disease or Multiple Sclerosis? (P02.150)

Objective: To evaluate patients with Behcet9s disease (BD) and white matter lesions (WML). Background BD is a systemic auto-inflammatory disorder of unknown cause. It affects CNS in around 5% of the patients, usually causing a brainstem meningoencephalitis. Occasionally patients with WML can be seen which necessitates differentiating from multiple sclerosis (MS). Design/Methods: Files of neuro-BD clinic between 1990-2010 were evaluated to find cases with BD and WML. All the MRIs were re-evaluated masked to the clinical status. Barkhof/Tintore criteria for MS were applied. Clinical characteristics of the patients were compared with the patients who had typical parenchymal neuro-BD. Results: 43 patients (32F, 11M) had WML. 22 (18F, 4M) had abnormal findings on neurological exam (Group 1); the remaining had primary headache disorders (Group2). In Group 1, 16 patient fulfilled Barkhof/Tintore criteria. One had a single lesion resembling a demyelination, and 5 had nonspecific WML. In Group 2 none fulfilled Barkhof/Tintore criteria; all showed nonspecific WML. Therefore, patients in Group 1 were compared with 63 consecutive parenchymal neuro-BD cases (Group 3; 12F, 51M). There were significantly more females in Group I. Distribution of systemic BD findings, age at onset, disease duration, attack numbers were similar in both groups. CSF oligoclonal band positivity was significantly higher in Group 1 (9/17 vs 5/47). All patients received steroids at the acute setting. As long term treatment, Group 1 patients did not respond sufficiently to azathioprine, usually interferon beta or glatiramer acetate had to be added; whereas Group 3 patients usually responded to azathioprine. Conclusions: A subgroup of the patients with BD have predominantly WML resembling MS. Although the diagnostic criteria for MS require that all other possible diagnoses should be ruled out, patients with BD and predominantly MS-like WML tend to behave like MS cases, rather than neuro-BD. This should be kept in mind when chosing disease modifying treatments. Supported by: Neuroimmunology Society, Turkey. Disclosure: Dr. Akman-Demir has received personal compensation from Merck Serono, Bayer, Novartis, Teva, for consulting or giving lectures. Dr. Mutlu has nothing to disclose. Dr. Kiyat-Atamer has nothing to disclose. Dr. Shugaiv has nothing to disclose. Dr. Kurtuncu has nothing to disclose. Dr. Tugal-Tutkun has nothing to disclose. Dr. Tuzun has nothing to disclose. Dr. Bahar has nothing to disclose.

Neurobehçet disease: clinical and demographic characteristics

Neurobehçet disease (NBD) is a rare complication of Behçet disease (BD) but with important burdens of morbidity and mortality. Little is known about this complication because there are no validated diagnostic criteria, and all the studies have small number of patients. The prevalence reported normally ranges between 5% and 15% and it is more frequent amongst men between 20 and 40 years old. The typical presentations include focal parenchymal lesions, vascular thrombosis, arterial vasculitis, and aseptic meningo-encephalitis. We retrospectively studied medical histories of all patients admitted to the hospital and discharged from it with diagnosis of BD from January 1996 to September 2009. NBD was defined as having neurological and/or psychiatric symptoms with compatible abnormalities in MRI and/or cerebrospinal fluid and without another possible explanation for their symptoms. Behcet disease was diagnosed in 25 patients and seven from these patients fulfilled our criteria of Neurobehcet disease (28%). Patients with NBD were significantly younger at the onset of their symptoms and had a significantly longer evolution until diagnosis and treatment compared to patients with non-Neuobehçet disease. Six presented a relapsing-remitting pattern, with a good outcome with corticosteroids. As reported in previous studies, progressive course was less frequent, with only one case, and had a more aggressive disease. Brainstem involvement bears a poorer prognosis because it is linked with a progressive evolution. In our series, NBD complication was not that infrequent. It is very important to be highly suspicious of this possibility to start early a correct treatment.

Vascular neurobehcet disease:correlation with current disease activity forum and systemic vascular involvement

Behcet's syndrome (BS) is a chronic relapsing vascular inflammatory disease of unknown etiology with high morbidity and mortality. This research aims to study the clinical patterns of CNS disease in a group of patients with BS as well as the frequency and type of the associated radiographic findings suggestive of structural cerebral vascular disease. The findings were studied in relation to disease activity and features of systemic vascular involvement. Forty patients fulfilling the diagnostic criteria of the International Study Group for Behcet's Disease, mean age of 33.56 ± 9.7 years, were enrolled. Patients were subjected to magnetic resonance imaging with conjugate survey of cerebral blood vessels' flow pattern abnormalities by transcranial Doppler study. Thirty healthy controls were included. Behcet's Disease Current Activity Form Score was used. Neuro-Behcet's syndrome (NBS) was diagnosed in 37.5% with headache being the most common (86.6% of cases), pyramidal affection (signs of upper motor neuron lesions/hemiplegia) was reported in 33.3%, attacks of disturbed conscious level in 26.6%, and cranial nerve affection in 6.5%. Of the patients, 66.6% with clinical features of NBS had statistically significant radiographic evidences of cerebrovascular disease (p = 0.01). Patients with NBS had significantly higher disease activity index score (r = 0.69, p = 0.0001). Radiographic findings and flow abnormalities were significantly less in patients on immune suppressants and antiplatelet drugs (p = 0.003, 0.04). BS patients with clinical neurologic disease were found to have radiographic findings suggestive of cerebral vascular disease with high disease activity index score. Drugs like immunosuppressants and oral antiplatelets might retard cerebral vascular disease progression and flow abnormalities, respectively.

Bladder involvement in Behcet's disease.

To review different aspects of the bladder involvement in Behcet's disease as a rare complication. We searched PubMed, Ovid, and Google Scholar for Behcet's and neuro-Behcet's disease and neurogenic and neuropathic bladder, bladder involvement, voiding dysfunction, and urologic manifestations. Fourteen full-texts and one abstract were retrieved. Most involved patients are young to middle-aged men. Both bladder filling and emptying problems can be seen, with the storage symptoms being the most common finding. Sphincter function could be normal, dyssynergic, or deficient. The most common urodynamic finding is detrusor overactivity. In cystoscopic examination, ulcers or nodules due to vasculitis can be seen, which along with neurologic causes give rise to the voiding symptoms. The rate of cancers does not increase in Behcet's disease. Surgery and chemotherapy are tolerated well. However, radiotherapy may be associated with increased complication rates. Treatment plan should be tailored according to the specific type of the bladder involvement. Periodic re-evaluation is required because of the changing nature of the bladder behavior.

Pseudotumoural presentation of neuro-Behcet's disease: case series and review of literature

To describe the pseudotumoural presentation of neuro-Behçet's disease (NBD). We report here the main characteristics, treatment and outcome of 23 patients (5 personal cases and 18 patients from the literature) with a pseudotumoural presentation of NBD. Pseudotumoural NBD patients were compared with 69 consecutive patients, with a classical form of NBD. The median age was 39 (range 27-48 years) years, with a male predominance (65.2%). Clinical features of the pseudotumoural NBD included hemi- or tetra-pyramidal symptoms (n = 20), headache (n = 17), cerebellar syndrome (n = 3), sphincter impotence (n = 3) and pseudobulbar signs (n = 2). CNS imaging showed pseudotumoural lesions mainly in the capsulo-thalamic area (69.6 vs 11.6% for classical NBD; P < 0.01). Histological analysis revealed necrotic lesions with perivascular inflammatory infiltrate without signs of tumoural or infectious lesions. Patients with pseudotumoural NBD had more severe initial disability status (Rankin's score ≥3 in 65.2 vs 24.7%; P < 0.01) and had a 3 years' longer duration between neurological signs and BD diagnosis (P = 0.01) compared with patients with classical NBD. Treatment consisted of CSs (n = 21, 95.5%) and immunosuppressive agents (n = 10, 35.7%) that led to complete clinical and imaging remission in 60.9% of patients. Two (8.7%) of the 23 patients with pseudotumoural NBD died of bedridden state complications. The pseudotumoural form of NBD is a rare and life-threatening condition.

Simultaneous Involvement of Nervous and Gastrointestinal Systems in Behçet's Disease

Simultaneous Involvement of Nervous and Gastrointestinal Systems in Behçet's Disease

Transverse Myelitis in Patient with Behçet's Disease

Behcet's disease (BD) is a multisystem disorder presenting recurrent oral and genital ulcerations as well as ocular lesions, involving the nervous system in a subgroup of patients. BD develops at a young age and is frequently presented with an acute or subacute brainstem syndrome or hemiparesis, as well as with other various neurological manifestations, the syndrome is often included in the differential diagnosis of multiple sclerosis, stroke of the young adult, and other neurological disorders. Transverse myelitis (TM) is a clinical syndrome in which an immune-mediated process causes neural injury to the spinal cord, resulting in varying degrees of weakness, sensory alterations and autonomic dysfunction. Spinal Neuro-behcet's disease is rare case. We reported a 33 -year old man who had been treated for BD for 3 years.

Ring-enhanced Brainstem Lesion in a Patient with Neuro-Behcet's Disease

Ring-enhanced Brainstem Lesion in a Patient with Neuro-Behcet's Disease

Behcet’s disease presenting with sudden-onset paraplegia due to anterior spinal artery involvement: 1-year follow-up of rehabilitation in conjunction with medication

A 26-year-old male patient with sudden-onset paraplegia was presented. Clinical and imaging evaluation revealed isolated spinal cord lesions at thoracal levels and anterior spinal arterial involvement. Diagnosis of Behcet's disease was established with associating clinical findings with medical history. Vigorous medication and rehabilitation program were performed. Through the 1-year rehabilitation period in conjunction with medication, strength and functions improved gradually. A satisfactory functional gain as a rehabilitative goal in independence in activities of daily living and long-distance ambulation achieved around 4 months. The patient reached full independence after 1-year. As conclusion, Behcet's disease can present with sudden-onset paraplegia. In case of no evident etiology for paraplegia in young male, neuro-Behcet's disease also should be kept in mind. Contrary to assumption, early aggressive treatment and continuous rehabilitation in conjunction with medication might provide good prognosis with excellent clinical outcome in spinal cord involvement. Satisfactory functional recovery should be expected only after 3-4 months, and complete independence can be achieved after 1 year.

Fractalkine (CX3CL1) levels in patients with Behçet's disease and Neuro-Behçet's disease

ObjectiveThe aim of the present study was to assess the role of CX3CL1 in patients with active and inactive Behçet's Disease (BD), Neuro-Behçet's Disease (NBD) and control subjects. MethodsFifty-six patients admitted to the BD and NBD Outpatient Clinics, and 30 healthy controls were enrolled in the study. Serum CX3CL1 levels were measured by an enzyme linked immunosorbent assay (ELISA). ResultsNo significant difference was found between the serum CX3CL1 levels of control subjects, and patients with active and inactive BD or NBD, regardless of treatment. ConclusionTo our knowledge, this is the first study analyzing CX3CL1 levels in patients with BD and NBD. Our results demonstrated that serum CX3CL1 levels were not changed in active and inactive BD and NBD. However, further large-scale studies are needed to confirm our results.

Atypical manifestations in Brazilian patients with neuro-Behçet’s disease

Type and frequency of systemic and neurologic manifestations of Behçet's disease (BD) vary with ethnicity. In Brazil, BD occurs as sporadic cases. We describe clinical and radiological features of 36 Brazilian patients of mixed ethnicity with neuro-Behçet's disease (NBD). Medical records of 178 BD patients were reviewed and 36 (20%) NBD patients were identified. Twenty-one NBD patients (58.3%) were female and 27 (75%) presented with parenchymal manifestations. Brainstem involvement was the most common neurologic syndrome (41.7%). Seizures (27.8%), isolated aseptic meningitis (16.7%), optic neuropathy (ON) (16.7%), cerebral venous thrombosis (CVT) (8.3%), peripheral neuropathy (2.8%), and spinal cord involvement (5.6%) were other neurologic manifestations observed among Brazilian NBD patients. Eighteen (50%) had at least one relapse, and isolated aseptic meningitis was the most common relapsing manifestation. No significant differences concerning the number of relapses between parenchymal and non-parenchymal groups were found. A multivariate model including disease duration, cell count in spinal fluid, cyclosporine use, immunosuppressive use at disease onset, age at NBD onset, and ON did not reveal any significant associations with NBD relapse. There was a low frequency of CVT and an unexpected higher number of isolated aseptic meningitis. Brazilian NBD patients present more parenchymal and atypical manifestations, and relapse more often than NBD patients from other populations.

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

To delineate the clinical characteristics of neuro-Behçet’s disease (NBD), a multicenter retrospective survey was performed in BD patients who had presented any neurological manifestations between 1988 and 2008. The diagnosis of acute NBD, chronic progressive (CP) NBD, and non-NBD was confirmed by retrospective review of clinical records. Data on a total of 144 patients were collected; 76 with acute NBD, 35 with CP NBD, and 33 with non-NBD. High-intensity lesions on T2-weighted magnetic resonance imaging (MRI) were found in 60.5% of the patients with acute NBD, 54.2% with CP NBD, and 42.4% with non-NBD, whereas brainstem atrophy was observed in 7.5% with acute NBD, 71.4% with CP NBD, and 9.0% with non-NBD. The cerebrospinal fluid (CSF) cell count was prominently elevated in patients with acute NBD, but was normal in about 15% of those with CP NBD. The sensitivity and specificity of the CSF cell count for the diagnosis of acute NBD versus non-NBD were 97.4 and 97.0%, respectively (cut-off 6.2/mm3). The sensitivity and specificity of CSF interleukin (IL)-6 for the diagnosis of CP NBD versus the recovery phase of acute NBD were 86.7 and 94.7%, respectively (cut-off 16.55 pg/ml). The results indicate that elevation of the CSF cell count and CSF IL-6 and the presence of brainstem atrophy on MRI are useful for the diagnosis of NBD.

Anti-neuronal and stress-induced-phosphoprotein 1 antibodies in neuro-Behçet's disease

No disease-specific neuronal antibodies have so far been defined in neuro-Behçet's disease (NBD). Immunohistochemistry and immunocytochemistry studies showed antibodies to hippocampal and cerebellar molecular layers and the surface antigens of cultured hippocampal neurons in sera and/or cerebrospinal fluids (CSF) of 13 of 20 NBD and 6 of 20 BD patients but not in multiple sclerosis or headache controls. Screening with a protein macroarray led to identification of stress-induced-phosphoprotein-1 (STIP-1) as an antigenic target. High-titer STIP-1-antibodies were detected in 6 NBD patients' sera but not in controls. These results suggest that neuronal antibodies could be useful as diagnostic biomarkers in NBD.

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis.

A Complex Case of Neuro-Behçet's Disease in a Patient Previously Diagnosed with multiple Sclerosis: A Case Report.

Multiple sclerosis (MS) and Neuro-Behçet's disease (NBD) have been associated with a range of neuropsychiatric symptoms, including fatigue, cognitive impairment, depression, bipolar disorder, anxiety, sexual dysfunction, and other behavioral disturbances that are characterized by remissions and exacerbations at different points during the course of the disease. We present an interesting case of NBD in a 48-year-old female who had previously been diagnosed with MS. Exploration of this patient's various neuropsychiatric symptoms, their misattribution first to psychopathology and then subsequently to a variety of neurological problems exemplifies the potential pitfalls in diagnosis of a seemingly rare disorder. The role of psychosocial stress-related inflammatory changes in the patient's behavioral and neurological symptoms is explored as well as the potential psychological and medical effects of delayed diagnosis and treatment.