neuro-Behcet's Disease Research Articles

Fecal GABA levels are reduced in multiple sclerosis but not in neuro-Behcet disease (P2.375)

Fecal GABA levels are reduced in multiple sclerosis but not in neuro-Behcet disease (P2.375)

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.

A fatal case of probable neurobehcet

Abstract Behcet's disease (BD) is a systemic vasculitis characterized by recurrent oral and genital ulcers, with a frequent ocular and skin involvement. Neurological involvement in BD has been reported in 4–49% of cases and determines functional and vital prognosis of the disease. Based on clinical and imaging evidence, two major forms can be identified: a parenchymal or an extra parenchymal involvement essentially represented by cerebral vein thrombosis. Awareness disorders are rarely reported as tell-tale signs of neurological involvement in BD. We hereby report the peculiar case of a young patient, 39 years old, admitted to the emergency department for an acute onset of altered mental status in a non-traumatic setting where investigations led to the diagnosis of neurobehcet disease. Patient was placed on high doses corticosteroids with unfavorable outcome; patient passed away after 01 week.

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.

Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNFα versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

Neuro-Behcet's Disease: A Review of Neurological Manifestations and Its Treatment

Behcet’s disease (BD) is an inflammatory disorder characterized by recurrent oral and genital ulcers, ocular inflammation, arthritis and skin lesions. Neuro-Behcet’s disease (NBD) is found in 5–30% of patients and is classified into parenchymal and non-parenchymal manifestations. Most common parenchymal NBD manifestation is brainstem meningoencephalitis and patients may also have cranial nerve palsies, myelitis, epilepsy and peripheral neuropathy. Non-parenchymal NBD manifestations are cerebral venous thrombosis and aseptic meningitis. NBD usually develop abruptly and generally clear completely within weeks, however a third of patients evolve with progressive course. Moreover, patients with BD without overt neurological manifestations may present silent neurological involvement, with abnormal findings on neuropsychological, neurophysiological and neuroimaging studies. NBD is an adverse prognostic factor. Herein we review NBD manifestations and its treatment.

Unusual Late Onset of Parenchymal Neuro-Behçet Disease.

Neuro-Behçet disease (NBD) is a multisystem inflammatory disorder characterized by oral lesions, genital lesions, uveitis, and neurological deficits. If left untreated, it may lead to worsening neurological function and can be fatal. Here we present a case of a 52-year-old woman who was diagnosed with Behçet disease (BD) as a teenager and had a relatively mild disease course. Decades later after her initial DB diagnosis, she presented to our hospital with a chief complaint of headache. She did not have focal neurological deficits or any active mucosal lesions. Upon further investigation, the patient was found to have multiple inflammatory changes on neuroimaging and abnormal cerebrospinal fluid (CSF), consistent with the diagnosis of NBD. She was treated with intravenous corticosteroid therapy and her symptoms resolved. Although our patient presented with minimal symptoms decades after her initial diagnosis, any neurological complaint warranted a thorough investigation for a proper diagnosis and treatment given the multisystem involvement of BD.

Neurological manifestations of Behçet’s disease: 161 cases in one moroccan center

Introduction: Behçet’s disease (BD) is a chronic multisystemic inflammatory disease, predominant within the Mediterranean countries and characterized by oral, genital mucous ulcers and uveitis. Neurological involvement is one of the most serious complications of BD and represents a major cause of morbidity. Patients and methods: 161 moroccan cases of neurobehçet disease (NBD) have been categorized into two main groups: “Parenchymal” CNS involvement, which includes hemispheric, brain-stem, spinal, and multifocal presentations; and “non parenchymal” CNS involvement, which includes dural sinus thrombosis and arterial involvement. Results: Parenchymal CNS pattern was observed in 74% of our cases with a predominance of symptoms related to brainstem involvement (30%) such ophthalmoparesis, bulbar and pseudobulbar palsy. Other symptoms have been present with varying frequencies: cerebellar signs(52%), headache(52%), psychiatric and cognitive symptoms (34%), sphincter disturbances (22%), epilepsy (9%). Some features are less common such as optic neuropathy (2%) or peripheral neuropathy(1%). Non-parenchymal form was noted in 26% of our series essentially represented by cerebral venous thrombosis (CVT). Only 4 of cases have cerebral arterial involvement, three with intracranial aneurysm. All patients have cerebral imaging. Magnetic resonance imaging showed a caracteristic lesion in one third of our patients, located at the mesodiencephalic junction and the pontobulbar region. Treatment was based on corticosteroids in the two categories. Long-term maintenance with immunosuppressive agents was administrated in patients with parenchymal CNS involvement and anticoagulants in case of CVT. Conclusion: Neurological involvement represents a major complications of BD which requires early diagnosis and long terme management.

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.

PP13.13 – 2289: Delayed diagnosis of neuro-Behçet's disease: Report of 3 cases

Objective Behcet's disease is a rare chronic, relapsing multisystem vascular inflammatory disease of unknown cause in young adulthood. Only 8% of Behcet's disease cases are children. Methods We report 3 pediatric cases diagnosed as neuro-Behcet's disease, presenting with symptoms and signs of intracranial hypertension such as headache and papilledema due to cerebrovascular thrombosis. Case 1: A 16 year-old boy was admitted with a throbbing headache. Three months prior he was evaluated with fever of unknown origin, weight loss, and headache, however no specific etiology was discovered. His brain magnetic resonance venography revealed venous thrombosis in the right transverse sinus, in the sigmoid sinus extending to jugular bulbus and in the posterior part of superior sagittal sinus. When carefully questioned he had history of recurrent oral and genital ulcers. HLA B51 and patergy tests were positive. Case 2: A 14-year old boy was admitted with vertigo and headache. He was hospitalized elsewhere in a pediatric neurology clinic with 6th cranial nerve palsy and venous thrombosis, 3 years before. He had been suffering from aphthous lesions in relapsing and remitting manner for 4 years. His brain magnetic resonance venography revealed venous thrombosis in the right sigmoid sinus. Patergy test was negative, however, HLA B51 was positive. Case 3: A 17-year old boy was admitted with a headache and weight loss. His brain magnetic resonance venography revealed diffuse venous thrombosis in the superior sagittal sinus and in bilateral transverse sinuses. His father had established Behcet's disease. HLA B51 and patergy tests were positive. Results Cerebrovascular thrombosis is one of the diverse manifestations of neuro-Behcet's disease. Conclusion All of the three cases' diagnoses were delayed. The presence of intracranial hypertension related to a cerebral venous thrombosis in an adolescent boy should alert pediatric neurologists about the diagnosis of neuro-Behcet's disease.

Intracranial Germinoma Associated Rubral Tremor Mimicking Neuro-Behcet Disease: Importance of a tissue diagnosis (P3.012)

Intracranial Germinoma Associated Rubral Tremor Mimicking Neuro-Behcet Disease: Importance of a tissue diagnosis (P3.012)

Epileptic seizures in Neuro-Behcet disease: Why some patients develop seizure and others not?

PurposeBehcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. MethodsAll files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. ResultsThe mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. ConclusionCVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures.

Retrospective analysis of long-term outcome of chronic progressive neurological manifestations in Behcet's disease

ObjectivesChronic progressive neuro-Behcet's disease (CPNBD) is characterized by progressive deterioration leading to disability and death. Although methotrexate has been found effective for CPNBD, its influences on the long-term outcome remain unclear. We therefore explored the effects of various treatments on the prognosis. MethodsThirty-seven patients, who met the international classification criteria for BD and developed chronic progressive neuropsychiatric manifestations after 1988, were followed up until October 2013. The effects of various treatments on prevention of death or severe disability of bedridden state were examined by Kaplan–Meier analysis and Cox's proportional hazard model. ResultsTwenty-eight of 37 patients with CPNBD (75.7%) received methotrexate. Among the 28 patients, none died and only 5 patients progressed to disability with bedridden state. By contrast, among the 9 patients without methotrexate, 5 patients died and 3 patients progressed to bedridden state. Thus, methotrexate significantly improved the survival of patients with CPNBD (HR 0.0507, p=0.020) as well as reduced the rate of progression into bedridden state or death (HR 0.2082, p=0.0126), but none of high doses of steroids, azathioprine or cyclophosphamide did. ConclusionThe results indicate that methotrexate, but not high doses of steroids, azathioprine or cyclophosphamide, is effective to prevent the progression of CPNBD.

A Fatal Case of Full-Blown Neuro-Behcet Disease

We reported a 48-year-old man with Behcet disease, who presented with right hemiparesis. His first brain MRI showed multiple enhanced lesions. During the recovery, he had an episode of left 6th nerve palsy without new lesions in a follow-up MRI. Third episode was cervical myelitis, resulting in respiratory difficulty and quadriplegia without any reflexes. The myelitis was not responsive to immunotherapy. He died of respiratory failure complicated with pneumonia. This is a rare case of full-blown neuro-Behcet disease. (Korean J Clin Neurophysiol 2015;17:28-30)

Neuro-Behçet Disease and Autoinflammatory Disorders

Misregulation of innate immunity leads to autoinflammation. Behçet disease is an autoinflammatory condition involving recurrent attacks of inflammation in skin, eyes, joints, and even the nervous system. The etiology may involve vascular inflammation. Central nervous system involvement in neuro-Behçet disease (NBD) comes in the form of parenchymal NBD or nonparenchymal NBD. The parenchymal form has a predilection for the brainstem, diencephalon and cerebral hemispheres, and represents a meningoencephalitis thought to be related to small vessel vasculitis. Cerebral venous sinus thrombosis, arising from a vasculitic process of large veins, comprises the majority of vascular NBD cases. The rarer monogenetic autoinflammatory syndromes are characterized by periodic fever, and typically present in the pediatric population. Neurologic involvement in these syndromes typically presents in the form of an aseptic meningitis. Treatment of autoinflammatory disorders involves immune modulation with corticosteroids, disease-modifying antirheumatic medications, and increasingly antibodies targeting cytokines like tumor necrosis factor α and interleukin 1.

P019 - Intracranial Germinoma: Very rare mimicker of multiple sclerosis

Background Multiple sclerosis (MS) mimickers are neurological conditions that may share clinical, biologic and radiologic features similar to MS. Standard MS treatments often fail. Objectives To report a very rare case of intracranial Germinoma with clinical, biological and radiological features similar to MS. Methods We report 26 year old Emirati male patient who presented with history of recurrent attacks of neurological dysfunction and recurrent brain stem lesions since 2010. Results MRIs of the brain revealed recurrent brain stem T2 hyperintense lesions changing in size and location but remained localized in the brain stem. Initially CSF was positive for OCB so he was diagnosed as clinically isolated syndrome and was started on Rebif injections. In 2011 he developed another relapse and new lesion appeared in the left side of the brain stem like mirror image of the old right side lesion which has disappeared. The symptoms included episodic diplopia, facial paresthesias with subsequent brainstem symptoms that improve with a high dose of corticosteroids. He developed oral ulceration in 2011. Diagnostic work up excluded all other possibilities and Neuro Behcet's disease (NBD) was considered, he responded well to Azathioprine and steroid. He remained well but in 2013 he developed relapse and MRI revealed that left sided midbrain has expanded. CSF revealed lymphocytic pleocytosis without OCB. Patient refused brain biopsy. He received three cycles of Infliximab but he deteriorated clinically and radiologically. The behavior of the disease and the lesion was suggestive of MS in the first year and suggestive of NBD in the second and third year, but in the fourth year it was not typical of MS or NBD. Brain biopsy was performed at John Hopkins hospital in USA in April 2014 and the lesion was reported Germinoma responsive to radiotherapy. The tumor disappeared after radiotherapy. Conclusion Intracranial Germinoma is very rare intracranial tumor that occurs at 0.7 per million, it is even more rare to be a mimicker for MS. This patient was treated successfully with radiotherapy. Multiple sclerosis (MS) mimickers are neurological conditions that may share clinical, biologic and radiologic features similar to MS. Standard MS treatments often fail. To report a very rare case of intracranial Germinoma with clinical, biological and radiological features similar to MS. We report 26 year old Emirati male patient who presented with history of recurrent attacks of neurological dysfunction and recurrent brain stem lesions since 2010. MRIs of the brain revealed recurrent brain stem T2 hyperintense lesions changing in size and location but remained localized in the brain stem. Initially CSF was positive for OCB so he was diagnosed as clinically isolated syndrome and was started on Rebif injections. In 2011 he developed another relapse and new lesion appeared in the left side of the brain stem like mirror image of the old right side lesion which has disappeared. The symptoms included episodic diplopia, facial paresthesias with subsequent brainstem symptoms that improve with a high dose of corticosteroids. He developed oral ulceration in 2011. Diagnostic work up excluded all other possibilities and Neuro Behcet's disease (NBD) was considered, he responded well to Azathioprine and steroid. He remained well but in 2013 he developed relapse and MRI revealed that left sided midbrain has expanded. CSF revealed lymphocytic pleocytosis without OCB. Patient refused brain biopsy. He received three cycles of Infliximab but he deteriorated clinically and radiologically. The behavior of the disease and the lesion was suggestive of MS in the first year and suggestive of NBD in the second and third year, but in the fourth year it was not typical of MS or NBD. Brain biopsy was performed at John Hopkins hospital in USA in April 2014 and the lesion was reported Germinoma responsive to radiotherapy. The tumor disappeared after radiotherapy. Intracranial Germinoma is very rare intracranial tumor that occurs at 0.7 per million, it is even more rare to be a mimicker for MS. This patient was treated successfully with radiotherapy.

Poster 309 Neuro-Behcet's Disease, a Case Report and Review of the Literature

PM&RVolume 6, Issue 9S p. S291-S292 Saturday Poster Presentations - Poster Hall Poster 309 Neuro-Behcet's Disease, a Case Report and Review of the Literature Thomas Reilly MD, Thomas Reilly MD Montefiore Medical Center, Bronx, NY, United StatesSearch for more papers by this authorSteven A. Sparr MD, Steven A. Sparr MD Montefiore Medical Center, Bronx, NY, United StatesSearch for more papers by this author Thomas Reilly MD, Thomas Reilly MD Montefiore Medical Center, Bronx, NY, United StatesSearch for more papers by this authorSteven A. Sparr MD, Steven A. Sparr MD Montefiore Medical Center, Bronx, NY, United StatesSearch for more papers by this author First published: 29 September 2014 https://doi.org/10.1016/j.pmrj.2014.08.689Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume6, Issue9SSeptember 2014Pages S291-S292 RelatedInformation

Tocilizumab for severe refractory neuro-Behçet: Three cases IL-6 blockade in neuro-Behçet

ObjectivesTo describe the response to IL-6 blockade [tocilizumab (TCZ)] in three patients affected by highly refractory neuro-Behçet disease (NBD). MethodsThree patients who had failed synthetic immunosuppressants and TNF-α antagonists combined with glucocorticoids received TCZ after obtaining their informed consent. Two patients underwent TCZ infusions at 8mg/kg every 4 weeks for a mean period of 24 months, while in one patient, the frequency of TCZ infusions was increased to every other week after 21 months due to a disease flare. Concomitant therapy with synthetic agents and low-to-medium dose glucocorticoids was continued. Clinical and imaging findings were assessed before and after the onset of TCZ therapy. ResultsIn all our patients, a very short time lag between the onset of treatment with TCZ and the clinical response was observed. A partial response occurred in two patients and a nearly complete response in one. Some loss of efficacy occurred after 18 months in one patient, but there was again a significant improvement when the interval between the infusions was shortened. TCZ was overall well tolerated and no serious adverse events occurred. In two patients, the prednisone dose could successfully be tapered to about 20mg/day, while in another patient glucocorticoids could safely be withdrawn. Brain MRI remained virtually unchanged in all patients. ConclusionsAlthough TCZ has not yet been included among the medications recommended for the treatment of NBD, our data suggest that it may be considered for patients with refractory NBD.

Increased interleukin 33 in patients with neuro-Behcet's disease: correlation with MCP-1 and IP-10 chemokines.

Increased interleukin 33 in patients with neuro-Behcet's disease: correlation with MCP-1 and IP-10 chemokines