Neuro-Behçet Disease

Abstract & Commentary

By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.

Synopsis: Behçet's disease, while rare in North America, should be considered when appropriate, in light of the extensive travel and immigration patterns around the world.

Source: Casanova Peno I, et al. Neurobehcet disease: Clinical and demographic characteristics. Europ J Neurol 2012;19:1224-1227.

First described by Hippocrates, and characterized by anterior or posterior uveitis, aphthous ulcers, and painful genital lesions, Behçet's disease is a systemic inflammatory perivasculitis, predominantly occurring in the Middle and Far East and Mediterranean basin. Behçet's disease may affect any organ system, including the gastrointestinal tract, the skin and joints, and the large vessels, encompassing both the venous system, the superior and inferior vena cava and dural sinuses, and the arterial system, notably the aortic, carotid, pulmonary, iliac, femoral, and popliteal arteries. Neurologic involvement is more frequent in men than women and may affect the central or peripheral nervous system, but is seen in fewer than 15% of cases. In the absence of any pathognomonic laboratory test, and given the small number of patients reported, little is known of neuro-Behçet disease.

Retrospective review of all medical records of patients discharged from the Hospital Clinico San Carlos, in Madrid, Spain, between 1996-2009, with a diagnosis of Behçet's disease, was undertaken to determine the clinical and demographic characteristics of neuro-Behçet disease. Diagnosis of neuro-Behçet was based on neurological or psychiatric symptoms, with appropriate MRI findings including intraparenchymal focal lesions, aneurysms, arterial dissections or vasculitis, and/or cerebrospinal fluid abnormalities, encompassing increased cells, protein, or intracranial pressure, in the absence of another possible explanation. Statistical analysis utilized the nonparametric U Mann-Whitney test with P < 0.05 considered statistically significant.

Among 25 patients diagnosed with Behçet's disease, seven (28%) fulfilled neuro-Behçet criteria. Two had neuro-Behçet at the time of initial Behçet's disease diagnosis, but in no patient was it the initial symptom. Neurologic manifestations included focal epilepsy in two patients, and one each with a brainstem and cerebellar lesion, and one each with cerebral venous thrombosis, aseptic meningitis, or both. Relapsing-remitting disease was present in all but one, who had a progressive course, and intravenous steroid therapy followed by immunosuppressive medication, including azathioprine, methotrexate, cyclosporine, and infliximab, was beneficial to all. Among the remaining 18 non-neuro-Behçet patients, four each had a primary headache or psychiatric disorder, or nonspecific MRI abnormalities, and two had epilepsy with no evidence of neuro-Behçet. Overall, neuro-Behçet patients had a younger age-of-onset than the non-neuro-Behçet patients, 22.4 years vs 32.88 years, and had a significantly longer evolution until diagnosis, 3.3 years vs 0.35 years. Early suspicion of neuro-Behçet is needed for timely diagnosis and treatment.

Commentary

Indications are that Behçet syndrome may not be the same disease worldwide.1 Distinct regional differences exist, with northern European and American patients demonstrating mild ocular pathology and rare skin-test positivity, compared to severe eye disease seen in the Middle and Far East, and 60% skin-test positivity in countries of the Silk Road. Gastrointestinal disease is rare in Turkey (< 1%), but is seen in up to 50% of patients in Japan and Korea, whereas vascular disease is seen in only 5-10% of cases in the Far East but in 40% in the Middle East. Familial clustering of acne/arthritis cases also argue against one common pathological pathway for all, as does the variable responses of different organ systems to the same medication. Further research will be needed to allow us to fully understand this puzzling disease.

Reference

1. Yazici H, et al. Behcet syndrome: Is it one condition? Clin Rev Allerg Immunol 2012; Jun 7. DOI 10.1007/s12016-012-8319-x.