Central Nervous System Manifestations. CNS involvement is thought to affect 10% to 50% of patients, with a mortality rate of up to 20%. In general, CNS involvement is one of two presentations: parenchymal or nonparenchymal disease. Parenchymal involvement is a much more common manifestation (81% of CNS involvement). Parenchymal lesions present as recurrent meningoencephalitis involving the brainstem and less commonly the spinal cord and hemispheric regions of the brain. Common symptoms include pyramidal signs, hemiparesis, behavior change, sphincter dysfunction, impotence, and headaches. Nonparenchymal involvement is less common. In this group, intracranial hypertension is the most common manifestation and is frequently caused by a dural sinus thrombosis. Papilledema and arterial involvement are other manifestations. Poor prognostic signs include an abnormal CSF (elevated protein or cell count), parenchymal involvement, recurrent attacks, or a progressive course. There are no controlled trials regarding treatment of neurologic manifestations, but reports support the use of azathioprine, methotrexate, or cyclophosphamide in combination with glucocorticoids. Cyclosporine should generally be avoided in this setting because of the association with a higher rate of neurologic events.

Gastrointestinal Manifestations. Gastrointestinal involvement is present in 5% to 60% of patients. A high prevalence of gastrointestinal involvement exists in Japan, where up to one third of Behçet syndrome patients have gastrointestinal symptoms, but this is rare in Turkey. Symptoms may include anorexia, vomiting, dyspepsia, diarrhea, and abdominal pain. Mucosal ulcerations are most common in the ileum, followed by the cecum and other parts of the colon. In many instances, it is challenging to differentiate it from inflammatory bowel disease. The location, number, and patterns of ulcers as well as a pathergy test may give clues to help differentiate the two disorders because patients with Behçet syndrome tend to have fewer, more focal and rounded ulcers than patients with inflammatory bowel disease. Hepatic involvement is uncommon and should raise suspicion for Budd-Chiari syndrome. There are no controlled studies regarding treatment of gastrointestinal manifestations, but sulfasalazine, glucocorticoids, azathioprine, tumor necrosis factor antagonists, or thalidomide should be used before considering surgery in most cases. However, situations requiring emergent surgery can arise, such as bowel perforation.

Other Manifestations. Sporadic cases of systemic amyloidosis type AA can occur. Direct bladder involvement can lead to voiding dysfunction. Epididymitis occurs in around 5% of patients.