The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 3, 2009 —  Behcet’s disease (BD) is an uncommon, relapsing and remitting, multisystem inflammatory disorder characterized by the triad of oral ulceration, genital ulceration, and uveitis. [1] A number of additional features are commonly present, including arthritis, retinal and cutaneous vasculitis, thrombophlebitis, and gastroenteric disorders. The essential lesion is a focus of chronic inflammation, typically in the vicinity of a small blood vessel. Lesions in the CNS resemble those in other organ systems. Characteristically there are multiple small foci of softening that may eventually become confluent. These correspond to myelin loss and, to a lesser degree, drop out of neural elements with replacement by foamy macrophages. The lesions are not fundamentally demyelinative and more closely resemble minute ischemic foci. As in the periphery, lesions tend to occur near blood vessels, but vasculitis is uncommon. Pathologic findings are most extensive in the midbrain, pons (especially the basis pontis) and the medulla, and there is typically a lesser degree of involvement of the spinal cord, internal capsule, globus pallidus, optic nerves, and hypothalamus. In some cases, the cerebral white matter, cortex, hippocampus, basal ganglia, and thalamus are involved. The cerebellum is usually spared. The meninges are typically thickened and adherent to the brain surface, and acutely there may be considerable meningeal inflammation; hence the common reference to neuro-Behcet’s disease as a meningoencephalitis.

Between 5% and 20% of patients have neurologic disease. [1] The most common neurologic manifestation of BD is a relapsing and remitting, but often progressive, focal meningoencephalitis that most often affects the brain stem. [3,3] Patients present with a host of cranial nerve and long tract signs and eventually develop spastic quadriparesis and a bulbar or pseudobulbar palsy, frequently with rather dramatic emotional incontinence. [2,5,6,7,8] Cochlear and vestibular dysfunctions are common. Often there are additional features of impairment in frontal lobe and memory function characteristic of a subcortical dementia. A number of cases of nearly pure subcortical dementia have been reported, but typically long tract signs are prominent, and bulbar involvement eventually develops. Patients may also present initially with features of transverse myelitis, but bulbar signs characteristically appear as the disease progresses. Cerebral cortical involvement is unusual, but seizures and aphasia have been reported. The optic nerves are commonly involved, but symptoms are indiscriminable from those of uveitis, which is usually present in patients with neurologic features. CNS vasculitis is rare, but stroke caused by large artery involvement has been reported. Pseudotumor cerebri is relatively common and almost always caused by venous sinus thrombosis. Cerebral venous thrombosis may affect up to 10% of all patients with BD and one third of those with neurologic involvement. CNS involvement generally manifests several years after the onset of systemic BD, but occasionally it may be an initial feature and even precede other disease manifestations. As a rule, flares of neurologic disease parallel flares of systemic disease.

The diagnosis of BD is clinical. Patients with BD and venous thrombosis are often heterozygotes or homozygotes for the factor V Leiden allele. The CSF in patients with neurologic involvement is typically characterized by a pleocytosis (usually less than 100/mm³) that is equally likely to be neutrophil or lymphocyte predominant. CSF protein is only slightly elevated. There have been reports of intrathecal synthesis of oligoclonal IgA and IgM. An immunofixation electrophoretic pattern of oligoclonal bands has been reported in 16% of patients. Magnetic resonance imaging in patients with CNS disease typically reveals multiple 3-10 mm in diameter sharply marginated, irregular, and often confluent lesions in the spinal cord, brain stem, thalamus, basal ganglia, and deep cerebral white matter. The lesions may be quite extensive. In some cases, they may be difficult to distinguish from those of multiple sclerosis, but Dawson’s fingers are not seen.

Figure 4. Magnetic resonance (MR) images in Behcet’s disease with acute central nervous system (CNS) involvement (proton-density-weighted scan). Note the extensive, confluent region of increased signal involving much of the basis pontis and Pontine tegmentum and extending up through the midbrain into the left thalamus, basal ganglia, and periventricular white matter. (Click to enlarge figure)

High-dose corticosteroids (prednisone 60 mg/day) are effective in suppressing skin, mucosal, and arthritic manifestations of BD. Pulse cortico steroids (methylprednisolone I gm/day for 3 days) are often employed effectively for acute flares of neurologic disease, but the effect of cortico steroid treatment on chronic or recurrent neurologic disease is less satisfactory. Cortico steroids are clearly ineffective in halting the progression of uveitis and chlorambucil; 0.1-0.2 mg/kk/day has been used with considerable success in treating this disabling manifestation. [10] O’Duffy et al, [10] also induced remission in eight of nine patients with meningoencephalitis using chlorambucil. Azathioprine (Immuran), cyclosporine A, and colchicine have been shown in prospective, randomized studies to be highly effective in halting or preventing the ocular manifestations of BD; however, cyclosporine A is relatively contraindicated in the presence of neurologic disease. Acute neurologic symptoms are remarkably reversible and justify aggressive treatment during flares. Patients with cerebral venous thrombosis respond well to chronic anticoagulation without significant risk of intracranial hemorrhage. [9]

Thalidomide (Thalomid) is highly effective in suppressing oral and genital manifestations of Behcet’s disease; however, between 6% and 50% of patients develop an axonal sensorimotor polyneuropathy that may be dose related.

References

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11. Online case record….Behcet’s syndrome (Neuro-Behcet) [Full text]
12. Case of the week…..Neuro-Behcet [Click to download in PDF format]
13. Case of the week…..Neuro-Behcet [Click to download in PDF format]