Elsevier

The Lancet Neurology

Volume 8, Issue 2, February 2009, Pages 192-204
The Lancet Neurology

Review
Neuro-Behçet's disease: epidemiology, clinical characteristics, and management

https://doi.org/10.1016/S1474-4422(09)70015-8Get rights and content

Summary

Behçet's disease (BD) is a multisystem relapsing inflammatory disorder of unknown cause. In neuro-BD (NBD), the CNS can be involved in one or both of two ways: first, and most commonly, through the development of an immune-mediated meningoencephalitis, which predominantly involves the brainstem, but can also involve the basal ganglia, thalamus, cortex and white matter, spinal cord, or cranial nerves; and second, as a consequence of thrombosis within the dural venous sinuses. Headache is a common symptom in BD and does not necessarily indicate CNS involvement. Peripheral nervous system involvement is rare. New treatment options have recently become available, which have led to an improvement in morbidity after meningoencephalitis. Most of the reported studies on NBD are retrospective. Collaborative prospective studies of the natural history of the disease, particularly the nature and treatment of progressive neurological disease, and evidence-based studies of treatment are needed.

Introduction

Behçet's disease (BD) bears the name of a Turkish dermatologist, Hulusi Behçet, who described the triad of recurrent oral and genital ulcers and uveitis in 1937.1 BD is a multisystem disease of unknown cause in which an inflammatory perivasculitis can arise in almost any tissue.2, 3 The highest incidence of BD is in the Middle East, the Mediterranean basin, and the Far East regions, but it is rare in Europe and North America. The nature and prevalence of the various systemic features are summarised in table 1.4 The most widely accepted criteria for the diagnosis of BD are the International BD Study Group criteria (panel 1).5

Neurological involvement is one of the most serious causes of long-term morbidity and mortality in BD.6 Although BD is rare in neurological practice in most countries, it is commonly mentioned in the differential diagnosis of inflammatory or demyelinating CNS diseases. In this Review, we summarise and describe the current understanding of the various neurological aspects of BD with a special emphasis on practical aspects of the diagnosis and management of neurological complications.

Section snippets

Epidemiology

Over the past 15 years, increasing numbers of patients have been reported in different series that have described the various clinical and epidemiological features of neuro-BD (NBD). Table 2 summarises the findings of these reports.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25

The frequency of neurological involvement in BD is very variable; in hospital-based series, percentages as low as 1·3%26 and as high as 59%10 have been reported, but are likely to be biased for

Classification

The CNS is the major target of neurological involvement in BD. There are two categories of CNS involvement in BD that have been generally accepted (panel 2): parenchymal and non-parenchymal involvement.8, 11, 12, 13, 14, 19, 22, 25, 34, 35, 36 In the parenchymal category, meningoencephalitis occurs, whereas in non-parenchymal NBD, vascular complications involving thrombosis within large veins and occasionally arteries occur. Involvement of parenchymal tissue either does not occur in

Neuropathology

The neuropathology of parenchymal NBD in the acute phase involves meningoencephalitis with an intense inflammatory infiltration including polymorphs, eosinophils, lymphocytes, and macrophages, with areas of necrosis and apoptotic neuronal loss.37 Intense inflammatory infiltration of small vessels can occur, but fibrinoid necrosis is not seen. NBD is therefore not a cerebral vasculitis (as blood vessel walls are not infiltrated and there is no evidence for endothelial cell necrosis); rather, it

Diagnosis

The diagnosis of neurological involvement in BD is done mainly by clinical means; the ancillary investigations noted below help to suggest alternatives, and especially infective complications of treatment, but there is no diagnostic test for NBD. In a patient with a clinical syndrome characteristic of systemic BD, with, for example, retinal vasculitis, orogenital ulceration, pathergy, and joint involvement, the presence of a sagittal venous sinus thrombosis or an inflammatory brainstem lesion

Parenchymal NBD

Subacute meningoencephalitis accounts for 75% of cases in parenchymal NBD (table 2). Onset is commonly subacute,11, 12, 13 and often associated with exacerbation of the systemic features of BD, including fever, malaise, orogenital ulcers, skin lesions, or uveitis.11, 19, 24, 60 Headache is common before and during the attack. The symptoms and signs take a few days to reach a peak and last for several weeks, depending on the extent of the lesion and on how rapidly treatment is initiated. Less

Management

There have been no controlled or comparative trials of treatment of any aspect of neurological involvement in BD. There is a consensus among neurologists with experience in the management of these disorders that, in most cases of inflammatory parenchymal disease, corticosteroids should be given as infusions of intravenous methylprednisolone followed by a slowly tapering course of oral steroids. It is important to avoid an abrupt cessation of therapy to avoid early relapse. Whether

Clinical course and prognosis

Most patients who have an acute parenchymal inflammatory episode recover well after steroid treatment. Retrospective series from 10–15 years ago reported a mean of 20–30% of patients with residual neurological impairments,12, 14 and a high 10-year mortality of 10%. Around a third of patients have single episodes, a third have repeated relapses with remission, and a third undergo a progressive disease course with accrual of neurological impairments.11, 12, 13, 14 A primarily progressive disease

Conclusions and further perspectives

Over the past 10 years, our understanding of the clinical features and pathophysiology of neurological complications in BD has increased substantially due to the simultaneous interest of clinical researchers around the world. We have reviewed the current understanding of the nature, pathogenesis, and management of NBD. Parenchymal complications arise due to a meningoencephalitis that might occur in the brainstem, cerebral hemispheres, spinal cord, or cranial nerves. Diffuse and progressive

Search strategy and selection criteria

References for this Review were selected by a PubMed search of English language publications and covered the period from 1946 to November, 2008, by use of the terms “Behçet's”, “Behçet's disease”, “Behçet's syndrome”, and “neuro-Behçet's”. Further articles were identified from the references cited in those articles. Abstracts were reviewed, and when relevant findings were reported, the full article was retrieved and reviewed. We also identified articles from our personal knowledge of the

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