Chapter 110 - Neuro-Behçet syndrome

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Abstract

Behçet syndrome (BS) is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin. As the disease affects many organs and systems and shows a wide range of clinical manifestations and presentations, it is prefereable to call Behçet’s a syndrome (BS) rather than a disease. Nervous system involvement, known as “neuro-BS” (NBS), is seen in about 5–10% of all cases. Clinical and imaging evidence suggests that primary neurologic involvement in BS may be subclassified into two major forms: the first, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system disease with focal or multifocal parenchymal involvement, mostly presenting with a subacute brainstem syndrome and hemiparesis (intra-axial NBS); the other, which has few symptoms and a better neurologic prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension (extra-axial NBS), occurring in 10–20% of the cases. These two types are rarely seen in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a vascular type headache is relatively common and independent from neurologic involvement. Neurologic complications secondary to systemic involvement of BS, as well as neurologic complications related to BS treatments are considered as secondary neurologic involvement of the syndrome. The core histopathologic phenomenon seems to be a vasculitic involvement in some cases, and low-grade chronic nonspecific inflammation in others. As the neurologic involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and its response to treatment. Currently, treatment options for NBS are limited to attack therapies with high-dose intravenous methylprednisolone followed by a prolonged oral taper, symptomatic management, and generally the use of azathioprine, cyclophosphamide, interferon-α and anti-TNF agents for long-term preventive treatment, although there no evidence for their efficacy.

Introduction

Behçet’s disease, originally described in 1937 by Hulusi Behçet as a distinct disease with orogenital ulceration and uveitis (Behçet, 1937), known as the “triple-symptom complex,” is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin. The disease affects many organs and systems, causing mucocutaneous lesions, uveitis sometimes resulting in blindness, nervous system involvement, major vessel disease that may be fatal, musculoskeletal problems, gastrointestinal involvement, and others. Because of this multisystem involvement and the wide range of clinical manifestations and presentations, many prefer to call Behçet’s a syndrome (BS) rather than a disease (Yazici, 2003).

Section snippets

Epidemiology

The epidemiology of the disease shows a geographical variation, seen more commonly along the Silk Route that extends from the Mediterranean region to Japan. This is coupled by a similar variation in HLA-B51 association, which is strongly associated with the disease in high prevalence areas such as Middle and Far East (Yazici et al., 2010). Interestingly, BS also shows a geographical variation in disease expression, with severe eye involvement and inflammatory bowel disease being more common in

Diagnosis and systemic manifestations of behçet syndrome

Currently the most widely used diagnostic criteria are those of the International Study Group’s classification, according to which a definitive diagnosis requires recurrent oral ulcerations plus two of the following: recurrent genital ulcerations, skin lesions, eye lesions and a positive pathergy test (International Study Group for Behçet’s Disease, 1990, International Study Group for Behçet’s disease, 1992) (Table 110.1).

Pathology and pathogenesis of behçet syndrome

The core histopathologic phenomenon seems to be a vasculitic involvement in some cases and a low-grade, chronic, nonspecific inflammation in others (Sakane et al., 1999, Demirkesen et al., 2010). The vessel wall changes and perivascular mononuclear cell infiltration consistent with vasculitis involving both arterial and venous systems have been shown in histopathologic studies. However, vascular involvement in BS is predominantly venous in contrast to what is seen in most other systemic

Nervous system involvement in Behçet syndrome: “Neuro-Behçet syndrome”

Neuro-Behçet syndrome (NBS) is defined as the occurrence of neurologic symptoms in a patient with BS that is not better explained by any other well-known systemic or neurologic disease. The prevalence of NBS in BS is between 3% and 9% in nonselected large series (Akman-Demir et al., 1999, Kidd et al., 1999, Siva et al., 2001, Al-Araji and Kidd, 2009; Davatchi et al., 2010). Although rates up to 59% have been reported, most of these high rates come from hospital-based selected series from

Neuroimaging

Cranial magnetic resonance imaging (MRI) is both more specific and more sensitive than computed tomography (CT) in showing the reversible inflammatory parenchymal lesions of intra-axial NBS. Lesions are generally located within the brainstem, occasionally extending to the diencephalon, and less often, within the periventricular and subcortical white matter (Koçer et al., 1999). (Fig. 110.1, Fig. 110.2)

The most commonly affected region is the mesodiencephalic junction, followed by the

Differential diagnosis of intra-axial (parenchymal) neuro-Behçet syndrome

The major diseases to be included in the differential diagnosis of parenchymal NBS are shown in Table 110.5.

Patients with NBS are young and frequently present with an acute or subacute brainstem syndrome or hemiparesis, as well as with other various neurologic manifestations. Hence, the possibility of BS is often included in the differential diagnosis of multiple sclerosis and in the stroke of the young adult, especially in the absence of its known systemic symptoms and signs.

Multiple sclerosis

Prognosis

Neurologic involvement in BS is a remarkable cause of morbidity and approximately 50% of the NBS patients are moderately to severely disabled after 10 years of disease. We rated the neurologic disability of our patients with BS by using the Expended Disability Status Scale of Kurtzke (EDSS), which was originally devised for multiple sclerosis-associated disability. Taking into consideration that the visual disability is most commonly due to uveitis in BS, the visual function was eliminated from

Treatment

Neurologic involvement in BS is heterogeneous and it is difficult to predict its course and prognosis, and response to treatment. Therefore, it is not possible to reach a conclusion on the efficacy of any treatment unless properly designed, double masked, placebo controlled studies are carried out for each type. However, this is difficult to accomplish, as even in large centers the yearly numbers of new neuro-cases are very limited. Most studies which report some kind of efficacy with various

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