INTRODUCTION

 

Behçet’s disease (BD) is a chronic, multisystem disorder with vasculitis as its underlying pathological process. ¹ The classical triad of oral and genital ulcerations with uveitis was originally described by a Turkish dermatologist Hulusi Behçet in 1937.² Other structures reported to be involved through the course of the disease are the cardiovascular, CNS, pulmonary, and gastrointestinal systems.³ Neurological involvement is well described in BD (neuro-Behçet’s disease)⁴, with prevalence rates of (2.2-50%).^5,6

The aim of the study is to describe and categorize clinical neurological presentations of patients with Behçet’s disease.

 

SUBJECTS AND METHODS

 

Thirty patients (22 males and 8 females), selected from neurology and rheumatology department, Zagazig university hospitals, were retrospectively studied. The study period ranged from July 2010 to July 2012. Ages of patients ranged from 19 to 50 years (mean age, 36±2.3 years). All patients fulfilled the International Study Group criteria for the diagnosis of BD at presentation⁷ which requires the presence of recurrent oral ulceration plus any two of recurrent genital ulceration, typical defined eye lesions, typical defined skin lesions, or a positive pathergy test which is a test of cutaneous hypersensitivity to needle prick. Different methods have been used to perform this test⁸: single or multiple simple needle pricks, intradermal, subcutaneous or intravenous prick with or without normal saline. A positive test consists of sterile pustule that develops after 24-48 hours at the site of the needle prick.⁷

All patients were subjected to (1) Full history taking, (2) Full general and neurological examination, (3) Magnetic resonance imaging (MRI) of brain with and without contrast, (4) cerebrospinal fluid (CSF) examination(opening pressure ,cells, protein and sugar) was performed for all patients, and (5) Laboratory assessment including: ECG, complete blood count (CBC), liver and kidney function tests, chest X-ray and urine analysis and serological tests for rheumatoid factor  and antinuclear antibodies.

 

Statistical Analysis

Statistical analysis was carried out using mean, range, percentage and standard deviation, were applied. The Statistical Package for Social Sciences (SPSS) was used to obtain results.

 

RESULTS

 

Table 1. Demographic data of 20 patients with neuro-Behçet disease.

 

BD Behçet disease,  NP neurological presentation

 

Table 2. First clinical presentations in 30 patients with neuro-Behçet disease.

 

 

Table 3. Cumulative frequency of neurological signs and symptoms in 30 patients with  neuro-Behçet  disease.

 

 

 

DISCUSSION

 

The current study shows that NBD is a disease of young adults mainly in their third and fourth decades, which is comparable to reports from other countries.^9,10 This study shows also a marked male predominance. NBD was reported 2.8 times more often in men than in women.¹¹

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% have been reported, but are likely to be biased for various reasons (study design, definition of neurological involvement, availability of neurological expertise and investigations, and treatment protocols).¹²

The ‘parenchymal CNS’ pattern was the most common pattern in this series (60%), as was the case in most reports of NBD.^9,10 Parenchymal CNS’ pattern included patients whose clinical features were suggestive of focal or diffuse parenchymal CNS involvement with no prominent meningeal features; the CSF showed normal opening pressure, commonly with pleocytosis and/or high protein, and cranial CT scan was basically normal.

The commonly acute-subacute onset, widespread neurological symptoms and signs which do not respect medium or large vessel territories, inflammatory CSF findings, normal or multiple small infarcts on the cranial CT scan and the gradual improvement after each relapse suggest a widespread small vessel vasculitis as the basic pathological process in these cases. Although we have no histopathological confirmation from our cases, histopathological reports of similar cases confirm the proposed phenomenon.¹³ MRI findings in similar cases showed focal or diffuse changes with the same anatomical distribution as pathological lesions related to vasculitis.^10,14

Autopsy studies and biopsy specimens of the CNS lesions are consistent with vasculitis, and they show a clear venous predominance .Radiologic studies support this finding, in that lesions seen in NBD are not compatible with arterial territories. This information supports the probable inflammatory-venous pathogenesis for the CNS lesions seen in BD.¹⁵ Others believe that 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 neuronal loss. 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 is an inflammatory perivasculitis.¹⁶

The parenchymal distribution of lesions in NBS appears to support the hypothesis of small-vessel vasculitis; mainly, venular involvement. The anatomic distribution of intraaxial veins of the CNS explains the predominant involvement of the brain stem structures. This pattern of lesion distribution might help to differentiate NBD from other vasculitides as well as from the demyelinating diseases of the CNS, such as multiple sclerosis.¹⁷ CNS involvement due to SLE and other systemic vasculitis tends to involve arterial territories, and as a result, cortical involvement is frequently observed.¹⁸ We have not observed cortical involvement in NBS, despite previous pathologic studies in which such involvement has been reported.¹⁹

The main differential diagnosis of “parenchymal CNS” pattern is multiple sclerosis (MS). Internuclear ophthalmoplegia  is a common ocular finding in MS when brain stem involvement is prominent.²⁰ This sign was not encountered in our patients with NBD.

Clinical features of spinal cord involvement are relatively common in MS, but were uncommon in our patients. Pleocytosis of the CSF, when present, is more suggestive of NBD.²¹ Optic nerve involvement is common in MS ²², manifested by active optic neuritis or a history of visual disturbance, optic disc changes, or (visual evoked potential) VEP abnormalities suggestive of a previous attack. In NBD, when there is optic nerve involvement, it is either due to retinal vasculitis or optic nerve ischemia, or due to previous or present attack(s) of intracranial hypertension resulting in secondary optic atrophy.

The second main pattern was ‘intracranial hypertension’(IH) (30%) which was manifested by headache, vomiting and bilateral papilledema, commonly with no parenchymal CNS or meningeal involvement; the CSF opening pressure was elevated, commonly with normal cells and protein; cranial MRI brain showed a normal ventricular system and absence of intracranial mass. This pattern has frequently been reported from the Middle East.^23,24 The underlying pathological process in the IH pattern seems to be large venous occlusions involving large cerebral veins and/or sinuses due either to vasculitis involving the vasa vasorum of large veins or sinuses or due to a haemostatic abnormality or both. It is interesting to observe that large intracranial venous occlusion is relatively common in NBD²⁵, while large intracranial arterial occlusion is quite rare. The main differential diagnosis of patients presenting with intracranial hypertension, after exclusion of intracranial mass by proper neuroimaging, is idiopathic intracranial hypertension (IIH). The gender and the other systemic features of BD are helpful in the differentiation from IIH.²⁶

The third and least common main pattern (10%) was meningitis-like. These patients had features of acute meningitis manifested by headache, fever and meningeal signs, and their CSF showed pleocytosis with normal protein and sugar. The ‘meningitis-like’ pattern may simulate acute meningitis, especially viral meningitis, but the mild CSF pleocytosis in NBD rather than the usual high cell count encountered in viral meningitis is helpful in the differentiation.²⁶

 

Conclusion

In conclusion, NBD has characteristic clinical patterns of presentation. Features of BD should be carefully looked for in adults, especially men, in their twenties and thirties who present with IH, pseudobulbar palsy, brain stem syndrome, acute meningitis, stroke or myelopathy.

 

[Disclosure: Authors report no conflict of interest]

 

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