Behçet's disease patients with multiple sclerosis-like features: discriminative value of Barkhof criteria.

OBJECTIVES: Behçet's disease (BD) is a systemic auto-inflammatory disorder of unknown cause, which may affect the central nervous system in around 5% of the patients [neuro-BD (NBD)], usually causing large lesions encompassing brainstem, diencephalon and basal ganglia regions. Occasionally NBD patients present with white matter lesions necessitating differential diagnosis from multiple sclerosis (MS). In this study, the efficacy of Barkhof criteria was tested in diagnostic differentiation of NBD and MS. METHODS: Charts and MRIs of 84 NBD patients were retrospectively evaluated. Clinical and radiological features of NBD patients fulfilling (Barkhof+) and not fulfilling Barkhof criteria (Barkhof-) were compared. RESULTS: While the Barkhof- patients (n=73) mostly displayed typical large lesions covering brainstem, diencephalon and basal ganglia regions and neurological findings consistent with brainstem involvement, all Barkhof+ (n=11) patients demonstrated MS-like white matter lesions, fulfilled McDonald's criteria and showed reduced frequency of brainstem symptoms and increased frequency of hemiparesis, hemihypesthesia and spinal cord symptoms. Moreover, the Barkhof+ group had more female patients, increased number of attacks, higher rate of oligoclonal band positivity and less patients with cerebrospinal fluid pleocytosis. CONCLUSIONS: A subgroup of BD patients with neurological complaints displays MS-like lesions, fulfills the clinical and radiological criteria of MS and presents with clinical and laboratory features resembling those of MS rather than NBD. These results suggest that Barkhof+ patients are either an overlapping group between NBD and MS, or they represent MS patients with concomitant systemic findings of BD, rather than NBD. Barkhof criteria appear to be effective in discriminating these patients.

Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behçet's disease.

OBJECTIVES: Oligoclonal bands (OCB) of immunoglobulins (IgG) in the cerebrospinal fluid (CSF) provides an evidence for the humoral response and have been screened in the CSF and serum of patients revealing 5 different patterns. In this study, patients with Behçet's disease (BD) are screened in a larger sample to potentially provide information about the possible role of CSF oligoclonal immunoglobulins in the diagnosis of this disease. METHODS: Paired CSF and serum samples from 121 consecutive BD patients with neurological complaints (43 women and 78 men) were included in this study. Parenchymal NBD was diagnosed in 74 patients, and 22 patients had cerebral venous sinus thrombosis (CVST); of the remaining patients, 18 had primary headache disorders not directly associated with BD, and 7 had a cerebrovascular event. OCB of IgG were detected by isoelectric focusing on agarose and immunoblotting of matched serum and CSF sample pairs. Intrathecal production of IgG only is considered positive (Pattern 2 or 3). RESULTS: In the whole group, only 8 patients had OCB in the CSF showing pattern 2. All these positive cases had parenchymal neuro-BD (10.8% positive and 78.4% negative in parenchymal neuro-BD group). All other groups were negative. CONCLUSIONS: The rare presence of oligoclonal IgG bands in CSF can be utilized as another laboratory finding in the diagnosis of NBD.

Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study.

Both multiple sclerosis (MS) and neuro-Behcet's disease (NBD) can cause a cognitive dysfunction mainly involving the executive functions. We conducted this study to clarify the probable differential cognitive/behavioral profiles of MS and NBD. Twenty consecutive cases with parenchymal NBD (13 male, seven female), and 20 cases with MS (five male, 15 female) were evaluated. Both groups had a thorough neurological examination; an evaluation for Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Beck's Depression Scale; and a detailed neuropsychological evaluation masked to the diagnosis. Among the two groups, male/female ratio differed significantly while other demographic and clinical features were not different. In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe "frontal"-executive dysfunction than MS patients.

Association of amyotrophic lateral sclerosis and Behcet's disease: is there a relationship? A multi-national case series.

Neurological involvement may be seen in 5-30% of the patients with Behcet's disease (BD). Occasionally, parenchymal neurological involvement in BD can present as a spinal cord syndrome. However, motor neuron disease-like presentation is extremely uncommon. Here we are reporting five patients (all male; median age, 38) fulfilling both International Study Group criteria for BD and El Escorial criteria for amyotrophic lateral sclerosis (ALS). These patients were identified by a questionnaire sent to the members of the Neuro-Behcet Study Group of the International Study Group for BD. Three out of five patients had only motor presentations. In two patients, sensory and urinary manifestations were present as well. Spinal cord MRIs were normal in all, and brain MRIs were normal in four patients; one patient had nonspecific white matter changes. Two patients passed away 1-3 years after diagnosis of ALS, and two patients were lost to follow-up 3 and 11 years after admission; one patient is still alive 3 years after onset. The patients that are presented here might represent a rare form of neurological involvement in BD as well as sole coincidence. Larger prospective series are needed to further answer this issue.

Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro-Behçet's disease with parenchymal involvement: presentation of four cases.

OBJECTIVES: Behçet's disease is a multisystemic, relapsing, inflammatory disorder of unknown origin. Among Turkish cohorts, 5-15% of patients show involvement of the central nervous system (CNS) at some time during their disease. There are mainly two types of clinical presentation: parenchymal CNS inflammation manifesting mainly as meningoencephalitis of the brainstem, or dural sinus thrombosis. Several drugs like high-dose steroids or immunosuppressive agents, mainly azathioprine, are used in the treatment. For patients who do not respond sufficiently to these agents or are not able tolerate them, other options are needed. PATIENTS: We are presenting 4 cases with parenchymal neuro-Behçet's disease, where commonly used immunosuppressive drugs could not be continued due to intolerance or inefficacy. However, the patients benefited well from mycophenolate mofetil. The benefit was sustained during 3-7 years of follow-up (median 6.5 years). CONCLUSIONS: Mycophenolate mofetil seems to be an alternative drug in parenchymal neuro-Behçet's disease; however, large controlled studies should be performed for verification of our results.

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis.

Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients.

Neuromyelitis optica (NMO) is an inflammatory/demyelinating disorder predominantly affecting the optic nerves and spinal cord. Recent findings showed an underlying humoral abnormality in NMO, characterized by a serum antibody against aquaporin-4 (Aqp-4-Ab). In this study, we evaluated the Aqp-4-Ab status among Turkish patients with NMO to determine the clinical and prognostic relevance. Serum samples from 35 consecutive patients with NMO followed at a single center and diagnosed according to the 2006 revised criteria, were evaluated for Aqp-4-Ab. All samples were obtained during a relapse prior to any immunosuppressive treatment. Aqp-4-Ab was positive in 21/35 (60%) patients. Among these cases, 11 had an EDSS of 6.0 or more, whereas only two patients in the seronegative group had such severe disability (p < 0.05). Overall, seropositive cases had a mean EDSS score of 5.1 ± 2.2 compared with 3.5 ± 1.7 in seronegative cases (p < 0.01). There were trends towards female predominance in seropositive cases and a monophasic course predominance in seronegative cases. Disease duration, age at onset, number of attacks and time to definite NMO did not differ between groups. Our findings in this single-center cohort suggest that the presence of Aqp-4-Ab might have a prognostic significance indicating a more severe disease course.

Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients.

Anti-aquaporin-4 (Aqp-4) antibody and complement system have emerged as major pathogenic factors in neuromyelitis optica (NMO). To test the significance of interleukin-6 (IL-6), another important humoral immunity factor, in NMO pathogenesis, we measured serum and cerebrospinal fluid (CSF) IL-6 levels of 23 NMO, 11 transverse myelitis, 16 optic neuritis, 27 relapsing remitting multiple sclerosis patients, and 20 neurologically normal controls. NMO and transverse myelitis patients had higher serum and CSF IL-6 levels than other groups. Particularly, anti-Aqp-4 positive NMO patients (n = 12) had higher serum/CSF IL-6 levels than anti-Aqp-4 negative patients (n = 11) and CSF IL-6 levels correlated with anti-Aqp-4 levels and disease severity of the NMO patients. Our results suggest that IL-6 is involved in NMO pathogenesis presumably via anti-Aqp-4 associated mechanisms.

Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome.

Increased cerebrospinal fluid (CSF) IL-6 has been reported in patients with Behçet's disease (BD) and neurological involvement. To elucidate the value of IL-6 as a marker of disease activity, serum and CSF IL-6 levels of 68 BD patients with acute (26) or chronic progressive (14) parenchymal involvement (pNB), dural sinus thrombosis (10), ischemic stroke (5) or headache (13) were measured by ELISA. Samples from multiple sclerosis, subacute sclerosing panencephalitis, and noninflammatory neurological disorders were used as controls. CSF but not serum samples of neuro-BD patients with acute pNB displayed significantly increased IL-6 levels as compared to other groups. Chronic progressive pNB patients also showed increased CSF IL-6 levels, albeit less prominent. Patients with increased CSF IL-6 levels were more likely to have increased CSF cell counts and total protein levels and these three parameters were correlated with long-term (3 years) disease outcome. In four chronic progressive patients, IL-6 was elevated despite otherwise normal CSF. CSF IL-6 seems to be a marker of disease activity and long-term outcome for pNB along with CSF cell count and protein levels. CSF IL-6 could be used in chronic progressive patients who have normal CSF cell, or protein levels to detect disease activity.