Aksel Siva

EULAR recommendations for the management of Behçet disease

Objectives: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion. Methods: The multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a Rehabilitation Medicine doctor), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Problem areas and related keywords for systematic literature research were identified. Systematic literature research was performed using Medline and the Cochrane Library databases from 1966 through to December 2006. A total of 40 initial statements were generated based on the systematic literature research. These yielded the final recommendations developed from two blind Delphi rounds of voting. Results: Nine recommendations were developed for the management of different aspects of BD. The strength of each recommendation was determined by the level of evidence and the experts’ opinions. The level of agreement for each recommendation was determined using a visual analogue scale for the whole committee and for each individual aspect by the subgroups, who consider themselves experts in that field of BD. There was excellent concordance between the level of agreement of the whole group and the “experts in the field”. Conclusion: Recommendations related to the eye, skin–mucosa disease and arthritis are mainly evidence based, but recommendations on vascular disease, neurological and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. The need for further properly designed controlled clinical trials is apparent.

Impairment, disability, and handicap in multiple sclerosis A population-based study in Olmsted County, Minnesota

We studied functional status of MS patients in a geographically based cohort in Olmsted County, Minnesota. The 162 definite MS patients who were alive and residing in the study area on December 1, 1991, constituted the MS prevalence disability cohort. We identified 179 cases of definite or probable MS, providing an overall sex-and age-adjusted prevalence rate of 167.5 per 100,000. Median duration of MS from onset was 15.4 years, and median age on prevalence date was 47.5 years. The Minimal Record of Disability for MS determined the degree of impairment, disability, and handicap of the entire cohort within 4 months of the prevalence date. The frequency of Expanded Disability Status Scale scores of the MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5 [1 to 9.5], median [range]). Approximately one-third of the cohort had marked paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed intermittent or almost constant catheterization for bladder dysfunction. Few patients (3.7%) reported severe decrease in mentation or dementia requiring supervision. Many patients (53.1%) were working full-time. Most patients (72.2%) maintained their usual financial standard without external support. There were no differences in level of impairment, disability, or handicap observed between the subgroup of 122 patients (75.3%) who are incident cases (onset of disease as residents of Olmsted County) compared with the entire prevalence cohort. This geographically based study of MS demonstrates that the functional status is more favorable than previously recognized.

Behçet's disease : diagnostic and prognostic aspects of neurological involvement

Abstract This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçets disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçets Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzkes Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n=18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçets syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçets syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7±2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.

Management of Behçet disease: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for the management of Behçet disease

Objectives: To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD. Methods: Problem areas and related keywords regarding the management of BD were determined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A systematic literature research was performed using MedLine and Cochrane Library resources through to December 2006. Meta-analyses, systematic reviews, randomised controlled trials (RCTs), open studies, observational studies, case control studies and case series’ involving ⩾5 patients were included. For each intervention the effect size and number needed to treat were calculated for efficacy. Odds ratios and numbers needed to harm were calculated for safety issues of different treatment modalities where possible. Results: The literature research yielded 137 articles that met the inclusion criteria; 20 of these were RCTs. There was good evidence supporting the use of azathioprine and ciclosporin A in eye involvement and interferon (IFN)α in mucocutaneous involvement. There were no RCTs with IFNα or tumour necrosis factor (TNF)α antagonists in eye involvement. Similarly controlled data for the management of vascular, gastrointestinal and neurological involvement is lacking. Conclusion: Properly designed, controlled studies (new and confirmatory) are still needed to guide us in managing BD.

Behçet’s Syndrome and the Nervous System

Purpose of reviewBehçets syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The syndrome is rare, but as patients with BS are young and frequently present with an acute or subacute brainstem syndrome or hemiparesis, as well as with other various neurological manifestations, the syndrome is often included in the differential diagnosis of multiple sclerosis, stroke of the young adult, and another wide range of neurological disorders. The present review summarizes the neurological involvement in BS, and emphasizes recent clinical concepts and ethiopathogenetic findings. Recent findingsOver the last years the growing clinical and imaging evidence had suggested that neurological involvement in BS may be subclassified into two major forms: one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory CNS disease, with focal or multifocal parenchymal involvement; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. A nonstructural vascular type headache is relatively common, whereas isolated behavioral syndromes and peripheral nervous system involvement are rare. SummaryThe involvement of the nervous system in BS is heterogeneous as clinical and imaging data reveal. Currently it is unknown which factors determine or have a role in the development of neurological involvement, but some progress has been achieved in understanding the neurological spectrum of the syndrome, which may lead to a better management of these patients.

Vasculitis of the nervous system

Abstract Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PMS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. “Primary angiitis of the CNS” is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments.. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçets Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.

Survival and predictors of disability in Turkish MS patients

Objective: To examine the natural history, survival, and prognostic factors in a sample of Turkish MS patients. Method: This multicenter study included 1,259 definite MS patients diagnosed according to the criteria of Poser et al. Actuarial analysis of selected disability levels of 3, 6, 8, and 10 achieved with the Expanded Disability Status Scale (EDSS); a multivariate Cox regression analysis for prognostic factors related to time to reach EDSS ≥ 6; and Pearsons correlation coefficient for individual factors were performed. Results: The survival (±SE) at 15 years from onset was 94.6 ± 2.9%, and at 25 years was 89.0 ± 5.8%. The disability reached by 15 years was EDSS ≥ 3 in 66.4%, EDSS ≥ 6 in 41.2%, EDSS ≥ 8 in 10.5%, and EDSS = 10 in 5.4%. The most significant unfavorable prognostic factors were progressive course (relative risk [RR], 3.73; CI, 2.71 to 5.13) and sphincter symptoms at onset (RR, 1.86; CI, 1.23 to 2.82), followed by male sex, motor symptoms at onset, and a high attack frequency within the first 5 years. Primary progressive disease was correlated positively with male sex (r = 0.0895, p = 0.001), older age (r = 0.1807, p = 0.000), and motor (r = 0.1433, p = 0.000) or sphincter symptoms (r = 0.1001, p = 0.000) at onset, unlike relapsing-remitting and secondary progressive disease. Conclusions: Although a slightly better prognosis is observed in the Turkish MS population, early prognostic factors are similar to most of the previous Western series. Primary progressive disease, mostly seen in older men with motor and sphincter involvement at onset, has a worse prognosis and may represent a distinct behavioral variant of MS.

Radiologically Isolated Syndrome: 5-Year Risk for an Initial Clinical Event

Objective To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. Methods Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. Results Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11–74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01–21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96–0.99); p = 0.03], sex (male) [HR: 1.93 (1.24–2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06–4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event. Interpretation These data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.

The spectrum of nervous system involvement in Behçet’s syndrome and its differential diagnosis

Behçet’s Syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The growing clinical and imaging evidence suggests that primary neurological involvement in BS may be subclassified into two major forms: the first one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system (CNS) disease, with focal or multifocal parenchymal involvement mostly presenting with a subacute brainstem syndrome and hemiparesis; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a nonstructural vascular type headache is relatively common and independent from neurological involvement. Neurologic complications secondary to systemic involvement of BS such as cerebral emboli from cardiac complications of BS and increased intracranial pressure due to superior vena cava syndrome, as well as neurologic complications related to BS treatments such as CNS neurotoxicity with cyclosporine and peripheral neuropathy with the use of thalidomide or colchisin are considered as secondary neurological complications of this syndrome. As the neurological involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and response to treatment. Currently, treatment options are limited to attack and symptomatic therapies with no evidence for the efficacy of any long term preventive treatment.

The sensitivity and specificity of the case definition criteria in diagnosis of headache: a school-based epidemiological study of 5562 children in Mersin.

The objectives of the present study were to estimate the prevalence of recurrent headaches in schoolchildren (ranging from 2nd to 5th degrees) in Mersin city of Turkey and to determine the sensitivity, specificity, positive predictive value and positive likelihood ratio of the diagnostic headache characteristics in children with migraine and Tension Type Headache (TTH) using neurologists diagnosis as the gold standard. The stratified sample of study was composed of 5562 children. The prevalence of recurrent headache was 49.2% (2739 of 5562) and the prevalence of current headache was 31.3% (859 of 2739). TTH was more common than migraine (24.7% vs. 10.4%). The most sensitive headache characteristic for migraine was ‘severity of pain’ and the most sensitive definitive symptom is ‘duration of headache’ in children with TTH. IHS-based symptom definition criteria are highly beneficial in diagnosis of childhood headache, if used together with detailed clinical assessment.