Impact of factor VIII and von Willebrand factor plasma levels on cerebral venous and sinus thrombosis: are they independent risk factors?

BACKGROUND: The aim of this study was to assess the plasma levels of factor VIII (FVIII), von Willebrand factor (vWF) and their association in patients with cerebral venous sinus thrombosis (CVST). METHODS: We prospectively included 25 CVST patients admitted to the university hospital and 53 voluntary subjects as a control group. FVIII and vWF were measured after 6 months when anticoagulant therapy was stopped. RESULTS: The mean FVIII and vWF levels were significantly higher in the CVST group compared to the control group (126.21 ± 54.69 vs. 91.9 ± 48.8 IU/dl; p = 0. 012; 157.05 ± 107.74 vs. 94 ± 84%; p = 0.01, respectively). Using analyses calculating the 95th percentile cut-off values, we found high levels of FVIII in patients compared to controls (29.2 vs. 5%; p = 0.01) and the odds ratio with 95% confidence interval (CI) was 7.82 (1.46, 41.6). After adjustment for vWF levels, sex and age, the risk remained significantly increased and the odds ratio with 95% CI was 10.5 (1.1, 101.4) (p = 0.041). CONCLUSION: FVIII is one of the most prevalent risk factors of CVST and may be associated with an approximately tenfold increased risk for developing CVST. This effect is independent of vWF levels; however, vWF is not an independent risk factor of CVST.

Cerebral vein and dural sinus thrombosis in adults in Isfahan, Iran: frequency and seasonal variation.

OBJECTIVE: To estimate the frequency of cerebral vein and dural sinus thrombosis (CVST) and its seasonal variation. METHODS: A clinic-based prospective case-register study was conducted from 2001 to 2004. Hundred and twenty-two consecutive definite CVST patients (26 men and 96 women) treated in two major neurological centres of Isfahan, Iran, were included in the study. Part of examination included an assessment of CVST including conventional angiography and/or magnetic resonance imaging and self-reported medical history. Population data were obtained from the 1996 Iran Census. The mean (standard deviation) age of participants was 35.5 (11.9) years. RESULTS: The annual frequency (95% confidence interval) of CVST was 12.3 (10.1, 14.5) per million in a population of 2,472,751, with higher rate in women than in men [19.9 (15.5, 23.9) women and 5.1 (3.2, 7.1) men] and with increasing age in women (up to 50 years), but not in men. The female/male ratio was 3.9 (2.5-6.0). The monthly frequency of CVST ranged from 0.6 per million (0.1, 1.1) in August to 2.1 (1.2, 3.0) in September. The seasonal CVST rate ranged from 2.2 per million (1.3, 3.2) in summer to 4.3 (3.1, 5.7) in autumn. The differences were statistically significant either for the months or season (P < 0.05). CONCLUSION: The findings of this study show the CVST frequency in adults. More women than men are present with CVST and its frequency increased during autumn.

Clinical and demographical characteristics of primary progressive multiple sclerosis in Isfahan, Iran.

Primary progressive multiple sclerosis (PPMS) is an uncommon form of multiple sclerosis (MS) in which the course of disease is progressive from onset. In a retrospective study amongst 1606 MS patients registered in Isfahan MS Society (IMSS) from April 2003 to 31 December 2005, 92 PPMS cases were identified. That means, the frequency of PPMS amongst all included MS patients would be 5.7% (95% CI: 6.7% and 4.7%). The mean expanded disability status scale (EDSS) for the group was 5.09 +/- 1.3. The commonest mode of presentation was motor disturbance in 55 (59.8%), other modes of presentation were, vertigo in 15 (16.3%), visual problems in 12 (13%), sensory disturbances in six (6.5%), and diplopia in four (4.3%). The current [corrected] existing symptoms were motor problems in all 92 (100%), cerebellar symptoms in 46 (50%), and cognitive impairment in only 6[corrected](6.5%). Interestingly, two (2%) were affected by poliomyelitis during childhood and presenting symptom in both was limb weakness. Primary progressive form of MS is less common in Persian population and some of the rates observed in PPMS patients differ from those in other regions, these differences may be due to different ethnicity of Persian patients or to geographical differences.

Severe cognitive dysfunction in a patient with polyendocrinopathy.

BACKGROUND: Polyglandular Autoimmune syndromes (PGAs) or polyendocrinopathies are immune mediated multiple endocrine gland failure sometimes accompanied by nonendocrine autoimmune disorders with varieties of presentations. CASE REPORT: We describe a case of a middle aged man with severe cognitive dysfunction, brain atrophy, adrenal insufficiency, hypothyroidism, renal failure, thrombocytopenia, and positive antiphospholipid antibodies, with significant renal and cognitive improvement after hormone replacement. CONCLUSIONS: PGAs may present with a broad spectrum of manifestations related to different organs like nervous,renal,cardiac and hematopoietic systems, sometimes challenging both to physician and the patient.

Interferon-beta-1beta protects against multiple sclerosis-induced endothelial cells apoptosis.

Disruption of the blood-brain-barrier (BBB) due to endothelial cell (EC) injury is an essential step in formation of multiple sclerosis (MS) lesions. We investigated the role of endothelial cell (EC) apoptosis in the pathophysiology of MS, studying the therapeutic effect of IFN-beta-1b against MS sera-induced endothelial apoptosis. Human umbilical vein endothelial cells were treated with sera from patients with active MS (in relapse), MS in remission, or sera from healthy volunteers (each n = 5). Apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on EC apoptosis were tested at increasing doses (10, 100, and 1000 U/ml). Nitrite (NO2-⁻) levels were determined in culture supernatants. EC apoptosis was increased by sera from exacerbating MS patients, but not remission, compared to healthy individuals (p less than 0.001). Effects were blocked by IFN-beta-1b at 10 U/ml (p less than 0.05), but not higher doses, and was associated with increased NO/NO2- production (less than 0.05). EC apoptosis leading to disruption of the BBB may play a role in MS etiology and represents a novel therapeutic mechanism of action for IFN-beta-1b in MS therapy.

Modelling the interaction of ankle-foot orthosis and foot by finite element methods to design an optimized sole in steppage gait.

In this study, based on kinematics data in steppage gait, a finite element model of human gait with ankle-foot orthosis (AFO) has been proposed to optimize the role of AFO through minimizing stress in the patients' sole. The required kinetics data for the model were captured through a force plate and then analysed by 3D-DOCTOR and ANSYS software. In the proposed three-dimensional finite element model the transmitted tension in soft tissue and bones during gait was calculated. By changing the thickness and materials of different layers of sole in AFO the tension variations have been assessed. Unlike previous studies, the effect of orthosis on tension generated in bones and muscles has been dynamically and continuously modelled and the contact between AFO and sole has been considered in this model. By using the optimized sole the stress distribution has been changed by +50.38% in the forefoot, +15% in the midfoot and -37.79% in the hindfoot. The tension reduction in the sole can improve the effect of AFO during abnormal gait. It is possible to design each orthosis sole based on the kinetics data of each patient.

Modelling of human walking to optimise the function of ankle-foot orthosis in Guillan-Barré patients with drop foot.

INTRODUCTION: This paper deals with the dynamic modelling of human walking. The main focus of this research was to optimise the function of the orthosis in patients with neuropathic feet, based on the kinematics data from different categories of neuropathic patients. METHODS: The patient's body on the sagittal plane was modelled for calculating the torques generated in joints. The kinematics data required for mathematical modelling of the patients were obtained from the films of patients captured by high speed camera, and then the films were analysed through a motion analysis software. An inverse dynamic model was used for estimating the spring coefficient. RESULTS: In our dynamic model, the role of muscles was substituted by adding a spring-damper between the shank and ankle that could compensate for their weakness by designing ankle-foot orthoses based on the kinematics data obtained from the patients. The torque generated in the ankle was varied by changing the spring constant. Therefore, it was possible to decrease the torque generated in muscles which could lead to the design of more comfortable and efficient orthoses. CONCLUSION: In this research, unlike previous research activities, instead of studying the abnormal gait or modelling the ankle-foot orthosis separately, the function of the ankle-foot orthosis on the abnormal gait has been quantitatively improved through a correction of the torque.

Hormonal contraceptives as a risk factor for cerebral venous and sinus thrombosis.

This review will focus on recent developments in our understanding of cerebral venous and sinus thrombosis (CVST), as a side effect of combined oral contraceptives (COCs) use. Case-control studies have shown an increased risk of CVST in women who use COCs, especially third-generation contraceptives that contain gestodene or desogestrel. Several studies have indicated that the combination of COCs and thrombophilia greatly increased the risk of CVST, particularly in women with hyperhomocysteinaemia, factor V Leiden and the prothrombin-gene mutation. Women with thrombophilia who developed CVST while taking oral contraceptives should be definitively advised to stop using COCs. These patients should be considered for preventive therapy with low doses of heparin in prothrombotic situations such as bed rest or pregnancy, and the duration of anticoagulation should be considered on a case-by-case basis. Patients may be considered candidates for chronic treatment with antiplatelet agents. The best and most cost-effective screening method for thrombophilia in women who are planning to conceive is selective screening based on the presence of previous personal or family history of either prior extracerebral or cerebral venous thromboembolism events.

Conjugal multiple sclerosis in Isfahan, Iran: a population-based study.

Conjugal multiple sclerosis (MS) is a rare form of MS in which both spouses are affected, and at least one is affected after marriage. Among 1606 definite MS patients, 1076 were in marital relationship, among whom we identified six conjugal pairs, giving the conjugal rate of 0.5%. This rate is 12.5 times higher than the estimated risk of MS for the general population (0.04%). The observed conjugal rate suggests an increased risk of developing MS for MS patients' spouses, this could be due to transmission or, more likely, to the same environmental factors shared in adult life.