Cerebral venous thrombosis in children: a multifactorial origin (original) (raw)

Background-The present study was performed to assess the association of prothrombotic risk factors and underlying conditions (infections, vascular trauma, immobilization, malignancies, autoimmune diseases, renal diseases, metabolic disorders, obesity, birth asphyxia, cardiac malformations, and use of prothrombotic drugs) with cerebral venous thrombosis (CVT) in children. Methods and Results-From 1995 to 2002, 149 pediatric patients aged newborn to Ͻ18 years (median 6 years) with CVT were consecutively enrolled. In patients and in 149 age-and gender-matched children with similar underlying clinical conditions but without CVT, the factor V G1691A mutation, the factor II G20210A variant, lipoprotein(a) [Lp(a)], protein C, protein S, antithrombin, and antiphospholipid antibodies, as well as associated clinical conditions, were investigated. Eighty-four (56.4%) of the patients had at least 1 prothrombotic risk factor compared with 31 control children (20.8%; PϽ0.0001). In addition, 105 (70.5%) of 149 patients with CVT presented with an underlying predisposing condition. On univariate analysis, factor V, protein C, protein S, and elevated Lp(a) were found to be significantly associated with CVT. However, in multivariate analysis, only the combination of a prothrombotic risk factor with an underlying condition (OR 3.9, 95% CI 1.8 to 8.6), increased Lp(a) (OR 4.1, 95% CI 2.0 to 8.7), and protein C deficiency (OR 11.1, 95% CI 1.2 to 104.4) had independent associations with CVT in the children investigated. Conclusions-CVT in children is a multifactorial disease that, in the majority of cases, results from a combination of prothrombotic risk factors and/or underlying clinical condition. (Circulation. 2003;108:1362-1367.) Key Words: pediatrics Ⅲ lipoproteins Ⅲ thrombosis C erebral venous thrombosis (CVT) in childhood is a serious disease that is being increasingly diagnosed, mainly because of more sensitive diagnostic procedures and increasing clinical awareness of the disease. 1 The clinical presentation shows a wide spectrum of symptoms, eg, seizures, papilledema, headache, lack of consciousness or lethargy, and focal neurological deficits. 1,2 The origin and pathophysiology of CVT in the pediatric population is still poorly understood, mainly because of its low incidence, which is estimated at 0.67 per 100 000 children. 1 The disease is serious, and predisposing and influencing factors should be unraveled to identify patients at risk and to establish treatment regimens in children. Local or systemic infections, 3-6 vascular trauma, 7 cancer, acute lymphoblastic leukemia, drug toxicity, 8 lupus erythematosus, 9 nephrotic syndrome, 10 dehydration, 11 asphyxia, maternal problems during pregnancy, 12 Behçet's disease, 2 and metabolic disorders 13-15 have been described as predisposing factors. Recently published data have suggested that multiple additional factors including prothrombotic risk factors contribute to the symptomatic onset of CVT. 11,16,17 In contrast to childhood venous thrombosis, in which the influence of thrombophilic disorders is now well established, data describing prothrombotic risk factors contributing to the origin of CVT in adults and pediatric patients are still conflicting. 16-29 The present study was performed to assess the role of prothrombotic risk factors in combination with underlying clinical conditions as risk factors for CVT in children. Methods Ethics The present prospective multicenter follow-up study was performed in accordance with the ethical standards established in the updated