Cerebral Venous Thrombosis in Neonates, Children and Adolescents; Results from the German Pediatric Surveillance Unit for Rare Pediatric Diseases (ESPED)

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) is a serious disease, that leads to longterm neurological sequaelae in the majority of survivors. There is uncertainty with regard to age specific individual risk factors, the impact of hereditary thrombophilia or underlying diseases on development of thrombosis or outcome. Previously published cohort studies have described epidemiology, treatment practices and outcomes, but those studies are limited due to small sample size or diversity of the populations included. Neonatal CSVT is seen as a disease entity different from cerebral thrombosis in older children with regard to etiology and outcome, evidence is lacking.

OBJECTIVES: To evaluate the influence of transient risk factors and hereditary thrombophilia on clinical course, treatment practices and early outcome in a population based national cohort of children with CSVT. To study the influence of age (neonatal versus pediatric) on risk factors and outcome in CSVT.

METHODS: We conducted a prospective nationwide surveillance study in pediatric patients <18 years through the hospital-based German Pediatric Surveillance Unit (ESPED). We included consecutive patients from 0-18 years of age admitted to hospitals in Germany with diagnosis of a first CSVT with an enrolment period between 2001-2010. Diagnosis was confirmed using MRI or CT imaging. Laboratory analysis of coagulation parameters have either been analyzed according to standardized thrombophilia screening protocols in the local hospitals or centrally in study center at the University of Muenster. We followed the course of disease over a period of 36 months. Follow up investigation included repetitive MRI or CT imaging and questionnaires on clinical outcome and recurrence.

RESULTS: A total of 599 patients, from birth to 18 years with a diagnosis of CSVT were enrolled in the study. We have observed a male predominance with 61%. 138 (23%) CSVT cases were diagnosed during the neonatal period, 461 (77%) patients were older than one month at time of diagnosis. In our cohort 40% of neonates and 20% of older infants/children developed thrombosis without identified underlying predisposing diseases. The majority of transient triggers associated with the development of thrombosis were local (mastoiditis, 18%) or systemic (sepsis, meningitis, 13%) infections or asparaginase administration during treatment for leukemia or lymphoma (12%). Outcome, dependent both on age at onset and existence of transient triggers was worse in children with spontaneous CSVT compared to triggered CSVT with regard to mortality rate (11 vs. 3%), patency of the veins and neurological impairment. Moreover, presenting symptoms as well as the clinical course differed between neonates and older infants/children.

CONCLUSION: In the pediatric population studied most of CSVT events were associated with infections as transient trigger. CSVT in neonates and children older than 1 months of age differed both with regard to underlying risk factors, treatment and outcome. Age specific, randomized controlled trials comparing treatment strategies are needed to optimize care in these patients.