Paediatric Cerebral Sinovenous Thrombosis
This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Research ethics approval was obtained at each site by the local institutional review boards to include data of consecutively enrolled patients in the IPSS database maintained in Toronto, Canada.
The IPSS is an international paediatric stroke registry established in 2003 with the purpose of collecting data on demographic, clinical and radiological features, risk factors, treatment and outcomes at the time of hospital discharge among children from birth up to the age of 19 years with AIS and CSVT. We used the same methodology for enrolment, data abstraction and database management as previously described. This analysis included consecutively enrolled cases submitted to the database between 1 January 2003 and 1 July 2007. Sample size was determined by the number of cases enrolled in that time interval that met inclusion criteria. Local treating physicians determined diagnostic and treatment decisions.
Site investigators identified cases and determined eligibility. Patients were included in the current childhood cohort study who met consensus-based, published clinical and radiological criteria for the diagnosis of childhood CSVT, as follows: (1) age >28 days up to 19 years at onset of symptoms, (2) acute neurological syndrome with signs and symptoms of CSVT, such as altered mental status, headache, papilloedema, seizures or focal neurological deficits and (3) radiological confirmation of CSVT by one or more modalities (MRI with MR venogram, CT venogram or cerebral catheter venography) showing thrombus or flow interruption within cerebral veins or dural venous sinuses, with or without venous distribution infarction.
Site investigators abstracted data from medical records onto IPSS case report forms (CRF). Data were entered via a web-based data entry system to the IPSS database, created and maintained in the IPSS data coordinating centre at the Toronto Hospital for Sick Children. Clinical data abstracted included demographics (age, gender, country of origin); clinical symptoms at presentation (altered mental status, headache, seizures, focal neurological deficits); underlying disease conditions (heart disease, genetic disorder, connective tissue disorder, prothrombotic state (including acquired and genetic thrombophilias), haematological disorder, malignancy, pre-existing cerebrovascular disorder); acute illness or provoking condition (systemic disorders, head or neck infections, trauma, treatment with a prothrombotic drug such as L-asparaginase, cranial surgery); neuroimaging findings and treatment modalities (antithrombotic treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH), anticonvulsants, antibiotics, immunomodulatory therapy, neurosurgical interventions, transfusion or exchange transfusion). Initial and secondary antithrombotic treatments were reported, where secondary antithrombotic treatment refers to a treatment change from the initial agent to a different agent during admission. Data on prothrombotic states were reported to the registry database only for abnormal results. Practices varied widely across centres regarding testing for prothrombotic states. Data concerning the testing performed on each patient were not available as this was beyond the scope of the IPSS protocol. Data on neuroimaging included site of thrombosis, presence of infarction and presence and type of intracranial haemorrhage. Site of CSVT was classified as involving superficial or deep venous systems or both. Outcome data were collected on discharge disposition (home, inpatient rehabilitation unit, nursing facility), vital status at hospital discharge (alive or dead) and neurological status at discharge classified as normal or abnormal. Data on standardised functional outcomes at intervals past hospital discharge were beyond the scope of the IPSS registry.
Characteristics of the patient population were summarised with descriptive statistics, expressed as medians and IQRs. All statistical analyses were performed using the StatView 5 software package (SAS Institute, Cary, North Carolina, USA) and MedCalc (V.11.1.1., Mariakerke, Belgium). Continuous data are presented as median values and IQR. For categorical data, frequency distributions were compared between groups using χ test or Fisher's exact test (F), as appropriate. The criterion for statistical significance was set at p=0.05 based on two-sided test. In order to evaluate (i) clinical symptoms (no clinical symptoms vs. any clinical symptoms), (ii) underlying medical conditions (no underlying medical condition vs. any underlying medical condition), (iii) thrombophilic risk factors (no thrombophilia vs. any thrombophilia) and (iv) initial anticoagulation (UFH or LMWH vs. no anticoagulation), analysis was performed using logistic regression. Adjustment variables for anticoagulation included recruitment areas (Australia, Canada, Europe, South America, the USA). Risk ratios and adjusted risks were expressed as ORs together with 95% CIs. Clustering by centre was not accounted for in the analysis because of small numbers contributed by each centre.
Methods and Design
Ethics
This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Research ethics approval was obtained at each site by the local institutional review boards to include data of consecutively enrolled patients in the IPSS database maintained in Toronto, Canada.
Setting
The IPSS is an international paediatric stroke registry established in 2003 with the purpose of collecting data on demographic, clinical and radiological features, risk factors, treatment and outcomes at the time of hospital discharge among children from birth up to the age of 19 years with AIS and CSVT. We used the same methodology for enrolment, data abstraction and database management as previously described. This analysis included consecutively enrolled cases submitted to the database between 1 January 2003 and 1 July 2007. Sample size was determined by the number of cases enrolled in that time interval that met inclusion criteria. Local treating physicians determined diagnostic and treatment decisions.
Patients
Site investigators identified cases and determined eligibility. Patients were included in the current childhood cohort study who met consensus-based, published clinical and radiological criteria for the diagnosis of childhood CSVT, as follows: (1) age >28 days up to 19 years at onset of symptoms, (2) acute neurological syndrome with signs and symptoms of CSVT, such as altered mental status, headache, papilloedema, seizures or focal neurological deficits and (3) radiological confirmation of CSVT by one or more modalities (MRI with MR venogram, CT venogram or cerebral catheter venography) showing thrombus or flow interruption within cerebral veins or dural venous sinuses, with or without venous distribution infarction.
Data Collection
Site investigators abstracted data from medical records onto IPSS case report forms (CRF). Data were entered via a web-based data entry system to the IPSS database, created and maintained in the IPSS data coordinating centre at the Toronto Hospital for Sick Children. Clinical data abstracted included demographics (age, gender, country of origin); clinical symptoms at presentation (altered mental status, headache, seizures, focal neurological deficits); underlying disease conditions (heart disease, genetic disorder, connective tissue disorder, prothrombotic state (including acquired and genetic thrombophilias), haematological disorder, malignancy, pre-existing cerebrovascular disorder); acute illness or provoking condition (systemic disorders, head or neck infections, trauma, treatment with a prothrombotic drug such as L-asparaginase, cranial surgery); neuroimaging findings and treatment modalities (antithrombotic treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH), anticonvulsants, antibiotics, immunomodulatory therapy, neurosurgical interventions, transfusion or exchange transfusion). Initial and secondary antithrombotic treatments were reported, where secondary antithrombotic treatment refers to a treatment change from the initial agent to a different agent during admission. Data on prothrombotic states were reported to the registry database only for abnormal results. Practices varied widely across centres regarding testing for prothrombotic states. Data concerning the testing performed on each patient were not available as this was beyond the scope of the IPSS protocol. Data on neuroimaging included site of thrombosis, presence of infarction and presence and type of intracranial haemorrhage. Site of CSVT was classified as involving superficial or deep venous systems or both. Outcome data were collected on discharge disposition (home, inpatient rehabilitation unit, nursing facility), vital status at hospital discharge (alive or dead) and neurological status at discharge classified as normal or abnormal. Data on standardised functional outcomes at intervals past hospital discharge were beyond the scope of the IPSS registry.
Statistical Analysis
Characteristics of the patient population were summarised with descriptive statistics, expressed as medians and IQRs. All statistical analyses were performed using the StatView 5 software package (SAS Institute, Cary, North Carolina, USA) and MedCalc (V.11.1.1., Mariakerke, Belgium). Continuous data are presented as median values and IQR. For categorical data, frequency distributions were compared between groups using χ test or Fisher's exact test (F), as appropriate. The criterion for statistical significance was set at p=0.05 based on two-sided test. In order to evaluate (i) clinical symptoms (no clinical symptoms vs. any clinical symptoms), (ii) underlying medical conditions (no underlying medical condition vs. any underlying medical condition), (iii) thrombophilic risk factors (no thrombophilia vs. any thrombophilia) and (iv) initial anticoagulation (UFH or LMWH vs. no anticoagulation), analysis was performed using logistic regression. Adjustment variables for anticoagulation included recruitment areas (Australia, Canada, Europe, South America, the USA). Risk ratios and adjusted risks were expressed as ORs together with 95% CIs. Clustering by centre was not accounted for in the analysis because of small numbers contributed by each centre.
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