Abstract
Introduction: Cerebral sinovenous thrombosis (CSVT) in children is a rare, often underdiagnosed but serious event. The risk factors in children include head or neck infections, prothrombotic agents such as oral contraceptives and a chronic systemic illness. In the present study, we aimed to investigate the clinical manifestations, neuroimaging findings, risk factors and treatment of children suffering from CSVT in a reference paediatric centre for thrombosis. In addition, we assessed outcomes after CSVT.
Methods: Data were retrospectively collected for children with CSVT, referred between 2010 and 2020 to our hospital. There were 103 children that were used as controls concerning thrombophilic factors. The categorical variables were described by frequency distributions and compared with x2-homogeneity test.
Results: Sixty-five patients were included in the study (58% males). The mean age of the children at the time of diagnosis was 6.2 years (SD 4 years, range 1 month to 16 years). The most common presenting symptoms were headache (43%), decreased consciousness (32%), vomiting (12%), seizures (15%), diplopia (6%) and torticollis (5%). Papilloedema was found in 14 children (21.5%) and intracerebral haemorrhage in one. The most frequent risk factors were infections (74%), mainly acute otitis media with or without mastoiditis (55% και 19% respectively) and chronic medical conditions, such as polycythemia vera, nephrotic syndrome, arteriovenous malformation, ulcerative colitis-3% each. The use of oral contraceptives was not documented. For the diagnostic evaluation MRI/Magnetic Resonance Venography was performed in 72.3% of children. CT was diagnostic in 24.6% of patients and one infant underwent Power Doppler Ultrasound. Thrombosis was detected in 46% of children on left side, in 34% on right side and in 20% bilaterally. The deep venous system (straight venous, vein of Galen, transverse and sigmoid sinus, jugular veins) was more commonly affected (75%). Notably, sigmoid sinus thrombosis (40%) was predominantly involved, followed by transverse (31%), while extension to ipsilateral jugular vein occurred in 32%. Multiple sinus involvement was found in 64% of patients. Interestingly, simultaneous localization in the transverse and sigmoid sinuses had an increased probability of being accompanied by papilloedema (p <0.05). Venous infarctions were noticed in two children, while one child with hypoplastic venous sinus had an abdominal peritoneal CNS drain. Laboratory investigations for prothrombotic risk factors were available for all patients. One or more prothrombotic risk factor were found in 18 of the 65 (28%) children. To be more accurate, heterozygosity for FVLeiden and FII20210A mutations were found in 8% and 5% of patients, respectively and homozygosity for MTHFR-C776T in 15% (without raised homocysteine). Thrombophilic factors did not attain statistically significant results, apart from a trend for heterozygosity for FVLeiden and FII20210A mutations in patients (in controls 5% and 3% respectively). All patients received anticoagulation (68% coumarin anticoagulants, 32% Low Molecular Weight Heparin) for a mean duration of 7.5 ±3.3 months and 18.8 ±32.4 months respectively, while 7 children still receive anticoagulation. The duration of anticoagulation therapy was based on clinical outcome and follow-up investigations. No patient developed hemorrhagic events during the therapy. Follow-up imaging studies were available in most of the children. Six children showed no recanalization on 3.5 ±0.5 months, 19 children showed partial recanalization on 5±3 months and 20 children showed complete recanalization on 7± 5 months. No child died or had persisting neurological sequelae, apart from signs of attention deficit disorder, during a median follow-up of 4±3 years. One patient underwent remission of thrombosis in other site (pulmonary emboli) in adulthood.
Conclusions: Physicians should be suspicious of CSVT in children with otitis media/mastoiditis or chronic diseases, when referred for headache or other neurological signs. In a quarter of the cases a thrombophilic factor had eventually some contribution to the event. Longer follow-up may reveal the incidence of cognitive or behavioral disabilities due to CSVT.
Disclosures
Kattamis: Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Consultancy, Honoraria; Chiesi: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; VIFOR: Consultancy; Amgen: Consultancy.
Neonatal cerebral sinovenous thrombosis: two cases, two different gene polymorphisms and risk factors
