A bstract Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially life-threatening cause of pediatric stroke. Inherited thrombophilias play a significant role in children with CVST, particularly in severe or recurrent cases. Antithrombin III (AT-III) deficiency, most often caused by mutations in SERPINC1 gene, is a rare but highly thrombogenic condition, with cerebral venous thrombosis being an infrequent presentation. Here, we report a case of a 16-year-old previously healthy male who presented with progressive headache and generalized tonic–clonic seizures, followed by rapid neurological deterioration. Neuroimaging revealed hemorrhagic venous infarction with extensive sinus thrombosis. Thrombophilia evaluation demonstrated mildly reduced antithrombin activity. Despite decompressive craniectomy and anticoagulation, the patient developed recurrent, extensive CVST during perioperative interruption of anticoagulation, with new hemorrhagic infarcts. Genetic testing identified heterozygous SERPINC1 mutation classified as a variant of uncertain significance, in the setting of reduced antithrombin activity and recurrent thrombosis. The patient was stabilized on long-term anticoagulant and discharged with plans for lifelong anticoagulation and genetic counseling. CVST due to AT-III deficiency is rare, and recurrent, malignant CVST requiring neurosurgical intervention is exceedingly uncommon. This case highlights the aggressive thrombotic phenotype associated with SERPINC1 mutations and underscores the importance of early thrombophilia screening and genetic confirmation in pediatric patients with severe or recurrent CVST. Identification of AT-III deficiency has critical therapeutic implications, including anticoagulation strategy, potential heparin resistance, and the need for long-term management and family screening. Inherited AT-III deficiency should be considered in adolescents with recurrent or extensive CVST. Early diagnosis and tailored anticoagulation can improve outcomes and prevent recurrence.
Arora et al. (Thu,) studied this question.