Table 33-7 summarizes the main inherited prothrombotic clotting defects. They predispose primarily to cerebral venous thrombosis. Most arise from partial protein deficiencies as a result of heterozygous mutations in the genes encoding proteins in the clotting cascade (antithrombin III, proteins S and C) and from those that disturb clotting balance (resistance to activated protein C, or factor V Leiden mutation, and prothrombin mutations as well as excess factor VIII) (see discussion by Brown and Bevan). When homozygous, these mutations may be associated with devastating neonatal hemorrhagic conditions. In some series that report cases of strokes in youth, such as the one reported by Becker and colleagues, up to half of stroke cases had one of these disorders, the most common being the factor V Leiden mutation, but others have found this mutation to be much less frequent, which is more consonant with our experience. Nevertheless, in children with unexplained stroke, particularly venous ones or if there is a family history of stroke in early life, and especially if there has been a previous thrombosis or if the strokes are recurrent, it is advisable to carry out an extensive hematologic investigation, including testing for antiphospholipid antibody (an acquired defect), as described in the later section on “Antiphospholipid Antibody (Hughes) Syndrome.” Establishing a diagnosis of a prothrombotic clotting gene variant has further significance because strokes are prone to occur in the setting of additional risks, such as the use of oral contraceptives and smoking. In adults, the evaluation for inherited clotting defects is less fruitful. Furthermore, it should be kept in mind that the levels of proteins C and S and of antithrombin are temporarily depressed after stroke, so that any detected abnormalities must be confirmed months later and in the absence of anticoagulation.
Persistent cerebral ischemia and infarction may occasionally complicate migraine in young persons as discussed in Chap. 9. Wolf and colleagues identified a prolonged aura in young women with an established history of migraine as a risk for strokes, most of which occurred in the posterior circulation. The combination of migraine and oral contraception is particularly hazardous, as detailed below. Despite the common occurrence of mitral valve prolapse in young adults, it is probably only rarely a cause of stroke (see previous comments). Stroke because of either arterial or venous occlusion occurs occasionally in association with inflammatory bowel disease in young persons. Evidence points to a hypercoagulable state during exacerbations of the enteritis but a precise defect in coagulation has not been identified. Meningovascular syphilis and fungal and tuberculous meningitis and other forms of chronic basal meningitis are also considerations in this age group; the strokes are usually of the lacunar type, resulting from inflammatory occlusion of small basal vessels.