Anticoagulant therapy beginning with heparin or an equivalent for several days, followed by warfarin, and combined with antibiotics if the venous occlusion is infectious (it rarely is in recent times) has been lifesaving in some cases. Nonetheless, the overall mortality rate remains high, with large hemorrhagic venous infarctions found in 10 to 20 percent of cases. The clinical trial conducted by Einhaupl and colleagues only apparently settled the question of acute therapy in favor of the use of heparin, because these positive results could not be confirmed by de Bruijn and Stam, who found a minimal difference between patients who were treated with low-molecular-weight heparin compared to placebo, both followed by oral anticoagulation for 3 months. The newer anticoagulants are being considered in some cases. Most treated patients do well, but it may take weeks for the headaches to remit although administration of heparin will sometimes lead to relief of the headache. Coma and multiple cerebral hemorrhages, on the other hand, are usually fatal.
The local infusion of tPA has been used, but not subjected to the same randomized testing. Thrombolytic therapy by local venous or systemic infusion has been successful in small series of cases, such as the 5 patients treated with urokinase and heparin by DiRocco and colleagues. We have reserved thrombolysis for extreme cases of dural sinus thrombosis with stupor or coma and greatly raised CSF pressure.
Sterile vegetations, referred to also as nonbacterial thrombotic endocarditis, consist of fibrin and platelets and are loosely attached to the mitral and aortic valves and contiguous endocardium. They are a common source of cerebral embolism (almost 10 percent of all instances of cerebral embolism according to Barron et al, but lower in the experience of other series). In past series, almost half the patients had vegetations associated with a malignant neoplasm; the remainder occurs in patients debilitated by other diseases (Biller et al). Recent experience suggests that the majority is related to systemic cancer.
The setting in which embolism from nonbacterial endocarditis occurs is distinctive. There may also be prototypic clinical features that permit differentiation from other forms of cerebral embolism. In particular, the strokes may be multiple, sequential over days or weeks, and generally small, imparting a picture of incomplete stroke syndromes with a superimposed encephalopathy. The sudden nature of the embolic deficits helps to distinguish this process from the usual forms of cerebral metastases.
The disease is essentially a manifestation of chronic disseminated intravascular coagulation (DIC) discussed below and therefore it is not surprising that similar laboratory changes are found, including an elevation in circulating fibrin split products, specifically D-dimer and indications of microangiopathic hemolysis in the blood smear. There is typically moderate thrombocytopenia. The echocardiogram is often obtained but it is insensitive.
The hazards of using anticoagulants in gravely ill patients with widespread malignant disease may outweigh the benefits from this treatment, but drugs that prevent platelet aggregation, while possibly helpful, have not been studied systematically for this condition. Quite often the embolic strokes continue despite treatment.
Stroke as a Complication of Hematologic Disease
The brain is involved in the course of many hematologic disorders, some of which have already been mentioned. A number of the better-characterized ones are discussed here.