AHA/ASA Guideline Guidelines for the Prevention of Stroke in ...

256 Stroke January 2011hemoglobin, hydroxyurea, or bypass surgery incases of advanced occlusive disease (Class IIb; Levelof Evidence C) (Table 10).F. Cerebral Venous Sinus ThrombosisThe estimated annual incidence of cerebral venous thrombosis(CVT) is 3 to 4 cases per 1 million population. 448Although CVT accounts for 1% of all strokes, it is animportant diagnostic consideration because of the differencesin its management from that of arterial strokes. 448Early anticoagulation is often considered as both treatmentand early secondary prophylaxis for patients with CVT,although controlled trial data remain limited to 2 studies.449,450 The first trial compared dose-adjusted unfractionatedheparin (UFH; partial thromboplastin time at least 2times control) with placebo. The study was terminated earlyafter only 20 patients had been enrolled, because of thesuperiority of heparin therapy (P0.01). Eight of the 10patients randomly assigned to heparin recovered completely,and the other 2 patients had only mild neurological deficits. Inthe placebo group, only 1 patient had a complete recovery; 3patients died. 449 The same research group also reported aretrospective study of 43 patients with cerebral venous sinusthrombosis associated with intracranial bleeding; 27 of thesepatients were treated with dose-adjusted heparin. The mortalityrate in the heparin group was considerably lower than inthe nonanticoagulation group. 449A more recent and slightly larger randomized study ofcerebral venous sinus thrombosis (n59) compared nadroparin(90 anti–Xa U/kg twice daily) with placebo. 450 After 3months of follow-up, 13% of patients in the anticoagulationgroup and 21% in the placebo group had poor outcomes(RRR, 38%; PNS). Two patients in the nadroparin groupdied, compared with 4 patients in the placebo group. Patientswith intracranial bleeding were included, and no new symptomaticcerebral hemorrhages occurred in either group.In a Cochrane meta-analysis of these 2 trials, anticoagulanttherapy was associated with a pooled relative risk of death of0.33 (95% CI, 0.08 to 1.21) and death or dependency of 0.46(95% CI, 0.16 to 1.31). No new symptomatic ICHs wereobserved in either study. One major gastrointestinal hemorrhageoccurred after anticoagulant treatment. Two controlpatients (on placebo) had a diagnosis of probable pulmonaryembolism (one fatal). 451 On the basis of these 2 trials, the useof anticoagulation with heparin or LMWH given acutely inthe setting of CVT is recommended, regardless of thepresence of hemorrhagic conversion.No randomized trial data exist to guide duration of anticoagulationtherapy. For an initial event, periods between 3 and12 months have been reported. Patients with inherited thrombophiliaoften undergo anticoagulation for longer periodsthan someone with a transient (reversible) risk factor such asoral contraceptive use. Given the absence of data on durationof anticoagulation in patients with CVT, it is reasonable tofollow the externally established guidelines set for patientswith extracerebral DVT, which includes anticoagulationtreatment for 3 months for first-time DVT in patients withtransient risk factors and at least 3 months for an unprovokedfirst-time DVT and anticoagulation for an indefinite period inpatients with a second unprovoked DVT. 452 Antiplatelettherapy is generally given indefinitely after discontinuation ofwarfarin.Given the relatively high proportion of pregnancy-relatedCVT, which ranges from 15% to 31%, 453 the risk forrecurrent CVT during subsequent pregnancies is a commonlyencountered question. Sixty-three pregnancies in patientswith prior CVT have been reported in the literature, including21 with pregnancy-related CVT, with normal delivery and norecurrence of CVT. Although this suggests that future pregnanciesare not an absolute contraindication, given the scarcityof available data, decisions about future pregnanciesmust be individualized. 454Recommendations1. Anticoagulation is probably effective for patientswith acute CVT (Class IIa; Level of Evidence B).2. In the absence of trial data to define the optimalduration of anticoagulation for acute CVT, it isreasonable to administer anticoagulation for at least3 months, followed by antiplatelet therapy (ClassIIa; Level of Evidence C) (Table 10).G. Fabry DiseaseFabry disease is a rare X-linked inherited deficiency of thelysosomal enzyme -galactosidase, which causes lipid depositionin the vascular endothelium and results in progressivevascular disease of the brain, heart, skin, and kidneys. 455Stroke may occur due to dolichoectasia of the vertebral andbasilar arteries, cardioembolism, or small-vessel occlusivedisease. 455–457 Fabry disease may be underdiagnosed as acause of seemingly cryptogenic stroke in the young. 458Antiplatelet agents are believed to be useful in preventingischemic events related to existing vascular disease, 458 but thedisease itself was untreatable and the prognosis quite pooruntil recombinant -galactosidase A became available. Inrandomized controlled trials, administration of intravenous-galactosidase (also known as agalsidase beta) at a dose of1 mg/kg every other week reduced new and cleared oldmicrovascular endothelial deposits in the kidneys, heart, andskin 459 and modestly reduced the composite of renal, cardiac,or cerebrovascular events or death (HR, 0.47; 95% CI, 0.21 to1.03). 460 Enzyme replacement therapy also leads to clinicalimprovements in kidney function, 460,461 but the impact oncardiac function has been inconsistent. 462,463 Enzyme replacementtherapy has been shown to have a favorable effect oncerebral blood flow, 464 but the risk of stroke appears substantialdespite therapy. 465 Earlier intervention or higher enzymedoses or both may be needed for stroke prevention, and thisis an area of active research. 466 The major adverse effects ofrecombinant -galactosidase A infusions are fever and rigors,which may occur in 25% to 50% of treated patients but maybe minimized with slow infusion rates and premedicationwith acetaminophen and hydroxyzine. An expert panel recommendedenzyme replacement therapy for all male patientsstarting at age 16 and all other patients if there is evidence ofsymptoms or progressive organ involvement. 467Recommendations1. For patients with ischemic stroke or TIA and Fabrydisease, -galactosidase enzyme replacement ther-Downloaded from stroke.ahajournals.org by on March 8, 2011