(COR IIb; LOE C-LD) Extracranial cervical dissections IV alteplase in AIS known or suspected to be associated with extracranial cervical arterial dissection is reasonably safe within 4.5 h and probably recommended. (COR IIa; LOE C-LD) Intracranial arterial dissection IV alteplase usefulness and hemorrhagic risk in AIS known or suspected to be associated with intracranial arterial dissection remain unknown, uncertain and not well established. (COR IIb; LOE C-LD) Unruptured intracranial aneurysm For patients presenting with AIS who are known to harbor a small or moderate-sized (<10 mm) unruptured and unsecured intracranial aneurysm, administration of IV alteplase is reasonable and probably recommended. (COR IIa; LOE C-LD) Usefulness and risk of IV alteplase in patients with AIS who harbor a giant unruptured and unsecured intracranial aneurysm are not well established. (COR IIb; LOE C-LD) Intracranial vascular malformations For patients presenting with AIS who are known to harbor an unruptured and untreated intracranial vascular malformation the usefulness and risks of administration of IV alteplase are not well established. (COR IIb; LOE C-LD) Because of the increased risk of ICH in this population of patients, IV alteplase may be considered in patients with stroke with severe neurological deficits and a high likelihood of morbidity and mortality to outweigh the anticipated risk of ICH. (COR IIb; LOE C-LD) CMBs In otherwise eligible patients who have previously had a small number (1 10) of CMBs demonstrated on MRI, administration of IV alteplase is reasonable. (COR IIa; Level B-NR) In otherwise eligible patients who have previously had a high burden of CMBs (>10) demonstrated on MRI, treatment with IV alteplase may be associated with an increased risk of sICH, and the benefits of treatment are uncertain. Treatment may be reasonable if there is the potential for substantial benefit. 