Additional recommendations for treatment with IV alteplase for patients with AIS (COR IIa) And (COR IIb) 3 to 4.5 h Age For patients >80 y of age presenting in the 3- to 4.5-h window, IV alteplase is safe and can be as effective as in younger patients. (COR IIa; LOE B-NR) 3 to 4.5 h Diabetes mellitus and prior stroke In AIS patients with prior stroke and diabetes mellitus presenting in the 3- to 4.5- h window, IV alteplase may be as effective as treatment in the 0- to 3-h window and may be a reasonable option. (COR IIb; LOE B-NR) 3 to 4.5 h Severe stroke The benefit of IV alteplase between 3 and 4.5 h from symptom onset for patients with very severe stroke symptoms (NIHSS score >25) is uncertain. (COR IIb; LOE C-LD) 3 to 4.5 h Mild disabling stroke For otherwise eligible patients with mild disabling stroke, IV alteplase may be reasonable for patients who can be treated within 3 and 4.5 h of ischemic stroke symptom onset or patient last known well or at baseline state. (COR IIb; LOE B-NR) Wake-up and unknown time of onset IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min) administered within 4.5 h of stroke symptom recognition can be beneficial in patients with AIS who awake with stroke symptoms or have unclear time of onset >4.5 h from last known well or at baseline state and who have a DW-MRI lesion smaller than one- third of the MCA territory and no visible signal change on FLAIR. 