1. The document discusses treatment strategies for patients who have experienced a large hemispheric infarction (LHI). It provides a timeline of evidence-based therapies for LHIs including intravenous tissue plasminogen activator (tPA), endovascular thrombectomy, antithrombotic therapy, and decompressive craniectomy. 2. Emerging therapies and targets for managing cerebral edema in LHI patients are discussed, including the drugs conivaptan, fingolimod, celecoxib, and glyburide which have various mechanisms of action targeting aquaporin receptors, sphingosine-1-phosphate, cyclooxygenase-2, and SUR1/TRPM4 channels respectively

1. Access the activity, “Large Hemispheric Infarction: Exploring the Latest Clinical
Advances in the Diagnosis and Treatment,” at PeerView.com/NDJ40
Management of Acute Ischemic
Stroke: AHA/ASA Guidelines1
PRACTICE AID
a
For intravenous eligibility criteria, see current AHA/ASA guidelines. b
Intracranial internal carotid artery or M1 occlusion. c
For DAWN and DEFUSE 3 criteria, see supplemental table 1 in reference.
AHA: American Heart Association; AIS: acute ischemic stroke; ASA: American Stroke Association; ASPECTS: Alberta Stroke Program Early CT Score; CTA: CT angiography; CTP: CT perfusion;
DWI: diffusion-weighted imaging; EVT: endovascular therapy; ICH: intracerebral hemorrhage; LHI: large hemispheric infarction; LKW: last known well; LVO: large vessel occlusion; mCTA: multiphase CT
angiography; MRA: magnetic resonance angiography; NCCT: noncontrast CT; NIHSS: National Institutes of Health Stroke Scale.
1. Ospel JM et al. J Am Coll Cardiol. 2020;75:1832-1843.
Suspected AIS
NIHSS ≥6
No ICH or
stroke mimic
IV alteplase if
indicateda
ICH
NCCT or MRI:
ICH and ASPECTS
mCTA or MRA
Imaging recommendation
LVOb
(includes LHI)
No LVO
No EVT
0-6 h from LKW
and ASPECTS ≥6
6-24 h from LKW
EVT
CTP or DWI: infarct core
quantification
EVT if DAWN/DEFUSE 3
criteria are fulfilledc

2. Treatment Strategies for Patients Who
Have a Large Hemispheric Infarction
PRACTICE AID
Access the activity, “Large Hemispheric Infarction: Exploring the Latest Clinical Advances in the Diagnosis
and Treatment,” at PeerView.com/NDJ40
A Timeline of Evidence-Based Therapies for Treating Patients With an LHI
Tissue plasminogen activator (tPA)1,2
• Initiate within <4.5 hours
• Increases survival in patients
experiencing a severe stroke
Endovascular thrombectomy3-9
• Initiate within 6 hours
(earlier is better)
• Improves patient outcome
over tPA alone
Antithrombotic therapy10
• Initiate within 48 hours
Decompressive craniectomy10
• Dramatically reduced mortality
in patients with a malignant
MCA infarction
• High likelihood of permanent
and severe disability
Antiosmotic therapy10
• Initiate 1-4 days for cerebral edema
• Mannitol and hypertonic saline are
reasonable choices; avoid steroids
and barbiturates

3. Treatment Strategies for Patients Who
Have a Large Hemispheric Infarction
AIS: acute ischemic stroke; AS: ankylosing spondylitis; COX-2: cyclooxygenase-2; JRA: juvenile rheumatoid arthritis; LHI: large hemispheric infarction; MCA: middle cerebral artery; MOA: mechanism of action; MS: multiple sclerosis; OA: osteoarthritis; RA: rheumatoid arthritis;
S1P: sphingosine-1-phosphate; SUR1: sulfonylurea receptor 1; TRPM4: transient receptor potential cation channel subfamily M member 4.
1. Jauch EC et al. Stroke. 2013;44:870-947. 2. Demchuk AM et al. Stroke. 2005;36:2110-2115. 3. Powers WJ et al. Stroke. 2015;46:3020-3035. 4. Campbell BC et al. N Engl J Med. 2015;372:1009-1018.5. Saver JL et al. N Engl J Med. 2015;372:2285-2295. 6. Jovin TG et al. N Engl J Med.
2015;372:2296-2306. 7. Nogueira RG et al. N Engl J Med. 2018;378:11-21. 8. Goyal M et al. N Engl J Med. 2015;372:1019-1030. 9. Albers GW et al. N Engl J Med. 2018;378:708-718. 10. Torbey MT et al. Neurocrit Care. 2015;22:146-164. 11. Stokum JA et al. Annu Rev Pharmacol Toxicol.
2020;60:291-309. 12. Vaprisol (conivaptan hydrochloride). Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021697s005lbl.pdf. 13. Gilenya (fingolimod). Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/
label/2019/022527s031lbl.pdf. 14. Celebrex (celecoxib). Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020998s054lbl.pdf. 15. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=20165393.
PRACTICE AID
Access the activity, “Large Hemispheric Infarction: Exploring the Latest Clinical Advances in the Diagnosis
and Treatment,” at PeerView.com/NDJ40
Managing Cerebral Edema: Potential Targets, Emerging Therapies, and Mechanisms of Action11
• Emerging therapy: conivaptan
– Currently indicated for hyponatremia12
• MOA: absorbs free water in kidneys
• Emerging therapy: fingolimod
– Currently indicated for relapsing MS13
• MOA: reduces vascular permeability
• Emerging therapy: celecoxib
– Currently indicated for OA, RA, JRA, AS,
acute pain, and primary dysmenorrhea14
• MOA: reduces inflammation
• Emerging therapy: glyburide
– Orphan desgination for severe edema
in patients who had an AIS15
• MOA: conducts monovalent cations
Target:
aquaporin
receptor
Target:
S1P
Target:
COX-2
Target:
SUR1/TRPM4