What is the recommended rate of intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) in acute stroke patients with a confirmed stroke mimic?

Rate of Intravenous Thrombolysis in Stroke Mimics

Stroke mimics receive intravenous thrombolysis in approximately 1.8% to 3.5% of all patients treated with tPA for presumed acute ischemic stroke, and importantly, these patients experience very low complication rates with no increased risk of symptomatic intracranial hemorrhage compared to true stroke patients. 1, 2

Reported Rates Across Studies

The frequency of stroke mimic treatment varies by study design and center experience:

• Multicenter European cohort (2013): 1.8% (100 of 5,581 patients; 95% CI, 1.5-2.2%) 1
• US Get With The Guidelines-Stroke Registry (2010-2017): 3.5% (2,548 of 72,582 patients) across 485 hospitals 2
• Single-center study (6-year period): 10.4% (56 of 539 patients; 95% CI, 7.9-13.3%) 3

The American Heart Association guidelines note that stroke mimics were identified in approximately 3% of patients in two series of patients treated with fibrinolytics, and more recently, one registry reported 21% of 512 patients treated with intravenous rtPA were later determined to be stroke mimics 4

Most Common Stroke Mimic Diagnoses

The conditions most frequently misdiagnosed as acute stroke include:

• Conversion disorder/functional disorder: 26.8-38.2% of stroke mimics 3, 2
• Seizures: 19.5-19.6% of stroke mimics 4, 3, 2
• Complicated migraine: 19.6% of stroke mimics 3, 2
• Toxic-metabolic disorders/electrolyte imbalances: 30.1% of stroke mimics 2, 5

Safety Profile in Stroke Mimics

The complication rate of tPA administration in stroke mimics is remarkably low and substantially safer than in true ischemic stroke patients:

• Symptomatic intracranial hemorrhage rate: 0-1.0% in stroke mimics versus 6.4-7.9% in true ischemic strokes 1, 3, 2
• In-hospital mortality: 0.8% in stroke mimics versus 6.2% in ischemic strokes (adjusted OR 0.31; 95% CI, 0.20-0.49) 2
• Functional independence at discharge: 83.8-96% of stroke mimics achieved independent ambulation or were discharged home 3, 2

The American Heart Association guidelines explicitly state that no evidence of increased fibrinolytic treatment risk was identified for stroke mimic patients 4

Clinical Characteristics of Stroke Mimics

Patients ultimately diagnosed with stroke mimics differ from true stroke patients in predictable ways:

• Younger age: median 54-56 years versus 66-71 years in true strokes 3, 2
• Lower stroke severity: median NIHSS 6 versus 8 in true strokes 3, 2
• More often female 1
• Fewer cardiovascular risk factors except higher rates of prior stroke/TIA (31.3% versus 26.1%) and smoking 1, 2
• Later arrival to emergency department 5

Why Stroke Mimics Don't Receive Thrombolysis

When stroke mimics are correctly identified before treatment, the most common exclusion criteria are:

• Beyond therapeutic window: Present in 63% of excluded stroke mimics 5
• Mild or non-measurable deficits: Present in 24% of excluded stroke mimics 5
• Both contraindications simultaneously: 21.2% of stroke mimics 5

Clinical Implications and Acceptable Error Rate

The American Heart Association suggests that stroke mimic treatment rates at experienced centers should be less than 3% using noncontrast CT alone, though an accompanying editorial acknowledged the need to balance speed to treatment with diagnostic accuracy. 4

The low complication rate in stroke mimics should not encourage diagnostic complacency, but it does provide reassurance that the urgency required for true stroke treatment—where earlier treatment provides substantially greater benefit (OR 2.55 when treated within 0-90 minutes versus 1.32 when treated within 181-270 minutes)—justifies accepting a small misdiagnosis rate 4

Common Pitfalls

• Do not delay treatment in patients with convincing stroke presentations simply to achieve 100% diagnostic certainty, as the time-dependent benefit in true strokes far outweighs the minimal risk to stroke mimics 4
• Recognize that higher stroke mimic rates (>10%) may indicate inadequate diagnostic protocols or insufficient stroke expertise, warranting quality improvement initiatives 4, 3
• Be aware that certain presentations (aphasia, younger age, lower NIHSS, history of prior stroke/TIA) should heighten suspicion for stroke mimics without delaying appropriate treatment 3, 2, 5