What is transient global amnesia (TGA)?

Transient Global Amnesia: Clinical Overview

Transient global amnesia (TGA) is a benign, self-limited clinical syndrome characterized by sudden-onset profound anterograde amnesia with variable retrograde memory impairment, lasting up to 24 hours, without other neurological deficits. 1, 2

Clinical Presentation

Core Features:

• Sudden onset of severe anterograde amnesia where patients cannot form new memories for longer than 30-180 seconds 3
• Repetitive questioning about current events due to inability to retain new information 4, 5
• Mild retrograde amnesia with variable impairment of past memories 4
• Preservation of all other cognitive functions including personal identity, language, attention, and previously learned skills (e.g., driving, cooking) 3, 5
• Time disorientation and confusion during the episode 5
• Complete resolution within 24 hours by definition 1, 4

Associated Symptoms:

• Vomiting, headache, blurry vision, dizziness, and nausea may accompany the episode 5
• Patients typically appear anxious and bewildered but maintain normal consciousness 4

Precipitating Events

Common triggers include: 5

• Physical exertion with Valsalva-like maneuvers 3, 6
• Emotional or psychological stress 5
• Exposure to extreme temperatures 5
• High-altitude conditions 5
• Sexual intercourse 5
• Acute illness 5

Epidemiology

• Annual incidence: Approximately 15 cases per 100,000 people (significantly higher than previously estimated) 3
• Age distribution: Most commonly affects patients over 50 years of age 3, 5
• Recurrence rate: 10% of patients experience 1-5 recurrences; lifetime recurrence rate ranges from 2.9% to 23.8% 3, 5

Diagnostic Criteria

The American Heart Association recommends diagnosis based on clinical criteria including: 1

• Witnessed episode of memory loss with anterograde amnesia 6
• Absence of focal neurological signs or deficits 1, 6
• No history of recent head trauma 1, 6
• No features of epilepsy or active epilepsy 6
• Resolution within 24 hours 1, 6

Critical differential diagnoses to exclude: 2

• Stroke and TIA - share overlapping features but carry significantly worse prognosis 2
• Epileptic seizures - may present with acute confusion and memory impairment 2
• Head trauma - must be ruled out by history 1

Neuroimaging

MRI Findings:

• Punctate lesions in the CA1 field of the hippocampal cornu ammonis appear on diffusion-weighted imaging (DWI) 24-96 hours after symptom onset 4, 7
• Detection rates: 50% with 1.5 or 3 Tesla MRI; up to 85-90% with 7 Tesla MRI 7, 3
• Distribution: Two-thirds unilateral, one-third bilateral 3
• Resolution: Lesions fully resolve on follow-up imaging without residual damage 7

Imaging Recommendations:

• Routine MRI is NOT recommended in typical TGA without focal neurological signs 1, 2
• Consider neuroimaging if: 1, 2
  • Focal neurological symptoms present
  • Recurrent or brief episodes (atypical duration)
  • Suspected alternative etiologies (stroke, seizures)
  • Significant cerebrovascular disease risk factors 1

Common pitfall: Initial MRI performed within 4 hours of symptom onset may be negative; characteristic hippocampal lesions appear 24-72 hours after onset 7

Pathophysiology

The exact mechanism remains unclear, but proposed theories include: 3, 5

• Impaired venous drainage of the hippocampus (most supported) 5
• Vascular mechanisms 3
• Migraine-like spreading depression 3
• Epilepsy-like mechanisms 3
• Memory-related network disorders including the default network 3

Management and Prognosis

Acute Management:

• Reassurance of patients and anxious relatives about the benign and self-limited nature of the episode 3
• No established treatment for acute episodes 5
• Observation until symptom resolution (typically within hours) 4

Critical Management Principle:

• Unlike TIA, TGA does NOT require aggressive cardiovascular risk factor modification as there is no increased risk of stroke or cardiovascular events 2
• Avoid inappropriate antiplatelet or anticoagulation therapy with associated bleeding risks 2
• Do not initiate unnecessary statin therapy 2
• Prevent patient anxiety about stroke risk through appropriate education 2

Long-term Prognosis:

• Benign condition with no increased mortality 2, 6
• No increased risk of TIA or stroke in patients who have had TGA 2, 6
• Conflicting evidence regarding future risk of seizures or dementia 5
• Possible association with migraine headaches and takotsubo cardiomyopathy 5
• Complete recovery except for amnesia of the episode itself 4