Makindo Medical Notes

Introduction

Transient Global Amnesia (TGA) is a benign, temporary, and isolated episode of anterograde amnesia, lasting up to 24 hours, without other neurological deficits. First described by Fisher and Adams in 1964, TGA is characterized by sudden onset of memory loss and confusion about recent events, while long-term memory and personal identity remain intact. The exact etiology remains unclear, with various hypotheses including vascular, migrainous, and epileptic mechanisms. TGA is often misdiagnosed as a transient ischemic attack (TIA) or seizure but has distinct clinical features and an excellent prognosis.

Epidemiology

TGA primarily affects middle-aged and older adults:

• Incidence: Estimated at 5 to 10 per 100,000 people annually; higher in those over 50 years old.
• Age: Most patients are between 50 and 70 years old.
• Gender: Slightly more common in men, though some studies report equal distribution.
• Recurrence: Recurs in about 5-25% of patients, usually as a single additional episode.

Etiology and Pathophysiology

The exact cause of TGA is unknown, but several theories have been proposed:

• Venous Congestion: Transient disturbance in cerebral venous outflow leading to hippocampal dysfunction.
• Migrainous Mechanism: Shared pathophysiological processes with migraine without the typical headache.
• Ischemia: Brief hypoperfusion of medial temporal lobes; however, no consistent vascular occlusions are identified.
• Epileptic Activity: Transient epileptic discharges affecting memory circuits; less supported due to lack of typical EEG findings.
• Emotional or Physical Stress: Precipitating factors such as sudden immersion in cold water, strenuous activity, or emotional events.

Clinical Presentation

TGA is characterized by the sudden onset of anterograde amnesia with the following features:

• Anterograde Amnesia: Inability to form new memories; repetitive questioning about recent events.
• Preserved Personal Identity: Patients know who they are and recognize family and familiar surroundings.
• No Loss of Consciousness: Patients are alert and responsive.
• Normal Neurological Examination: No focal neurological deficits or aphasia.
• Duration: Symptoms last from 1 to 24 hours (typically 4 to 6 hours) and resolve completely.
• Retrograde Amnesia: Variable loss of memory for events preceding the attack, which may persist.
• Emotional Distress: Patients may be anxious or agitated due to awareness of memory loss.
• Precipitating Events: Physical exertion, emotional stress, pain, immersion in cold or hot water, sexual activity, or medical procedures.

Diagnostic Criteria

The diagnosis of TGA is clinical and based on established criteria:

• Witnessed Episode: The attack was observed by a reliable witness.
• Anterograde Amnesia: Obvious inability to form new memories during the attack.
• Alertness: No clouding of consciousness or loss of personal identity.
• No Focal Neurological Deficits: Absence of motor, sensory, or coordination abnormalities.
• No Features of Epilepsy: No convulsions or recent history of epilepsy.
• Duration: Symptoms resolve within 24 hours.
• Exclusion of Recent Head Injury: No history of trauma preceding the event.

Differential Diagnosis

It's essential to differentiate TGA from other conditions that can cause transient amnesia:

• Transient Ischemic Attack (TIA):
  • Typically involves focal neurological deficits.
  • Amnesia alone is an uncommon presentation of TIA.
• Epileptic Amnesia:
  • Often brief episodes (minutes), may have automatisms or altered consciousness.
  • EEG may show epileptiform activity.
• Psychogenic Amnesia (Functional):
  • Often associated with psychological stressors.
  • Loss of personal identity and autobiographical memory.
• Head Injury:
  • History of trauma preceding symptoms.
  • May have other signs of concussion.
• Wernicke-Korsakoff Syndrome:
  • Associated with chronic alcoholism and thiamine deficiency.
  • Presents with confabulation and other neurological signs.
• Drug-Induced Amnesia:
  • Related to benzodiazepines or other sedative medications.

Investigations

In cases with classic presentation, extensive investigations may not be necessary. However, if atypical features are present, consider the following:

• Neuroimaging:
  • MRI with DWI: May show small punctate lesions in the hippocampus; findings are often transient and appear after 24-48 hours.
  • CT Scan: Generally unremarkable; used to rule out acute pathology.
• Electroencephalogram (EEG):
  • To exclude epileptic activity if seizures are suspected.
  • EEG is typically normal in TGA.
• Laboratory Tests:
  • Blood glucose, electrolytes, and metabolic panels to rule out metabolic causes.
• Cardiac Evaluation:
  • If TIA is suspected, consider ECG and echocardiogram.
• Carotid Doppler Ultrasound:
  • To assess for carotid artery stenosis if vascular etiology is considered.

Management: no specific treatment is required:

• Reassurance: Explain the benign nature of the condition to the patient and family.
• Observation: Monitor until symptoms resolve to ensure no progression or emergence of new symptoms.
• Avoid Misdiagnosis: Ensure accurate diagnosis to prevent unnecessary interventions or anxiety associated with mislabeling as TIA or seizure.
• Address Precipitating Factors: Advise on managing stress and avoiding potential triggers if identified.
• Follow-Up: Arrange outpatient follow-up if atypical features were present or if further evaluation is deemed necessary.

Prognosis for TGA is excellent:

• Most patients experience a single episode in their lifetime.
• No increased risk of stroke or epilepsy compared to the general population.
• Cognitive function returns to baseline without residual deficits.
• Recurrence is uncommon but can occur; patients should be reassured of the benign nature.

Conclusion

Transient Global Amnesia is a benign, transient episode of memory loss with a sudden onset and complete recovery. It is essential to recognize the characteristic features to differentiate it from other serious conditions like TIA or seizures. Reassurance and education are key components of management. Ongoing research continues to explore the underlying mechanisms of TGA to enhance understanding and patient care.

References

• Hodges JR, Warlow CP. Syndromes of transient amnesia: towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry. 1990;53(10):834-843.
• Fisher CM, Adams RD. Transient global amnesia. Trans Am Neurol Assoc. 1964;89:143-147.
• Bartsch T, Deuschl G. Transient global amnesia: functional anatomy and clinical implications. Lancet Neurol. 2010;9(2):205-214.
• Sattler JM, Rabinstein AA. Transient global amnesia. Mayo Clin Proc. 2019;94(4):662-672.
• Jäger T, Szabo K, Griebe M, et al. Selective disruption of hippocampus-mediated memory encoding during functional cerebral hypoxia. Proc Natl Acad Sci U S A. 2009;106(31):11589-11594.