What is the likely diagnosis for an elderly patient presenting with a sudden onset of memory loss, having lost a significant period of time from Saturday afternoon to Sunday morning?

Transient Global Amnesia (TGA)

This clinical presentation is most consistent with transient global amnesia (TGA), a benign syndrome characterized by sudden-onset anterograde amnesia with preserved consciousness and other cognitive functions that resolves within 24 hours. 1, 2, 3

Defining Clinical Features

TGA presents with the following hallmark characteristics that distinguish it from other causes of acute memory loss:

• Sudden onset of profound anterograde amnesia (inability to form new memories) with variable retrograde amnesia (inability to recall recent past events), while remote memories remain intact 1, 2, 3
• Repetitive questioning reflecting disorientation to time and situation, as patients cannot retain answers to their questions 1, 3
• Preservation of personal identity - patients know who they are 2, 3
• Normal neurological examination except for the memory deficit - no focal deficits, no altered consciousness, no seizure activity 2, 3, 4
• Complete resolution within 24 hours with return to baseline cognitive function, though patients have permanent amnesia for the episode itself 1, 2, 3

Diagnostic Criteria (Hodges and Warlow)

To diagnose TGA, all of the following must be present:

• The episode must be witnessed by an observer who can verify the memory impairment 2
• Clear evidence of anterograde amnesia during the attack 2
• No clouding of consciousness or loss of personal identity 2
• No focal neurological signs or deficits 2
• No features of epilepsy and no active epilepsy 2
• No recent head injury 2
• Resolution within 24 hours 2

Critical Differential Diagnoses to Exclude

While TGA is ultimately a diagnosis of exclusion, several conditions must be ruled out:

Transient Ischemic Attack (TIA) or Stroke

• TGA does not increase risk of subsequent stroke or TIA, and mortality is not elevated in TGA patients 2
• Posterior circulation strokes can cause acute amnesia but typically have additional brainstem or cerebellar signs 3
• The pathophysiological mechanism of transient global amnesia has not been clearly established as related to cerebrovascular disease 5

Transient Epileptic Amnesia

• Distinguished by shorter episodes (typically <1 hour), recurrent episodes, and may show epileptiform activity on EEG 3
• TGA patients should have no features of epilepsy 2

Delirium

• Delirium involves inattention as a cardinal feature with fluctuating consciousness and global cognitive dysfunction beyond just memory 5
• TGA patients maintain normal attention and other cognitive functions except memory 1, 3

Psychogenic Amnesia

• May involve loss of personal identity, which does not occur in TGA 3
• Often associated with psychological stressors and may have atypical features 3

Diagnostic Workup

Neuroimaging

• MRI brain with diffusion-weighted imaging (DWI) is the imaging modality of choice 1, 3
• Characteristic finding: punctate areas of restricted diffusion in the hippocampi (particularly CA1 region), though these may not appear until 24-48 hours after symptom onset 1
• Initial MRI within hours of onset may be normal; repeat imaging at 24-48 hours increases detection rate 1
• These hippocampal lesions typically resolve completely on follow-up imaging without residual damage 1
• The prevalence of typical MRI findings varies widely (reported up to 85% in some studies) and may be underdetected without high clinical suspicion 1

Additional Testing

• EEG to exclude seizure activity if diagnostic uncertainty exists 4
• Laboratory evaluation to exclude metabolic causes: complete blood count, comprehensive metabolic panel, thyroid function, vitamin B12 4
• Extensive investigations in TGA typically reveal no abnormal findings 4

Common Precipitating Factors

TGA episodes are often triggered by:

• Physical exertion or strenuous activity 2
• Valsalva-like maneuvers (coughing, straining, sexual activity) 2
• Emotional stress or psychological triggers 3, 6
• Cold water immersion 3
• General anesthesia (rare but reported) 6

Prognosis and Management

• TGA is benign with excellent prognosis and no increased mortality 2
• No specific treatment is required beyond reassurance and observation 2, 3
• Recurrence rate is low (approximately 5-10% over subsequent years) 3
• Patients can be reassured that this does not represent a stroke or indicate increased stroke risk 2
• No driving restrictions are typically necessary after full recovery, as TGA does not confer ongoing risk 3

Critical Pitfalls to Avoid

• Do not misdiagnose TGA as TIA or stroke - this leads to unnecessary anticoagulation or antiplatelet therapy and inappropriate stroke workup 2
• Do not assume early negative MRI excludes TGA - hippocampal lesions may not appear until 24-48 hours after onset 1
• Do not confuse with dementia - TGA resolves completely within 24 hours, whereas dementia is progressive 5, 7
• Ensure the episode was witnessed - unwitnessed episodes require more extensive workup to exclude other causes 2