Transient global amnesia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

Overview

Transient global amnesia is a sudden, reversible syndrome characterized by complete anterograde amnesia with a variable period of retrograde amnesia, lasting several hours and resolving within 24 hours, with preservation of alertness and other cognitive functions.

Clinical Features

The typical episode involves abrupt inability to retain new information, repetitive stereotyped questioning, preserved personal identity, and normal neurologic examination during and after the event.

Patient Characteristics and Preceding Factors

Transient global amnesia most commonly affects middle-aged and older adults, and episodes may be preceded by physical or emotional stress, although many cases occur without a clear precipitating factor.

Other Causes of Transient Amnesia

Several conditions may mimic transient global amnesia, including seizures, stroke, head trauma, and metabolic disturbances, particularly when atypical features such as confusion or focal neurologic deficits are present.

Putative Mechanisms

No definitive pathophysiological explanation has been established, though proposed mechanisms involve transient dysfunction of medial temporal structures, possible vascular factors, migraine-related processes, or altered hippocampal connectivity.

Insights into Memory Function

The syndrome highlights the close relationship between anterograde and retrograde memory and implicates the hippocampus and related structures as central to memory formation and retrieval.

Diagnostic Imaging

Early imaging is typically normal, but delayed diffusion-weighted MRI may reveal small, transient punctate lesions in the hippocampus.

Conclusions

Transient global amnesia is a benign, self-limited disorder with good prognosis and occasional recurrence, though its precise cause remains unknown.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

Transient global amnesia (TGA) was recognized as a distinct clinical syndrome only after earlier, similar cases of acute, transient amnesia had been reported under other descriptions. It was formally codified and named in 1958 by Fisher and Adams, and then characterized in detail in a later comprehensive report, which helped establish its clinical boundaries and typical features. ^{[1] [2] [3]}

• Before the term transient global amnesia was introduced, single episodes of confusion with amnesia and amnesic events were reported in the literature.^{[1] [2]}
• In 1958, Fisher and Adams codified and named the syndrome transient global amnesia, bringing together its key clinical characteristics. ^[3]
• The same authors subsequently produced a detailed monograph on the disorder, further defining its phenomenology and natural history. ^[3]
• These reports laid the foundation for viewing transient global amnesia as a distinct, recognizable neurologic syndrome, later supported and refined by larger clinical series and proposed diagnostic criteria. ^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

The underlying pathophysiology of transient global amnesia (TGA) remains uncertain. No single mechanism fully explains the abrupt and transient disturbance of memory, and early seizure-based theories have not been supported by electroencephalographic data. Current concepts focus on transient dysfunction of the medial temporal structures and related networks, often framed in terms of unusual vascular or ischemic phenomena. Supportive evidence comes from stroke-risk analyses, delayed hippocampal lesions on diffusion-weighted MRI, perfusion and connectivity imaging, migraine-related mechanisms such as cortical spreading depression, and proposed (but not yet confirmed) venous congestion of the temporal lobes. ^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

• No adequate pathophysiological explanation of transient global amnesia has emerged.
• Early theories attributing episodes to seizures are not supported by electroencephalography or other neurophysiologic techniques.
• Most current premises involve unconventional vascular or ischemic mechanisms affecting the medial temporal lobes, thalamus, or posterior cerebral circulation.^[3][4]
• Analyses of several series indicate that the risk of subsequent ischemic stroke is not clearly increased, although one large propensity-matched study suggested a minimally higher risk. ^{[1] [4] [5]}
• Delayed, small hippocampal lesions on diffusion-weighted MRI, appearing many hours after the episode, provide tentative support for a vascular mechanism, but it is unclear whether they represent ischemia or altered neuronal physiology.^[10]
• Functional imaging has shown bitemporal hypoperfusion during episodes.^[6]
• Network-based studies demonstrate reduced connectivity of the hippocampi and parahippocampal gyri bilaterally, as well as altered connectivity of the amygdala and parts of the lateral temporal lobe.^[7]
• Migraine has been linked to transient global amnesia through the proposed mechanism of cortical spreading depression, but supporting evidence remains circumstantial. ^{[2] [3]}
• A proposed venous-reflux mechanism suggests transient vascular congestion of the temporal lobes due to retrograde jugular venous flow or jugular valve incompetence; however, this has not been confirmed.^{[8] [9]}
• Occasional episodes occurring immediately after vertebral artery angiography support a vascular mechanism or cortical irritation similar to that seen in migraine-related phenomena.^[3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

Transient global amnesia (TGA) is diagnosed clinically and must be distinguished from other causes of sudden memory loss. The diagnosis becomes doubtful when features deviate from the typical pattern.^[1]

• Sudden onset of clear anterograde amnesia.
• Repetitive, stereotyped questioning.
• Preservation of alertness and personal identity.
• No clouding of consciousness.
• No focal neurologic signs during or after the episode.
• Resolution within 24 hours, leaving a memory gap for the episode.

The following findings are not typical of transient global amnesia and suggest another cause:

• Clouding of consciousness or delirium^[2].
• Inattention or incoherence^[2].
• Aphasia, paresthesias, vertigo, ataxia, or other focal neurologic deficits^[2].
• Cognitive deficits beyond memory detected on bedside testing^[2].
• Loss of personal identity (more typical of functional or psychogenic amnesia)^[2].
• Epileptic features^[2].
• Recent head injury^[2].

• Often of short duration (15–30 minutes).
• May occur in repeated episodes separated by weeks.
• May include olfactory hallucinations, tearfulness, or unusual memory disturbances.
• Frequently lacks the classic repetitive stereotyped questioning seen in TGA.
• Patients are generally younger than those with typical TGA.

• Rare cases of isolated hippocampal infarction may initially resemble TGA^[4][5].
• The key difference is that the memory deficit does not resolve^[4][5].
• Some ischemic syndromes may include repetitive questioning, but the pattern is not typically as stereotyped or frequent as in TGA^[6].

• May closely resemble TGA, including repetitive questioning.
• Occurs in the setting of head trauma, distinguishing it from TGA.

• Transient amnesia during or preceding migraine has been described but is rare^[7].

• In children, it may appear as part of a migrainous confusional state^[8].

• Electroconvulsive therapy produces memory loss for the period of the procedure and for some time before and after.
• This pattern can simulate TGA, but the cause is obvious and procedure-related, and therefore clearly distinguishable from spontaneous TGA.
  

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Each year, approximately 3 to 8 persons per 100,000 population experience an episode of transient global amnesia^[1].
• The condition occurs more frequently in persons older than 50 years of age^[1].

• In a retrospective series of 277 cases, the mean age was 62 years^[2].
• Sex distribution has varied across studies:
  • Some series report slightly more men than women^[2][3],
  • Other series show the opposite pattern^[2][3].

• In most series, about 15% of patients have had more than one episode^[2].
• Among those with recurrent episodes, the average interval between episodes was approximately 2 years, and almost two thirds had three or more definite or probable episodes^[2].
• Estimates of recurrence frequency and intervals vary among studies^[2][4].
• Data from a retrospective series of 1044 patients suggested that younger age at first episode and a personal or family history of migraine were associated with future episodes, although these findings have not been consistently affirmed^[4].
• Cardiovascular risk factors have been overrepresented in some series but are considered commensurate with the typical age range of affected patients^[5].

• A higher risk of transient global amnesia has been reported among patients with migraine compared with those without migraine^[6].

• Rare reports of transient global amnesia in adolescents have been linked to athletic activity and a history of migraine^[7].

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Migraine: Several case series and a meta-analysis have identified a higher risk of transient global amnesia among patients with migraine than among those without migraine.^[1]
• Younger age at the first episode: In a retrospective series involving 1044 patients, younger age at the time of the first episode was associated with future episodes^[2].
• Personal or family history of migraine: The same retrospective series suggested that a personal or family history of migraine presaged future episodes, although these findings have not been affirmed.^[2]
• Cardiovascular risk factors: Cardiovascular risk factors have been overrepresented in some series but are probably commensurate with the typical age range of patients with transient global amnesia.^[3]
• History of migraine in adolescents: Rare reports of transient global amnesia in adolescents have been linked to athletic activity and a history of migraine.^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Transient global amnesia is a sudden, reversible syndrome of memory disturbance characterized by complete anterograde amnesia and a variable period of retrograde amnesia.^[1]
• The episode usually lasts for several hours and gradually resolves as the patient regains the ability to form new memories.^[1]
• During recovery, the period of retrograde memory loss gradually shrinks from days or hours to minutes.^[1]
• The episode leaves a permanent gap in memory for the period of the attack and for several hours before its onset.^[1]
• In a retrospective series of 277 cases, episodes lasted a mean of 6 hours, with most lasting 2 to 12 hours.^[2]
• In most series, approximately 15% of patients have had more than one episode, with an average interval between episodes of about 2 years.^[2]
• Almost two thirds of patients with recurrent episodes had three or more definite or probable episodes.^[2]

• Estimates of recurrence frequency and intervals have varied among studies.^[1]˒^[2]˒^[3]

• After the episode, some patients have a mild headache.^[1]
• Nausea and dizziness have been reported infrequently.^[1]
• The neurologic examination is normal during and after the episode.^[1]
• A permanent memory gap remains for the epoch of the episode and for a period before onset.^[1]

• Extensive evaluation is generally not necessary unless there are atypical features suggesting another diagnosis such as transient ischemic attack, stroke, seizure, or postconcussive amnesia.^[1]

• The overall prognosis is good.^[1]
• Transient global amnesia is described as a benign, self-limited disorder.^[1]
• Approximately 15% of patients experience recurrences years later.^[1]˒^[2]
• Analyses from several series indicate that the risk of subsequent ischemic stroke is not increased after transient global amnesia, although one propensity-matched study suggested a minimally higher risk.^[4]˒^[5]˒^[6]

• Despite many theories, the cause remains unknown.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

Transient global amnesia is a sudden, temporary disturbance of memory in which the patient cannot retain new information and has a period of retrograde amnesia, while remaining alert, oriented to person, and otherwise neurologically normal. Diagnostic criteria focus on a witnessed, isolated episode of amnesia that resolves within 24 hours, without seizures, head trauma, or other major neurologic deficits.^[1][2][3]

• Attack is witnessed
  • The episode is seen by someone who can describe how it began and evolved^[2][3].
• Clear anterograde amnesia
  • The patient cannot lay down new memories.
  • Often asks repetitive, stereotyped questions (e.g., “Where am I?”, “What happened?”)^[1][2][3].
• Disturbance limited to memory
  • Dysfunction is confined to repetitive queries and amnesia^[2][3].
  • No clouding of consciousness^[2][3].
  • No general cognitive defect aside from memory disturbance on bedside testing^[1].
  • No loss of personal identity (the patient knows who they are and recognizes familiar people, except for events within the retrograde gap)^[2][3].
• No other major neurologic signs
  • No focal neurologic signs during or after the attack^[2][3].
  • No major neurologic symptoms suggesting stroke or other focal brain disease^[1][2].
• No seizure or recent head trauma
  • No epileptic features^[2][3].
  • No recent head injury^[2][3].
  • No active epilepsy^[2][3].
• Transient course
  • Memory loss is transient, typically lasting several hours^[4].
  • The episode resolves within 24 hours^[1][2][3].
  • A permanent gap in memory remains for the episode itself and for a period before onset^[1].

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Transient global amnesia typically presents with a sudden onset of memory disturbance in a middle-aged or older person.^[1]
• The episode is characterized by complete inability to retain new information for several hours.^[2]˒^[3]
• During the attack, there is anterograde amnesia together with a period of retrograde amnesia that may extend back for hours, days, or longer.^[3]
• Patients often reveal their difficulty through repetitive, stereotyped questions, sometimes asked repeatedly at short intervals.^[2]
• Personal identity is preserved, and patients can usually state their name and recognize close relatives.^[3]

• Episodes may be preceded by physical or mental shock or extreme exertion, such as cold-water exposure, news of a death, sexual intercourse, assault, medical procedures, or severe pain, although many cases have no obvious precipitant.^[1]

• Sudden inability to form new memories.^[2]˒^[3]
• Retrograde memory loss for a period before the event.^[3]
• Repetitive questioning.^[2]
• Preserved alertness and preservation of other cognitive functions apart from memory.^[3]
• No loss of personal identity.^[3]
• After the episode, some patients report a mild headache.
• Nausea and dizziness have been reported infrequently.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• During the episode, the patient remains alert and otherwise cognitively intact apart from the memory disturbance.^[1]
• There is no clouding of consciousness.^[1]
• There are no focal neurologic signs during or after the attack.^[1]
• The neurologic examination is normal during and after the incident.
• Bedside testing may show memory disturbance, but other major neurologic signs or symptoms are absent.^[2]˒^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Brain imaging is commonly performed to exclude infarction or other structural lesions, especially in the emergency setting.
• Initial imaging studies are usually normal early in the course of the episode.^[1]

Diffusion-Weighted MRI (DWI) – Key Modality

• Most patients have one or more punctate lesions in the hippocampus or adjacent structures on diffusion-weighted MRI^[2].
• In a series of 390 patients, such lesions were seen in about 70% of cases^[2].

Timing of MRI Findings

• Lesions are often not visible immediately after symptom onset^[1][2].

• They are most often detected 12 to 48 hours after the episode^[2].
• The lesions are usually fleeting, but may persist for several days^[2].

Typical Lesion Characteristics

• Lesions are small, punctate areas of restricted diffusion in the hippocampus^[1][2].

• Left-sided lesions have been reported more often than right-sided or bilateral ones^[2].

Atypical / Expanded Patterns

• Unusual anatomical or temporal patterns of diffusion restriction have been described in some patients who did not have the typical clinical syndrome^[3].
• Similar hippocampal lesions may occasionally be found incidentally in patients with cognitive or emotional symptoms without amnesia, leading some authors to broaden the imaging-based definition^[3].

Functional / Perfusion Imaging

• Functional studies have shown bitemporal hypoperfusion during episodes^[4].
• Network analyses demonstrate reduced connectivity of the hippocampi, parahippocampal gyri, amygdala, and parts of the lateral temporal lobe during the attack^[5].

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS.

• Transient Global Amnesia is a benign and self limited condition.
• Patients are often discharged with reassurance that the disorder is not a stroke.

• Explanations are usually well received by the patient and family, although additional neurologic consultation is sometimes sought.
• An extensive evaluation is generally not required unless the history or examination suggests an alternative diagnosis such as transient ischemic attack, stroke, seizure, or postconcussive amnesia.^[1]
• Brain imaging is often performed to exclude infarction or other structural lesions and to reassure both the patient and the physician.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS. Intervention is not required unless we suspect and prove the diagnosis other than Transient Global Amnesia.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS. No role of Surgery in this disease.