Transient global amnesia

Did You Know?

• The estimated annual incidence of TGA varies from 2.9 per 100,000 in Spain to 5.2 per 100,000 in the US.
• Among people aged over 50, the rate of TGA incidence ranges from approximately 23 per 100,000 in a US population to 32 per 100,000 in a Scandinavian population.

Signs and symptoms

Transient global amnesia, or TGA, strikes suddenly, leaving a person nearly unable to form any new memories. Despite this, they typically appear fully alert and lucid. They know who they are and recognize close family members. Their perceptual skills and ability to perform complex learned behaviors, like driving or fixing a car, remain intact.

The memory loss is severe: they cannot recall anything beyond the last few minutes. Older memories may or may not be preserved. When they become aware of their condition, anxiety often sets in. For clinical research, a TGA episode must meet specific criteria: a capable witness reports a clear loss of recent memory; there is no confusion or other cognitive problem besides amnesia; no focal neurological signs appear during or after the attack; there is no sign of epilepsy or active epilepsy in the past two years; no recent head injury; and the episode resolves within 24 hours.

Onset is rapid, and the attack typically lasts between 2 and 8 hours. A hallmark of TGA is perseveration: the person repeatedly asks the same questions or makes the same statements, with identical tone and gestures, almost like a stuck recording. This occurs in nearly all cases and is often considered a defining feature. Throughout the episode, social skills and significant older memories, including personal identity and family recognition, stay intact.

Personality remains unchanged. There is no loss of consciousness, no reduced awareness, and no cognitive deficits beyond the memory impairment.

Causes

The exact cause of transient global amnesia is still not well understood. The main theories suggest it could be related to a seizure, a temporary issue with blood flow in or around the brain, or a migraine-like process. These possibilities are different enough that TGA might actually be a group of related conditions with various causes, mechanisms, and outcomes. At least a third of TGA episodes happen after a specific trigger.

Common triggers include intense physical activity, such as sex, swimming in cold water or other sudden temperature shifts, and emotionally upsetting or stressful events. Some cases have also been reported after medical procedures or illnesses. One study found two instances where two family members had TGA out of 114 total cases, hinting at a possible but small genetic link. When the definition of a trigger is broadened to include events from days or weeks before, like financial worries, attending a funeral, or exhaustion from overwork or heavy childcare, over 80% of TGA attacks seem to be linked to a precipitating event.

People experiencing TGA show higher levels of anxiety or depression. This emotional instability might make some individuals more vulnerable to stressful triggers and thus more likely to have TGA. Compared to people who have had a transient ischemic attack (TIA), those who have had TGA are more likely to have a personal or family history of emotional problems, such as depression or phobias, or to have faced a phobic or emotionally challenging trigger.

The idea that reduced blood flow to the brain (cerebral ischemia) causes TGA is heavily debated. Until the 1990s, TGA was often seen as a type of TIA caused by cerebrovascular disease. However, evidence against a vascular cause shows that people who have had TGA are no more likely than the general population to develop future cerebrovascular disease. In fact, compared to TIA patients, TGA patients have a much lower risk of stroke, heart attack, and death.

Diagnosis

There is no universally accepted diagnostic criteria for TGA, but proposed criteria include the absence of seizures, absence of head injury, symptoms that resolve within 24 hours, and the dysfunction being limited to amnesia (both retrograde and anterograde). TGA is a clinical diagnosis, and brain imaging or other testing is not required for the diagnosis, though brain imaging is often obtained to rule out other serious causes of sudden amnesia such as stroke.

Brain imaging is usually normal during and immediately after an episode, but delayed diffusion weighted MRI (obtained 12–48 hours after the episode) can sometimes show punctate lesions in the hippocampus or adjacent areas, which are transient and often persist for several days. Functional MRI may show bitemporal hypoperfusion during an episode, and other affected areas include the hippocampus, parahippocampal gyrus, and amygdala. The neurological exam is usually normal and without focal deficits other than memory impairment.

Laboratory tests may be obtained to rule out other causes of sudden amnesia, including a complete blood count, electrolytes, kidney function, liver function, inflammatory markers, ammonia level, urine toxicology screening, alcohol level, and thyroid stimulating hormone level. Differential diagnosis should include thrombosis of the basilar artery, cardioembolic stroke, complex partial seizures, frontal lobe epilepsy, lacunar syndromes, migraine variants, posterior cerebral artery stroke, syncope and related paroxysmal spells, and temporal lobe epilepsy.

If the event lasts less than one hour, transient epileptic amnesia might be implicated; if longer than 24 hours, it is not considered TGA by definition.

Prognosis

For classic cases of transient global amnesia, the outlook is generally excellent. By definition, the confusion and memory loss fade within a day, and the condition does not raise the risk of death or long-term disability. There is no specific treatment. The main focus after diagnosis is supporting the emotional well-being of the patient and their family, since watching a capable loved one suddenly unable to remember recent moments is deeply upsetting, and relatives often need the most reassurance.

Whether a TGA episode increases the chance of a later stroke remains uncertain. Some large studies find no added risk, while others suggest a slight increase. The chance of having another episode is reported differently across studies, but one careful estimate puts it at less than 6% per year. About 15% of people who have TGA will experience multiple episodes, typically with about two years between them.

TGA may have several different causes and outcomes. Atypical cases can resemble epilepsy and might actually be transient epileptic amnesia. People whose memory loss does not fit the strict definition of pure TGA may have a less favorable prognosis.

More recent research has challenged the idea that TGA is entirely harmless. In one brain imaging study, every person who had experienced TGA showed cavities in the hippocampus, and these cavities were more numerous, larger, and more suggestive of damage than those seen in healthy people or in a large group of people with tumors or strokes. Days after an attack, some people still have verbal and cognitive problems so significant that researchers believe they are unlikely to resolve quickly.

A large study of patients more than a year after their episode found that one-third had lasting difficulties consistent with amnestic mild cognitive impairment. Another study noted selective cognitive problems even after clinical recovery, pointing to a possible impairment in the prefrontal cortex. These issues may not be with memory itself but with retrieval, where the speed of accessing information is reduced in people who have had TGA and continue to have memory complaints.