Sudden onset of amnesia in a healthy woman

In TGA, procedural memory is unaffected. Thus, activities of daily living and instrumental activities of daily living remain intact—eg, the patient retains the necessary skills to drive a car.

TABLE 2
Categories of memory function¹

Most often the prognosis is good

TGA is an unusual manifestation of anterograde amnesia that is self-limited and tends not to recur.⁵ An episode typically lasts 1 to 8 hours.⁶ Although the disorder was first described in 1956, a set of clinical criteria (TABLE 3) was not defined until 1990.⁷ The highlights of these criteria are that self-identity is preserved and no evidence exists for neurologic deficit or seizure activity.⁶ The incidence of TGA is 3 to 10 in 100,000.⁵ TGA usually affects patients in their early 60s,² and men and women are affected equally.

Interestingly, more than half of patients with TGA report a precipitating event, usually involving physical activity or a Valsalva maneuver.⁶ Classically, the patient repeatedly asks the same questions. The most common associated symptoms are headache, dizziness, and nausea.^2,6

Generally, the patient’s prognosis is good, without long-term sequelae. Importantly, reassure patients and their families that there will be no memories of the event itself, as their memory-making ability was impaired.²

TABLE 3
Clinical criteria for transient global amnesia, as defined by Hodges and Warlow⁷

If episodes do recur

A small subset of people may have recurrent episodes. Recurrence rates over a 5-year span have been reported as 3% to 26%; however, this range includes cases and studies recorded before the diagnostic criteria were developed in 1990.⁶ Although the clinical criteria for TGA can be helpful in diagnosing the disorder, there is no standardized workup because TGA has no clear etiology or known underlying mechanism. Many causal theories exist, however, and have evidence to support them.

Possible underlying conditions. One proposed explanation is ischemia of the hippocampus. This raises questions of whether vascular risk factors place people at higher risk.⁸ Recent studies have not confirmed this theory, and patients with diabetes, hypertension, or hyperlipidemia appear not to be at higher risk of TGA. Still, it is interesting that TGA is a disease affecting older adults and that evidence of small-vessel ischemia is often discovered incidentally.^6,8

On the other hand, some experts take into account the high association of TGA with migraines documented in multiple studies, and therefore propose a spreading depression as the cause.⁵ Another hypothesis is a valvular insufficiency of the jugular veins that allows reflux, resulting in venous ischemia of the hippocampal area, especially during a Valsalva maneuver.⁹ Indeed, jugular valve insufficiency has been noted in up to two-thirds of TGA patients. However, if valvular insufficiency is truly the mechanism of disease, why do recurrence rates remain so low?¹⁰

MRI may be helpful. Given the many theories of TGA origin, several imaging mechanisms have been tried with mixed results: single photon emission computed tomography, magnetic resonance imaging (MRI) with diffusion-weighted imaging, and positron emission tomography.

The lack of reliable results makes it difficult to establish diagnostic criteria. Some generalized guidelines are as follows:

If there are any neurologic findings or concern about a transient ischemic attack or cerebrovascular accident, obtain an MRI. This should include diffusion-weighted imaging, which may reveal a transient lesion in the hippocampus.⁶ If the patient has recurrent episodes, or has episodes that last less than 1 hour, suspect the possibility of seizure and consider arranging for an electroencephalogram.^4,6 Likewise, recurrence may also be due to a patent foramen ovale (PFO) causing paradoxical emboli and transient ischemia of the hippocampus. In 1 study, the rate of PFO in the TGA arm was 55%; it was 50% in those with recurrent episodes.¹¹