Hodges and Ward have made detailed psychologic observations in 5 patients during an episode. The psychologic deficit, except for its transience, was much the same as that in a permanent amnesia syndrome. Personality, cognition involving high-level functioning, semantic language, and visuospatial discrimination were all preserved. So-called immediate memory—that is, registration (see earlier)—was likewise operating normally, but memory was essentially obliterated. The duration of retrograde amnesia was variable, but characteristically it shrank after the attack, leaving a permanent retrograde gap of about 1 h. However, subtle impairment of new learning persisted for up to a week after the acute attack insofar as this defect could be detected by special testing.
In a survey conducted in the Rochester, Minnesota, area, transient global amnesia (TGA) occurred at an annual rate of 5.2 cases per 100,000 population. The recurrence of such attacks is not uncommon, having been noted in 66 of 277 older adults who were observed for an average period of 80 months (Miller et al) and in 16 of 74 patients followed for 7 to 210 months (Hinge et al). Hinge and colleagues estimate the mean annual recurrence rate to be so low (4.7 percent) that most patients are likely to experience only one attack. One of our patients had more than 50 attacks, but among all the rest (more than 100 cases), 5 was the maximum. It seems children are not susceptible to the condition; however, a 13-year-old and 16-year-old with migraine were reported to have had similar attacks during participation in sports (Tosi and Righetti).
No consistent antecedent events have been identified, but certain ones—such as a highly emotional experience like hearing of the death of a family member, pain, exposure to cold water, sexual activity, and mild head trauma—have been reported in some cases (Haas and Ross; Fisher). The similarity to postconcussive amnesia is notable; this is always a concern if the patient was not under observation at the onset of the attack. We have also seen several patients in whom the attacks appeared after minor diagnostic procedures such as colonoscopy, but the residual effects of sedation are suspect in some of these. Several cases have been reported in high-altitude climbers and have created difficulty in distinguishing TGA from altitude sickness.
The main concern in differential diagnosis is a temporal lobe seizure (see in the following text). Transient ischemic attack involving the same posterior regions is another. Whether migrainous episodes can produce a clinical syndrome is uncertain, as noted later, but by far the largest number of cases are idiopathic after extensive evaluation.
The pathogenesis of idiopathic TGA has not been determined. It has been suggested that typical case represents an unusual form of temporal lobe epilepsy (transient epileptic amnesia [TEA]), but this seems an unlikely unifying hypothesis. A number of patients have been studied with EEGs during an attack or shortly thereafter and have not shown seizure activity (Miller et al). Moreover, amnesic episodes caused by seizures are usually much briefer than those of TGA, and most or all temporal lobe seizures are associated with impairment of consciousness and an inability to interact fully with the social and physical environment. Using EEG and nasopharyngeal leads, Rowan and Protass found mesiotemporal spike discharges in 5 of 7 patients. They attributed the discharges to ischemic lesions during drug-induced sleep, which we do not find entirely plausible. Palmini and coworkers cite exceptional cases of pure amnesic seizures in temporal lobe epilepsy, but even in their best examples, ictal and postictal function was not normal.
An interesting functional correlate has been identified by Peer and coworkers using functional MRI. Several of the structures that were identified as participating in episodic memory retrieval showed reduced activity during TGA; the effect was bilateral, waned as the spell progressed, was and reversible. However, many other regions besides the hippocampus and its immediate connections were also affected.