Transient Global Amnesia
John C. M. Brust
Transient global amnesia (TGA) is characterized by sudden inability to form new memory traces (anterograde amnesia) in addition to retrograde memory loss for events of the preceding days, weeks, or even years.
Patients are usually middle aged or elderly and otherwise healthy. Recurrent attacks occur in 15% to 30% of cases, and fewer than 3% have more than three attacks. Intervals between attacks range from 1 month to 19 years.
The cause of TGA is uncertain. Case-control series and anecdotal reports variably implicate seizures, stroke, or migraine. Against an epileptic basis for TGA are the infrequency of recurrence, absence of other seizure phenomena, and normal electroencephalogram (EEG) even during attacks. In transient epileptic amnesia (TEA), attacks are usually less than an hour in duration, tend to occur on awakening, are often accompanied by other ictal symptoms, and are likely to recur; ictal and interictal EEG abnormalities are often present, and symptoms respond to anticonvulsant therapy.
TGA has been anecdotally described in association with carotid artery occlusion and amaurosis fugax, with infarction of the inferomedial temporal lobe, the cingulate gyrus, or the retrosplenial corpus callosum and with cerebral angiography (especially vertebral). In large series, however, major risk factors for stroke (hypertension, diabetes mellitus, tobacco, ischemic heart disease, atrial fibrillation, and past stroke or transient ischemic attack [TIA]) are no more common among patients with TGA than in age-matched controls, and TGA is not a risk factor for stroke. Studies addressing a possible association of TGA with cardiac valvular disease or patent foramen ovale have been inconsistent. Patients with amnestic stroke owing to documented posterior cerebral artery occlusion do not report previous TGA; their neurologic signs usually include more than simple amnesia (e.g., visual impairment), and they do not exhibit repetitive queries. Reduced blood flow to the thalamus or temporal lobes has been documented during attacks of TGA but could be secondary to neuronal dysfunction rather than its cause.
Valve incompetence of the internal jugular vein is present in many patients with TGA, raising the possibility of cerebral venous congestion during Valsalva-like activities. Intracranial venous reflux during Valsalva maneuver could not be demonstrated in the same patients, however, and such a mechanism is unlikely to explain symptoms that last hours and seldom recur.
Epidemiologic studies confirm an association of TGA with migraine, even though in most migraine patients, headache attacks are recurrent, whereas attacks of TGA are not. Sometimes, both amnestic and migrainous attacks (including visual symptoms and vomiting) occur simultaneously or follow one another. A case report described a man with repeated episodes of TGA associated with sexual activity whose spells cleared as long as he took the β-blocker metoprolol. Cortical spreading depression (possibly the pathophysiologic basis of cerebral symptoms of migraine) could, by affecting the hippocampus, explain some cases of TGA.
During attacks, which affect both verbal and nonverbal memory, there is often bewilderment or anxiety and a tendency to repeat one or several questions (e.g., “Where am I?”). Physical and neurologic examinations, including mental status, are otherwise normal. Immediate registration of events (e.g., serial digits) is intact, and self-identification is preserved. Attacks last minutes or hours, rarely longer than a day, with gradual recovery. Retrograde amnesia clears in a forward fashion, often with permanent loss for events occurring within minutes or a few hours of the attack; there is also permanent amnesia for events during the attack itself. Headache frequently accompanies attacks; less often, there is nausea, dizziness, chills, flushing, or limb paresthesias. TGA is frequently precipitated by physical or emotional stress, such as sexual intercourse, driving an automobile, pain, photogenic events, or swimming in cold water. Because amnesia can accompany a variety of neurologic disturbances, such as head trauma, intoxication, partial complex seizures, or dissociative states, criteria for diagnosing TGA should include observation of the attack by others.