Clinician: The patient’s symptom profile is confusing, especially because his test results are normal. Are his amnesic episodes related to his migraine?
Headache specialist: Your patient’s clinical presentation suggests transient global amnesia (TGA), a reversible and relatively short-lasting amnesic syndrome of sudden onset that is sometimes associated with migraine.
Clinician: How common is TGA and in which patients is it likely to develop?
Headache specialist: TGA was originally described about 45 years ago. The incidence in the general population is unknown, but some authorities estimate that the rate is 1 per 10,000.1 Most patients are middle-aged or elderly; the mean age is 55 years. However, TGA is also seen in children and adolescents. The attacks tend to be isolated; only 12% to 18% of patients report 1 or more recurrences. The male to female ratio is approximately 4:3. Affected patients who are middle-aged or older usually do not have a history of migraine; however, TGA can be associated with migraine, as well as with epilepsy, vertebrobasilar insufficiency, and hypoglycemia. In older patients, stroke and transient ischemic attack (TIA) must be ruled out. It is important to differentiate TGA from acute confusional migraine, which occurs more frequently in young persons and may be the initial manifestation of migraine in children (Table). Young patients with acute confusional migraine present with sudden onset of confusion, unresponsiveness to verbal commands, agitation, and combativeness. Their symptoms usually resolve within 24 hours. Drug intoxication, metabolic disturbances, epilepsy, encephalitis, and head trauma must be ruled out in these patients.2
Clinician: What are the other typical features of a TGA attack?
Headache specialist: Patients are unable to form new memories, although consciousness, personal identity, long-term memory, and ability to perform routine activities are preserved. During the attack, the patient is bewildered, anxious, and aware of the memory impediment. The attack usually lasts for a few hours, and there are no other neurologic signs and symptoms. The retrograde amnesia can extend from several hours to years, but it recedes spontaneously as the attack abates. The anterograde amnesia lasts 4 to 8 hours. The repetition of questions is a unique and very common feature. Patients retain their ability to perform complex activities, such as driving, typing, cooking, and dressing. TGA may present during the aura phase, during the acute headache, or as a migraine equivalent (visual aura or other neurologic symptoms that usually last for 15 to 30 minutes and are not followed by a headache).
Clinician: What are the usual triggers of TGA?
Headache specialist: Precipitating factors in middle-aged and elderly patients include sexual activity, orgasm, exposure to or immersion in cold water, exercise, pain, and physical and emotional stress. In young adults and adolescents, TGA occurs in association with migraine, as well as during and immediately after a competitive sports activity or other exercise. It may also be precipitated by sexual intercourse, the Valsalva maneuver, and hyperventilation. In children, TGA is most likely to be precipitated by migraine or sports activity. The pathophysiology of TGA is not well understood. It appears that in some amnesic syndromes, including TGA, hypoperfusion or transitory ischemia resulting from vasospasm or vasomotor disturbances in the vertebrobasilar arterial system affects the mamillohippocampal region, which is involved in the formation and preservation of memory.3 Increased blood flow to the superior vena cava during vigorous exercise may stimulate sympathetic activity, which leads to increased central venous return and may precipitate TGA. The Valsalva maneuver, which has also been linked to TGA, causes increased intrathoracic pressure and decreased venous return to the heart with obstruction of venous flow from the internal jugular vein.Such transient retrograde venous congestion and venous ischemia in bilateral diencephalic or hippocampal structures may be responsible for TGA.4
Clinician: What is the prognosis?
Headache specialist: TGA is usually benign; however, recurrent TIAs or stroke may develop in patients who have repeated episodes of TGA. Some experts advocate prophylactic antiplatelet therapy to reduce the risk of a cerebrovascular accident.
1. Koski KJ, Marttila RJ. Transient global amnesia: incidence in an urban population.
Acta Neurol Scand. 1990;81:358-360.
2. Toffol GJ, Swiontoniowski M. Transient global amnesia. Postgrad Med.
3. Olivarius BD, Jensen TS. Transient global amnesia in migraine. Headache.
4. Lewis SL. Aetiology of transient global amnesia. Lancet. 1998;352:397-399.