eMedicine Specialties > Neurology > Neuro-vascular Diseases

Transient Global Amnesia

Author: Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Contributor Information and Disclosures

Updated: Dec 7, 2009

Introduction

Background

Transient global amnesia (TGA) has been a well-described phenomenon for more than 40 years. Clinically, it manifests with a paroxysmal, transient loss of memory function. Immediate recall ability is preserved, as is remote memory; however, patients experience striking loss of memory for recent events and an impaired ability to retain new information. In some cases, the degree of retrograde memory loss is mild.

Many patients are anxious or agitated and may repeatedly ask questions concerning transpiring events. Upon mental status examination, language function is preserved, which indicates a preservation of semantic and syntax memory. Attention is spared, visual-spatial skills are intact, and social skills are retained. Symptoms typically last less than 24 hours. As the syndrome resolves, the amnesia improves, but the patient may be left with a distinct lapse of recollection for events during the attack.

Generally, TGA is solitary event, however, patients can experience more than one event with very similar symptoms and recovery.

Pathophysiology

The precise pathophysiology of transient global amnesia is not clear. The findings reported with positron emission tomography (PET), diffusion-weighted MRI (DWI), single photon emission computed tomography (SPECT) and MR spectroscopy (MRS) have indicated various brain regions that are affected in TGA.

• On PET and DWI, blood flow to specific brain areas that involve memory appears to be disrupted transiently during TGA. This includes the thalamus and/or mesial temporal structures (in particular the amygdala and hippocampus).
• Hakan et al demonstrated tiny increases in signal in the left parahippocampal gyrus and splenium of the corpus callosum on DWI in one patient. This method of imaging allows detection of hyperacute ischemic change. Liang et al and Yang et al have also recently used DWI to document tiny lesions in the hippocampus of patients with acute TGA.^1,2 However, Eustache et al reported a PET study consistent with a spreading depression in the left lateral frontal cortex. This case also featured oligemia in the left occipital cortex.³ Strupp et al found mainly medial temporal changes on DWI in 7 of 10 patients with TGA. They suggested that cellular edema or spreading depression could be responsible, not just ischemia.⁴
• Winbeck et al found a significant incidence (10/28) of acute DWI changes in patients with TGA, which is comparable to the TIA group (21/74). Although the patients who presented with a TIA had a higher prevalence of vascular risk factors, those in the TGA group (who had DWI changes) were found to have significantly more carotid atherosclerosis.⁵
• Nakada et al demonstrated via high-resolution T2-reversed MRI a high incidence of hippocampal cavities compared with their normal or disease controls. The authors conclude that their findings may indicate that TGA can be associated with neuronal loss in the CA1 region of the hippocampus.⁶
• Generally, the territory of the vertebrobasilar system is most often rendered ischemic and dysfunctional. However, since ischemia typically does not progress to infarction, symptoms are expected to resolve completely.
• Yamane et al reported rather diffuse cerebral hypoperfusion on SPECT that improved months later upon repeating the test in a patient with TGA.⁷ Yang et al also reported hypoperfusion in the cerebellar vermis that recovered by the time of follow-up examination.¹
• Bartsch et al found that in 7 patients with TGA, 4 had a diffusion abnormality corresponding with a T2 lesion in the CA-1 sector of the hippocampus. In 3 of these patients, MRS revealed a lactate peak. The authors suggest that this represents an acute stress reaction of this particular area and indicates the pathological substrate of TGA.⁸

Overall, the variety of findings on functional imaging studies may support the notion that TGA is a syndrome with not only a variety of precipitating causes but also of differing mechanisms.

Frequency

United States

Based on data from Rochester, Minnesota, Miller et al determined an incidence of 5.2 cases per 100,000 population. However, among individuals older than 50 years, the incidence was 23.5 cases per 100,000 population per year.⁹

International

Estimates vary, but Matiea-Guiu et al found a lower incidence in Alcoi, Spain, of 2.9 cases per 100,000 population.¹⁰ On the other hand, Lauria et al found an incidence of 10 cases per 100,000 population in Belluno, Italy.¹¹

Mortality/Morbidity

• As the name implies, transient global amnesia symptoms are transient.
• The mean annual recurrence rate is thought to be low (approximately 4-5%). However, in the study by Miller et al, the calculated recurrence rate could be as high as 24% over a lifetime depending on inclusion criteria.⁹ These occasional recurrences usually involve no long-term morbidity or death.
• If transient ischemic attack (TIA) is suspected, then the patient should be evaluated for stroke risk factors. Likewise, if a seizure is suspected, appropriate testing should be initiated.

Race

No consistent racial predilection is known.

Sex

No sex predilection has been observed. However, one study found that particular triggers may be associated with men and women. For men, transient global amnesia occurs more often after a physical precipitating event. In women, episodes may be more associated with emotional precipitating events, a history of anxiety, or pathological personality.

Age

The typical age of occurrence is older than 50 years.

Clinical

History

The syndrome of transient global amnesia (TGA) was described initially by Morris Bender in the Journal of the Hillside Hospital in 1956. Fisher and Adams later wrote extensively about TGA in Acta Neurologica Scandinavica in 1964. Since that time, TGA has become a well-described syndrome, but one whose exact etiology is not yet completely understood.

• TGA specifically affects memory function. As mentioned previously, patients can register information, but retentive memory ability is affected dramatically.
  • Many mechanisms have been proposed, but no single cause can explain fully all the features of TGA.
  • These include migraine variant, temporal lobe seizure, and TIA. If a patient is young or has repeated attacks, then the possibility of seizure or even migraine is higher. Some authors have stated that patients with TGA have age and risk factor profiles similar to those of patients with stroke or TIA,¹² but patients with TGA have a low incidence of strokes on follow-up.
• Precipitants of TGA frequently include physical exertion, overwhelming emotional stress, pain, cold-water exposure, sexual intercourse, and Valsalva maneuver. These triggers may have a common physiologic feature: increased venous return to the superior vena cava.
• The effects of drugs must be considered. For instance, sedative-hypnotic medications, either over-the-counter or prescribed for sleep (especially if used in conjunction with a transoceanic flight), or premedication with midazolam for medical procedures, may cause similar symptoms. Excessive alcohol can cause a blackout phenomenon. Hence, any history of drug-related amnesia may help clarify mitigating causes.
• Sporadic reports of TGA occur very rarely in a variety of circumstances such as dobutamine-atropine stress echocardiography, infusion of DMSO-cryopreserved autologous peripheral blood stem cells, breathing of hyperoxic mixtures (Nitrox) in diving, intrathecal baclofen treatments, and withdrawal symptoms from a beta-blocker. In this report, the authors suggest that vasospasm might be an etiology versus venous conjestion.¹³
• Social history and family history is relevant. Pantoni et al found that patients with TGA have a higher incidence of personal or family background of psychiatric conditions compared with patients who have had a TIA.¹⁴ Prognostically, patients with TGA are less likely to experience a cardiovascular or cerebrovascular event compared with patients who have had a TIA.

Physical

• Neurologic examination of the patient typically fails to demonstrate any abnormalities (other than memory dysfunction).
• If any lateralizing or focal findings are noted on the examination, then the diagnosis of transient global amnesia should be questioned.

Causes

The exact mechanism that produces transient global amnesia is unclear.

• The most compelling evidence in favor of migraine is that patients who suffer from a TGA event have a slightly higher incidence of a previous migraine.
  • However, patients with TGA rarely report an associated headache.
  • They also do not report nausea, photophobia, or phonophobia.
• Seizure (eg, temporal lobe) is unlikely.
  • TGA events are not associated with alteration of consciousness or stereotypical movements.
  • EEG does not demonstrate epileptiform activity.
• TIA as indicative of cerebrovascular disease is unlikely.
  • Studies have demonstrated that patients with TGA have fewer cerebrovascular risk factors than those with known cerebrovascular or coronary artery disease.
  • The prognosis for TGA is often better than for TIAs.
• One theory proposed by Lewis is that venous congestion causes disrupted blood flow to the thalamic or mesial temporal structures.¹⁵ More recently, one study used cranial 3-dimensional time-of-flight (TOF) MR angiography (MRA) to try to detect any intracranial retrograde venous flow in 10 patients with TGA. By using left brachiocephalic vein occlusion, retrograde intracranial venous flow was found only in patients (5 of 10) versus controls. The authors suggest that this may indicate that patients have an impairment of cerebral venous outflow that make them at risk for a TGA event.
• The frequently cited triggers for TGA can increase either sympathetic activity and/or intrathoracic pressure. This, in turn, could cause back-pressure in the jugular venous system, disrupting intracranial arterial flow with secondary venous congestion/ischemia to memory areas in the brain.
• Conditions predisposing to this scenario might include venous anatomy anomalies, integrity of jugular vein valves, timing of the trigger, and severity of the inciting event. In support of the above concept of venous congestion are Schreiber et al's finding of a higher prevalence of internal jugular vein valve incompetence in patients with TGA versus normal controls and Cejas et al's similar findings.^16,17 However, the authors of this study could find no particular internal jugular vein valve incompetence associated venous circulatory patterns that could indicate a direct cause/effect with TGA.¹⁶

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