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 a solitary event, however, patients can experience more than one event with very similar symptoms and recovery.
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.
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.
Age- and sex-related demographics
The typical age of occurrence is older than 50 years.
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.
Transient global amnesia (TGA) is 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.
There is a demonstrated association between TGA and migraine. In one nationwide cohort study, migraine was associated with an increased risk of TGA, particularly in female patients aged 40-60 years.[13]
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.[14]
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.[15] Prognostically, patients with TGA are less likely to experience a cardiovascular or cerebrovascular event compared with patients who have had a TIA.
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.[16] 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.[17, 18] 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.[17]
When a patient initially presents with transient global amnesia, stroke must be ruled out. This can be done using screening clotting tests, including prothrombin time (PT), activated partial throboplastin time (aPTT), and INR.
Any patient presenting with features of transient global amnesia should receive an imaging test to rule out a stroke possibility, especially if significant risk factors are present.
MRI with DWI can readily demonstrate acute ischemic changes early and guide management. In one study, higher resolution DWI imaging increased detection of hippocampal lesions in 27 patients with transient global amnesia, from 11 with standard resolution MRI to 22 with high resolution MRI.[19] If an MRI cannot be obtained readily, then at least a CT scan should be done initially if the patient is presenting to an emergency department.
These tests are important if the diagnosis of TGA is in doubt. If symptoms have occurred more than once, then at least a routine EEG should be done to help investigate a seizure possibility by demonstrating any interictal activity.
What is transient global amnesia (TGA)?What is the pathophysiology of transient global amnesia (TGA)?What is the incidence of transient global amnesia (TGA) in the US?What is the global incidence of transient global amnesia (TGA)?What is the recurrence rate for transient global amnesia (TGA)?What assessments are needed in patients with suspected transient global amnesia (TGA)?How does the incidence of transient global amnesia (TGA) vary by sex and age?What should be the focus of history in the evaluation of transient global amnesia (TGA)?Which neurologic findings are characteristic of transient global amnesia (TGA)?What are the causes of transient global amnesia (TGA)?What are the differential diagnoses for Transient Global Amnesia?What is the role of lab studies in the workup of transient global amnesia (TGA)?What is the role of imaging studies in the workup of transient global amnesia (TGA)?What is the role of EEG in the workup of transient global amnesia (TGA)?How is transient global amnesia (TGA) treated?Which activity modifications used in the treatment of transient global amnesia (TGA)?
Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Helmi L Lutsep, MD, Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center
Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Consultant, Abbott Vascular, Inc. .
Additional Contributors
Carmel Armon, MD, MSc, MHS, Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel
Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel<br/>Received income in an amount equal to or greater than $250 from: JNS - Associate Editor. UpToDate - Author Royalties.