Transient global amnesia (TGA)
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. On 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.
Pathophysiology: The precise pathophysiology of TGA is not clear. On positron emission tomography (PET) and diffusion-weighted MRI (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. 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. 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.
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.
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.
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.
Frequency:
In the US: Based on data from Rochester, Minnesota, Miller et al determined an incidence of 5.2 per 100,000. However, among individuals older than 50 years, the incidence was 23.5 per 100,000 per year.
Internationally: Estimates vary, but Matiea-Guiu et al found a lower incidence in Alcoi, Spain, of 2.9 per 100,000. On the other hand, Luria et al found an incidence of 10 per 100,000 in Belluno, Italy.
Mortality/Morbidity:
As the name implies, TGA 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. 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 gender predilection has been observed.
Age: The typical age of occurrence is older than 50 years.
History: The syndrome of 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 (Shuping et al), 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.
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. 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 TGA should be questioned.
Causes: The exact mechanism that produces TGA 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.
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 is Schreiber et al's finding of a higher prevalence of internal jugular vein valve incompetence in patients with TGA versus normal controls. 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.
Basilar Artery Thrombosis
Cardioembolic Stroke
Complex Partial Seizures
Frontal Lobe Epilepsy
Lacunar Syndromes
Migraine Variants
Posterior Cerebral Artery Stroke
Syncope and Related Paroxysmal Spells
Temporal Lobe Epilepsy
Other Problems to be Considered:
Lab Studies:
CBC with differential
Electrolyte panel
Screening clotting tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), INR
When a patient initially presents with TGA, stroke must be ruled out.
Imaging Studies:
Brain MRI and/or CT scan
Any patient presenting with features of TGA 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.
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.
Other Tests:
ECG, EEG: 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.
Medical Care: Once TGA is diagnosed, provide reassurance to the patient and schedule at least one follow-up visit with a neurologist.
Diet: No dietary restrictions are necessary.
Activity: Avoid activities that could produce an unusual increase in intrathoracic pressure (see trigger factors).
Medical/Legal Pitfalls:
Remember that stroke is in the differential diagnosis of TGA, especially if presenting within 24 hours of symptom onset.
Strokes, particularly in the distribution of the posterior cerebral circulation, can present with an amnestic state.
Stroke should be ruled out in the initial workup.
Look for risk factors and treat accordingly. For example, smoking, hypercholesterolemia, diabetes, and hypertension are all modifiable risk factors.
If seizures are a consideration, then perform appropriate workup, including EEG and MRI of the brain. Treatment with an anticonvulsant depends on the outcome of this workup.