eMedicine Specialties > Neurology > Neuro-vascular Diseases

Transient Global Amnesia

Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital

Updated: Dec 3, 2008

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. 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.¹ 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.²
• 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.³
• 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.⁴
• 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.⁵  
• 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.⁶

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.⁷

International

Estimates vary, but Matiea-Guiu et al found a lower incidence in Alcoi, Spain, of 2.9 cases per 100,000 population.⁸ On the other hand, Lauria et al found an incidence of 10 cases per 100,000 population in Belluno, Italy.⁹

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.⁷ 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 TIA¹⁰ , 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.¹¹
• 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.¹² 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.¹³ 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 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.¹⁴

Differential Diagnoses

Other Problems to Be Considered

Complex partial status epilepticus

Workup

Laboratory Studies

• CBC count with differential
• Electrolyte panel
• Screening clotting tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), INR
• When a patient initially presents with transient global amnesia, stroke must be ruled out.

Imaging Studies

• Brain MRI and/or CT scan
  • 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.
  • 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.

Treatment

Medical Care

Once transient global amnesia (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.

Miscellaneous

Medicolegal Pitfalls

• Remember that stroke is in the differential diagnosis of transient global amnesia, 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.

References

1. Eustache F, Desgranges B, Petit-Taboué MC, et al. Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage. J Neurol Neurosurg Psychiatry. Sep 1997;63(3):357-67. [Medline].

2. Strupp M, Bruning R, Wu RH, et al. Diffusion-weighted MRI in transient global amnesia: elevated signal intensity in the left mesial temporal lobe in 7 of 10 patients. Ann Neurol. Feb 1998;43(2):164-70. [Medline].

3. Winbeck K, Etgen T, von Einsiedel HG, et al. DWI in transient global amnesia and TIA: proposal for an ischaemic origin of TGA. J Neurol Neurosurg Psychiatry. Mar 2005;76(3):438-41. [Medline].

4. Nakada T, Kwee IL, Fujii Y, Knight RT. High-field, T2 reversed MRI of the hippocampus in transient global amnesia. Neurology. Apr 12 2005;64(7):1170-4. [Medline].

5. Yamane Y, Ishii K, Shimizu K, Sofue K, Yoshikawa T, Miyamoto N, et al. Global cerebral hypoperfusion in a patient with transient global amnesia. J Comput Assist Tomogr. May-Jun 2008;32(3):415-7. [Medline].

6. Bartsch T, Alfke K, Wolff S, Rohr A, Jansen O, Deuschl G. Focal MR spectroscopy of hippocampal CA-1 lesions in transient global amnesia. Neurology. Mar 25 2008;70(13):1030-5. [Medline].

7. Miller JW, Petersen RC, Metter EJ, et al. Transient global amnesia: clinical characteristics and prognosis. Neurology. May 1987;37(5):733-7. [Medline].

8. Matias-Guiu J, Blanquer J, Falip R, et al. Incidence of transient global amnesia in a Alcoi (Spain). Acta Neurol Scand. Aug 1992;86(2):221. [Medline].

9. Lauria G, Gentile M, Fassetta G, et al. Incidence of transient global amnesia in the Belluno province, Italy: 1985 through 1995. Results of a community-based study. Acta Neurol Scand. May 1997;95(5):303-10. [Medline].

10. Shuping JR, Rollinson RD, Toole JF. Transient global amnesia. Ann Neurol. Mar 1980;7(3):281-85. [Medline].

11. Saura D, Peñafiel P, Morales A, Albert L, Martínez F, de la Morena G. Transient global amnesia after dobutamine--atropine stress echocardiography. Eur J Echocardiogr. Jul 2008;9(4):567-8. [Medline].

12. Pantoni L, Bertini E, Lamassa M, et al. Clinical features, risk factors, and prognosis in transient global amnesia: a follow-up study. Eur J Neurol. May 2005;12(5):350-6. [Medline].

13. Lewis SL. Aetiology of transient global amnesia. Lancet. Aug 1 1998;352(9125):397-9. [Medline].

14. Schreiber SJ, Doepp F, Klingebiel R, Valdueza JM. Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia. J Neurol Neurosurg Psychiatry. Apr 2005;76(4):509-13. [Medline].

15. Adams RD, Victor M, Ropper AH. Transient global amnesia. In: Principles of Neurology. 1997. New York: McGraw-Hill; 429-30.

16. Ay H, Furie KL, Yamada K, Koroshetz WJ. Diffusion-weighted MRI characterizes the ischemic lesion in transient global amnesia. Neurology. Sep 1998;51(3):901-3. [Medline].

17. Chung CP, Hsu HY, Chao AC, et al. Detection of intracranial venous reflux in patients of transient global amnesia. Neurology. Jun 27 2006;66(12):1873-7. [Medline].

18. Grande LA, Loeser JD, Samii A. Recurrent transient global amnesia with intrathecal baclofen. Anesth Analg. Apr 2008;106(4):1284-7, table of contents. [Medline].

19. Hinge HH, Jensen TS, Kjaer M, et al. The prognosis of transient global amnesia. Results of a multicenter study. Arch Neurol. Jul 1986;43(7):673-6. [Medline].

20. Lauria G, Gentile M, Fassetta G, et al. Transient global amnesia and transient ischemic attack: a community- based case-control study. Acta Neurol Scand. Jun 1998;97(6):381-5. [Medline].

21. Otrock ZK, Beydoun A, Barada WM, Masroujeh R, Hourani R, Bazarbachi A. Transient global amnesia associated with the infusion of DMSO-cryopreserved autologous peripheral blood stem cells. Haematologica. Mar 2008;93(3):e36-7. [Medline].

22. Quinette P, Guillery-Girard B, Dayan J, et al. What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases. Brain. 2006;129:1640-58. [Medline].

23. Schmidtke K, Ehmsen L. Transient global amnesia and migraine. A case control study. Eur Neurol. Jul 1998;40(1):9-14. [Medline].

24. Spigno F, De Lucchi M, Migliazzi L, Cocito L. Transient global amnesia after breathing hyperoxic mixtures in otherwise regular dives. Clin Neurol Neurosurg. Mar 2008;110(3):259-61. [Medline].

25. Vyhnálek M, Bojar M, Jerabek J, Hort J. Long lasting recurrent familiar transient global amnesia after betablocker treatment withdrawal: case report. Neuro Endocrinol Lett. Feb 2008;29(1):44-6. [Medline].

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Keywords

amnesia, global amnesia, transient memory loss, paroxysmal loss of memory, transient loss of memory, immediate recall ability, remote memory, retrograde memory loss, semantic memory, syntax memory, visual-spatial skills, TGA, vertebrobasilar system, migraine variant, temporal lobe seizure, transient ischemic attack, emotional stress, cold-water exposure

Valsalva maneuver, venous anatomy anomalies, jugular vein valves, ischemia to memory areas in brain, back-pressure in jugular venous system, disruption of intracranial arterial flow, increased sympathetic activity, increased intrathoracic pressure, disrupted blood flow to thalamic structures, disrupted blood flow to mesial temporal structures, increased venous return to superior vena cava

Contributor Information and Disclosures

Author

Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Roy Sucholeiki, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and American Neuropsychiatric Association
Disclosure: UCB Pharma Honoraria Speaking and teaching

Medical Editor

Carmel Armon, MD, MSc, MHS, Professor of Neurology, Tufts University School of Medicine, Chief, Division of Neurology, Baystate Medical Center, Springfield, Massachusetts
Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Movement Disorders Society, and Sigma Xi
Disclosure: Nothing to disclose.

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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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
Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Novartis Consulting fee Review panel membership

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Boston Scientific Honoraria Speaking and teaching; Concentric Medical None Review panel membership; Northstar Neuroscience  Review panel membership; ev3 Consulting fee Review panel membership

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