Transient Global Amnesia: Emergency Department Evaluation And Management

Table of Contents

 

1. Abstract
2. Opening Cases
3. Introduction
4. Critical Appraisal of the Literature
5. Epidemiology
   1. Inciting Factors
6. Pathophysiology
7. Differential Diagnosis
8. Prehospital Management
9. Emergency Department Evaluation
   1. History
      1. Historical Features Of Transient Global Amnesia
   2. Physical And Cognitive Evaluation
10. Diagnostic Studies
    1. Basic Laboratory Studies
    2. Toxicology Studies
    3. Cardiac/Vascular Testing
    4. Imaging
    5. Neurologic Testing
11. Treatment
12. Special Considerations
    1. Decisional Capacity
    2. At-Risk Subgroups
13. Controversies And Cutting Edge
14. Disposition
15. Summary
16. Time- And Cost-Effective Strategies
17. Risk Management Pitfalls For Transient Global Amnesia
18. Case Conclusions
19. Clinical Pathway For Sudden And Persistent Amnesia (< 24 Hours)
20. Tables and Figures
    1. Table 1. Transient Global Amnesia Mimics
    2. Table 2. Diagnostic Features Of Transient Global Amnesia
    3. Table 3. Types And Features Of Memory Loss
    4. Table 4. High-Risk Features In Patients With Suspected Transient Global Amnesia
21. References

Abstract

Transient global amnesia is a clinically distinct syndrome characterized by the acute inability to form new memories. It can last up to 24 hours. The diagnosis is dependent on eliminating other more serious etiulogies including toxic ingestions, acute strokes, complex partial seizures, and central nervous system infections. Transient global amnesia confers no known long-term risks; however, when abnormal signs or symptoms are present, they take precedence and guide the formliation of a differential diagnosis and investigation. In witnessed transient global amnesia with classic features, a minimalist approach is reasonable, avoiding overtesting, inappropriate medication, and medical interventions in favor of observation, ensuring patient safety, and reassuring patients and their families. This review provides a detailed framework for distinguishing transient global amnesia from its dangerous mimics and managing its course in the emergency department.

Opening Cases

A 60-year-old man with no significant medical history is brought to the ED by EMS after 2 hours of sudden memory loss. His wife has been with him since the onset of symptoms, when he started asking her the same question repeatedly every few minutes. The patient is calm, cooperative, and oriented to person, place, and time, but he frequently repeats himself and does not appear to be forming new memories. He knows what he did yesterday and this morning but cannot seem to recall events of the past few hours. He is perseverating about what he was doing 1 hour ago. When you step away and subsequently return to the bedside a few minutes after the initial encounter, the patient does not recognize you and asks, “Have we met before?” The patient has no other complaints, and there are no neurologic or infectious symptoms. His vital signs are normal. You wonder if you should activate the stroke team and order an emergent CT of the brain.

A 54-year-old woman with hypertension presents with sudden memory loss. She was smoking a cigarette with her friend when she became confused and started asking, “How did we get here?” repeatedly. The witness called 911. EMS providers detected no stroke symptoms and transported her to your ED. In the ED, the patient is alert and oriented to self and place, but not to time. She demonstrates clear anterograde amnesia, failing to remember you on multiple occasions. She also complains of a mild diffuse headache, but she has no other symptoms and is found to be neurologically and, otherwise, cognitively normal. She states that she feels fine and wants to sign out against medical advice. You explain to her repeatedly that, because she is not encoding memories, she cannot be discharged, and lacks decisional capacity. You place her on hospital involuntary hold. Twenty hours later, her amnesia has fully resolved. She has not repeated any questions during the past 2 hours and remembers your latest conversations. In the meantime, she has developed new mild ataxia. She says “I’m not worried about that. I’ll be fine once I have a cigarette. I’d like to sign out against medical advice.” She is alert and oriented and lacks psychiatric risk factors. She consistently and accurately verbalizes, without reminders, several times over 30 minutes, the risks associated with leaving. You wonder: Should you discharge this patient against medical advice?

Introduction

Transient global amnesia (TGA) is a clinical syndrome marked by the acute onset of profound anterograde amnesia (the inability to form new memories) lasting up to 24 hours in the absence of other neurologic deficits or changes in alertness and cognition. Retrograde amnesia (the loss of pre-existing memories) can also occur. In TGA, isolated loss of new memory formation is limited to facts and events (declarative memory), and patients retain implicit and procedural memory (motor tasks and coordination). The classic TGA patient exhibits the “broken-record” phenomenon (asking the same questions repeatedly) in the absence of other signs or symptoms. Typical questions include “How did I get to the hospital?” and asking medical staff, “Have we met?” despite several introductions.

The mean duration of symptoms in TGA events is approximately 4 to 6 hours and, in a majority of cases, symptoms resolve within 8 hours of initial onset.^1-3 In TGA, symptoms resolve gradually and spontaneously within 24 hours without the need for medical intervention.⁴ The definitive diagnosis of TGA cannot be made until symptoms have resolved. Failure of symptom resolution and other worrisome signs and symptoms excludes the diagnosis.

Descriptions of TGA first appeared in the medical literature in the 1950s.^5-7 In the following decades, consensus emerged regarding the clinical features required for diagnosis. Classically, the syndrome occurs in a functional middle-aged or elderly patient; fewer than 10% of cases present in patients aged < 50 years.³ TGA patients are notable to the clinician and their family and friends for repetitive questioning, but patients remain oriented to person and place. In uncomplicated cases (ie, in which TGA is not coincidentally presenting with another unrelated process), TGA patients maintain hemodynamic stability and are otherwise cognitively intact, retaining the ability to perform complex tasks. Often, the patient will have little to no memory of the entire event.^8,9

In order to confidently make the diagnosis of TGA, a prehospital witness is helpful in providing a reliable history of the symptoms, including a description of the onset. By convention, patients with head trauma in the preceding 72 hours, those with known epilepsy, patients with any other neurologic abnormalities (motor deficits, aphasia, dysarthria, cognitive impairment, loss of attention span, etc), and patients with known psychiatric disorders are excluded from the diagnosis of TGA.^8,9

While diagnostic criteria are clear, disagreement as to the causes and etiology of TGA continues. In the past 2 decades, neuroimaging and other testing modalities have suggested potential etiologies, but controversies among researchers persist amid limited and conflicting evidence. From the standpoint of the emergency clinician, however, a definition of the clinical syndrome and the required features for diagnosis are now widely agreed upon, and TGA is a relatively easy diagnosis to make when it presents with classic features; however, upon initial presentation, rare mimics must be considered and any unusual features and symptoms must be investigated. (See Table 1.) It is the role of the emergency clinician to recognize TGA syndrome and to exclude other more dangerous conditions that present with an amnestic component among a constellation of other features that, though exceedingly rare, can mimic TGA.^8,10

Once definitively diagnosed, patients and their families need education on the diagnosis and its benign prognosis. This issue of Emergency Medicine Practice provides a comprehensive review of the literature on TGA and its diagnostic criteria. We also suggest a simplified workflow in order to facilitate decision-making and minimize unnecessary diagnostic testing.

Critical Appraisal Of The Literature

A PubMed literature search was performed using the search terms transient global amnesia as well as amnesia and emergency. The National Guideline Clearinghouse (www.guideline.gov), and the Cochrane Database of Systematic Reviews were searched with the term amnesia; this search yielded only mentions of amnesia in the context of differential diagnoses for stroke syndromes, but no guidelines, policies, or reviews focused primarily on amnesia were found. We also searched for guidelines released by the American College of Emergency Physicians and the American Academy of Neurology. There are no known published guidelines by these bodies related specifically to amnesia.

Little high-quality research on TGA exists. Most of the literature is comprised of case reports and case series. Unfortunately, close reading of many case reports of TGA with unusual features reveals a frequent, incorrect conflation of TGA as a distinct clinical entity and its sine qua non symptom, anterograde amnesia. However, much has been learned through higher-quality retrospective chart reviews, retrospective cohort studies, prospective case-control studies, and prospective cohort studies. Case-control studies have been performed in an attempt to understand the etiology of TGA. These studies primarily focused on imaging and electroencephalogram (EEG) studies in an attempt to elucidate the etiology of TGA. Several studies have attempted to link TGA to serologic markers, and the results have been marked by minimal success. Retrospective studies designed to identify risk factors for the development of TGA have been conducted and have also yielded mixed results. No trial assessing any medical intervention has ever been reported in the medical literature.

Risk Management Pitfalls For Transient Global Amnesia

1. “She has a history of repeated memory loss that began 3 hours ago, and did not report any neurologic deficits. I assumed this episode was TGA. I performed my usual neurologic examination because I felt comfortable, based on history, that the patient had TGA.”
   In cases of suspected TGA, an especially thorough neurologic examination is essential, as the presence of even mild neurologic deficits may be the only indication of a rare stroke syndrome presenting with amnesia as the most conspicuous feature. In cases in which rare stroke syndromes have been mistaken for TGA, the vast majority of patients exhibited subtle neurologic deficits that a cursory neurologic examination might have missed.
2. “I gave my patient 100 mg of intravenous thiamine because I read that it is a treatment for suspected TGA. My patient improved, confirming the diagnosis of TGA.”
   Given the poorly understood pathophysiologic pathways of TGA, using the response to any empiric treatment to rule in or rule out this syndrome should be avoided. There are currently no studies suggesting that thiamine, or any other pharmacologic agent, is an effective treatment for TGA in either hastening symptom resolution or preventing future episodes.
3. “I thought the patient had less than 6 hours of memory recall abnormalities and no fevers or headaches, which made me suspect TGA. I forgot to ask about encephalitis risk factors. I made the mistake of early diagnostic closure.”
   While some red flags of infectious encephalitis— such as fever and focal neurological deficits—are apparent on examination, it is the emergency clinician’s job to take a detailed history and physical examination, which should include immunosuppression status, as those patients have a higher predisposition for specific central nervous system infections (most notably herpes simplex virus encephalitis) that can, rarely, present as isolated anterograde amnesia.
4. “Part of my routine workup for a new neurologic complaint includes a noncontrast CT of the brain and sometimes a lumbar puncture, especially if the patient has altered mental status, as it captures many dangerous etiologies such as bleeding, strokes, and infection.”
   In amnestic patients, the differential diagnosis can be inappropriately broad if the emergency clinician incorrectly conflates anterograde amnesia with altered mental status. Neuroimaging (such as CT) is only indicated for patients who have concurrent signs or risk factors that would normally lead an emergency clinician to acquire imaging in the absence of memory impairment. Such signs would include any signs or symptoms of an acute stroke syndrome, a history of head trauma, or historical and physical findings consistent with aneurysms. A lumbar puncture is indicated only in the presence of symptoms that would normally lead the clinician to suspect a central nervous system infection or high-risk intracranial hemorrhage.
5. “The patient began to recall some events and otherwise looked well. Her family wanted her to go home and follow up with her primary care doctor the next day, so I discharged the patient in spite of the fact that she was still having occasional amnestic symptoms.”
   This is one of the great pitfalls of TGA, as patients appear largely well and retain executive functions, such as the ability to get dressed without assistance. As TGA begins to resolve, amnestic features often wax and wane. It is important to observe patients until they are consistently asymptomatic in order to rule out abnormally long courses (worrisome for rare alternate diagnoses) and for patient safety, as described previously. TGA patients can be frustrating in their repetitive requests to leave, as they may not remember that you have asked them to stay until symptoms have completely resolved. They often will not remember the discussed care plan or have any sense of how much time has elapsed since your last evaluation. All efforts should be made to maintain the patient’s safety and not discharge the patient prior to complete and consistent symptom resolution. TGA patients should be considered elopement risks until all symptoms have resolved, as the diagnosis of TGA cannot actually be made until symptoms resolve.
6. “I try to provide a specific diagnosis for every neurologic complaint of my patients at the time of disposition.”
   In the case of suspected TGA, it is difficult to assign a specific diagnosis in the emergency setting since the diagnosis relies on resolution of symptoms within 24 hours after a well-documented, witnessed time of onset. Further, an incorrect diagnosis can mislabel a patient as having a benign process and might lead to anchoring bias by future physicians who will reassess the neurologic examination. This could potentially lead to failure to detect dangerous alternative etiologies such as seizures or developing central nervous system infections. Until symptoms resolve, the diagnosis of “amnesia” is appropriate, but not TGA.
7. “I often feel pressure to ‘do something’ and intervene on behalf of my patients. My patient’s family kept asking me to do something to help her.”
   It is difficult to alleviate the concerns of family members of patients experiencing an acute TGA event. TGA events are often understandably frightening for patients, their families, and their friends witnessing the event. We recommend talking with patients and their families and setting appropriate expectations. Directing expectations through careful guidance and reassurance of your comfort managing this syndrome can help. Counseling patients and family so that they fully understand the expected time course of the syndrome and its expected benign outcome can reduce anxiety. Avoiding the pitfall of overtesting and treating can be difficult, but reassurance and the provision of a safe environment are arguably the most critical interventions an emergency clinician can offer in classic TGA cases.
8. “My patient’s family was very concerned about dementia, given that the patient had sudden memory loss at the age of 67.”
   The mean age of patients with TGA attacks (65 years) makes it difficult to counsel patients and their families through an event with full reassurance, as elevated age is itself the primary risk factor for dementia. However, dementia presents with a gradual onset, and unless the patient has exhibited symptoms of memory loss prior to an acute attack, sudden anterograde amnesia is not consistent with the initial presentation of dementia, nor does it predict the development of dementia in the future.
9. “My patient had a past medical history of seizures and a sudden episode of amnesia, without any other symptoms. Since she has not required antiepileptic medication in over 1 year, TGA was my primary diagnosis.”
   Patients with a known seizure should cause the emergency clinician to maintain a broader differential diagnosis, including transient epileptic amnesia and, in cases without resolution in an appropriate timeframe, nonconvulsive status or even a rare stroke syndrome. These may require neurologic consultation, evaluation, and potentially neuroimaging, a neurologic consultation to discuss the role of an EEG, and consideration of anticonvulsant medication.
10. “My patient with TGA wanted to sign out against medical advice and go home. He seemed reliable and lived next to the hospital. To protect myself, I allowed him to sign out against medical advice.”
    Despite appearances, patients with acute amnesia do not have decisional capacity. It is the healthcare provider’s responsibility to verify that a patient has capacity to sign out against medical advice. Patients must be able to understand the information they are given and make logical decisions based on that information. This relies on the patient’s ability to understand his current medical status or condition over time, not just “in the moment.” Patients with TGA suffer from short-term memory impairment and may not remember their current medical condition or follow-up instructions. They should be appropriately marked as a high elopement risk, according to local protocol at your institution. While TGA itself is not medically dangerous, the inability to form memories could pose genuine hazards to the patient in other environments. For example, a TGA patient could turn on a kitchen stove and forget he did this. He might repeatedly take his normal medications, leading to unintended overdose. For the patients' own safety, they should not be discharged against medical advice or otherwise until they are consistently asymptomatic.

Tables And Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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