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?
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.
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.
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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Jeremy Samuel Faust, MD, MS, MA; Andreea Nemes, MD
August 1, 2016
September 1, 2019
Upon completion of this article, you should be able to:
Physician CME Information
Date of Original Release: August 1, 2016. Date of most recent review: July 10, 2016. Termination date: August 1, 2019.
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