Continuing Education Activity

Transient global amnesia is a sudden onset of anterograde amnesia accompanied by a temporary period of retrograde amnesia, primarily affecting middle-aged and older individuals. These episodes typically last from 1 to 24 hours. Transient global amnesia is relatively common in emergency medicine practice settings, making recognition and understanding of its typical clinical features crucial.

Characterized by a combination of retrograde and anterograde amnesia, patients with transient global amnesia often repeat the same questions during the episode. They may experience disorientation regarding people and places but retain self-awareness. The condition is benign, typically resolving without recurrence and leaving no lasting neurological deficits. Diagnosis of transient global amnesia is primarily clinical, and neither advanced imaging nor treatment is required. Patients with transient global amnesia do not develop serious neurological conditions such as stroke, epilepsy, or neurodegenerative disorders.

This activity reviews the clinical presentation, diagnostic criteria, management strategies, and long-term prognosis of patients with transient global amnesia, highlighting the role of interprofessional team members in collaborating to provide well-coordinated care for affected patients. After participation, learners recognize the characteristic presentation of transient global amnesia, understand the clinical criteria for diagnosis, and incorporate evidence-based management practices for transient global amnesia, emphasizing the condition's benign nature and the minimal requirement for advanced imaging or therapeutic intervention.

Objectives:

• Assess the typical clinical features of transient global amnesia and the appropriate management approach.

• Determine the underlying pathophysiology of transient global amnesia.

• Identify the atypical features of transient global amnesia and the differential diagnoses.

• Collaborate with an interprofessional team, including neurologists, primary care physicians, and nurses, to provide comprehensive care for TGA patients.

Introduction

Transient global amnesia is sudden-onset anterograde amnesia with a temporary period of retrograde amnesia, typically occurring in adults aged 50 to 70. The amnesic episode typically lasts for several hours, between 1 and 24 hours. Transient global amnesia is not uncommon, especially in emergency medicine practice settings.

Recognizing and characterizing this benign clinical entity with typical clinical features is essential, and no advanced imaging or treatment is required. The clinical picture is limited to combined retrograde and anterograde amnesia, with the patient repeatedly asking the same question during the episode. Although disorientation may exist concerning other people and locations, affected patients never lose self-awareness.

Once resolved, the symptoms of transient global amnesia rarely recur. When the patient recovers from the transient global amnesia episode, the retrograde amnesia recovers in a telescopic manner, with the most remote memory recovering before more recent events. The events occurring during the amnesic episode are typically permanently lost. No other neurological deficits are present with this condition.

The diagnosis of transient global amnesia is mainly clinical. Patients with transient global amnesia do not end up with serious neurological sequelae, including stroke, epilepsy, or neurodegenerative disorders. Any atypical clinical feature should prompt the possibility of an alternative diagnosis, necessitating further diagnostic testing.[1][2][3]

Etiology

The etiology of transient global amnesia remains largely unknown, with multiple theories proposed but none conclusively proven. The most supported theory suggests a link to migraines, as 12% to 30% of transient global amnesia patients have a migraine history. Some researchers propose that transient global amnesia may involve cortical spreading depression similar to migraine aura.[4] Other suspected causes include vascular phenomena, epilepsy, and psychogenic origins. Studies have both supported and refuted arterial ischemia as a cause. Vascular congestion is a leading hypothesis, yet questions about its association with specific age groups and absence in venous thrombosis remain unresolved. Transient global amnesia rarely recurs more than a few times in a patient's life. Ultimately, no single theory fully explains all clinical aspects of transient global amnesia.[5][6][7][8]

Epidemiology

The incidence of transient global amnesia ranges from 3.4 to 10.4 per 100,000 people per year in the general population. In individuals aged 50 or older, this increases to 23.5 to 32 per 100,000 per year, with most cases occurring in those aged 50 to 80. There is no gender difference.[9]

Although no clear risk factors have been identified, transient global amnesia is more frequently noted in patients with a history of ischemic heart disease and hyperlipidemia but not with prior ischemic stroke, diabetes, or hypertension. Individuals with migraine have an increased risk, with an incidence risk ratio of 2.48.[9]

Transient global amnesia recurrence is uncommon but not rare, with rates varying from 2.9% to 26.3%.[9] Interestingly, transient global amnesia episodes occur more often in the morning between 10 and 11 AM and late afternoon between 5 and 6 PM.[10]

Pathophysiology

The origin of transient global amnesia is believed to involve the mediobasal temporal lobe, including the hippocampus, particularly the CA1 or Sommer sector. These structures are crucial for memory consolidation and retrieval.[4] The hippocampus is especially vulnerable to various metabolic stresses, potentially due to its sensitivity to cytotoxic glutamatergic uptake or release. Affected areas can be unilateral or bilateral, although they are more commonly found on the left side. Functional magnetic resonance imaging (MRI) has shown bilaterally reversible defects; both functional MRI and quantitative electroencephalography (EEG) studies have demonstrated changes in functional connectivity in the hippocampus and limbic system.[11][12]

History and Physical

The diagnosis of transient global amnesia is primarily clinical, based on a detailed history and a thorough neurological examination during the acute stage. Advanced neuroimaging, cerebrospinal fluid analysis, and EEG are unnecessary unless the clinical diagnosis is uncertain. Diagnostic criteria have been established by Caplan, Hodges, and Warlow, and most recently, the German Society of Neurology guidelines.[13][14][15]

Patients typically present with a sudden onset of memory loss lasting several hours, featuring retrograde and pronounced anterograde amnesia. They often repeat questions and lack recall of recent events leading up to the episode. Accompanying individuals may report recent vigorous exertion, coitus, or severe stress but no loss of consciousness. Patients retain self-identity and demonstrate no neurological or cognitive deficits. They remain cooperative and can name objects, with no history of trauma or epilepsy. Symptoms last between 1 and 24 hours, typically occurring later in the day rather than after waking.

Clinical features making transient global amnesia unlikely include evidence of toxic or metabolic disturbances, a history of trauma or epilepsy, impaired awareness or consciousness, and focal neurological signs. If a patient can describe the episode details and timing, or if they experience more than 3 episodes a year, transient global amnesia should be strongly reconsidered.[15]

Evaluation

Further evaluation is generally unnecessary when a patient presents to the emergency department with typical clinical features of transient global amnesia. A toxicology screen, alcohol level, and basic laboratory studies, including glucose and electrolytes, are typically performed. Once the amnesic episode resolves, typically within a few hours, the patient can be discharged home.

However, if clinical evidence or routine laboratory studies raise doubts about the diagnosis, the patient should be admitted for monitoring and further diagnostic evaluation. The most important study is brain imaging with MRI. Brain MRI results should be normal during the acute transient global amnesia episode. Diffusion-weighted MRI (DWI) lesions, typical for transient global amnesia, most commonly appear 24 to 72 hours after the episode. These are punctate DWI and T2 hyperintensity lesions in 1 or both hippocampi, particularly in the CA1 region.[16]

EEG results are generally normal in patients with transient global amnesia, except for occasional nonspecific theta and delta waves. EEG is useful in differentiating transient global amnesia from amnestic epileptic episodes or transient epileptic amnesia.[17]

Cerebrospinal fluid analysis is not indicated unless there is clinical suspicion of an underlying infectious or inflammatory cerebral disorder.

Treatment / Management

Treatment for transient global amnesia primarily involves supportive care and reassurance, as no specific therapy is required or available. A thorough examination is crucial to identify any neurological deficits or signs of head trauma that could suggest an alternative diagnosis. Hospital observation may be necessary until the memory deficit resolves. Intravenous thiamine should be considered. Although rare, recurrences can occur. Following the resolution of memory deficits, patients do not require restrictions on activities such as driving.

Differential Diagnosis

In cases where the clinical features of the amnesic episode are unusual, or there is a focal neurological deficit, it is crucial to rule out acute ischemic stroke affecting the hippocampus (posterior cerebral artery territory infarct) through MRI.

Another significant consideration is transient epileptic amnesia, often observed in patients with a history of focal impaired awareness seizures or epilepsy. These episodes typically last less than an hour and may recur frequently (>3 times per year). In seizure-related memory loss, there is typically seizure-like activity before the onset, and the memory loss is almost purely retrograde; this differs from transient global amnesia, which involves anterograde amnesia presenting with minimal retrograde amnesia confined to events surrounding the onset. Interictal EEG is the primary diagnostic tool to distinguish between these 2 conditions.[17]

Other important differential diagnoses include the following:

• Basilar artery thrombosis
• Cardioembolic stroke
• Complex partial seizures
• Lacunar syndrome
• Migraine variants
• Posterior cerebral artery stroke
• Syncope
• Temporal lobe epilepsy
• Hypoglycemia
• Wernicke encephalopathy
• Transient ischemic attack
• Toxic encephalopathy
• Hypoxia
• Head injury
• Substance intoxication

These differential diagnoses frequently involve patients presenting with atypical features, often involving global confusion rather than the specific memory loss and symptoms typical of transient global amnesia.

Prognosis

Most cases of transient global amnesia occur as isolated events with favorable outcomes and negligible morbidity or mortality reported. Although recurrences are possible, their incidence varies from 2.9% to 26.3% over different follow-up periods, with a 10-year study showing a recurrence rate of 6.3%.[18] A recent study from Korea suggested a potential increased risk of epilepsy following a transient global amnesia episode, with an adjusted hazard ratio of 1.46.[19] However, this finding also underscores the importance of confirming the initial diagnosis of transient global amnesia.

Complications

Complications directly attributable to transient global amnesia are rare, given its typically benign and self-limiting nature. However, the episodic nature of transient global amnesia can lead to significant anxiety and distress for patients and their families during the acute episode. Although uncommon, Recurrence can occur, impacting quality of life and necessitating repeated medical evaluations. In a small subset of cases, some studies have reported that transient global amnesia might be linked to an increased risk of developing epilepsy, highlighting the importance of thorough diagnostic evaluation and follow-up care to monitor for any emerging neurological conditions or sequelae. Despite these considerations, most patients with transient global amnesia experience complete resolution of symptoms without long-term complications or functional impairment.

Consultations

Consultations for transient global amnesia patients may involve neurologists to confirm the diagnosis and exclude other neurological conditions that may mimic transient global amnesia. Neurologists may recommend brain imaging studies, such as MRI, to rule out acute ischemic stroke or other structural abnormalities. In cases where the diagnosis is uncertain or if atypical features are present, consultations with neuropsychologists or epilepsy specialists may be necessary to perform detailed cognitive assessments or EEG studies to differentiate transient global amnesia from conditions such as transient epileptic amnesia. 

Deterrence and Patient Education

Deterrence and patient education play crucial roles in managing transient global amnesia. Educating patients about the benign nature of transient global amnesia is essential, emphasizing its typically isolated occurrence and favorable prognosis without long-term consequences. Patients should be informed about the importance of seeking medical evaluation during the acute episode to confirm the diagnosis and rule out other potential causes of transient amnesia. Encouraging lifestyle modifications, such as stress reduction techniques and adequate management of vascular risk factors such as hypertension and hyperlipidemia, may potentially mitigate the risk of recurrent episodes. Furthermore, educating patients to recognize warning signs or symptoms that warrant urgent medical attention, such as focal neurological deficits or prolonged episodes of confusion, enhances their ability to respond appropriately and seek timely medical care. Empowering patients with accurate information promotes proactive management and ensures optimal outcomes in cases of transient global amnesia.

Pearls and Other Issues

Key clinical pearls can enhance the understanding of transient global amnesia, a fascinating yet often perplexing neurological phenomenon. These pearls help guide clinicians in recognizing, diagnosing, and managing transient global amnesia effectively in clinical practice and include the following:

• Transient global amnesia presents abruptly with a sudden onset of anterograde and retrograde amnesia.

• This disorder predominantly affects adults aged 50 to 80 without gender predilection.

• Transient global amnesia episodes resolve spontaneously within hours without residual cognitive deficits.

• Clinical diagnosis is mainly based on history and examination; neuroimaging and EEG results are generally normal during the acute phase.

• No advanced imaging studies or tests are indicated in these patients.

• Transient global amnesia has an excellent prognosis.

• The differential diagnosis includes acute ischemic stroke involving the hippocampus and transient epileptic amnesia if symptoms recur frequently.

• Episodes may follow vigorous physical activity, emotional stress, or sudden temperature changes.

• Although rare, recurrence rates vary and warrant long-term follow-up and lifestyle modifications.

• Patients should be reassured about the transient nature of symptoms and advised when to seek urgent medical attention if symptoms change or worsen.

• Healthcare professionals must carefully consider alternative diagnoses in atypical presentations or when additional neurological deficits are present to avoid misdiagnosis.

• Neurology consultation should be considered to confirm the diagnosis and guide appropriate management and follow-up care.

Enhancing Healthcare Team Outcomes

The diagnosis and management of transient global amnesia are best handled by an interprofessional team, including neurologists, internists, radiologists, primary care physicians, advanced practitioners, nurses, and other healthcare providers. Physicians and advanced practitioners utilize their diagnostic acumen to recognize typical characteristics of transient global amnesia and differentiate it from other neurological emergencies. Failure to recognize the typical clinical syndrome can lead to a broad differential diagnosis when patients present with amnesia, often resulting in an exhaustive and time-consuming workup. Posterior cerebral artery territory stroke and transient epileptic amnesia are the two primary conditions that must be considered and ruled out.

Once transient global amnesia is diagnosed, physicians oversee treatment decisions and care plans. The treatment is supportive. Nurses provide continuous monitoring and patient education, whereas pharmacists ensure medication safety and efficacy. Effective communication among team members ensures cohesive care delivery. Physicians consult with neurology specialists to confirm diagnosis and seek guidance on imaging studies. Collaborative care planning involves multidisciplinary rounds to discuss patient progress, coordinate interventions, and address evolving clinical needs.

The healthcare team must educate caregivers and patients about the benign nature of the disorder. The condition resolves spontaneously and rarely recurs. Patients are advised to maintain a healthy lifestyle, including weight management, smoking cessation, medication adherence, alcohol avoidance, and regular follow-up with their primary care clinician. The outcome in most patients is excellent.[20][21] Transient global amnesia is one of the more perplexing yet benign neurological emergencies. The interprofessional team can enhance patient-centered care, promote favorable outcomes, ensure patient safety, and optimize team performance in managing patients with transient global amnesia.