Evidence-Based Reviews

Transient global amnesia: Psychiatric precipitants, features, and comorbidities

Current Psychiatry. 2023 April;22(4):30-35,40 | doi: 10.12788/cp.0345

References

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Toxic and metabolic etiologies of amnesia include opioid and cocaine use, general anesthetics,²² and hypoglycemia.^7,23 Toxic and metabolic causes of amnesia may mirror TGA in their acute onset as well as anterograde nature. However, these patients will likely present with fluctuating consciousness and/or other neuropsychiatric features, such as pressured speech, delusions, and/or distractability.²³ Obtaining a patient’s medical history, including substance use, medication use, and the presence of diabetes,²⁴ is typically sufficient to rule out toxic and metabolic causes.⁷

Posttraumatic amnesia (PTA) describes transient memory loss that occurs after a traumatic brain injury. Anterograde amnesia is most common, though approximately 20% of patients may also experience retrograde amnesia pertaining to the events near the date of their injury. Unlike TGA, which typically resolves within 24 hours, the recovery time of amnestic symptoms in PTA ranges from minutes to years.⁷ A distinguishing feature of PTA is the presence of confusion, which often resembles a state of delirium.²⁵ The presentation of PTA can vary immensely with regards to agitation, psychotic symptoms, and the time to resolution of the amnesia. Though TGA can be distinguished from PTA based on a lack of clouding of consciousness, a case of anterograde amnesia warrants inquiry into a potential history of head injuries to rule out a traumatic cause.²⁶

Box 2^1,3,23,27-33 outlines current theories of the etiology and pathogenesis of TGA.

Box 2

Etiology and pathogenesis of transient global amnesia: Current theories

The etiology and pathogenesis of transient global amnesia (TGA) are poorly understood, and TGA remains one of the most enigmatic syndromes in clinical neurology.²⁷ Theories regarding the pathogenesis of TGA are diverse and include vascular, epileptic, migraine, and stress-related etiologies.^1,23

Early theories suggested arterial ischemia²⁸ and epileptic phenomena²⁹ as etiologies of TGA. The venous theory posits that TGA stems from jugular venous incompetency, causing venous flow and subsequent venous congestion in the medial temporal lobe, wherein lies the hippocampus. This theory is supported by several studies showing venous valve insufficiency as detected by ultrasonographic evaluation during the Valsalva maneuver in patients with TGA.³⁰ This pathophysiologic mechanism may explain the occurrence of TGA in a specific cluster of cases, including men whose TGA episodes are precipitated by physical stress or the Valsalva maneuver.³ The migraine theory and stress theory share a similar proposed neurophysiologic mechanism.

The migraine theory stems from migraines being a known risk factor for TGA, particularly in middle-aged women.³¹ The stress theory is based on the known emotional precipitants and psychiatric comorbidities associated with TGA. Notably, both the migraine theory and stress theory implicate the role of excessive glutamate release as well as CNS depression.^31,32 Glutamate targets the CA1 region of the hippocampus, which is involved in TGA and is known to have the highest density of N-methyl-D-aspartate receptors among hippocampal regions.³³

Given the heterogeneity of the demographics and stressors associated with TGA, multiple mechanisms for the disease process may coexist, leading to a similar clinical picture. In 2006, Quinette et al³ performed a multivariate analysis of variables associated with TGA, including age, sex, medical history, and presentation. They demonstrated 3 “clusters” of TGA pictures: women with anxiety or a personality disorder; men with physical precipitating events; and younger patients (age <56) with a history of migraine. These findings suggest TGA may have unique precipitants corresponding to multiple neurophysiologic mechanisms.

Transient global ischemia: Psychiatric features

Several studies have demonstrated psychiatric precipitants, features, and comorbidities associated with TGA. Of the TGA cases associated with precipitating events, 29% to 50% are associated with an emotional stressor.^3,4 Examples of emotional stressors include a quarrel,⁴ the announcement of a birth or suicide, and a nightmare.¹⁵ For Ms. A, learning her daughter worked in the sex industry was an emotional stressor.²

During its acute phase, TGA has been shown to present with mood and anxiety symptoms.³⁴ Moreover, during episodes, patients often demonstrate features of panic attacks, such as dizziness, fainting, choking, palpitations, and paresthesia.^3,35

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