Differential diagnosis and workup
The differential diagnosis for acute-onset memory loss in the absence of other neurologic or psychiatric features is broad. It includes:
- dissociative amnesia
- ischemic amnesia
- transient epileptic amnesia
- toxic and metabolic amnesia
- posttraumatic amnesia.
Dissociative amnesia (DA), otherwise known as psychogenic amnesia, is “an inability to recall important autobiographical information, usually of a traumatic or stressful nature, that is inconsistent with ordinary forgetting.”13 According to this definition, DA features only retrograde amnesia, as opposed to TGA, which features anterograde amnesia, with possible retrograde amnesia. A subtype of DA—specifically, “continuous amnesia” or “anterograde dissociative amnesia”— is in DSM-5.13 However, the diagnostic criteria are unclear, and no cases have been identified in the literature since 1903, before TGA became a diagnostic entity.5,14 Moreover, patients with DA cannot recall autobiographical information, which is not a feature of TGA. Within DSM-5, TGA is an exclusion criterion for DA.13 Thus, an episode of anterograde amnesia with acute onset best meets criteria for TGA, even if there are substantial psychiatric risk factors.
Ischemic amnesia—including stroke and transient ischemic attack (TIA)—is often the primary concern of patients with TGA and their families upon initial presentation, as was the case with Ms. A.6,15 TIA presenting with isolated, acute-onset amnesia would be highly unusual, because these attacks usually present with focal symptoms including motor deficits, sensory deficits, visual field deficits, and aphasia or dysarthria. A patient with amnesia experiencing a TIA would likely have symptoms lasting from seconds to minutes, which is much shorter than a typical TGA episode.16
Amnesia secondary to stroke may be transient or permanent.7 Amnesia is present in approximately 1% of all strokes and in approximately 19.3% of posterior cerebral artery strokes.7,17 Unlike TIA and TGA, ischemic amnesia would present with MRI findings detectable at symptom onset. TGA does reveal MRI findings, particularly punctate lesions in the CA1 area of the hippocampus; however, these lesions are typically much smaller than those found in stroke, and are not detectable until 12 to 48 hours after episode onset.1,17 MRI findings in ischemic amnesia are typically associated with extrahippocampal lesions.17 Finally, the presence of vascular risk factors such as hyperlipidemia, smoking, diabetes, and hypertension may also favor a diagnosis of stroke or TIA as opposed to TGA, which is not associated with these risk factors.18 Though ischemic amnesia and TGA usually can be differentiated based on history and presentation, MRI with fluid-attenuated inversion recovery and diffusion-weighted imaging may be performed to definitively distinguish stroke from TGA.7
Transient epileptic amnesia (TEA), a focal form of epilepsy within the temporal lobe, should also be considered in patients who present with acute-onset amnesia. Like TGA, TEA may present with simultaneous anterograde and retrograde amnesia accompanied by repetitive questioning.19 Amnesia can be the sole symptom of TEA in up to 24% of cases. However, several key features distinguish TEA from TGA. TEA most often presents with other clinical signs of seizures, such as oral automatisms and/or olfactory hallucinations.20 There is also a significant difference in episode length; TEA episodes last an average of 30 to 60 minutes and tend to occur upon wakening, whereas TGA episodes last an average of 4 to 6 hours and do not preferentially occur at any particular time.1,21 In the interictal period—between seizures—patients with TEA may also experience accelerated long-term forgetting, autobiographical amnesia, and topographical amnesia.19,20 Finally, a diagnosis of TEA also requires recurrent episodes. Recurrence can happen with TGA, but is less frequent.21 Generally, history and presentation can distinguish TEA from TGA. Though there is no formal protocol for TEA workup, Lanzone et al21 recommend 24-hour EEG or EEG sleep monitoring in patients who present with amnesia as well as other clinical manifestations of epileptic phenomenon.
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