What is the recommended diagnostic work‑up and first‑line therapy for an adult presenting with brief, recurrent episodes of sudden inability to form new memories lasting minutes, typically upon waking, with otherwise normal neurological examination, suggestive of transient epileptic amnesia?

Transient Epileptic Amnesia: Diagnostic Work-up and First-Line Therapy

For an adult presenting with brief, recurrent episodes of sudden memory loss lasting minutes to an hour, especially upon waking, with otherwise normal neurological examination, perform an EEG (preferably sleep EEG) and initiate levetiracetam as first-line therapy once the diagnosis is confirmed. 1, 2

Clinical Recognition and Diagnostic Criteria

Transient epileptic amnesia (TEA) is a distinctive temporal lobe epilepsy syndrome that typically begins in later life (mean age 62–65 years) and is frequently misdiagnosed at initial presentation. 1, 2 The diagnosis requires three elements:

• Recurrent, witnessed episodes of transient amnesia – attacks are typically brief (median duration 30–60 minutes), frequent (median 12 per year), and characteristically occur upon waking in 74% of cases. 1, 2
• Preservation of other cognitive functions during attacks – patients often exhibit repetitive questioning but maintain language, attention, and other non-memory abilities during episodes. 1
• Compelling evidence of epilepsy – provided by EEG abnormalities, co-occurrence of other seizure types, or clear response to anticonvulsant therapy. 1

A critical diagnostic clue is that patients may "remember not being able to remember" – they retain awareness that a memory disturbance occurred, distinguishing TEA from transient global amnesia where the episode itself is typically forgotten. 1

Essential Diagnostic Work-up

Electroencephalography (EEG)

Order both wake and sleep EEG, as epileptiform abnormalities arising from the temporal lobes are most often detected on interictal sleep EEG rather than routine wake recordings. 1 The American Academy of Neurology recommends obtaining EEG as part of the neurodiagnostic evaluation in all patients with apparent first unprovoked seizure. 3

• Abnormalities typically localize to the dominant or bilateral temporal lobes, though non-dominant temporal lobe discharges can occur with preserved consciousness during attacks. 4
• Brief, stereotyped, repetitive symptoms suggestive of transient cerebral dysfunction raise the possibility of partial seizure, and electroencephalography may be useful in such cases. 5

Neuroimaging

Obtain MRI brain with epilepsy protocol as the preferred imaging modality – MRI is more sensitive than CT for detecting epileptogenic lesions in the temporal and orbitofrontal regions. 6

• Deferred outpatient MRI is acceptable for patients who have returned to baseline, have normal neurologic examination, and have reliable follow-up arrangements. 3, 6
• Emergent CT is not required unless high-risk features are present (age >40 with first seizure, focal neurologic deficits, anticoagulation, recent trauma, fever, or persistent headache). 6

Laboratory Testing

Obtain serum glucose and sodium levels – these are the only laboratory abnormalities that consistently alter acute management in seizure presentations. 3, 6

• Pregnancy test is mandatory in all women of childbearing age to guide medication selection and avoid teratogenic agents. 3, 6
• Additional metabolic panels should be obtained only when specific clinical clues suggest them (vomiting, diarrhea, dehydration, known renal disease, or malignancy). 6

Neuropsychological Assessment

Administer comprehensive neuropsychological testing to assess both anterograde and retrograde memory, as standard memory tests often appear normal despite significant patient complaints. 1, 2

• Patients with TEA exhibit accelerated long-term forgetting (ALF) of verbal and visual material over 3 weeks compared to matched controls (p < 0.001). 2
• Autobiographical amnesia (AbA) for personal events extending back 40+ years is common (p < 0.05), affecting epochs that may predate epilepsy onset by many years. 2
• Despite normal performance on standard anterograde memory tests, 80% of patients describe persistent interictal memory difficulties. 2, 7

First-Line Therapy

Initiate levetiracetam as the preferred first-line antiepileptic drug – it has efficacy and overall good tolerability with fewer drug interactions than older agents. 3

• Attacks cease on anticonvulsant medication in 88–94% of treated patients (44 of 47 in the largest series). 2
• Lamotrigine is an alternative first-line option, though it requires several weeks of slow titration to reach therapeutic levels and minimize Stevens-Johnson syndrome risk. 3, 6
• Avoid valproic acid in women of childbearing potential due to teratogenic risk, despite its efficacy. 3
• Phenytoin, phenobarbital, and carbamazepine are no longer recommended as first-choice agents due to side-effect profiles and significant drug interactions. 3

Critical Pitfalls to Avoid

Do not misdiagnose TEA as transient global amnesia (TGA) – TEA episodes are recurrent (median 12/year vs. TGA's typical single or rare episodes), brief (30–60 minutes vs. TGA's 4–8 hours), occur on waking (74% vs. TGA's daytime onset), and respond to anticonvulsants. 1, 2

Do not dismiss persistent memory complaints as unrelated to seizure control – autobiographical amnesia and accelerated long-term forgetting persist despite successful seizure suppression with anticonvulsants, posing ongoing challenges for patients. 2, 7

Do not overlook TEA in memory clinic settings – epilepsy was the initial specialist diagnosis in only 24% of cases (12 of 50), with many patients initially referred for evaluation of probable dementia. 2, 7 TEA should be included in the differential diagnosis of dementia to avoid misdiagnosis and needless medication. 7

Do not rely solely on wake EEG – sleep EEG is essential because temporal lobe epileptiform abnormalities are most often detected during sleep recordings. 1

Do not assume consciousness is always impaired during amnestic attacks – confinement of epileptic discharge to the non-dominant temporal lobe can lead to partial preservation of consciousness during seizure attacks that produce transient amnesia. 4

Long-term Management Considerations

Monitor for persistent interictal memory dysfunction – the mechanism of autobiographical amnesia may result from impairment of very long-term memory consolidation due to epileptic activity in mesial temporal structures. 1

Recognize that TEA may evolve into a broader syndrome – some patients develop accelerated long-term forgetting and/or autobiographical amnesia without suffering any type of epileptic seizure for extended periods, a pattern termed "transient epileptic amnesia complex syndrome (TEACS)." 8

Ensure appropriate follow-up with neurology – neuropsychological performance should be reassessed 6 months after treatment initiation to document response and identify persistent cognitive deficits requiring additional intervention. 7