Transient Epileptic Amnesia: Under-Diagnosed but Treatable Cause of Memory Dysfunction

A 62-year-old man was referred for “Alzheimer’s dementia.” He presented with memory loss for significant life events (autobiographical memory) developing 5 years before and involving memories spanning many decades, including childhood memories, trips to Las Vegas, a Bette Midler concert backstage pass, as well as his wedding day. His wife described concomitant difficulties navigating previously familiar routes and recognizing landmarks (topographical memory) along with anosmia. Upon further questioning, he described frequent, brief spells consisting of a sudden, fearful feeling with memory difficulties during the event. His wife, who witnessed many episodes, stated that his cognition seemed otherwise intact. Aside from a few episodes occurring upon waking, there were no preceding triggers. He continued to run a multimillion-dollar company, performing accounting duties satisfactorily. There was no history of head trauma, but he had a small cerebellar stroke 3 years prior and had well-controlled hypertension and obstructive sleep apnea. He scored 30/30 on the Montreal Cognitive Assessment, displaying no problems in immediate or delayed word recall. However, he stated that if asked to recall the words tomorrow, he would not only be unable to recall them but would likely not remember even having visited the physician. The rest of the assessment, including general and neurologic examinations, was unremarkable. Repeat electroencephalograms (EEGs), brain magnetic resonance imaging, and basic bloodwork, including thyroid-stimulating hormone, vitamin B12, and cortisol levels, were unrevealing. Formal neuropsychology testing revealed no evidence of cognitive impairment.

Suspecting a diagnosis of transient epileptic amnesia, we started him on levetiracetam, an antiepileptic that has been effective in reported cases. Since initiation of treatment 4 years ago, he has experienced no further amnestic periods. He can now retain new autobiographical memories. Topographical memory and sense of smell have also noticeably improved. Memory deficits prior to levetiracetam initiation have, however, remained lost.

Transient epileptic amnesia tends to affect middle-aged individuals (mean 57 years), and men more than women (2:1). Reasons for this predilection and even the underlying etiology remain unclear. Transient epileptic amnesia is primarily a clinical diagnosis and in contrast to Alzheimer’s dementia, which initially affects recent memories, transient epileptic amnesia is characterized by patchy loss of autobiographical memory, extending back in time for several years, as well as brief and recurrent amnestic episodes, which tend to occur on awakening. Patients often have normal neuropsychological testing but may demonstrate accelerated long-term forgetting—the phenomenon whereby information is acquired but fades within a short timespan (ie, days to weeks)—as well as topographical amnesia. Olfactory deficits have recently been reported as well. Brain imaging is typically normal and EEG may or may not show temporal lobe epileptiform activity. Ambulatory 24-hour EEG can increase this yield, but was not available in our case. Anticonvulsant monotherapy is the gold standard of treatment, with levetiracetam, carbamazepine, lamotrigine, and zonisamide all reported to be effective in abolishing/minimizing seizure activity, while interictal memory improvement is more variable. Lost autobiographical memories do not typically recover. Importantly, long-term follow-up has revealed no elevated risk of dementia. Transient epileptic amnesia is important to recognize as being distinct from dementia because it is highly responsive to treatment.