Loss of Autonoetic Awareness of Recent Autobiographical Episodes and Accelerated Long-Term Forgetting in a Patient with Previously Unrecognized Glutamic Acid Decarboxylase Antibody Related Limbic Encephalitis

Abstract

We describe a 35-year-old male patient presenting with depressed mood and emotional instability, who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic awareness regarding autobiographical memories of the last 3 years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression, or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left >right). Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over 6 months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment, the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit, vocational reintegration was successfully in progress. In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting, and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with repeated assessments.

Specific B- and T-cell populations are associated with cognition in patients with epilepsy and antibody positive and negative suspected limbic encephalitis

“…Both tests, either taken alone or and in combination, are well-suited for monitoring memory in limbic encephalitis [ 11 , 18 , 34 , 45 , 57 ].…”

Epilepsy and cognition – A bidirectional relationship?

“…The patient complained about anterograde as well as retrograde episodic memory problems (loss of autonoetic awareness of recent biographical memories and accelerated long-term forgetting). Over several months, the patient searched for a doctor and was diagnosed as suffering from burn-out and depression [85]. Here, the cognitive and behavioral problems preceded the epilepsy.…”

Volumetry of Mesiotemporal Structures Reflects Serostatus in Patients with Limbic Encephalitis

“…Studies in patients with focal lesions limited to the CA1 region of the hippocampus attribute a crucial role in autobiographic memory retrieval, mental time travel, and autonoetic consciousness to CA1. 32,33 Most interesting, these cognitive functions have been shown to be impaired in GAD-LE, 34 It is open to discussion why CA1 is selectively affected in GAD-LE. It has been shown that CA1 is particularly vulnerable to a variety of pathologic conditions such as ischemia, inflammation, or increased metabolic demand related to epileptic activity 27,35 and CA1 neurons express an extraordinary high density of N-methyl-D-aspartate NR2 subunits.…”