Re-mind the gap: Learnings, warnings, insights, and predictions about transient global amnesic syndromes

Especially for neurologists, transient global amnesia (TGA) is quite a renowned nosological entity, characterized by the sudden onset of typically anterograde amnesia and traditionally considered as a benign, isolated and self-limiting condition, that results in a persisting memory “gap”. Actually, TGA is the mere literal definition of this specific clinical event, which can look familiar to neurologists although it is often associated with many uncertainties about its management. Indeed, TGA is as easily recognizable, as its clinical hallmarks, pathophysiology, and recurrence risk are hard to define precisely. Atypical TGA cases are increasingly reported. The potential
occurrence of significant mimics, such as seizures (transient epileptic amnesias and other forms) and cerebrovascular diseases (transient ischemic attacks and stroke), should lead to a thorough, instrumental examination of patients especially in the Emergency Department setting. Also, TGA may occur in association with other acute neurological conditions, further complicating the diagnostic work-up and the prognostic implications. In addition, long-term clinical outcome in these patients remains unclear and predicting recurrence and development of dementia remains a challenge.

TGA has been usually thought pinpointing a transient, reversible hippocampal disfunction, as suggested by the frequent finding of vanishing hippocampal punctate lesion on diffusion-weighted
imaging (HPDL). However, more recently: HPDL have been reported also in other acute neurological disorders, in the absence of clinical symptoms of TGA; also, TGA may have atypical clinical manifestations despite typical neuroimaging; in addition, patients with typical TGA may show vanishing extra-hippocampal punctate diffusion lesions. These findings lead some Authors to propose the existence of a wider "disease spectrum” including all these variants.

Furthermore, as TGA has been typically linked to peculiar situations such as Valsalva manoeuvre, hypertensive fits, emotional stress and coitus, the recent literature suggests that TGA may also be triggered by, or occur simultaneously, other acute neurological conditions such as ischemic and hemorrhagic stroke, potentially through the involvement of autonomic pathways.

Despite the original descriptions pointed to a benign course, the increasing reporting of atypical situation as well as the many potential mimics and clinical confounders are currently evoking many questions on this topic:

What is, eventually, transient global amnesia? Is it a stand-alone entity, or an epiphenomenon of multiple conditions? Therefore, should we keep talking about “differential diagnoses” for transient global amnesia, or rather about different conditions leading to the same clinical expression? Could we identify some red flags for “secondary” forms? What are the major prognostic implications? How can we predict recurrence, complications and long-term outcome?

This research topic collection about TGA and other transient global amnesic syndromes aims to further characterize clinical and neuroimaging features, diagnostic and prognostic tools of these bizarre, yet intriguing and important clinical phenomena.

We welcome original research articles on clinical case series, preclinical studies, reviews and case- based review articles, clinical pictures, especially focusing on common and unusual clinical
expression, neuropsychological characterization, neuroimaging and neurophysiological features, biomarkers, comorbidities, differential diagnoses, acute phase management and long-term follow up assessment.

Through a dive into the pathophysiological hypotheses that have been elaborated throughout the years, we aim to collect further evidence supporting or distorting the previous knowledge on this topic, to potentially implement the current management of transient global amnesic syndromes.