Factors associated with recurrent transient global amnesia: systematic review and pathophysiological insights

The examination of the risk factors that affect the recurrence of transient global amnesia (TGA) may shed light on the pathophysiological substrate of the disease. A systematic review was performed to identify the factors associated with the recurrence of TGA. MEDLINE, EMBASE, CENTRAL and PsycINFO were meticulously searched. Observational controlled studies involving patients with single (s-TGA) and recurrent TGA (r-TGA) according to Hodges and Warlow's criteria were retrieved. Differences in the demographic characteristics, personal and family medical history, previous exposure to precipitating events and laboratory findings were examined. Retrieved evidence was assessed in the context of the individual article validity, based on the numerical power and methodological quality of each study. Nine cohort studies with retrospective, prospective or mixed design were retrieved. In total, 1989 patients with TGA were included, 269 of whom suffered from r-TGA (13.5%). R-TGA presented an earlier age of onset. Evidence was suggestive of a relationship between recurrence and a family or personal history of migraine, as well as a personal history of depression. There was weaker evidence that associated recurrence with a positive family history of dementia, a personal history of head injury and hippocampal lesions in diffusion-weighted MRI. On the other hand, no connection was found between recurrence and electroencephalographic abnormalities, impaired jugular venous drainage, cardiovascular risk factors, atrial fibrillation, previous cerebrovascular events, exposure to precipitating events, a positive family history of TGA and hypothyroidism. Important pathophysiological insights that arised from these findings were discussed.