References for this Review were identified through searches of PubMed with the search terms “amnesia”, “transient global amnesia”, “TGA”, “hippocampus”, and “CA1” between January, 1990, and August, 2009. Only papers published in English were reviewed. The references from identified papers and the authors' own files were also searched for relevant publications. The final reference list was chosen on the basis of relevance to the topics covered in this Review (eg, their originality,
ReviewTransient global amnesia: functional anatomy and clinical implications
Introduction
The syndrome of transient global amnesia (TGA) was described independently in two case series by Bender1 and by Guyotat and Courjon2 in 1956. However, in 1882 and 1909, Ribot3 and Benon4 had already described transient amnestic states suggestive of a TGA.5 In 1964, Fisher and Adams6 published a large case series and introduced the term as used today. Since then, the clinical characteristics of TGA have been well described, although the exact aetiology and pathophysiology of this disorder are still not completely understood.7
TGA is defined by a sudden onset of an anterograde and retrograde amnesia that lasts up to 24 h. The clinical and neuropsychological aspects of this syndrome have been characterised in recent studies, and several aetiological factors, such as migraine-related mechanisms, focal ischaemia, venous flow abnormalities, and epileptic phenomena, have been suggested to be involved in the pathophysiology.8, 9, 10 Data from neuropsychological studies that characterise the memory impairment of patients with acute TGA show a profound reduction of anterograde and a milder reduction of retrograde episodic memory, including executive functions and recognition.7, 11, 12, 13, 14, 15, 16, 17 Thus, given the memory impairment in TGA, an involvement of temporal lobe structures including the hippocampus has long been suggested.18
Although the core amnestic syndrome usually lasts substantially less than 24 h, mild subclinical neuropsychological deficits with concomitant vegetative symptoms can last for days after the episode.7, 11, 13, 17, 19 Some studies indicate that a subclinical impairment of memory functions might persist for months after the acute episode.11, 20, 21, 22, 23 A recent meta-analysis including 25 studies, however, could not find differences in the long-term cognitive performance between patients and healthy controls.17
Recent high-resolution imaging data suggest an involvement of memory circuits in the mesiotemporal region, as hyperintense MRI lesions can be detected in the hippocampal formation in TGA.7, 10, 24, 25, 26, 28 An analysis of the functional anatomy of these lesions shows a selective distribution within the CA1 subfield of the hippocampal cornu ammonis.7, 24 Further imaging findings have implicated cellular mechanisms in the development of these lesions, suggesting that the selective vulnerability of CA1 neurons to metabolic stress plays a crucial part in the pathophysiological cascade that leads to a transient perturbation of memory pathways in TGA.
In this Review, we summarise clinically relevant aspects and give practical recommendations for the diagnosis and imaging of patients with acute TGA. We describe recent imaging findings and epidemiological studies and we present a pathophysiological framework of TGA.
Section snippets
Epidemiology
Most systematic epidemiological studies show that the incidence of TGA ranges between 3 and 8 per 100 000 people per year.29, 30, 31, 32 75% of attacks occur in people aged between 50 and 70 years, and occurrence in patients younger than 40 years of age is rare. The rate of recurrence of a second or a third episode varies across studies; a recent thorough meta-analysis described the rate of annual recurrence to be between 6% and 10%.31
The nature of precipitating events directly before a TGA has
Diagnostic criteria and differential diagnosis
The diagnosis of TGA is primarily a clinical one and can be made if the following diagnostic criteria by Caplan37 and Hodges18 are fulfilled: (i) presence of an anterograde amnesia that is witnessed by an observer, (ii) no clouding of consciousness or loss of personal identity, (iii) cognitive impairment limited to amnesia, (iv) no focal neurological or epileptic signs, (v) no recent history of head trauma or seizures, and (vi) resolution of symptoms within 24 h (panel 1). A temporally graded
Pathophysiological mechanisms
Since its description, several pathophysiological mechanisms, such as migraine-related mechanisms, hypoxic–ischaemic events, venous flow abnormalities, psychological mechanisms, and epilepsy-related activity, have been suggested to be associated with the pathophysiology of TGA.9 As many patients report Valsalva-associated manoeuvres before the onset of TGA, recent studies have investigated the possibility of an increased venous pressure leading to a hippocampal venous congestion with subsequent
PET and SPECT
Quantitative imaging of changes of regional cerebral glucose, oxygen metabolism, or cerebrovascular blood flow in TGA have been studied by use of PET and single photon emission computed tomography (SPECT). In some studies, mesiotemporal flow changes have been described.80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 However, most studies have also noted concomitant decreased or increased changes in cerebral blood flow in other anatomical structures, such as unilateral or bilateral
Conclusions and clinical implications
Recent neuroimaging findings suggest that a transient perturbation of hippocampal function is the correlate of TGA, as focal lesions can be reliably detected in the CA1 field of the cornu ammonis by use of DWI. The maximum level of detection of these lesions is 24–72 h after onset of symptoms. Although the diagnosis of TGA is primarily a clinical one, neuroimaging in TGA can positively support the diagnosis. Further investigations, including imaging, can be recommended if cerebrovascular risk
Search strategy and selection criteria
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Transient global amnesia with unexpected clinical and radiological findings: A case series and systematic review
2022, Journal of the Neurological SciencesCitation Excerpt :Whereas TGA diagnosis is based on well-established clinical criteria, [1–3] MR-based neuroimaging is helpful to confirm the diagnosis [12] and exclude alternative explanations. Nevertheless, TGA pathogenesis remains poorly understood, and several mechanisms such as migraine, focal ischemia, venous flow abnormalities and epileptic phenomena, have been proposed. [3,13] Interestingly, unusual TGA cases, as with unusual clinical manifestations, [14] or displaying extra-hippocampal punctate DWI-lesions (E-HPDL), [15] have been described.
Acute amnesia caused by left fornix infarction: A case report of an unusual entity
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