Prevalence of Mimics and Severe Comorbidity in Patients with Clinically Suspected Transient Global Amnesia.

BACKGROUND: Transient global amnesia (TGA) is a syndrome featuring acute anterograde amnesia as the most striking clinical symptom. Its etiology is still a matter of debate. Most neurological guidelines allow the diagnosis on the basis of clinical criteria only; a more extensive evaluation is recommended only for patients with "red flags" like severe headache, nausea or vomiting, or metabolic abnormalities. The aim of our study was to assess the frequency of a severe underlying disease or alternative diagnoses (mimics) in patients fulfilling the clinical criteria. METHODS: We evaluated the medical records and the imaging data of an unselected consecutive cohort of patients with suspected TGA over a 7-year period. All patients were hospitalized and received a neurological workup including brain imaging, color-coded duplex sonography of the brain supplying arteries, electroencephalography, and laboratory studies of blood and (in selected cases) cerebrospinal fluid. RESULTS: 163 patients with 166 episodes of suspected TGA were hospitalized (3 patients twice). After the workup, the diagnosis of TGA was confirmed in 148/166 (89.2%) episodes ("simple TGA"). Eighteen patients (10.8%) either had an alternative diagnosis or a severe comorbidity that was assumed to have had an impact on the occurrence of the amnestic episode ("complicated TGA/mimic"). The most important differential diagnosis was stroke (11 patients, 6.6% of all TGA suspects and 61.1% of the complicated TGA/mimic group). Other mimics were transient epileptic amnesia (2 patients) and steroid-induced delirium (1 patient). Important comorbidities that had not been obvious at the time of presentation were severe sleep apnea (2 patients), triptan overuse (1 patient), and an involuntary amlodipine intoxication during TGA. CONCLUSION: As approximately every tenth patient with suspected TGA either had an alternative diagnosis or a severe comorbidity, which had not been obvious at the time of admission, we consider in-patient treatment of all suspected TGA cases as appropriate, preferably in the setting of a stroke unit, as ischemic stroke was the by far most important diagnosis mimicking TGA.

Transient Global Amnesia: Commentary on Trip Gabriel's First-Person Account.

This paper comments on a companion article, a first-person account of an episode of transient global amnesia written by New York Times reporter Trip Gabriel (Gabriel T. 2017. Cogn Behav Neurol. 30:1-4). Mr Gabriel describes having no memories of a cold, rainy day that he had spent on a sailboat competing in two races. The episode may have been triggered by his exposure to water. Afterward, the skipper recalled that Mr Gabriel had functioned fine on the boat, although after returning to shore he needed help finding his car. When he told his wife over the phone that he could not remember where he lived, she got him home and to the hospital. The staff excluded stroke and other causes of amnesia. He felt some awareness after about 9 hours, and the episode ended after about 23 hours. He has been left with a permanent memory gap of 12 hours.The commentary on the case outlines the state of knowledge about transient global amnesia. The diagnosis is well established: a witnessed sudden-onset retrograde and anterograde amnesia lasting <24 hours in a fully conscious person who knows who he/she is and has no other cause for amnesia. Triggers include exposure to water, stress, and sexual intercourse. A normal magnetic resonance imaging scan can help with the often challenging differential diagnosis. Apart from the gap in memory, patients recover fully and only 15% to 20% have recurrences. The underlying pathophysiology has not been explained.

The Day That Went Missing: A First-Person Account of Transient Global Amnesia.

In this vivid first-person case history, political reporter Trip Gabriel describes experiencing a classic episode of transient global amnesia. He was near the average target age of 61. Although no cause has been established for the syndrome, as with many other patients his episode appears to have been triggered by contact with water: He was racing a sailboat. While remaining alert and handling complex sailing maneuvers, he suddenly developed amnesia that left him with no recollection of finishing two races, returning to shore, drinking a beer with his friends, needing help finding his car, and not knowing where he was or where he lived. When he did not arrive home on time, his wife called him and quickly recognized his disorientation. She helped him drive himself home and took him to the hospital, where he was evaluated for a stroke. A brain magnetic resonance imaging scan was normal. He started to become aware again about 9 hours after the start of the attack, but was kept in the hospital until his anterograde amnesia resolved fully about 23 hours after onset. He has no memories of 12 hours (from 3 hours before the attack started through the time he regained awareness in the hospital). He was reassured to learn that a recurrence is unlikely. He finds parallels to his experience in the films Memento and Inside Out. A companion article provides expert commentary on the case report (Kirshner HS. 2017. Cogn Behav Neurol. 30:5-7).

The Still Enigmatic Syndrome of Transient Global Amnesia: Interactions Between Neurological and Psychopathological Factors.

Transient global amnesia (TGA) is a neurological syndrome that usually occurs in middle-aged or older people. It is characterized by the abrupt onset of profound anterograde amnesia, associated with more variable retrograde amnesia and repetitive questioning. The whole episode lasts no more than 24 h. Almost 60 years after its first descriptions, the etiology of TGA remains unknown. Until now, TGA has been described exclusively as a memory disorder, but there is a growing body of evidence to show that emotional and psychological factors (as anxious and depressive symptoms) are present at different times of TGA. Their role therefore needs to be clarified. First, these factors seem to play a part in triggering TGA, at least for a subgroup of patients, suggesting the existence of an emotional TGA subtype. Second, recent research shows that almost all the TGA patients displayed modifications of their emotional state during the episode, possibly linked to sudden memory loss. The level of depressive and anxious symptoms could even reach a pathological threshold in patients with the so-called "emotional TGA subtype". Third, the persistence of these depressive and anxious symptoms after the end of the episode could account for lasting memory disorders in some patients. Finally, the analysis of these emotional syndrome and emotional factors and the recent data in neuroimaging could allow us to gain a better understanding of the pathophysiological mechanisms behind TGA. The aim of this review was thus to discuss whether the anxious and depressive symptoms are causative, resultant or coincidental of TGA.

Transient global amnesia in legal proceedings.

Transient global amnesia (TGA) is a neurological disorder characterized by an acute onset of severe anterograde amnesia. While retrograde amnesia may be present-although to a lesser extent-patients have no further cognitive disturbances or neurological signs. These symptoms resolve fully within several hours leaving a permanent memory gap for the duration of the episode and do not lead to long-term neurological deficits. In addition to well-defined clinical diagnostic criteria, in up to 80 % of patients, small, point-shaped lesions in the hippocampus are detected 24-48 h after symptom onset on diffusion-weighted magnetic resonance images. Despite several etiological hypotheses, to date, there is no scientific proof for the etiology of TGA or the small hippocampal lesions. Interestingly, in a large number of cases, an emotionally or physically straining event precipitates the onset of TGA, suggesting a stress-related mechanism. We report two cases of TGA occurring in legally relevant settings: affecting the victim of brutal burglary and the key witness in a murder trial. In the context of forensic medicine, the knowledge of this disorder and recognition of its typical features are essential.

Hippocampal modifications in transient global amnesia.

Transient global amnesia (TGA) is an acute and transient syndrome with a remarkably stereotypical set of signs and symptoms. It is characterized by the abrupt onset (no forewarning) of massive episodic memory impairment, both anterograde and retrograde. Ever since it was first described, TGA has fascinated neurologists and other memory experts, and in recent years, there has been a surge of neuroimaging studies seeking to pin down the brain dysfunction responsible for it. Several pathophysiological hypotheses have been put forward, including the short-lived suggestion of an epileptic mechanism. All the available data indicate that the brain modifications are reversible, and that the mechanism behind TGA is of a functional nature. However, while diffusion-weighted imaging studies have clearly identified the hippocampus and, more specifically, the CA1 area, as the locus of brain modifications associated with TGA, researchers have yet to determine whether the origin of the mechanism is vascular or neurochemical. Spectroscopy may provide a means of settling this issue once and for all.

[Transient global amnesia: A descriptive study of 12 Polynesian patients]. / Ictus amnésique: étude descriptive de 12 patients polynésiens.

INTRODUCTION: According to the criteria of Hodges and Warlow, transient global amnesia is defined by sudden onset of isolated anterograde amnesia of spontaneous resolution within one to twenty-four hours. Its pathophysiological mechanisms are still uncertain. METHODS: In a retrospective study, we have analyzed epidemiological, clinical and MRI data from twelve patients admitted to the only neurological department of French Polynesia for transient global amnesia corresponding to the criteria of Hodges and Warlow between January 2010 and December 2013. RESULTS: The median age of the cohort was 61.5 (53-72), the sex ratio was 1. Ten patients had one or more cardiovascular risk factors, 3 had migraine headaches and 3 had anxiodepressive disorders. Among triggers found, the occurrence during the rest was noted in one case. Retrograde amnesia was observed in 42% of cases, repetitive questioning in 75% of cases, anxious bewilderment in 67% of cases and disorientation in 33% of cases. The median episode duration was 9 hours and the duration of hospitalization was 3 days. Three patients had a recurrence. MRI was abnormal in all patients and showed diffusion-weighted hyperintensities in right (n=8), left (n=3) and bilateral (n=1) hippocampi. CONCLUSION: Epidemiological, clinical and MRI data from our cohort are similar to those from the literature except for the highest prevalence of cardiovascular risk factors and the most frequent right hippocampus involvement. Transient global amnesia occurring exceptionally while sleeping was also observed in one of our patients.

[Syndrome of transient epileptic amnesia and epileptic amnesic syndrome: the same entity?]. / Le syndrome of transient epileptic amnesia et l'epileptic amnesic syndrome sont-ils une même entité ?

A chronic subjective cognitive impairment can be symptomatic of temporal lobe epilepsy (TLE); it is thereby frequently reversible with the use of antiepileptic monotherapy. In this field, two distinct syndromes have been described: the Epileptic Amnesic Syndrome (EAS) and the Syndrome of Transient Epileptic Amnesia. Their diagnostic criteria have much in common but identification of STEA is based only on transient amnesic attacks. On the contrary, EAS takes into account subtle temporal lobe seizures. Here, we report a case where chronic cognitive disturbances were combined with very limited temporal lobe seizures while amnesic attacks were lacking. Antiepileptic drug treatment led to normalization of cognitive function. The criteria of STEA were not applicable because of the lack of transient amnesia in the patients' medical history. Considering brief episodes of flashbacks and abdominal pain as possibly seizure-related, the criteria of EAS were more operative: they allowed proper investigation to confirm TLE in our patient.

Long-term outcome in transient global amnesia patients with and without focal hyperintensities in the CA1 region of the hippocampus.

Focal hippocampal diffusion-weighted imaging (DWI) lesion patterns are detected in transient global amnesia (TGA) patients in different frequency. It has been speculated that acute diffusion restrictions are associated with a worse outcome. Therefore, we evaluated the influence of acute DWI lesions on the cognitive long-term outcome in TGA patients. Seventeen otherwise healthy patients with the clinical syndrome of TGA, who had MRI investigations on admission as well as 1 day later, were investigated with a comprehensive neuropsychological test battery 2 years later. Acute hippocampal DWI lesions in TGA patients were detected in almost two thirds of the patients. Psychometric evaluation revealed no differences in cognitive performance between patients with and without DWI lesions as well as compared to healthy subjects. In addition, no relapse of the attack has been recognized in either group of TGA patients.

Can we remember future actions yet forget the last two minutes? Study in transient global amnesia.

Transient global amnesia (TGA) is a clinical syndrome characterized by the abrupt onset of a massive episodic memory deficit that spares other cognitive functions. If the anterograde dimension is known to be impaired in TGA, researchers have yet to investigate prospective memory (PM)--which involves remembering to perform an intended action at some point in the future--in this syndrome. Furthermore, as executive functions are thought to be spared in this syndrome, TGA provides an opportunity to examine the impact of a massive "pure" memory impairment on PM. We assessed 38 patients with a newly designed protocol that distinguished between the prospective (remembering to do something at the appropriate time) and retrospective (remembering what has to be done) components of PM. Moreover, we investigated episodic memory with an anterograde memory task and assessed executive functions, anxiety and mood, as well as their links with PM. We demonstrated that PM is impaired during TGA, with a greater deficit for the retrospective component than for the prospective component. Furthermore, we highlighted a strong link between these two components. Anterograde episodic memory impairments were correlated with retrospective component deficits in TGA patients, although we were able to confirm that executive functions are globally spared. We discuss this pattern of results within the theoretical framework of PM, putting forward new arguments in favor of the idea that PM deficits can occur mainly because of a massive anterograde memory deficit. The clinical consequences of PM impairment in TGA are examined.

Transient global amnesia: a brief review and update.

Transient global amnesia (TGA) is a transitory syndrome of memory loss, lasting less than 24 h. Although there are many known causes of transient amnesia, the syndrome of TGA remains of unknown etiology. Known causes of transient amnesia, theories of pathogenesis of TGA, and recommended evaluation and treatment are discussed.

Significance of serum neuron-specific enolase in transient global amnesia.

Neuron-specific enolase (NSE) is a glycolytic enzyme, which is associated with neuronal cell dysfunction in the brain. This study evaluated the role of serum NSE levels of patients with transient global amnesia (TGA). In addition, the relationship between serum NSE levels and the clinical features of TGA was explored. Forty-eight patients with TGA were prospectively included, and their serum NSE levels were measured. We investigated serum NSE levels in patients with TGA. In addition, we analyzed the differences in clinical characteristics between patients with elevated and normal serum NSE levels. Of the 48 patients with TGA, 16 patients (33.3%) had elevated serum NSE levels (25.0 ± 11.5 ng/mL), whereas 32 patients (66.7%) showed normal serum NSE levels (12.8 ± 2.1 ng/mL). The patients with elevated serum NSE levels exhibited higher levels of cognitive impairment than those with normal serum NSE levels (4/16 vs. 1/32, p = 0.036). The serum NSE levels showed a relatively high discrimination (AUC 0.684) between patients with and without cognitive impairment, with 80.0% sensitivity and 74.4% specificity at a cut-off value 17.3 ng/mL. A third of all patients with TGA carry elevated serum NSE levels, which suggests that the neuronal cell dysfunction could be associated with TGA pathogenesis. In addition, it might be correlated with cognitive impairment.

Diffusion-weighted MRI in transient global amnesia and its diagnostic implications.

OBJECTIVE: To analyze how the evidence of hippocampal diffusion-weighted imaging (DWI) lesions may support the clinical diagnosis of transient global amnesia (TGA). METHODS: In this retrospective observational study, 390 consecutive patients with isolated TGA were analyzed, who were evaluated at our institution between July 1999 and August 2018. The size, location, and number of lesions and time-dependent lesion detectability were examined. The incidence of DWI lesions was reviewed with regard to different levels of clinical diagnostic certainty upon presentation to the emergency department. RESULTS: Hippocampal DWI lesions were detected in 272 (70.6%) patients with TGA, with a mean of 1.05 ± 0.98 (range 0-6) and a mean lesion size of 4.01 ± 1.22 mm (range 1.7-8.6 mm). In the subgroups of lower diagnostic certainty (amnesia witnessed by layperson or self-reported amnestic gap), DWI was helpful in supporting the diagnosis of TGA in 76 (69.1%) patients. In 187 patients with information about the exact onset, DWI lesions were analyzed in relation to latency between onset and MRI. Lesions could be detected at all time points and up to 6 days after symptom onset in individual patients; the highest rate of DWI-positive MRI (93%) was in the 12-24 hours time window. CONCLUSION: MRI findings can support the diagnosis of TGA and may be particularly valuable in situations of low clinical certainty. DWI-ideally performed with a minimum delay of 20 hours after onset-should therefore be considered a useful adjunct to the diagnosis of TGA.

A Tc-99m SPECT study of regional cerebral blood flow in patients with transient global amnesia.

OBJECTIVES: This study aimed to determine whether regional cerebral blood flow (rCBF) is abnormal in patients who have Transient Global Amnesia (TGA). METHODS: We obtained noninvasive rCBF measurements using Tc-99m-ethyl cysteinate diamer Single Photon Emission Computed Tomography (SPECT) in 7 patients diagnosed with TGA within 4 days of onset of the amnestic episode while the patients were still symptomatic and in 17 age-matched healthy control subjects. We assessed memory functioning using the Hopkins's Verbal Learning Test (HVLT) and Statistical Parametric Mapping to compare rCBF across diagnostic groups. RESULTS: The patients with TGA were significantly impaired in their performance on the 20-minute delayed recall of the HVLT. They also exhibited significantly decreased rCBF on their SPECT scans in the inferior and middle frontal gyrus bilaterally, with more prominent left-sided reductions in the superior temporal, precentral, and postcentral gyri, as well as increased rCBF primarily in the right hemisphere within the middle temporal, superior temporal, and inferior frontal gyri, cerebellum, and thalamus, compared with the normal control group. CONCLUSION: These findings suggest that lateralized abnormalities in brain functioning are an important component of the pathophysiology of TGA. Lateralized abnormalities may disrupt functions that are relatively specific to the left hemisphere, including receptive language, symbolic representation, and the processing of local features in the environment, while preserving anterograde memory processes. Increased flow to the right hemisphere centered on regions that subserve the functions of expressive language and visuospatial processing, and may represent processes that compensate for flow reductions to the left hemisphere.

Simultaneous transient global amnesia and Takotsubo syndrome after death of a relative: a case report.

INTRODUCTION: Simultaneous occurrence of transient global amnesia and Takotsubo syndrome has been only rarely reported. Here we report another patient with a transient global amnesia and concomitant Takotsubo syndrome. CASE PRESENTATION: Our patient is a 64-year-old white man with a previous history of myocarditis from borreliosis who developed sudden-onset confusional state with perseverations and repetition of the same questions during a funeral for his brother-in-law. Upon neurological work-up and after spontaneous resolution of most of the neurological deficits, transient global amnesia was diagnosed. Blood tests revealed moderate renal insufficiency, elevated troponin-T, and elevated N-terminal prohormone of brain natriuretic peptide. Electrocardiography showed left anterior hemiblock and negative T-waves in V2-V6. Upon transthoracic echocardiography the apical type of a Takotsubo syndrome was suspected. Since coronary angiography was normal and electrocardiography and echocardiographic abnormalities resolved under candesartan, bisoprolol, acetyl-salicylic acid, and atorvastatin within a few days after onset, Takotsubo syndrome was diagnosed. CONCLUSIONS: Since Takotsubo syndrome may be associated with transient global amnesia a causal relation may exist. A possible trigger for both conditions could be severe emotional stress from the loss of a close relative. A possible common pathomechanism could be overstimulation of adrenergic receptors in the myocardium, the cerebrum, or the coronary or cerebral arteries. Whether pre-existing myocardial compromise promotes the development of Takotsubo syndrome requires further investigations.

[Idiopathic transient global amnesia]. / L'ictus amnésique idiopathique.

Transient global amnesia (TGA) is characterized by a severe disturbance of memory, occurring rapidly, lasting less than a day and mainly affecting elderly subjects. During its acute phase, it is characterized by a severe anterograde amnesia, partial retrograde amnesia and anxiety with repetition of the same questions. The diagnosis is purely based on patient's clinical features. Complimentary examinations are only requested when atypical symptoms are present. The pathophysiology of TGA remains unknown, but it appears to be related to transient disturbances of the perfusion and oxygenation of the hippocampal structures, following a precipitating factor (stress, effort...). Spontaneous recovery is usual in less than 24 hours and without sequelae. Relapse is rare. Nevertheless, TGA represents a psychological traumatism pathology for the patients and their family.

What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases.

Since the first reports of transient global amnesia (TGA) were published in 1956, several neuropsychological and functional imaging studies have shed light on different aspects of this neurological syndrome. By establishing diagnostic criteria, Hodges and Warlow (1990b) have made it far easier to identify clinical TGA-related features. However, no comprehensive survey has been yet carried out in order to validate their criteria/findings or provide information about previously unknown features. In the present paper, (i) we review the literature published since Hodges and Warlow's study and seek to characterize the demographic and clinical features of TGA more accurately, (ii) we report 142 personal TGA cases, with supplementary information regarding both episodes and patients, such as precipitating events, associated symptoms and personality, and (iii) we suggest the existence of different groups of TGA patients, on the basis of a hierarchical cluster analysis. This revealed that in women, episodes are mainly associated with an emotional precipitating event, a history of anxiety and a pathological personality. In men, they occur more frequently after a physical precipitating event. In younger patients, a history of headaches may constitute an important risk factor. No link was found with vascular risk factors. The relevance of each of the above-mentioned variables is discussed in the light of our classification. An extensive description of cases from both the literature and our patient population allows us to refine the characterization of clinical TGA features.

Selective affection of hippocampal CA-1 neurons in patients with transient global amnesia without long-term sequelae.

The aetiology, pathomechanisms and anatomical correlates of transient global amnesia (TGA) still remain obscure. Recently, focal MR-signal diffusion-weighted imaging (DWI) changes in the hippocampus have been described in patients with TGA, but the exact localization, long term outcome and pathophysiological nature of these lesions still remain unknown. The topography and time course of hippocampal DWI lesions in 41 TGA patients was studied using serial 3 T high-resolution MR-imaging and correlated to clinical and neuropsychometric results. Of these, 29 patients showed 36 DWI lesions with corresponding T(2) lesions in the hippocampus within a time window of 48 h after onset. Almost all lesions (94%; 34/36) were selectively found in the CA-1 sector (Sommer sector) of the hippocampal cornu ammonis. Most DWI lesions (8/10) were already detectable in the peri-acute phase <6 h after onset of symptoms. A follow-up study 4-6 months after the episode did not show evidence for residual structural sequelae of these lesions (n = 20/20). A venous MR angiography of the intracranial dural sinus showed an asymmetric venous drainage in 21/24 (88%) patients. In 11/16 (69%) patients with unilateral lesions, the asymmetry corresponded to the side of the DWI lesion. Significant episodic verbal memory deficits in the acute phase (n = 14/18) were associated with lesions of the dominant hemisphere while impairment of visuospatial memory was associated with lesions of the non-dominant hemisphere. Persistent neuropsychological sequelae were not detected 4-6 months after the episode (n = 16). This is the first prospective study combining high-resolution imaging and neuropsychometry analysing the detailed functional anatomy and outcome of hippocampal DWI/T(2) lesions in TGA supporting the view the TGA being a benign transient disorder. The TGA can be considered a model for a focal transient perturbation of memory circuits in the temporo-mesial region.