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.

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.

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.

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.

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).

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.

Isolated punctuate hippocampal infarction and transient global amnesia are indistinguishable by means of MRI.

Background Small punctuate lesions in the hippocampus on diffusion-weighted images are a typical finding in transient global amnesia. Consequently, it has been suggested that diffusion-weighted images findings might corroborate the diagnosis of transient global amnesia. However, isolated punctuate hippocampal infarction might be a differential diagnosis of transient global amnesia. Aim Evaluation of isolated punctuate hippocampal infarction frequency and comparison of its clinical presentation and MRI findings to transient global amnesia. Methods From an MRI database, we identified 10 patients with isolated punctuate hippocampal infarction and compared these to 12 patients with transient global amnesia with diffusion-weighted images lesion with regard to clinical symptoms and MRI findings. Results Disorientation and memory deficits were more common in transient global amnesia patients, whereas dysphasia/aphasia and vertigo were more common in hippocampal infarction patients. MRI findings in isolated punctuate hippocampal infarction and transient global amnesia did not differ significantly, neither regarding the affected hemisphere, lesion distribution, size, nor relative ADC values. Conclusions Differentiation of isolated punctuate hippocampal infarction and transient global amnesia based on neuroimaging findings is not possible. Thus, in the case of isolated punctuate hippocampal diffusion-weighted images lesions the final diagnosis of hippocampal infarction or transient global amnesia should be based on the clinical presentation.

Influence of depressive symptoms on memory in transient global amnesia.

INTRODUCTION: Recent studies have shown that patients with transient global amnesia (TGA) experience a depressive mood during the episode. However, little evidence has been found of possible mood congruency effects on memory, which are probably masked by the massive anterograde amnesia. An implicit assessment could provide a means of settling this question. METHODS: First, we measured patients' emotional states on psychopathological scales. Second, we administered a lexical decision task to assess three priming effects: Semantic priming (SP; table-chair), emotional priming (EP; murder-garbage), and emotional plus semantic priming (ESP; cemetery-coffin). RESULTS: Patients displayed a more depressed mood than controls. For patients, we found a SP effect in the ESP condition and a striking inhibition effect (i.e., negative target recognized more slowly when preceded by a negative prime rather than a neutral one) in the EP condition. For controls, a priming effect was found in the SP and ESP conditions, but not the EP condition. Finally, whereas the priming effect was greater in SP than in the other two conditions for controls, for patients it was the EP condition that stood out from the other two, being the only condition that led to an inhibition effect. CONCLUSIONS: We highlighted a mood congruency effect in TGA which could impel patients to focus their attention on negative information. While the negative valence of items always led to a slowdown in reaction times for both patients and controls, attesting to a negativity bias, this bias was greater in patients, leading to an inhibition effect.

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology.

A rare case of aortic dissection presenting as pure transient global amnesia.

Transient global amnesia (TGA) is a well-described neurological phenomenon. Clinically, it manifests with the sudden onset of a paroxysmal, transient loss of anterograde memory and disorientation but with intact consciousness. Typically, symptoms last for only a few hours. We present an unusual case of aortic dissection presenting with pure TGA in a patient, who had a positive outcome. This is the second case report of a patient with aortic dissection presenting with pure TGA syndrome, but it is the first case in which the patient survived.

[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.

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.

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 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.

Mental simulation of future scenarios in transient global amnesia.

Researchers exploring mental time travel into the future have emphasized the role played by episodic memory and its cerebral substrates. Recently, owing to controversial findings in amnesic patients, this role has become a matter of intense debate. In order to understand whether episodic memory is indeed crucial to future thinking, we assessed this ability in 11 patients during an episode of transient global amnesia (TGA), a unique and severe amnesic syndrome that primarily affects episodic memory. In the first of two experiments, TGA patients were asked to recall personal past events as well as to imagine personal future events, without any guidance regarding content. Under this condition, compared with controls, they provided fewer past and fewer future events, and the latter were less closely related to their personal goals. Furthermore, TGA patients׳ descriptions of past and future events were scant, containing fewer descriptive elements in total and fewer internal details. In order to assess whether TGA patients might have been basing their future event narratives on their general knowledge about how these events usually unfold, in our second experiment, we asked them to imagine future events in response to short descriptions of common scenarios. Under this condition, inherently eliciting less detailed descriptions, not only were all the TGA patients able to describe common events as happening in the future, but their narratives contained comparable amounts of internal detail to those of controls, despite being less detailed overall. Taken together, our results indicate that severe amnesia interferes with TGA patients׳ ability to envisage their personal past and future on a general level as well as in detail, but less severely affects their ability to imagine common scenarios, which are not related to their personal goals, probably owing to their preserved semantic memory, logical reasoning and ability to create vivid mental images.

Just do it! How performing an action enhances remembering in transient global amnesia.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a massive episodic memory deficit that spares other cognitive functions. As such, it provides a unique human amnesia model for testing the enactment effect (i.e., better memory for performed actions than for verbally encoded sentences). Our main aim was to test whether the enactment effect is preserved in TGA patients, both to have a better understanding and to test the robustness of this effect in a massive amnesia. Object-action pairs were encoded under four conditions: verbal, experimenter-performed, and two enacted conditions (self-performed and self-performed with choice). We tested object-action pair retrieval using cued recall (CR) and recognition tasks, and source memory using a free recall task. We also assessed binding, executive functions, short-term memory, episodic memory, anxiety and mood. We run correlations to control for their putative effects on memory for action. Data were collected from 24 patients, 16 of whom were examined during the acute phase and eight the day-after, as well as from 18 healthy controls. The memory performances of the patients in the acute phase improved for both (i) the CR score, between the verbal, experimenter-performed and self-performed with choice conditions, and (ii) the total recognition score, between the verbal condition and the two enacted conditions. Correlations were found between self-performed task (SPT) enhancement and both the binding and anxiety. In spite of their severely impaired episodic memory, patients with TGA benefit from the enactment effect. These results are discussed in relation to the role of motor components and episodic integration in memory for actions. We suggest that enactment effect can be used in clinical practice and rehabilitation, possible even for patients with a massive memory impairment.