Acute Transient Global Amnesia Research Articles

Vertebral artery hypoplasia and hemodynamic impairment in transient global amnesia: a case control study.

The aetiology of transient global amnesia (TGA) is still a matter of debate. Besides ischemia of the mesial temporal lobe including the hippocampus, migraine-like mechanisms, epileptic seizures affecting mnestic structures, or venous congestion in the (para) hippocampal area due to jugular vein insufficiency have been discussed. We assessed the diameters of the intracranial arteries of TGA patients compared to controls to identify differences that support the hypothesis of reduced hippocampal perfusion as a pivotal factor in the pathophysiology of TGA. We reviewed magnetic resonance imaging time of flight angiographies (TOF-MRA) that were acquired during in-patient treatment of 206 patients with acute TGA. The diameters of the vertebral artery (VA) in the V4 segment, the proximal basilar artery, and the internal carotid arteries were measured manually. We compared the findings with TOF-MRA images of an age and sex matched control group of neurological patients without known cerebrovascular pathology. In TGA patients the diameter of the right VA was significantly (p < 0.01) smaller compared to controls (2.09 mm vs. 2.35 mm). There were no significant differences in the diameters of the other vessels. Only the fetal variant of the posterior cerebral artery was slightly more common in TGA. The smaller diameter (hypoplasia) of the right VA supports the hypothesis of a contribution of hemodynamic factors to the pathophysiology of TGA. The fact that hypoplasia represents a congenital condition might be the explanation why previous studies failed to find an increased rate of the classical (acquired) vascular risk factors.

Ventral Anterior Cingulate Atrophy as a Predisposing Factor for Transient Global Amnesia.

This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset.

The objective was to systematically evaluate the sensitivity of diffusion-weighted magnetic resonance imaging (DW-MRI) for transient global amnesia (TGA) across various time frames compared to the reference-standard clinical criteria. All indexed publications related to TGA and MRI through June 2020 were retrieved by a medical librarian. Two independent reviewers identified original research studies of adults with a clinical diagnosis of TGA using Caplan and Hodges and Warlow criteria (reference standard) who were evaluated with DW-MRI. Pooled estimates and its 95% confidence intervals (CI) for the proportion of acute TGA patients with positive DW-MRI (i.e., sensitivity) were obtained using random-effects meta-analysis for various time frames. Quality assessment was performed using the revised Quality of Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. After screening 665 reports, we identified 81 potentially relevant studies. Twenty-three studies representing 1688 patients met eligibility criteria, but not all studies had data available for meta-analysis. The pooled sensitivity (also described as positivity rate) of DW-MRI was 15.6% (95% CI=2.6%-35.0%) between 0 and 12h from symptom onset, 23.1% (95% CI=6.1%-45.7%) at 0-24h, 72.8% (95% CI=40.8%-96.3) at 12-24h, 68.8% (95% CI=44.8%-88.8%) at 24-36h, 72.4% (95% CI=59.8%-83.5%) at 36-48h, 82.8% (95% CI=54.7%-99.6%) at 48-60h, 66.9% (95% CI=47.5%-83.9%) at 60-72h, and 72.0% (95% CI=30.1%-100.0%) at 72-96h. There was significant concern for risk of bias in the QUADAS-2 domains of patient selection and index test, yielding a low level of certainty in the pooled estimates. DW-MRI lesions are uncommon in patients with TGA early after symptom onset, but the sensitivity (i.e., positivity rate) of DW-MRI increases with time. Despite the limited quality of existing evidence, obtaining an early DW-MRI in patients with clinical diagnosis of TGA in the acute setting is likely a low-yield test.

Impaired semantic memory during acute transient global amnesia.

As a clinical model of hippocampal dysfunction, transient global amnesia (TGA) causes reversible memory disturbance. While episodic memory deficits in TGA patients have been extensively described, data regarding semantic memory involvement are sparse and contradictory. We report impaired semantic fluency performance in 16 patients with hippocampal lesions on MRI during acute TGA compared to their performance one day later and to that of 20 healthy subjects. Our findings support the involvement of the hippocampus in semantic retrieval.

What remains after transient global amnesia (TGA)? An ultra-high field 7 T magnetic resonance imaging study of the hippocampus.

The aim was to study whether ultra-high field 7 T magnetic resonance imaging (MRI) can demonstrate chronic focal defects in the hippocampus corresponding to the former acute diffusion-weighted imaging (DWI) lesions and to assess chronic T2-hyperintense hippocampal lesion load in transient global amnesia (TGA) patients. Follow-up of 7 T MRI of the hippocampus was performed in 13 patients with documented hippocampal DWI lesions (detected via 3 T MRI) after acute TGA. The location of the DWI lesions was transformed to 7 T T2 images after data co-registration. Additionally, the T2-hyperintense lesion load was estimated in each patient and compared with that of 13 healthy controls. Magnetic resonance imaging (7 T) was performed after a median of 4 months. No structural abnormality at the site of the previous TGA lesion was observed in any case. None of the controls showed DWI lesions. There was no significant difference between patients and controls concerning the number (P=0.67) or volume (P=0.45) of T2-hyperintense hippocampal lesions. Diffusion-weighted imaging lesions in patients with TGA do not provoke any visible sequelae and do not result in hippocampal cavities. The occurrence of incidental hippocampal T2 lesions after TGA is not more frequent than in controls.

Transient hippocampal CA1 lesions in humans impair pattern separation performance.

Day-to-day life involves the perception of events that resemble one another. For the sufficient encoding and retrieval of similar information, the hippocampus provides two essential computational processes. Pattern separation refers to the differentiation of overlapping memory representations, whereas pattern completion reactivates memories based on noisy or degraded input. Evidence from human and rodent studies suggest that pattern separation specifically relies on neuronal ensemble activity in hippocampal subnetworks in the dentate gyrus and CA3. Although a role for CA1 in pattern separation has been shown in animal models, its contribution in the human hippocampus remains elusive. In order to elucidate the contribution of CA1 neurons to pattern separation, we examined 14 patients with an acute transient global amnesia (TGA), a rare self-limiting dysfunction of the hippocampal system showing specific lesions to CA1. Patients' pattern separation performance was tested during the acute amnestic phase and follow-up using an established mnemonic similarity test. Patients in the acute phase showed a profound deficit in pattern separation (p < .05) as well as recognition memory (p < .001) that recovered during follow-up. Specifically, patients tested in a later stage of the amnesia were less impaired in pattern separation than in recognition memory. Considering the time dependency of lesion-associated hippocampal deficits in early and late acute stages of the TGA, we showed that the pattern separation function recovered significantly earlier than recognition memory. Our results provide causal evidence that hippocampal CA1 neurons are critical to pattern separation performance in humans.

Resting-state connectivity alterations during transient global amnesia.

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level

Enhanced cortisol secretion in acute transient global amnesia

IntroductionStress-related transient inhibition of memory formation in the hippocampus has been hypothesized as one of the underlying pathomechanisms of transient global amnesia (TGA). TGA episodes, during which patients cannot encode and recall new information (anterograde amnesia affecting episodic long-term memory), are frequently preceded by a psychologically or physically stressful event. MethodsWe measured salivary cortisol during acute TGA in 14 patients, as well as cortisol day-profiles and the effect of experimental exposure to stress (using the socially evaluated cold pressor test) on cortisol levels during the subacute phase. We assessed psychiatric comorbidity as well as depression, trait anxiety and chronic stress. These findings were compared with data of 20 healthy controls. FindingsNine patients reported a precipitating stressor and all 14 developed typical hippocampal lesions on follow-up MRI. During TGA, salivary cortisol levels were more than 3-fold higher compared to time-matched day levels. While there was no difference in mean cortisol levels of the diurnal rhythm, we found a significant interaction between groups during experimental stress exposure (p = 0.049) with the TGA group revealing a higher cortisol increase. The TGA group reported higher levels of depressive symptomatology (CES-D) and higher scores of chronic stress (TICS) compared with the control group and there was a significant correlation between cortisol increase during TGA and the results of self-rating according to the CES-D (r = 0.615; p = 0.004), as well as to the STAI (r = 0.702; p = 0.001). ConclusionOur findings of enhanced secretion of cortisol in acute TGA patients correlating with symptoms of depression and anxiety and a persisting hyperreactivity to experimental stress in the subacute phase support the hypothesis that stress might be significant for the pathogenesis of TGA.

Abnormal EEG Power Spectra in Acute Transient Global Amnesia: A Quantitative EEG Study.

Transient global amnesia (TGA) is a clinical syndrome characterized by retrograde and anterograde amnesia without other neurological deficits. Although electroencephalography (EEG) methods are commonly used in both clinical and research setting with TGA patients, few studies have investigated neurophysiological pattern in TGA using quantitative EEG (qEEG). The main aim of the present study was to extend these previous findings by exploring EEG power spectra differences between patients with acute TGA and healthy controls using the exact low-resolution brain electromagnetic tomography software (eLORETA). EEG was recorded during 5 minutes of resting state. Sixteen patients (mean age: 66.81 ± 7.94 years) during acute TGA and 16 healthy subjects were enrolled. All patients showed hippocampal or parahippocampal signal abnormalities in diffusion-weighted magnetic resonance imaging performed from 2 to 5 days after the onset of TGA. Compared with healthy controls, TGA patients showed a decrease of theta power localized in the temporal lobe (Brodmann areas, BAs 21-22-38) and frontal lobe (BAs 8-9-44-45). A decrease of EEG beta power in the bilateral precuneus (BA 7) and in the bilateral postcentral gyrus (BAs 3-4-5) was also observed in TGA individuals. Taken together, our results could reflect the neurophysiological substrate of the severe impairment of both episodic memory and autobiographical memory which affect TGA patients during the acute phase.

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.

Transient amnesic syndromes

Transient amnesic syndromes are striking clinical phenomena that are commonly encountered by physicians in acute medical settings. Diagnosis of such syndromes can be challenging, and their causes have been debated for over 50 years. Critical clinical distinctions, such as between transient global amnesia (TGA) and transient epileptic amnesia (TEA), as well as important clues to the underlying pathophysiology, have recently been revealed. TGA is characterized by the sudden onset of a profound anterograde and retrograde amnesia that lasts for up to 24 h, with neuroimaging after an acute TGA event showing transient perturbation of specific hippocampal circuits that are involved in memory processing. Some cases of transient amnesia are attributable to focal seizure activity and are termed TEA, which has a clinical presentation similar to that of TGA, but can be distinguished from the latter by the brevity and frequency of amnesic attacks. Moreover, TEA carries a risk of persistent memory impairment that can be mistaken for dementia. Here, we summarize clinically relevant aspects of transient amnesic syndromes, giving practical recommendations for diagnosis and patient management. We describe results from imaging and epidemiological studies that have shed light on the functional anatomy and pathophysiological mechanisms underlying these conditions.

Levels-of-processing effects on recollection and familiarity during transient global amnesia and after recovery.

The aim of the present study was to investigate the pattern of recollection and familiarity deficits and the modulation of recognition memory performance by the depth of encoding (deep vs. shallow) in transient global amnesia (TGA). Ten patients with TGA and 11 control subjects were assessed during the acute stage and after recovery 7 to 19 days later. Both recollection and familiarity were impaired in the acute stage and showed significant, albeit not complete, recovery by the time of the postacute assessment. The patients did, however, show a significant levels-of-processing effect, which was significantly reduced in acute TGA, but not at follow-up. The significant levels-of-processing effect during acute TGA might be linked to recruitment of the prefrontal cortex.

Focal MR spectroscopy of hippocampal CA-1 lesions in transient global amnesia

The pathomechanisms of transient global amnesia (TGA) remain enigmatic. Focal MR signal diffusion changes in the CA-1 sector of the hippocampus have been described in transient global amnesia, but the pathophysiologic correlate of these lesions is unknown. We studied the metabolic spectra of diffusion lesions in the CA-1 sector hippocampus of seven patients with TGA using MR spectroscopy (MRS) between 24 and 72 hours after onset and 2 to 5 months later. The amnestic deficit was studied using a neuropsychometric test battery. Four out of seven patients with an acute TGA showed a diffusion lesion with a corresponding T2 lesion in the CA-1 sector of the hippocampus. Selective hippocampal MRS of diffusion lesions showed a lactate peak in three of four patients, but not in patients without a diffusion lesion. The NAA/creatine ratio was normal. Lactate as a marker of anaerobic glycolysis indicates acute metabolic stress of CA-1 neurons in TGA whereas long-term neuronal metabolic changes are not found. This implies that the acute effect on hippocampal CA-1 neurons is the functional correlate of a transient global amnesia reflecting a transient perturbation of memory relevant circuits in the hippocampus.

Understanding medial temporal activation in memory tasks: Evidence from fMRI of encoding and recognition in a case of transient global amnesia

We used fMRI to examine the activation patterns of patient AE during encoding and recognition of visual scenes during an episode of transient global amnesia (TGA) and 3 months later. Controls (n = 5) showed bilateral (R > L) activation in parahippocampal and fusiform gyri during encoding and right-sided activation in the same regions associated with recognition of previously viewed scenes. AE showed a similar pattern at follow-up. During acute TGA, when performance was profoundly impaired, AE showed no medial temporal activation associated with encoding of new scenes or recognition of old scenes. In both contrasts, the percent signal change in relevant medial temporal regions was more than three standard deviations below the control sample mean. She did, however, show striking bilateral hippocampal activation for recognition attempts (old + new scenes > baseline) even though retrieval was unsuccessful (55% recognition accuracy). This finding was unique to AE on this occasion. This is the first study to document normalization of both encoding and recognition activation patterns in TGA. Furthermore, the strong hippocampal activation during unsuccessful retrieval highlights important issues in interpreting memory-related activations, particularly in dysfunctional systems.

Evolution of hippocampal CA‐1 diffusion lesions in transient global amnesia

Selective focal MR-Signal (diffusion-) changes in the CA-1 sector of the hippocampus have been described in transient global amnesia (TGA), but the pathophysiological substrate of these lesions is largely unknown. As several imaging and epidemiological findings point to a vascular origin an analysis of the temporal evolution of the hippocampal apparent diffusion coefficient (ADC) changes may offer new understanding of the pathomechanisms of TGA. The time course of the ADC of hippocampal DWI lesions in TGA patients was studied using serial 3 T high-resolution MR-imaging within 1-10 days as well as 4-6 months after TGA. ADC values from 76 MR-studies were analyzed and expressed as ratio ADC (rADC) in reference to the unaffected hemisphere. Twenty-nine patients with TGA showed 34 DWI lesions with corresponding T2 lesions in the CA-1 sector of the hippocampal cornu ammonis within a time window of 24-72 h after onset. Ratio ADC decreased below 1.0 (0.66 +/- 0.08) 24 h after the acute TGA episode and did show a further significant decrease to 0.57 +/- 0.1 after 3 days (p < 0.05). After 72 h, rADC increased and normalized around day 10 with rADC values of 1.0 (p < 0.05). The temporal evolution of the rADC in hippocampal signal changes in TGA shows a time course previously described for ischemic lesions in human stroke patients. This might imply a vascular origin of diffusion changes leading to a transient perturbation of memory relevant circuits in the hippocampus.