Amnesia global transitoria: una entidad infrecuente pero presente en Pediatría / Transient global amnesia: an infrequent entity but present in Pediatrics

Introducción: La amnesia global transitoria es una entidad caracterizada por la aparición súbita de amnesia anterógrada con amnesia retrógrada variable, conservando intacta la memoria inmediata. No asocia otros déficits neurológicos. La recuperación es progresiva en pocas horas, habitualmente menos de 12, aunque suele persistir amnesia del episodio y presentar posteriormente cefalea leve. Caso clínico. Niño de 10 años, sin antecedentes de interés, que consulta en Urgencias por aparición brusca de amnesia retrógrada de las últimas 48 horas, así como incapacidad para la fijación de nueva información. Se mostraba ansioso y desorientado, y repetía la misma pregunta varias veces. La exploración neurológica por lo demás era estrictamente normal y negaba cefalea u otra sintomatología asociada. No antecedente de traumatismo craneoencefálico. Se realiza analítica sanguínea y gasometría venosa, sin alteraciones significativas; tóxicos en orina, negativos; TAC cerebral que descarta patología intracraneal aguda y punción lumbar, que es normal. Ingresa en planta de hospitalización con evolución favorable, con cese espontáneo de la clínica a las 8 horas, permaneciendo amnesia del episodio, con resto de la memoria conservada. Comentarios. La fisiopatología de la amnesia global transitoria no está del todo aclarada, aunque hay trabajos que sugieren un origen vascular de la misma, produciéndose durante estos episodios una hipoperfusión del lóbulo temporal medial. Es una entidad típica de adultos de mediana edad y ancianos siendo excepcional en pediatría. Sin embargo, debemos considerar este diagnóstico ante niños con clínica típica, normalidad de la neuroimagen y resolución espontánea de los síntomas.(AU)

Introduction: Transient global amnesia is an entity characterized by the sudden onset of anterograde amnesia with variable retrograde amnesia, preserving immediate memory intact. It is not associated with other neurological deficits. Recovery is progressive in a few hours, usually less than 12 hours, although amnesia of the episode usually persists and later presents mild headache. Case report. A 10-year-old boy, with no previous history of interest, consulted the emergency department for sudden onset of retrograde amnesia of the last 48 hours, as well as inability to fix new information. He was anxious and disoriented and repeated the same question several times. The neurological examination was otherwise strictly normal, and he denied headache or other associated symptoms. There was no history of cranioencephalic trauma. Blood analysis and venous blood gas analysis were performed, with no significant alterations; urine toxins were negative; brain CAT scan ruled out acute intracranial pathology and lumbar puncture was normal. She was admitted to the hospital ward with favorable evolution, with spontaneous cessation of the clinical symptoms after 8 hours, remaining amnesia of the episode, with the rest of the memory preserved. Comments. The pathophysiology of transient global amnesia has not been fully clarified, although some studies suggest a vascular origin, with hypoperfusion of the medial temporal lobe occurring during these episodes. It is a typical entity of middle-aged and elderly adults, being exceptional in pediatrics. However, we should consider this diagnosis in children with typical clinical symptoms, normal neuroimaging and spontaneous resolution of symptoms.(AU)

Transient Global Amnesia.

Transient global amnesia (TGA) is a clinical syndrome characterized by anterograde amnesia, mild retrograde amnesia, and confusion up to 24 hours. Most commonly seen in patients older than 50 years, TGA results from the temporary impairment of short-term memory formation. Clinically, patients have time disorientation and often ask repeated questions regarding the day's events. Vomiting, headache, blurry vision, dizziness, and nausea may be present. A physically or psychologically stressful precipitating event, such as emotional stress, significant physical exertion, exposure to extreme temperatures, high-altitude conditions, Valsalva maneuver, acute illness, or sexual intercourse, is often the cause. The pathophysiology of TGA is not well understood but may be related to impaired venous drainage of the hippocampus. The diagnosis is primarily clinical, but recent studies suggest that magnetic resonance imaging may be helpful. TGA is self-limited and resolves within 24 hours. There is no established treatment for episodes. The lifetime recurrence rate is 2.9% to 23.8%. Recent evidence suggests an association between TGA and migraine headaches as well as takotsubo cardiomyopathy. No apparent increased risk of cerebrovascular events occurs in patients who have had an episode of TGA. There is conflicting evidence as to whether an episode of TGA predisposes to future seizures or dementia.

Aberrantly higher functional connectivity in the salience network is associated with transient global amnesia.

Triple intrinsic brain networks including the salience network (SN), default mode network (DMN), and central executive network (CEN), are known to be important in human cognition. Therefore, investigating those intrinsic brain networks in transient global amnesia (TGA) may offer novel insight useful for the pathophysiology of TGA. Fifty TGA patients underwent the resting state functional magnetic resonance imaging (rsfMRI) within 24 h, at 72 h, and 3 months after TGA onset. Twenty-five age, gender matched controls also underwent rsfMRI. Within 24 h of TGA onset, TGA patients showed greater functional connectivity in the SN and lower functional connectivity in the DMN, while relatively preserved functional connectivity was observed in the CEN. Interestingly, TGA patients continued to show decreased connectivity in the DMN, while no alterations were shown in the SN 72 h after illness onset. Three months after TGA onset, alterations of functional connectivity in the SN or the DMN were normalized. Our findings suggest that TGA is associated with transient greater functional connectivity in the SN and lower connectivity in the DMN.

Structural Connectivity and Cortical Thickness Alterations in Transient Global Amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is a sudden onset of anterograde and retrograde amnesia. We aimed to assess differences in terms of cortical thickness and structural brain connectome between patients with TGA (at acute and delayed postrecovery stages) and matched controls. MATERIALS AND METHODS: We report on 18 consecutive patients with TGA who underwent 3T MR imaging, including DTI and MPRAGE sequences, at the acute (mean delay postonset: 44 hours) and delayed post-recovery (mean delay: 35 days) stages. Structural connectome was assessed in patients with TGA and in 18 age- and sex-matched controls by using probabilistic fiber- tracking and segmentation of 164 cortical/subcortical structures ("nodes"). Connectivity graphs were computed and global network metrics were calculated. Network-based statistical analysis (NBS) was applied to compare patients with TGA at each stage with controls. We also compared cortical thickness between patients with TGA and healthy controls. RESULTS: Global network metrics were not altered in patients with TGA. NBS-analysis showed structural connectome alterations in patients with TGA compared with controls, in core regions involving the limbic network, with 113 nodes and 114 connections (33 left intrahemispheric, 31 right intrahemispheric, and 50 interhemispheric connections) showing significantly decreased structural connectivity (P < .05 NBS corrected, t-values ranging from 3.03 to 8.73). Lower cortical thickness compared with controls was associated with these structural alterations in patients with TGA, involving the orbitofrontal, cingulate, and inferior temporal cortices. All the abnormalities were visible at both acute and delayed postrecovery stages. CONCLUSIONS: Our preliminary study suggests there are structural abnormalities of the limbic network in patients with TGA compared with controls, including decreased structural connectivity and cortical thickness.

Serum cortisol levels in patients with a transient global amnesia.

Transient global amnesia (TGA) can be triggered by a high level of blood cortisol. We assessed whether patients had a higher level of cortisol during the TGA than shortly after. We included 52 patients, 21 with blood collected during the TGA episode and 31 shortly thereafter. We compared these two groups after adjustment for time of blood collection. The cortisol level was significantly higher in the per-ictal group (P=0.03) and negatively correlated with the time elapsed from symptom onset (P=0.005). The results are consistent with of the hypothesis of a hyperreactivity of the hypothalamic-pituitary-adrenal axis.

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.

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.

Transient global amnesia: clinical features and prognostic factors suggesting recurrence.

OBJECTIVE: The risk of recurrence of new amnesia events in patients having previously experienced transient global amnesia (TGA) ranges between 2.9-23.8%. Our objective was to search for recurrence predictors in TGA patients. METHODS: Retrospective analysis to identify recurrence predictors in a cohort of 203 TGA patients from a single center in Buenos Aires, Argentina, diagnosed between January 2011 and March 2017 Clinical features and complementary studies (laboratory results, jugular vein Doppler ultrasound and brain MRI) were analyzed. Comparison between patients with recurrent versus single episode TGA was performed, applying a multivariate logistic regression model. RESULTS: Mean age at presentation was 65 years (20-84); 52% were female. Median time elapsed between symptom onset and ER visit was two hours, with the average episode duration lasting four hours. Mean follow-up was 22 months. Sixty-six percent of patients referred to an identifiable trigger. Jugular reflux was present in 66% of patients; and 22% showed images with hippocampus restriction on diffusion-weighted MRI. Eight percent of patients had TGA recurrence. Patients with recurrent TGA had a more frequent history of migraine than patients without recurrence (37.5% vs. 14%; p = 0.03). None of the other clinical characteristics and complementary studies were predictors of increased risk of recurrence. CONCLUSIONS: Patients with migraine may have a higher risk of recurrent TGA. None of the other clinical characteristics evaluated allowed us to predict an increased risk of recurrence. Although the complementary studies allowed us to guide the diagnosis, they did not appear to have a significant impact on the prediction of recurrence risk.

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.

Transient global amnesia: clinical features and prognostic factors suggesting recurrence / Amnesia global transitoria: características clínicas y factores pronósticos sugestivos de recurrencia

ABSTRACT The risk of recurrence of new amnesia events in patients having previously experienced transient global amnesia (TGA) ranges between 2.9-23.8%. Objective: Our objective was to search for recurrence predictors in TGA patients. Methods: Retrospective analysis to identify recurrence predictors in a cohort of 203 TGA patients from a single center in Buenos Aires, Argentina, diagnosed between January 2011 and March 2017 Clinical features and complementary studies (laboratory results, jugular vein Doppler ultrasound and brain MRI) were analyzed. Comparison between patients with recurrent versus single episode TGA was performed, applying a multivariate logistic regression model. Results: Mean age at presentation was 65 years (20-84); 52% were female. Median time elapsed between symptom onset and ER visit was two hours, with the average episode duration lasting four hours. Mean follow-up was 22 months. Sixty-six percent of patients referred to an identifiable trigger. Jugular reflux was present in 66% of patients; and 22% showed images with hippocampus restriction on diffusion-weighted MRI. Eight percent of patients had TGA recurrence. Patients with recurrent TGA had a more frequent history of migraine than patients without recurrence (37.5% vs. 14%; p = 0.03). None of the other clinical characteristics and complementary studies were predictors of increased risk of recurrence. Conclusions: Patients with migraine may have a higher risk of recurrent TGA. None of the other clinical characteristics evaluated allowed us to predict an increased risk of recurrence. Although the complementary studies allowed us to guide the diagnosis, they did not appear to have a significant impact on the prediction of recurrence risk.

RESUMEN El riesgo de recurrencia de nuevos eventos de amnesia en pacientes que han experimentado previamente Amnesia Global Transitoria (AGT) oscila entre el 2.9-23.8%. Objetivo: Nuestro objetivo fue buscar predictores de recurrencia en pacientes con AGT. Métodos: Análisis retrospectivo de una cohorte de 203 pacientes con AGT de un único centro en Buenos Aires, Argentina, diagnosticados entre enero-2011 y marzo-2017 Se analizaron las características clínicas y los estudios complementarios (laboratorio, Doppler de vena yugular y RM encéfalo). Se comparó el grupo de AGT recurrente versus episodio único, aplicando un modelo de regresión logística multivariada. Resultados: la edad promedio de presentación fue de 65 años (20-84); 52% mujeres. La mediana del tiempo transcurrido entre el inicio de los síntomas y la visita a la sala de emergencia fue de 2 horas, con una duración promedio del episodio de 4 horas. El seguimiento medio fue de 22 meses. 66% de los pacientes tuvieron un desencadenante identificable. El reflujo yugular estuvo presente en el 66% de los pacientes y el 22% mostró imágenes restrictivas en DWI a nivel hipocampal. 8% de los pacientes presentaron recurrencia. Los pacientes con AGT recurrente tuvieron un historial de migraña más frecuente (37.5% vs. 14%; p=0.03). Ninguna de las otras características clínicas y estudios complementarios fueron predictores de mayor riesgo de recurrencia. Conclusiones: los pacientes con migraña pueden tener un mayor riesgo de recurrencia de AGT. Ninguna de las otras características clínicas evaluadas nos permitió predecir un mayor riesgo de recurrencia. Aunque los estudios complementarios nos permitieron orientar el diagnóstico, no pareció tener un impacto significativo en la predicción del riesgo de recurrencia.

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.

Enhanced cortisol secretion in acute transient global amnesia.

INTRODUCTION: Stress-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. METHODS: We 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. FINDINGS: Nine 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). CONCLUSION: Our 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.

Juvenile absence epilepsy relapsing as recurrent absence status, mimicking transient global amnesia, in an elderly patient.

We describe a 68-year-old woman who had typical absence seizures since 14 years of age. The absences were refractory to treatment and persisted into adulthood, with no seizure-free periods until seizure control at 59 years of age. After six years of being seizure-free, she presented with an episode characterized by mental confusion, abnormal behaviour, and amnesia, lasting for several hours. An EEG performed the day after, when the patient had already recovered, was unremarkable. The episode was interpreted as transient global amnesia. After two and three years, respectively, she presented with two analogous episodes lasting >24 hours. An EEG disclosed, on both occasions, subcontinuous generalized spike-and-wave discharges, consistent with absence status epilepticus (AS). The last episode occurred at 68 years of age and was successfully treated with intravenous lorazepam. After one month of follow-up, no further episodes occurred. AS is common in juvenile absence epilepsy, however, our patient showed a rather atypical course, characterized by refractory and persistent absences during adolescence and adulthood, and a tendency for AS to recur with no more absences in later life. Despite the known epilepsy history, AS episodes were initially misdiagnosed. Moreover, EEG recording and subsequent treatment were not performed until the second day of status.

Is Transient Global Amnesia a Network Disease?

BACKGROUND: We evaluated a brain network using graph theoretical analysis and microstructural abnormalities of the white matter in patients with transient global amnesia (TGA). METHODS: Twenty patients with TGA and healthy control subjects were recruited, and they underwent diffusion tensor imaging (DTI) scans. Graph theory was applied to obtain network measures based on DTI data. We investigated the network measures and microstructural abnormalities of white matter using tract-based spatial statistics (TBSS) analysis in the patients with TGA. RESULTS: Measures of global topology were not different between the patients with TGA and healthy subjects. However, there were significant differences of hubs organization; the strength of the right superior and inferior orbitofrontal, the right inferior frontal operculum, the left superior parietal, and left postcentral gyrus, the cluster coefficient of the right middle orbitofrontal and left inferior parietal gyrus, the betweenness centrality of the left angular gyrus, and the pagerank centrality of the right superior and inferior orbitofrontal, right inferior frontal operculum, left superior parietal, and left postcentral gyrus in the patients with TGA were significantly lower than those in healthy subjects. Regarding the analysis of the white matter microstructure with TBSS, there were no differences in the fractional anisotropy and mean diffusivity values between the 2 groups. CONCLUSIONS: We newly identify a reorganization of network hubs of the brain network in patients with TGA, especially in the regions of the default-mode network. These alterations of the brain network may play a role in the pathophysiologic mechanism underlying TGA and suggest that TGA is a network disease.

Comprehensive Ultrasound Assessment of the Craniocervical Circulation in Transient Global Amnesia.

OBJECTIVES: Structural changes and metabolic stress have been reported on diffusion-weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA. METHODS: One hundred patients with TGA and 50 age- and sex-matched control participants underwent ultrasound examinations of the cervicocranial circulation. RESULTS: The most significant risk factor for TGA was arterial hypertension (P < .01). There were no significant atherosclerotic lesions on the large arteries of the neck (mean internal carotid artery stenosis ± SD, 28.7% ± 11.7%) or on the large intracerebral arteries (good structural and hemodynamic status; P > .05). Rarely detected microembolic signals or a right-left cardiopulmonary shunt excluded an emboligenic mechanism of TGA (P > .05). The internal jugular vein valves were incompetent in 54% of patients with TGA, and this condition was associated with an increased risk of TGA (odds ratio, 4.16; 95% confidence interval, 1.91-9.04). The mean values of the breath holding index and pulsatility index, as parameters of small-vessel function, were within normal ranges and without differences between the TGA and control groups (P > .05). CONCLUSIONS: Our ultrasound examination did not detect significant structural atherosclerotic changes of cervicocranial arteries, and an emboligenic mechanism was excluded. Only a significant rise of blood pressure in TGA and significant valvular insufficiency of the internal jugular vein were established. New research should clarify whether these simultaneous functional circulatory changes have relevance for metabolic stress in the cornu ammonis of the hippocampus.

Vascular Risk Factors and Internal Jugular Venous Flow in Transient Global Amnesia: A Study of 165 Japanese Patients.

BACKGROUND: The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. SUBJECTS AND METHODS: TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). RESULTS: Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference (P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. CONCLUSION: Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA.