Chronic hippocampal subfield damage in transient global amnesia revealed by 7T MRI: All is not reversible?

Transient global amnesia (TGA) is a neurological condition characterized by temporary memory loss and classically associated with a reversible unilateral punctate focus of restricted diffusion in the cornu ammonis 1 (CA1) region of the hippocampus. Historically, the lesions were considered to be transient in nature with no long-term imaging abnormality. However, more recent studies have challenged the concept that there are no long-term neurological sequelae. In line with this evidence, we explore the role of ultra-high-resolution imaging using 7 Tesla MRI to evaluate for long-term imaging abnormalities in a 63-year-old woman with a typical clinical course and acute TGA imaging findings. The 7 Tesla MRI revealed a residual lesion on susceptibility-weighted imaging (SWI) with evidence of gliosis and volume loss at the site of the acute lesion in CA1 eight months after the acute episode. This case challenges the traditional mantra of TGA as a fully reversible condition with no long-term imaging findings, suggesting the need for further research using ultra-high-field MRI to determine TGA's potential long-term imaging sequelae and any association with neurocognitive sequelae.

Involvement of the default mode network in patients with transient global amnesia: multilayer network.

INTRODUCTION: We aimed to investigate the alterations in the multilayer network in patients with transient global amnesia (TGA). METHODS: We enrolled 124 patients with TGA and 80 healthy controls. Both patients with TGA and healthy controls underwent a three-teslar brain magnetic resonance imaging (MRI). A gray matter layer matrix was created using a morphometric similarity network derived from the T1-weighted imaging, and a white matter layer matrix was constructed using structural connectivity based on the diffusion tensor imaging. A multilayer network analysis was performed by applying graph theoretical analysis. RESULTS: There were no significant differences in global network measures between the groups. However, several regions, related to the default mode network, showed significant differences in nodal network measures between the groups. Multi-richness in the left pars opercularis, multi-rich-club degree in the right posterior cingulate gyrus, and weighted multiplex participation in the right posterior cingulate gyrus were higher in patients with TGA compared with healthy controls (15.47 vs. 12.26, p = 0.0005; 41.68 vs. 37.16, p = 0.0005; 0.90 vs. 0.80, p = 0.0005; respectively). The multiplex core-periphery in the left precuneus was higher (0.96 vs. 0.84, p = 0.0005), whereas that in the transverse temporal gyrus was lower in patients with TGA compared with healthy controls (0.00 vs. 0.02, p = 0.0005). CONCLUSION: We newly find the alterations in the multilayer network in patients with TGA compared with healthy controls, which shows the involvement of the default mode network. These changes may be related to the pathophysiology of TGA.

Transient global amnesia: 7 Tesla MRI reveals more hippocampal lesions with diffusion restriction compared to 1.5 and 3 Tesla MRI.

PURPOSE: To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI. METHODS: Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls. RESULTS: Thirteen TGA patients with a median age of 68.5 years (range 46-77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3-23 h) and 7 T (median 23 h after onset, range 15-46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1-28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T. CONCLUSION: Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

[Memory Loss - a Case of Sudden Amnesia]. / Herr B. kann sich nicht mehr erinnern ­ wenn das Gedächtnis gelöscht ist.

Memory Loss - a Case of Sudden Amnesia Abstract. Transient global amnesia (TGA) is a clinical diagnosis with typical signs of an anterograde and retrograde amnesia. The underlying mechanisms are yet unknown, different hypotheses are being discussed. Ultimately there is a temporary dysfunction of the hippocampi. Consistent with this, transient uni- or bilateral punctiform hyperintense lesions may be found on DWI-MRI sequences, usually without correlation on FLAIR-weighthed MR-images. Symptoms usually resolve within twenty-four hours. There is no need for a specific therapy. A prophylactic therapy, such as antithrombotic treatment, is not indicated. The prognosis is usually good, the risk of a recurrence is about 18%.

Increased biological antioxidant potential in the cerebrospinal fluid of transient global amnesia patients.

Oxidative stress may accompany the pathological process in transient global amnesia (TGA). We measured the biological antioxidant potential (BAP) in the cerebrospinal fluid (CSF) of TGA patients. We enrolled 13 TGA patients (7 men, 6 women; mean age 65.0 years [48-70 years]) and 24 control subjects (12 men, 12 women; mean age 38.2 years [17-65 years]; age did not correlate with csfBAP in this group). We performed brain MRI in all TGA patients, and CA1 lesions were noted by MRI in 5 subjects. We measured csfBAP, total antioxidant properties, in all TGA patients and controls. csfBAP levels were higher in TGA patients than in controls (p = 0.024, 0.028). csfBAP levels in TGA patients did not differ between MRI-positive and -negative subgroups. Elevated csfBAP levels were observed in TGA patients, suggesting that oxidative stress may have a role in the pathogenesis of TGA.

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.

A controlled Valsalva Maneuver causes neither Diffusion-Positive Hippocampal Lesions nor Clinical Symptoms after Transient Global Amnesia.

Valsalva maneuver (VM) precedes frequently transient global amnesia (TGA) and up to 84% of the patients with TGA present hippocampal diffusion-weighted imaging-positive (DWI+) lesions on brain magnetic resonance imaging (MRI). We studied 20 patients with TGA and hippocampal DWI+ lesions. Median age (range) of the patients was 67 (57-80) years and 55% were women. TGA had been preceded by a VM-associated activity in 14 patients (70%), and brain MRI had been performed at a median (range) of 47.5 (42-79) h after TGA. These patients underwent a second MRI after a controlled-induced VM at least 3 months after TGA. This MRI was performed at a median (range) of 46.8 (41-138) h after the controlled-induced VM. None of the patients who reproduced TGA symptoms presented new DWI+ lesions on the second MRI. In patients with a previous episode of TGA, VM cannot elicit TGA in isolation and the interplay of other simultaneous factors is needed.

Prolonged allocentric navigation deficits indicate hippocampal damage in TGA.

OBJECTIVE: To investigate long-term recovery of allocentric and egocentric spatial orientation as a sensitive marker for hippocampal and extrahippocampal network function in transient global amnesia (TGA). METHODS: A group of 18 patients with TGA performed an established real-space navigation paradigm, requiring allo- and egocentric spatial orientation abilities, 3 days (postacute stage) and 3 months (follow-up) after symptom onset. Visual exploration behavior and navigation strategy were documented by a gaze-controlled, head-fixed camera. Allo- and egocentric spatial orientation performance was compared to that of 12 age-matched healthy controls. Navigation-induced brain activations were measured using [18F]-fluorodeoxyglucose-PET in a subgroup of 8 patients in the postacute stage and compared to those of the controls. RESULTS: In the postacute stage, the patients navigated worse and had higher error rates than controls in allocentric (p = 0.002), but not in egocentric, route planning (p = 0.30), despite complete recovery of verbal (p = 0.58) and figural memory (p = 0.11). Until follow-up, allocentric navigation deficits improved, but higher error rates and reduced use of shortcuts persisted (p < 0.0001). Patients still exhibited relatively more fixations of unique landmarks during follow-up (p = 0.05). PET measurements during the postacute stage showed increased navigation-induced brain activations in the right hippocampus, bilateral retrosplenial, parietal, and mesiofrontal cortices, and cerebellar dentate nucleus in patients compared to controls (p < 0.005). CONCLUSIONS: Patients with TGA show selective and prolonged deficits of allocentric spatial orientation. Activations in right hippocampal and extrahippocampal hubs of the cerebral navigation network functionally substitute for the deficit in creating and updating the internal cognitive map in TGA.

Relationship between Cytotoxicity in the Hippocampus and an Abnormal High Intensity Area on the Diffusion-weighted Images of Three Patients with Transient Global Amnesia.

Objective An abnormal high intensity area (HIA) on diffusion-weighted imaging (DWI) indicates the presence of cytotoxic edema and has been reported to be observed in the hippocampus of patients with transient global amnesia (TGA). The appearance of an HIA on DWI is usually delayed after the onset of patients with amnesia in TGA; thus, the significance of the HIA was evaluated in patients with TGA. Methods Three adult TGA patients who had a unilateral HIA on DWI (right, n=2; left, n=1) were enrolled. These patients were hospitalized due to acute-onset amnesia. Amnesia subsided within 24 hours of hospitalization in all three patients. Results The HIA was confined to the upper lateral zone of the body in the unilateral hippocampus where the CA1 region exists. The lesions were confirmed after the improvement of amnesia in the three patients. The location of the lesions corresponded to the watershed area where the upper and lower hippocampal arteries were anastomosed. Conclusion Cytotoxicity caused by glutamate-mediated calcium influx in the neurons of the CA1 region was recently reported in the pathogenesis of TGA. Based on the pathogenesis, the cytotoxicity was considered to have been caused by calcium overload throughout the entire CA1 region, and amnesia occurred due to this cytotoxicity. The cytotoxicity was more marked in the lesions because of the lower blood flow in the watershed area and was prolonged after the function of the CA1 region (excluding the watershed area) improved, which led to cytotoxic edema in the lesions.

Cortical morphology in patients with transient global amnesia.

Objective: This study evaluated alterations in cortical morphology in patients with transient global amnesia (TGA). Materials and Methods: Diagnoses of TGA occurred at our hospital. Evaluation involved a structured interview to obtain clinical information and a brain magnetic resonance imaging scan. We analyzed whole-brain T1-weighted MRI data using FreeSurfer 5.1. Measures of cortical morphology, such as thickness, surface area, volume, and curvature were compared between patients with TGA and healthy controls. We also quantified the correlations between clinical variables and each measure of abnormal cortical morphology. Results: Seventy patients met the inclusion criteria. Compared to healthy controls, patients with TGA had significant alterations in cortical thickness in several regions of bilateral hemisphere. Moreover, several regions of cortical volumes in left hemisphere were significantly different between patients with TGA and healthy controls. In addition, there were significant correlations between the durations of episodes and cortical thickness, especially in the parietal cortex. However, there were no differences between groups in other measures of cortical morphology, including surface area and curvatures. Conclusions: We observed significant alterations in cortical morphology in patients with TGA; these alterations are implicated in the pathogenesis of TGA.

[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.

Obstruction of Venous Drainage Linked to Transient Global Amnesia.

Abnormal extracranial venous drainage modality has been considered an etiology of transient global amnesia (TGA). Evidence suggests that the transmission of the intrathoracic/intraabdominal pressure during a Valsalva maneuver (VM) is mainly through the vertebral venous system, and patency of internal jugular vein (IJV) is essential for venous drainage and pressure releasing. We hypothesize that obstruction of IJV venous drainage is a contributing factor in TGA pathogenesis. A magnetic resonance (MR) imaging protocol was used in 45 TGA patients and 45 age- and sex-matched controls to assess the morphologies of IJV, brachiocephalic vein (BCV) and asymmetry of transverse sinus (TS). The IJV was divided into the upper- and middle-IJV segments. Compared to the controls, TGA patients had significantly higher rates of moderate and severe compression/stenosis at the bilateral upper-IJV segment (left: 37.8% vs. 17.8%, P = 0.0393; right: 57.8% vs.15.6%, P<0.0012), in left BCV (60% vs. 8.9%, P<0.0004), and in TS hypoplasia (53.3%% vs. 31.1%, P = 0.0405). The prevalence of at least one site of venous compression/stenosis in IJV or BCV was significantly higher in patients than in controls (91.1% vs. 33.3%, P<0.0004). The diameter of the left TS in MRV, but not in T1 contrast imaging, was significantly smaller in TGA patients than in controls (0.31 ± 0.21 vs. 0.41 ± 0.19, P = 0.0290), which was compatible with downstream venous stenosis/obstruction. TGA patients have a higher prevalence of compression/stenosis of the bilateral IJV and the left BCV and TS hypoplasia, which is new evidence that supports the role of extracranial veins in TGA pathogenesis.

Selective neuronal vulnerability of human hippocampal CA1 neurons: lesion evolution, temporal course, and pattern of hippocampal damage in diffusion-weighted MR imaging.

The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n=50), limbic encephalitis (n=30), after status epilepticus (n=17), and transient global amnesia (n=53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.