A case report on concomitant reversible cerebral vasoconstriction syndrome and transient global amnesia.

Reversible Cerebral Vasoconstriction Syndrome clinically presents as severe headaches with or without neurological deficits accompanied by multilocal caliber variation of the cerebral arteries on imaging studies. Transient Global Amnesia is a benign neurological condition that implies sudden temporary antero- and retrograde amnesia. The exact pathophysiological mechanisms involved in transient global amnesia and reversible cerebral vasoconstriction syndrome remain unclear but suggest similar pathways as both can be triggered by factors that activate the sympathetic nervous system. We herein discuss a potential relationship of the two conditions in a 65-year-old woman that initially presented herself to the emergency department with temporary memory impairment, indicating Transient Global Amnesia. Four days later, the patient revealed a thunderclap headache accompanied by a subarachnoid hemorrhage with transient segmental narrowing of the arteries of the anterior circulation on neuroimaging. In this case report we hypothesize that Reversible Cerebral Vasoconstriction Syndrome might be a potential cause for the clinical symptoms and imaging patterns with Transient Global Amnesia as a possible prodromal stage of Reversible Cerebral Vasoconstriction Syndrome.

Automated CT perfusion analysis reveals medial temporal perfusion abnormalities during transient global amnesia.

INTRODUCTION: The underlying pathophysiology of Transient global amnesia (TGA) remains elusive. Reports of perfusion abnormalities in TGA were inconsistent, but semi-automated analysis of perfusion CT (CTP) may improve reliability and precision of perfusion deficit detection. METHODS: Per institutional protocol, all TGA patients undergo multiphasic contrast-CT with arch to vertex CT angiography, intracranial CT venography, MRI, and EEG upon admission. During the study period consecutive patients diagnosed with TGA underwent CTP during the early acute amnestic phase. We retrospectively reviewed the clinical and radiological findings. RESULTS: Five patients (3 female. median age 71, range 47-74) fulfilled entry criteria. Automated CTP analysis revealed the absence of an ischemic core (defined by CBF < 30%) or conventionally defined clinically relevant hypoperfusion area (defined by Time-to-maximum (Tmax) >6 s) in any of the patients. However, four of the five patients demonstrated territories of benign oligemia defined as Tmax>4 s in areas supplied by the Posterior Cerebral Artery. Three of these four patients had clear involvement of the bilateral medial temporal lobes. None of the patients had epileptic activity on their EEG. Both CTA and MRI were normal apart for small foci of restricted diffusion in the hippocampus of four patients. DISCUSSION: Deficits in perfusion were found in the hippocampi of 60% of patients in the acute phase of TGA using automated image analysis software. This method may provide a quick and simple method to detect these abnormalities. These perfusion abnormalities could help solidify the diagnosis at an early stage and may advance our understanding of this elusive syndrome.

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.

The link between reversible cerebral vasoconstriction syndrome and transient global amnesia.

Reversible cerebral vasoconstriction syndrome (RCVS) and transient global amnesia (TGA) are acute and self-limiting intra-cerebral conditions. Although previously studied as independent phenomena, there are increasing reports of co-occurrence of these two pathologies. We report a 55-year-old male who presented to the hospital with recurrent thunderclap headaches over the course of 1 week with sudden onset of anterograde memory loss. His medications included a selective serotonin reuptake inhibitor and intermittent use of pseudoephedrine. On examination he was amnestic to recent events and notably perseverating. Magnetic resonance imaging of the brain without contrast showed a small, punctate focus of restricted diffusion in the left hippocampus. He was diagnosed with TGA based on his clinical presentation. His headaches and amnesia resolved over the next 12 h throughout the course of his stay with acetaminophen and oral verapamil and he was discharged. Repeat computed tomography angiogram at 2 weeks revealed diffuse and segmental narrowing of the anterior and posterior intracranial circulation, which resolved on follow-up imaging at 3 months, confirming RCVS. The acute and reversible nature of these conditions and increasing reports of co-occurrence suggests a common pathophysiologic link. We review the literature highlighting similar cases and the presumed pathophysiology.

Network localization of transient global amnesia beyond the hippocampus.

BACKGROUND: Transient global amnesia is common in the older adult, but the cause and mechanism remain unclear. Focal brain lesions allow for causal links between the lesion location and resulting symptoms, and we based on the reported TGA-causing lesions and used lesion network mapping to explore the causal neuroanatomical substrate of TGA. METHODS: Fifty-one cases of transient global amnesias with DWI lesions from the literature were identified, and clinical data were extracted and analyzed. Next, we mapped each lesion volume onto a reference brain and computed the network of regions functionally connected to each lesion location using a large normative connectome dataset. RESULTS: Lesions primarily occurred in the hippocampus, and in addition to the hippocampus, there are also other locations of TGA-causing lesions such as the cingulate gyrus, anterior thalamic nucleus (ATN), putamen, caudate nucleus, corpus callosum, fornix. More than 90% of TGA-causing lesions inside the hippocampus were functionally connected with the default mode network (DMN). CONCLUSION: Structural abnormality in the hippocampus was the most consistently reported in TGA, and besides the hippocampus, lesions occurring at several other brain locations also could cause TGA. The DMN may also be involved in the pathophysiology of TGA. According to the clinical and neuroimaging characteristics, TGA may be a syndrome with multiple causes and cannot be treated simply as a subtype of TIA.

Transient global amnesia - hippocampal lesions in magnetic resonance imaging.

BACKGROUND: Transient global amnesia is a benign syndrome characterized by a sudden onset loss of anterograde amnesia with full recovery. Magnetic resonance of the brain including diffusion-weighted imaging of patients with transient global amnesia revealed the presence of punctate hyperintense signal abnormalities in the hippocampus. OBJECTIVE: Analysis of the presence of hippocampal lesions in brain magnetic resonance imaging in patients with transient global amnesia and the possible influence of additional factors on their appearance. METHODS: In this retrospective, an observational study we assessed brain magnetic resonance imaging in 38 consecutive patients with transient global amnesia. The incidence of brain magnetic resonance imaging lesions was analyzed for the coexisting cardiovascular risk factors and precipitating events. RESULTS: Hippocampal brain magnetic resonance imaging lesions were detected in 47% of patients with transient global amnesia. Of those, 65% had unilateral lesions, 82% were left-sided, and 28% were right-sided. Most lesions were located in the CA1 subfield. The incidence of hypertension in patients with transient global amnesia was higher than in the general population. Stress and exercise preceded the onset of transient global amnesia only in 13% and 16% of patients, respectively. There was no higher incidence of migraine in transient global amnesia patients (13%). CONCLUSIONS: We found that nearly 50% of patients with transient global amnesia had hyperintense hippocampal brain magnetic resonance imaging lesions. In addition to hypertension, individuals with transient global amnesia had similar cardiovascular risk factors as the general population. We did not identify any precipitating events prior to the onset of transient global amnesia.

[Transient Global Amnesia in the Reykjavik area].

BACKGROUND: Transient Global Amnesia (TGA) is a benign syndrome characterized by sudden anterograde memory loss, that resolves spontaneously within 24 hours. TGA appears without other focal neurological symptoms. The aim of this study was to study TGA in the greater Reykjavik-area. METHODS: We retrospectively analysed the medical history of patients with a diagnosis of TGA (ICD-10 G45.4) at the University Hospital in Iceland in 2010-2021. Medical records were reviewed, and information about year and age at diagnosis, sex, symptoms, precipitating events, imaging results and risk factors were collected. Statistical processing was performed with Excel and Rstudio. RESULTS: Overall, 348 attacks of TGA were identified with a mean frequency of 29 attacks/year, where 9.9% had an earlier history of TGA. The mean age was 64.1, with 50% of subjects between 58-70 years old. The sex distribution was equal (49.9% female). Possible precipitating events were found in 53.7% of cases, with physical activity being the most common one (24.4%), followed by sudden temperature change and emotional stress. In 96% of patients a computerized tomography was performed (no sign of acute changes were found), and magnetic resonance imaging (MRI) in 36.2% of cases. MRI showed restricted diffusion in the hippocampal area in 10.3% of cases. DISCUSSION: TGA is not a rare but a benign syndrome. Our findings regarding age, sex distribution and precipitating events were in accordance with other studies. TGA is thought to result from a temporary hippocampal dysfunction supported by the clinical presentation and MRI findings. The cause of TGA is however still unknown.

Transient global amnesia with unexpected clinical and radiological findings: A case series and systematic review.

BACKGROUND: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate diffusion-weighted imaging lesions (HPDL). The literature suggests that TGA may present with unusual features. This study analyses atypical clinical and radiological manifestations of patients with TGA and/or HPDL. METHODS: We retrospectively reviewed patients with atypical clinical or radiological presentations of TGA and/or HPDL in three neurology centers. We also performed a systematic review of literature using predefined search terms. Results were classified as: A) Atypical clinical manifestations of TGA (such as amnesia with additional manifestations, or only non-amnesic manifestations); B) Atypical radiological manifestations of clinically typical TGA. RESULTS: We identified 83 patients: 18 in our centres (median age 63.5 years, 39% female) and 65 in the literature. In group A, 43 patients presented atypical clinical manifestations such as TGA with added transitory cognitive or sensory-motor deficits, seizures, headaches, but also non-amnesic presentations associated with HPDL and incidental HPDL without symptoms. In group B, 40 patients with typical clinical TGA showed extra-hippocampal punctate diffusion lesions (E-HPDL) which disappeared on follow-up imaging. Using clinical and radiological manifestations, we classified these patients into different categories describing a "TGA-PDL spectrum". CONCLUSIONS: TGA may have atypical clinical manifestations despite typical neuroimaging and patients with typical TGA may show vanishing extra-hippocampal punctate diffusion lesions. TGA, related clinical manifestations, and vanishing punctate diffusion lesions should be considered part of a larger "TGA-PDL spectrum", allowing for better diagnosis of typical and atypical cases and stimulating further studies.

Glymphatic System Function in Patients with Transient Global Amnesia.

BACKGROUND: The purpose of this study was to examine glymphatic system function in patients with transient global amnesia (TGA), as well as to conduct a recurrence analysis. METHODS: We enrolled patients with TGA and healthy controls from our hospital retrospectively. The patients and healthy controls were all scanned with the same 3T scanner, which included diffusion tensor imaging (DTI). We investigated the function of the glymphatic system using DTI analysis along the perivascular space (DTI-ALPS). The ALPS index was compared between patients with TGA and healthy controls, as well as between patients who had recurrent TGA events and those who had only a single TGA event. RESULTS: Seventy-two patients with TGA and 53 healthy controls were enrolled. Sixty-five patients with TGA had a single TGA event, while seven patients had recurrent TGA events. The ALPS index did not differ significantly between patients with TGA and healthy controls (1.665 vs. 1.618, p = 0.436). The ALPS index, on the other hand, varied significantly according to recurrence in patients with TGA. The ALPS index was significantly higher in patients with recurrent TGA events compared to those with a single event (1.928 vs. 1.636, p = 0.049). CONCLUSIONS: We investigated the glymphatic system function in patients with TGA compared to healthy controls for the first time using the DTI-ALPS method. We discovered that these groups did not differ in terms of glymphatic system function. However, glymphatic system function in patients with TGA may differ according to recurrence. Additional research is required to substantiate these findings.

Distorted time perception in patients with transient global amnesia: time perception task and imaging analysis.

INTRODUCTION: Transient global amnesia (TGA) is defined as a sudden and transient episode of memory loss and accompanied by temporal disorientation. However, the mechanism by which time distortion occurs is not clearly elucidated yet. METHODS: Between March 2019 and November 2020, we subjected 30 TGA patients to several time perception tasks and analyzed their magnetic resonance image (MRI) scans and compared the results with age- and sex-matched control group. RESULTS: Among the 60 recruited subjects (64.5 ± 6.3 years), 70% were women. Fourteen patients had only anterograde amnesia. Furthermore, 46% of the patients with TGA (n = 14) had a history of Valsalva maneuver, and 70% of the patients (n = 21) had a pre-attack stress factor. The MRI scans of 14 patients (46.67%) showed hippocampal hyperintensity. With regard to the time production task, patients with TGA exhibited shorter times in all trials compared with their counterparts (5 s, 4.90 ± 1.16 vs. 5.53 ± 0.87; p value = 0.02: 15 s, 12.18 ± 4.55 vs. 14.42 ± 2.54; p value = 0.021). For the time comparison task, the number of correct answers given by patients with TGA was significantly lesser than that given by the control group (6.07 ± 1.23 vs. 6.90 ± 1.24; p value = 0.006). CONCLUSIONS: This is the first study to invesgating an altered time perception in patients with TGA. Although the exact neurophysiological mechanism remains unclear, our findings could aid in the elucidation of brain function across specific time frames.

Limbic covariance network alterations in patients with transient global amnesia.

BACKGROUND: We compared limbic structure volumes and graph theory parameters of the limbic covariance network between patients with transient global amnesia (TGA) and healthy controls, and between patients with single and recurrent TGA events. METHODS: We retrospectively enrolled 122 patients with TGA (single event, n = 107; recurrent events, n = 15) and 50 healthy controls who underwent three-dimensional T1-weighted MRI imaging of the brain. Volumetric analysis of the subcortical limbic structures, including the hippocampus, amygdala, thalamus, mammillary body, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens, was performed. We examined the limbic covariance network using a graph theory. RESULTS: Limbic structure volumes did not differ between patients with TGA and healthy controls, and between patients with a single event and those with recurrent events. However, the radius of the limbic covariance network was significantly greater in patients with TGA than in healthy controls (6.595 vs. 4.564, p = 0.040). Furthermore, the radius, diameter, eccentricity, and characteristics path length were greater (4.066 vs. 2.000, p = 0.009; 7.062 vs. 3.645, p = 0.029; 5.633 vs. 2.774, p = 0.013; 3.373 vs. 1.688, p = 0.004; respectively), whereas the average strength, global efficiency, local efficiency, mean clustering coefficient, transitivity, and small-worldness index were lower (5.595 vs. 10.831, p = 0.004; 0.350 vs. 0.642, p = 0.002; 0.531 vs. 1.724, p = 0.004; 0.304 vs. 0.624, p = 0.006; 0.456 vs. 0.935, p = 0.003; 0.913 vs. 0.993, p = 0.017; respectively), in patients with recurrent events than in those with a single event. CONCLUSION: The limbic covariance network shows significant alterations in patients with TGA, as well as differences between patients with recurrent events and those with a single event. These findings suggest that changes in the limbic covariance network could be related to the pathogenesis 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.

Pathophysiological insight into transient global amnesia from quantitative electroencephalography.

Transient global amnesia (TGA) is recognized as a benign memory disorder, with characteristic clinical and imaging features. However, the pathophysiology of TGA remains elusive. This study aims to elucidate the pathophysiological changes underlying TGA by exploring the brain activities. In total, 215 patients with TGA (age: 61.8 ± 7.8 years; women: 146) with MRI (within 7 days) and EEG studies (within 90 days) were recruited. Quantitative EEG (QEEG) power spectra and network analysis were performed by the artificial intelligence EEG analysis platform (iSyncBrain®). Subgroup analyses were conducted for different clinical groups, based on symptom duration, EEG timing after onset, and cytotoxic lesions on the MRI. Compared with 252 age- and sex-matched subjects (age: 64.5 ± 8.3 years, women: 182), TGA patients showed a global decrease in absolute power in all band waves, a relative decrease in alpha waves, a relative increase in theta waves, and atypical compensation activity. These QEEG changes were observed regardless of having cytotoxic lesions in MRI and they were significant up to 1 week after symptom onset. Network analysis showed that TGA was more activated than normal controls in alpha1 band-waves, exhibiting a compensatory process. TGA results in prolonged and widespread alterations of brain activity and connectivity. QEEG provide insight into pathophysiology of TGA.