Global Amnesia Research Articles

Forgetting the Unforgettable: Transient Global Amnesia Part II: A Clinical Road Map.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with profound anterograde amnesia and a variable impairment of the past memory. Usually, the attacks are preceded by a precipitating event, last up to 24 h and are not associated with other neurological deficits. Diagnosis can be challenging because the identification of TGA requires the exclusion of some acute amnestic syndromes that occur in emergency situations and share structural or functional alterations of memory circuits. Magnetic Resonance Imaging (MRI) studies performed 24–96 h after symptom onset can help to confirm the diagnosis by identifying lesions in the CA1 field of the hippocampal cornu ammonis, but their practical utility in changing the management of patients is a matter of discussion. In this review, we aim to provide a practical approach to early recognition of this condition in daily practice, highlighting both the lights and the shadows of the diagnostic criteria. For this purpose, we summarize current knowledge about the clinical presentation, diagnostic pathways, differential diagnosis, and the expected long-term outcome of TGA.

The Wernicke-Korsakoff encephalopathy: An updated review

Wernicke's encephalopathy is responsible for an acute neuropsychiatric syndrome that is associated with significant morbidity and mortality. It is most frequently due to alcoholism but can also be the result of chronic diseases, mainly systemic tumours, leading to thiamine deficiency. In the non-thiamine treated patients Korsakoff’s syndrome is the residual complication of the encephalopathy. The clinical diagnosis of Wernicke encephalopathy in alcoholics requires two of the following four signs: dietary deficiencies, eye signs, cerebellar dysfunction, and either disturbed mental state or mild memory impairment. These symptoms are less specific in the non-alcoholic patients. Korsakoff's syndrome is the residual condition in none thiamine treated patients. It is predominantly characterized by global amnesia, and in the more severe cases also by cognitive and behavioral dysfunction. Magnetic resonance imaging of the brain can detect the specific lesions and be helpful for the diagnosis. Treatment with 2500 mg thiamine intravenously is recommended as soon as possible.

Glymphatic System Function in Patients with Transient Global Amnesia.

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. 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. 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). 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.

Hot off the press: MRI sensitivity for transient global amnesia.

Transient global amnesia (TGA) is a rare and fascinating acute neurological disorder. It is characterized by idiopathic sudden onset anterograde memory loss that resolves within 24 hours of onset and results in no long-term sequelae. The gold standard diagnostic testing for this disorder are clinical criteria. Common emergency department investigations such as bloodwork and computed tomography scans are unremarkable. This paper reviews the yield of diffusion-weighted magnetic resonance imaging (DW-MRI) in the acute setting for the diagnosis of TGA.

Forgetting the Unforgettable: Transient Global Amnesia Part I: Pathophysiology and Etiology.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with a profound anterograde amnesia and a variable impairment of the past memory. Since the first description, dating back over 60 years, several cases have beenreported in the literature. Nevertheless, TGA remains one of the most mysterious diseases in clinical neurology. The debate regarding the etiology of this disease has focused mainly on three different mechanisms: vascular (due to venous flow changes or focal arterial ischemia), epileptic, and migraine related. However, to date there is no scientific proof of any of these mechanisms. Furthermore, the demonstration by diffusion-weighted MRI of lesions in the CA1 field of the hippocampus cornu ammonis led us to hypothesize that the selective vulnerability of CA1 neurons to metabolic stress could play a role in the pathophysiology of TGA. In this review, we summarize current knowledge on the anatomy, vascularization and function of the hippocampus. Furthermore, we discuss the emerging theories on the etiology and the pathophysiological cascade leading to an impairment of hippocampal function during the attacks.

Strong Selectional Forces Fine-Tune CpG Content in Genes Involved in Neurological Disorders as Revealed by Codon Usage Patterns.

Neurodegenerative disorders cause irreversible damage to the neurons and adversely affect the quality of life. Protein misfolding and their aggregation in specific parts of the brain, mitochondrial dysfunction, calcium load, proteolytic stress, and oxidative stress are among the causes of neurodegenerative disorders. In addition, altered metabolism has been associated with neurodegeneration as evidenced by reductions in glutamine and alanine in transient global amnesia patients, higher homocysteine-cysteine disulfide, and lower methionine decline in serum urea have been observed in Alzheimer’s disease patients. Neurodegeneration thus appears to be a culmination of altered metabolism. The study’s objective is to analyze various attributes like composition, physical properties of the protein, and factors like selectional and mutational forces, influencing codon usage preferences in a panel of genes involved directly or indirectly in metabolism and contributing to neurodegeneration. Various parameters, including gene composition, dinucleotide analysis, Relative synonymous codon usage (RSCU), Codon adaptation index (CAI), neutrality and parity plots, and different protein indices, were computed and analyzed to determine the codon usage pattern and factors affecting it. The correlation of intrinsic protein properties such as the grand average of hydropathicity index (GRAVY), isoelectric point, hydrophobicity, and acidic, basic, and neutral amino acid content has been found to influence codon usage. In genes up to 800 amino acids long, the GC3 content was highly variable, while GC12 content was relatively constant. An optimum CpG content is present in genes to maintain a high expression level as required for genes involved in metabolism. Also observed was a low codon usage bias with a higher protein expression level. Compositional parameters and nucleotides at the second position of codons played essential roles in explaining the extent of bias. Overall analysis indicated that the dominance of selection pressure and compositional constraints and mutational forces shape codon usage.

Catch of the day: hippocampal lesions on magnetic resonance imaging in transient global amnesia

Catch of the day: hippocampal lesions on magnetic resonance imaging in transient global amnesia

Transient Global Amnesia: A Bright Spot Not to be Missed

Transient Global Amnesia: A Bright Spot Not to be Missed

Transient global amnesia with transient anosmia: a curious case suggestive of middle cerebral artery occlusion

Transient global amnesia (TGA) is an enigmatic amnestic syndrome and affects people in middle or older age. During an episode of TGA, a person is not able to make new memories, which indicates hippocampal damage. The symptom anosmia may be associated with memory impairment. A 70-year-old woman presented to our emergency room with transient spatial memory loss. She also complained of a sudden loss of smell. Magnetic resonance angiography confirmed occlusion of the right middle cerebral artery. The mechanism causing the transient anosmia may have resulted in a transient loss of hippocampal function, resulting in amnesia. This rare case is consistent with recent research showing that olfaction has developed as a navigation system.

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.

COVID-19 Vaccine-Associated Transient Global Amnesia: A Disproportionality Analysis of the WHO Safety Database.

Coronavirus disease 2019 (COVID-19) spread rapidly, resulting in a global pandemic for which vaccines were quickly developed. As their safety continues to be monitored, cases of transient global amnesia (TGA) following mRNA vaccination with elasomeran have been reported. TGA is characterized by sudden onset of anterograde amnesia with preservation of other cognitive functions and resolution within 24 h. We aimed to investigate the potential link of TGA with COVID-19 vaccines. We queried the World Health Organization VigiBase® for all reports of “Transient global amnesia”, up to 6 December 2021. Disproportionality analysis relied on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI) and the Information Component (IC). A positive lower end of the 95% CI of the IC (IC025) is used to statistically detect a signal. Of all TGA cases, 289 were associated with a COVID-19 vaccine, representing the most frequent association. Tozinameran was mostly represented (147, 50.8%), followed by AZD1222 (69, 23,8%), elasomeran (60, 20.8%), and JNJ-78436735 (12, 4.2%). With an IC025 > 0, COVID-19 vaccines showed a significant ROR (5.1; 95%CI 4.4–6.0). Tozinameran reached the strongest ROR (4.6; 95%CI 3.9–5.0), followed by elasomeran (4.4; 95%CI 3.4–6.0), AZD1222 (3.8; 95%CI 3.0–5.0), and JNJ-78436735 (3.7; 95%CI 2.1–6.0). Our analysis of COVID-19 vaccines-related TGA reports shows significant disproportionality. Cerebrovascular, inflammatory, or migrainous mechanisms may underlie this association. Yet, numerous confounding factors cannot be tackled with this approach, and causality cannot be ascertained. The identification of this trigger of TGA may help the clinician in his etiological research.

Transient Global Amnesia Recurrence: Prevalence and Risk Factor Meta-analysis.

Transient global amnesia (TGA) is an acute amnestic disorder with unclear pathophysiology. Although considered a benign phenomenon, the possibility of a recurrence is a major concern for the patient. Our objective is to identify the prevalence and risk factors of relapse to help clinicians counsel patients about it. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidance, we screened 1,658 studies from MEDLINE, Lilacs, and Embase databases, published from 1985 to April 2021, in English or Spanish. We included 36 observational case-control and cohort studies that included patients with TGA according to the Caplan or Hodges and Warlow diagnostic criteria. We performed a meta-analysis with a random effect model for proportions and calculation of odds ratio (OR) for identified risk factors. Methodological quality was assessed according to the Newcastle-Ottawa scale. We identified 4,514 TGA cases and 544 recurrence events (12.73%). A follow-up had no effect on its variance. We identified a statistically significant association between recurrence and sexual activity as a trigger, a personal history or current state of migraine and depression (OR 1,481 95% CI [1.0341-2.1222] p = 0.04; OR = 2.0795 95% CI [1.3892-3.1128] p = 0.003; and OR = 4.4871 95% CI [1.890-10.651] p = 0.0288, respectively). The analysis showed that approximately 1 of 8 participants may experience recurrence, with an increased risk in the case of a history or current state of migraine, depression, or sexual intercourse before the event. A personal history of migraine and depression was associated with 2 and 4 times risk, respectively.

Neuroimaging and Electroencephalographic Correlation in Patients with Transient Global Amnesia: Clinical Case Series.

Objective. To determine if there is any correlation between the electroencephalographic and neuroimaging findings in patients with Transient Global Amnesia (TGA). Methods: We retrospectively reviewed files of the First Department of Neurology of AHEPA University Hospital, including patients with a clinical diagnosis of TGA. Only patients who had the characteristic high signal in the temporal lobes in the DWI MRI and those who underwent electroencephalographic recording (EEG) were selected. Results: Out of 28 patients, 8 were selected. We found that 6 out of 8 patients (75%) who had imaging findings in DWI, in at least one medial temporal lobe, also had had intermittent slow theta waves on the electroencephalographic recording. Of these 6 patients, 3 (50%) had bilateral EEG findings, 2 patients (33,3%) only had findings on the left hemisphere and 1 (17%) had on the right hemisphere. 3 out of 6 patients (50%) had electroencephalographic dominance on the left, while 2 out of the 6 (33%) had on the right. In 2 patients with imaging findings in DWI no anomalies were demonstrated on EEG. In 3 out of 8 patients, both MRI and EEG findings correlated on the same side, while 1 patient had opposite findings, depending on which hemisphere the EEG anomalies dominated. Conclusions: There is no absolute matching between the DWI MRI and EEG findings in patients with the clinical diagnosis of TGA. However, there is some degree of correlation, when we focus on the focal dominance of the EEG anomalies, although not statistically significant.

The remains of the day: neuropsychological findings in postacute transient global amnesia.

Current clinical diagnostic criteria of transient global amnesia (TGA) require the episode to completely resolve within 24h. Small case series investigating the neuropsychological profiles obtained during the first days after TGA are inconclusive, with some suggesting the persistence of memory deficits. In this retrospective observational study, neuropsychological data of 185 TGA patients obtained during the first days following an attack were analysed. Data of cognitive functions assessed in at least 50 patients were evaluated and dichotomised according to z-values as "impaired" or "unimpaired". Moreover, the results of magnetic resonance imaging (MRI) were collected. Neuropsychological assessment was performed within the first 3days after TGA in 158 (85.4%) of all patients. The majority of patients showed no significant neuropsychological sequelae in the postacute phase of TGA. However, Mini-Mental Status Examination showed impairment in 22.6% of 159 patients, and we found subtle reductions of patients' performance in tests of verbal long-term memory and executive function in 16.3-24.6% of patients. Patients with hippocampal diffusion-weighted imaging (DWI) lesions performed significantly worse in a verbal recognition task than those without DWI lesions. Our findings reflect subtle performance reductions in different cognitive domains in a small subgroup of TGA patients. This implies that the gradual resolution of subclinical symptoms may take longer than the 24h required as maximum episode duration by current diagnostic criteria.

Bedside echocardiography evaluation of a male with transient global amnesia.

Bedside echocardiography evaluation of a male with transient global amnesia.

The Significance of Atrial Fibrillation in Patients With Transient Global Amnesia.

Background and PurposeThe etiology of transient global amnesia (TGA) remains unclear in a large subset of patients. We aimed to determine the clinical and radiological characteristics of TGA-patients with suspected acute micro-embolic stroke on diffusion-weighted imaging (DWI).MethodsTGA-patients that had new DWI hippocampal lesions (DWI+) were compared to DWI negative TGA-patients (DWI–). Demographics, risk factors, clinical data, radiological data, and mortality were analyzed.ResultsOut of 83 patients diagnosed with TGA, 56 (65%) underwent MRI during the acute hospitalization and 26 (46%) had new hippocampal DWI lesions. DWI+ patients more often had a history of atrial fibrillation (AF, 26 vs. 7%, p = 0.04) but the frequency of other risk factors did not differ. None of the patients died, however, two DWI+ patients had subsequent stroke during a 2-year follow up and both had AF. In contrast, none of the DWI- patients had recurrent events.ConclusionAF is common among DWI+ TGA-patients. The presence of AF in patients with TGA could suggest an increased risk of subsequent stroke.

Acute coronary syndrome and transient global amnesia with sumatriptan

Triptans are potent serotoninergic vasoconstrictors. They are generally avoided in elderly patients age greater than 65 or in patients with a history of CAD. Although there are reported cases of Acute Coronary Syndrome (ACS) or Transient Global Amnesia (TGA) in patients after ingesting therapeutic doses of triptan or dihydroergotamine, this is the first case report, up to our knowledge, of a patient, who had no previous cardiac history, that was diagnosed with both ACS and TGA. A 59-year-old woman with a long-standing history of migraine, gastroesophageal reflux disease, and hypothyroidism, presented to the Emergency Department (ED) complaining of amnesia, chest pain, and left arm numbness after ingesting a single dose of oral sumatriptan approximately 1-2h prior to arrival. She had no recollection of the events that occurred after taking sumatriptan. No acute laboratory abnormalities were found except for an elevated troponin, which continued to trend upwards. Her EKG had no ST-T wave abnormalities. She was diagnosed with Acute Coronary Syndrome (ACS), non-ST elevation MI. She had a negative noncontrast CT head. Neurology was consulted for her amnesia and diagnosed her with Transient Global Amnesia (TGA). They recommended discontinuing sumatriptan and beginning topiramate as a prophylactic therapy. There is an increasing number of reports delineating sumatriptan's adverse effects. Emergency medicine physicians should promptly recognize the toxic effects and adverse reactions from triptans. Sumatriptan-induced vasoconstriction may lead to cardiac and cerebral ischemic events.

Hippocampal subfield involvement in patients with transient global amnesia.

Transient global amnesia (TGA) is a rare neurological disorder causing a transient disturbance of episodic long-term memory. Its etiology remains yet to be identified; the only consistently reported findings in patients with TGA are small hyperintense lesions in the hippocampus on diffusion-weighted magnetic resonance imaging (DWI). The aim of this study was to define whether these lesions are subfield specific, as suggested previously. High-resolution multiplanar reformation T1 and DWI of the hippocampus were acquired in 25 patients after TGA with a total of 43 hippocampal lesions. Hippocampal subfields were determined using the FreeSurfer software and the location of the DWI lesions was transformed to the T1 images after data co-registration. Additionally, hippocampal subfield volumes in each patient were calculated and compared with that of 20 healthy controls. Hippocampal lesions were most frequently detected in the cornu ammonis area 1 (CA1) subfield (30.2%), the hippocampal tail (28.0%), and the subiculum (21.0%); however, lesions were also found in other subfields. There was no significant difference between patients and controls concerning the volumes of the hippocampal subfields. Contrasting previous assumptions, we found DWI hyperintense lesions not to be restricted to the CA1 subfield. The visualization of focal hippocampal lesions on diffusion imaging located to several different hippocampal subfields suggests a potential pathophysiology of TGA independent of microstructural hippocampal anatomy and subfield-specific vulnerability.

Transient global amnesia after pain interventions such as nerve block and intramuscular stimulation: a case report

Transient global amnesia after pain interventions such as nerve block and intramuscular stimulation: a case report

Recurrent amnesia caused by early seizures after hippocampal infarction: a case report

BackgroundWe report the case of a patient with recurrent episodes of disturbed memory suggestive of transient epileptic amnesia, and a focal hippocampal lesion typically associated with transient global amnesia. We argue how careful consideration of clinical, electrophysiological and imaging findings can resolve this apparent contradiction and lead to a diagnosis of early symptomatic post-stroke seizures that links brain structure to function in a new, clinically relevant way.Case presentationA 70-year-old patient was identified in clinical practice in our tertiary care centre and was evaluated clinically as well as by repeated electroencephalography and magnetic resonance imaging. The presenting complaint were recurrent episodes of short-term memory disturbance which manifested as isolated anterograde amnesia on neurocognitive evaluation. EEG and MRI revealed predominantly right frontotemporal spikes and a punctate diffusion-restricted lesion in the left hippocampus, respectively. Both symptoms and EEG changes subsided under anticonvulsant treatment with levetiracetam.ConclusionsOur report contributes to the current discussion of clinical challenges in the differential diagnosis of transient memory disturbance. It suggests that focal diffusion-restricted hippocampal lesions, as seen in TGA, might be ischemic and thus highlights the importance of considering post-stroke seizures as a possible cause of transient memory disturbance.