2024 年 10 巻 p. 18-20
A 58-year-old woman presented to our hospital after she suddenly noticed symptoms of not being able to remember her smartphone password or safe deposit box number while she was at work. Magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) displayed hyperintensity in the right hippocampal CA1 region, and she was hospitalized with a diagnosis of transient global amnesia. Fifty hours after onset, MRI displayed hyperintensity in the bilateral hippocampal regions. In this patient, a lesion was detected early on MRI within 24 hours of symptom onset, and lesions were found bilaterally and symmetrically in the CA1 regions 50 hours after onset.
Transient global amnesia (TGA) is a clinical syndrome that is typically characterized by a sudden, complete inability to retain new information, lasting for several hours, in a middle-aged or older person, with preservation of alertness and all other cognitive functions1). Anterograde amnesia, which is an inability to retain new information is observed, and retrograde amnesia goes back over hours, days, or longer. Small ischemic lesions appear late on magnetic resonance imaging (MRI) performed many hours after the onset of symptoms. These lesions suggest that a vascular mechanism underlies TGA. It remains unclear as to why lesions appear after a delay, and whether they reflect changes in neuronal physiology rather than ischemia. Here, we report a case of a patient with TGA that was detected early on MRI within 24 hours of onset, and lesions were found bilaterally and symmetrically in the CA1 region.
A 58-year-old woman was referred to our hospital after she suddenly noticed symptoms of not being able to remember her smartphone password or safe deposit box number while she was at work. Her colleague, who was concerned about her, brought her to our department. She repeatedly asked questions that are typically asked by TGA patients, such as “What hospital is this?”. She was unable to remember recent events that occurred on the previous day or 2 days previously. She had typical anterograde and retrograde amnesia. A neurological examination showed no obvious abnormalities other than disorientation. A general physical examination showed no obvious abnormal findings, and her blood test results were normal. A diffusion-weighted head MRI scan taken 5 hours after the onset of symptoms displayed a 2-mm region of hyperintensity in the right hippocampal CA1 region (Fig. 1).
The patient was diagnosed as having transient global amnesia, and was admitted on the same day for follow-up. She had a past history of type 2 diabetes, which was well controlled and followed up without medication. By the morning of the day after admission, her disorientation and global amnesia had spontaneously subsided. A head MRI scan was performed 50 hours after the onset of symptoms, and diffusion-weighted imaging displayed hyperintensity in the bilateral hippocampal CA1 regions (Fig. 2).
There were no noteworthy findings on electroencephalography (EEG), and hence transient epileptic amnesia was not suspected. She showed favorable progress without any recurrence of symptoms, and was discharged from the hospital on the seventh hospital day. When a head MRI scan was performed at the outpatient clinic 44 days after the onset of symptoms, the abnormal signals observed at the time of admission had disappeared, and hence the disease course was consistent with TGA.
Transient global amnesia is a clinical syndrome characterized by the sudden onset of anterograde amnesia accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, and without the compromise of other neurologic functions2). Diagnostic criteria for TGA have been proposed3), including the absence of both seizures and head injury, and the resolution of symptoms within 24 hours after initial onset (Table 1).
| Adapted from Caplan 3) |
|---|
| ・Onset is witnessed by another person |
| ・Symptoms are limited to repetitive queries and amnesia |
| ・No other major neurologic signs or symptoms |
| ・Amnesia is transient, usually lasting from hours to a day |
In a report that investigated 277 cases4) of TGA patients, the average age of the patients was 62-years old, and there were slightly more women. Another report, which investigated 213 cases5) of TGA patients, found that TGA was more common in men than in women. Episodes of TGA are sometimes preceded by a precipitating event, such as an activity involving the Valsalva maneuver, emotional stress, immersion in cold or hot water, sexual intercourse, or pain2).
The present case was a 58-year-old woman, which is within the age range at which TGA tends to occur. Although it was not possible to definitively determine the cause of this patient’s illness based on interviews alone, we speculated that tension and stress at work may have been a trigger. Her episode spontaneously resolved within 24 hours, which is typical for TGA.
At present, there are no specific laboratory tests that can confirm the diagnosis of TGA. Diagnosis is based on a detailed medical history, cognitive assessment, and physical examination. The physician must keep differential diagnoses in mind, and perform the necessary tests to rule out other diseases. The usefulness of EEG in the diagnosis of TGA is also limited, as EEG findings have been reported to be normal both during and after typical TGA episodes6).
In the present patient, no abnormalities were found in the blood tests, and no abnormal findings were found on EEG performed after the disappearance of symptoms. The fact that no obvious abnormalities were observed in these tests is also considered to be consistent with TGA.
To our knowledge, no adequate pathophysiological explanation of TGA has been reported to date. It has been reported that the CA1 subfield of the hippocampal cornu ammonis is particularly vulnerable to metabolic stress caused by hypoxemia, β-amyloid-induced neurotoxicity, and ischemia; and the degree of this local susceptibility may be genetically determined7). In a study on patients after cardiac arrest/resuscitation and their autopsy brains demonstrated that selective damage to the bilateral hippocampal CA1 region resulted in anterograde memory impairment without other cognitive dysfunction8). This previous studies demonstrated an association between damage to the CA1 region of the hippocampus and impaired episodic memory, indicating that transient dysfunction in this region may cause TGA.
Small ischemic lesions appear late on MRI, many hours after a TGA episode. These lesions provide preliminary support for a vascular mechanism. It is unclear why lesions appear after a delay, and whether they reflect changes in neuronal physiology rather than ischemia. In a report that investigated 390 cases of TGA patients9), TGA lesions were present in 70% of the patients, most often appearing 12 to 48 hours after the onset of symptoms, and were often temporary, although in some cases symptoms persisted for several days.
One of the largest Emergency Department (ED)-based studies10) to date reported a median time from symptom onset to MRI of 6 hours (interquartile range = 4–9 hours), and reported a lesion positivity rate of 7.9% among 203 patients with acute TGA. This previous study suggests that the positivity rate of TGA lesions on DWI-MRI is indeed low within the hyperacute time frame.
Regarding TGA lesions, it has been reported that there are patients with only left-side lesions, only right-side lesions, and those with bilateral lesions, but it is thought that there are no differences in clinical symptoms depending on the side of the lesion. Left-side lesions are more common than right-side and bilateral lesions9). In the present patient, lesions were observed symmetrically on both sides.
Functional imaging has previously shown bitemporal hypoperfusion during a TGA episode11), but such a reduction may precede or result from neuronal dysfunction in these regions. Neural network studies have shown that during TGA episodes, connectivity is reduced bilaterally in the hippocampus and parahippocampal gyrus, as well as in other structures, such as the amygdala and parts of the temporal lobe12).
In conclusion, the patient of our present case displayed MRI abnormalities earlier than in typical TGA cases. Abnormal findings on MRI were bilaterally symmetrical, but followed the typical course of TGA.
We thank the patient of this case for her cooperation, and Y. Araki of the Department of Radiology of Tokyo Medical University for his support with the MRI analyses.
We are also grateful to the medical editors of the Center for International Education and Research of Tokyo Medical University for editing the manuscript.
The authors have no conflicts of interest.
