What is the Mechanism of Transient Global Amnesia?
What is the Mechanism of Transient Global Amnesia?
Abstract & Commentary
By Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College, Cornell University. Dr. Jamieson is a consultant for Boehringer Ingelheim and Merck, and is on the speaker's bureau for Boehringer Ingelheim, Merck, Ortho-McNeil, and Pfizer.
Synopsis: Patients show reversible MRI signal abnormalities in the CA-1 sector of the hippocampal cornu ammonis early in the course of TGA. They are not correlated with any specific clinical or memory features of the episode.
Source: Bartsch T, et al. Selective affection of hippocampal CA-1 neurons in patients with transient global amnesia without long-term sequelae. Brain. 2006;129:2874-2884.
During transient global amnesia (TGA), an older adult suddenly develops selective retrograde and antegrade amnesia, lasting generally less than 24 hours. Recovery of memory is complete, except for the period of time of the event. Attacks are differentiated from seizures or transient ischemic attacks by their length and the specificity of the deficit. Speculation about the pathogenesis of TGA includes association with migraine, physical or emotional stress, and cerebral venous congestion. While focal ischemia may factor into the etiology of TGA, patients generally lack traditional vascular risk factors such as hypertension and hypercholesterolemia. Neuroimaging abnormalities in TGA have been reported in various structures, but MRI studies have noted diffusion weighted lesions in the hippocampus. The localization of these lesions and their clinical and neuropsychological associations are investigated in this study.
Bartsch et al correlated MRI lesions and memory deficits in 41 patients with TGA. The diagnosis was confirmed by less than 24 hours of witnessed antegrade amnesia, without alternation of consciousness or neurological deficit, in the absence of head trauma or seizures. The neurological assessment included studies to rule out cerebrovascular disease. High-resolution 3T magnetic resonance imaging (MRI) evaluated the anatomical location of hippocampal changes in patients during the acute phase (4 - 6 hours after symptom onset) and during the 24 - 72 hours after the onset of symptoms of TGA. In those patients with DWI lesions in the hippocampus, follow-up MRI studies were performed at 10 - 20 days and at 4 - 6 months after the episode of TGA. Hippocampal lesions were defined as hyperintensities in both diffusion sequences and T2-weighted images. Neuropsychometric evaluations were performed during the acute episode, during the presence of the DWI lesions, and then again 4 - 6 months later.
Twenty women and 21 men with a mean age 65 years ± 7 (± SD) presented with 42 TGA episodes, the majority in the morning or afternoon. Seventy-one percent of attacks occurred after physical exertion, stress, Valsalva maneuver, or postural changes. Neurological and neurovascular evaluation did not show relevant abnormalities. Of the 41 patients, 29 patients showed a total of 36 DWI, and corresponding T2, lesions in the hippocampus, at 48-72 hours after onset of symptoms. Most patients (8/10) scanned in the acute stage (< 6 hours after onset of symptoms) showed DWI lesions that increased in signal intensity in the follow-up scans at 48-72 hours. The T2 weighted images did not show lesions on MRI until later than 24 hours after symptom onset. Almost all (34/36) of the hippocampal lesions were in the CA-1 sector of the hippocampus, with one lesion in the CA-3 sector and one lesion in an indeterminate location in the cornu ammonis. There was a slight left- sided predominance (20 versus 16) but no anterior - posterior vascular preference (anterior-choroidal artery versus posterior-cerebral artery distribution) was noted. In 13 out of the 42 attacks, no acute MRI lesions were detected. The follow-up MRI studies at 10 - 20 days and 4 - 6 months did not show persistence or residua of the lesions detected in the acute studies. No relevant MRA abnormalities were noted. A hypoplastic transverse sinus, with slight left-sided predominance, was seen in 88% of patients. In those patients with a unilateral hippocampal lesion, the hypoplastic transverse sinus side was more likely to correspond to the side of the DWI lesion.
Episodic verbal memory deficits on neuropsychometric assessment were found in 14 out of 18 patients who were tested < 24 hours after onset of symptoms, but memory testing normalized by 48-96 hours after onset of symptoms. Patients who had impairment of verbal memory, only, were more likely to have dominant hemisphere hippocampal lesions; whereas, patients who had additional visuospatial memory impairment were more likely to have non-dominant hemispheric lesions. Memory testing after 4-6 months of patients with acute DWI lesions in the hippocampus did not show any difference in recovery of memory, as compared to those patients without acute hippocampal lesions. Deficits in verbal and spatial memory did not correlate with specific clinical or radiological features.
Commentary
This study found reversible MRI signal abnormalities in the CA-1 sector of the hippocampal cornu ammonis in patients early in the course of TGA. These lesions could correlate with the impairment of episodic memory, which was limited to days or weeks after the episode of TGA, but no long-term neuropsychological sequelae could be detected. Do the lesions help to assess mechanistic theories? Hippocampal CA-1 neurons have a relay function in intrahippocampal circuits and lesions in this area produce memory impairment. These neurons show selective vulnerability to hypoxia and ischemia resulting in delayed neuronal death. Vascular susceptibility may be explained by the overlap of the upper and lower hippocampal arteries within the CA-1 sector. The CA-1 sector lesions do not support the venous congestion theory, as they do not resemble venous congestion or infarcts. While emotional and behavioral stress in animal models may alter CA-1 glutamatergic release and uptake, more data is needed to correlate these lesions with putative precipitants of TGA.
This study supports the view that TGA is a benign short-lived memory disorder, due to transient disturbance of hippocampal CA-1 neurons, without structural and neuropsychological sequelae. Further study is needed to determine if the structural involvement noted in the CA-1 sector extends to other memory-relevant structures of the hippocampal formation. Questions still remain about TGA triggers and susceptibility.
Patients show reversible MRI signal abnormalities in the CA-1 sector of the hippocampal cornu ammonis early in the course of TGA. They are not correlated with any specific clinical or memory features of the episode.Subscribe Now for Access
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