Thalamic (Diencephalic) Amnesia
This case posed a difficult diagnostic challenge. The patient clearly had a severe memory deficit. However, other cognitive abilities such as language, visuospatial abilities and the ability to solve complex arithmetic problems were remarkably well preserved, and have remained stable over the period of observation. This restriction of deficits principally to memory function, coupled with lack of progression over time, made a diagnosis of a primary dementia such as Alzheimer's disease unlikely. On neurobehavioral assessment, there were subtle frontal-lobe type deficits, including paratonia and mild motor disinhibition, as well as minor personality changes. However, these difficulties, often noticed and corrected by the patient, did not reach the proportions expected in a frontotemporal dementia. Furthermore, other executive functions such as abstract reasoning, judgment, and problem solving remained intact.
Other elements in this patient's history such as hypertension, cardiac arrhythmia, and transient focal neurological symptoms suggested that a vascular cause be considered. Inspection of the patient's MRI scans revealed multiple small infarcts in the basal ganglia bilaterally; however, the lack of obvious clinical correlates to these lesions, and the restriction of clinical deficits largely to memory dysfunction, make a diagnosis of a multi-infarct or vascular dementia less tenable at the present time. Of particular importance in this case, lesions were seen in the anterior nuclear group of the thalamus bilaterally.
Patients with strategically placed bilateral anterior thalamic lesions have been known to develop a permanent disabling amnesia. Patients with posterior thalamic lesions, on the other hand, do not typically develop such significant memory disturbances. Two major pathways involving the thalamus are known to be involved in memory function. The major hippocampal pathway is in the fornix, which leads to the mammillary bodies, and from there via the mammillothalamic tract to the anterior thalamic nucleus (this pathway nominally corresponds to the "Papez circuit" of classical neuroanatomy). A second pathway leads from the amygdala and perirhinal cortex to the dorsomedial thalamic nucleus via the ventral amygdalofugal pathway. The dorsomedial nucleus, in turn, projects to numerous areas of the prefrontal cortex. Damage in the anterior portions of the thalamus may thus affect both hippocampal (mamillothalamic) and perirhinal (ventral amygdalofugal) pathways with strategically located bilateral lesions (Graff-Radford, 1997).
Perhaps the best-studied individual with thalamic amnesia is the patient N.A., who has been amnestic since 1960 when he sustained a penetrating brain injury with a miniature fencing foil. The amnesia affected verbal material with no other detectable cognitive deficits. Initial CT studies showed a lesion in the left mediodorsal nucleus of the thalamus. However, more recent MRI studies have demonstrated that the major areas of damage also involve the rostral and caudal intralaminar nuclei, the ventral mediodorsal nucleus and the ventral lateral and ventral anterior thalamic nuclei. In this patient, the trajectory of the mamillothalamic tract was disrupted and the mammillary bodies were absent bilaterally (Squire, Amaral, et al., 1989).
Zola-Morgan and Squire (1985) demonstrated that circumscribed lesions in the mediodorsal thalamic nuclei could produce substantial amnesia in monkeys. Stuss et al. (1988) demonstrated that lesions of the dorsomedial nuclei and mamillothalamic tracts produced primarily a memory disorder, with mild fronto-limbic behavioral changes. The severity of syndrome depended of the location and extent of the lesion. Both anterograde and remote memory deficits were documented, as well as a dichotomy between left-verbal and right non-verbal material -specific amnesia.
Graff-Radford et al. (1990) studied four patients with bilateral thalamic infarctions with MRI and comprehensive neuropsychological testing. Patients developed amnesia when the lesions were placed anteriorly in the thalamus, and when the mamillothalamic and ventroamygdalofugal pathways were disrupted. The amnesia was characterized by deficits in anterograde verbal and visual learning. Retrograde amnesia was noted, but motor learning was preserved.
Pepin and Auray-Pepin (1993) reported on three patients with unilateral thalamic ischemic lesions that resulted in material-specific memory impairment and selective frontal lobe-related cognitive deficits. These deficits were associated with diencephalic, striatal and dorsolateral pre-frontal hypoperfusion on SPECT imaging studies. The damage involved the ventral anterior thalamus, the mamillothalamic tract, and the rostroventral internal medullary lamina. Similar findings were reported by Tsuboi et al. (1997) in their report of a patient with persistent thalamic amnesia. In this patient, T2-weighted MRI showed high signal intensity in the left anteromedial thalamus, and 99m Tc-HMPAO SPECT revealed decreased uptake in the left frontal and temporal lobes. Thus, the demonstration of decreased frontal or temporal uptake on SPECT studies cannot be taken as unequivocal evidence of a cortical disorder, given that appropriately placed thalamic lesions (presumably by interrupting thalamic projections to frontotemporal cortex) can produce similar findings.
In summary, the syndrome of thalamic amnesia is associated with lesions involving the anterior, dorsomedial and paramedian nuclei of the thalamus. These lesions have the effect of disrupting the fornix-mamillothalamic tract, and the ventral amygdalofugal pathway. Associated hypoperfusion on SPECT is seen in the frontal and anterior temporal lobes. These findings suggest functional involvement of the frontal and temporal lobe connections with the dorsomedial and anterior nuclei in patients with thalamic amnesia. In terms of neuropsychological analysis, the amnesia in these patients is characterized by severe anterograde memory loss with preservation of motor learning. Some patients also develop retrograde memory loss with a temporal gradient. The amnesia produced is material-specific, with left-sided lesions producing a verbal memory deficit, and right-sided lesions producing visual memory impairment. Bilateral lesions involving the anterior thalamus have been shown to produce a lasting global amnesia. Impairment of dorsolateral pre-frontal functions has also been documented in these patients by neuropsychological testing.
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