Strategic infarcts in vascular dementia. A clinical and brain imaging experience

The mechanisms of dementia resulting from small deep infarctions are incompletely understood. The thesis underlying the concept of multi-infarct dementia is that multiple lesions have a synergestic effect on mental functions, resulting in dementia irrespective of specific location or volume. In this report, we summarize our experience with six patients reported previously along with additional patients examined subsequently, whose clinical features and brain imaging findings allow an alternative formulation for dementia resulting from lacunar stroke. The six initial patients presented with an abrupt change in behavior after acute infarction involving the inferior genu of the internal capsule documented by computed tomography (CT) and magnetic resonance imaging (MRI). The acute syndrome featured fluctuating alterness, inattention, memory loss, apathy, abulia, and psychomotor retardation suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia were evident in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients using 133 xenon regional cerebral blood flow (rCBF) and single photon emission computed tomography (SPECT) showed focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. Perfusion was also defective in the medial and laterial temporal cortex. Important pathways of the limbic system traverse the inferior capsule in the region of the genu. Corticothalamic and thalamocortical fibers form the thalamic peduncles which detach from the internal capsule and enter the thalamus at its rostral and caudal poles and along its dorsal surface. The anterior thalamic peduncle, conveys reciprocal connections between the dorsomedial nucleus and the cingulate gyrus, as well as the prefrontal and orbitofrontal cortex. The inferior thalamic peduncle carries fibers which connect the thalamus with orbitofrontal, insular, and temporal cortex, as well as the amygdala via the ansa peduncularis to the ventral amygdalofugal pathway. Thus, damage to one or both white-matter tracts may occur with infarctions in the region of the inferior genu, causing striking frontal behavioral effects and memory loss in our patients associated with functional deactivation of the ipsilateral frontal and temporal cortex. Similar observations in additional patients with subcortical infarcts in other specific locations (e.g., anterior thalamus and caudate nucleus), consistent with reports in the literature, support the concept of a frontal-subcortical circuit including prefrontal and medial frontal cortex, basal ganglia, and thalamus, which from a network of interconnected sites involved in the regulation of human behavior. The clinical and brain imaging findings in our patients suggest that one mechanism for cognitive decline from a lacunar infarct is strategic disruption of this frontal-subcortical circuit either through thalamocortical disconnection of white-matter tracts in the capsular genu or damage to specific gray-matter sites. In some instances, the result is a strategic-infarct dementia, an effect that appears to be associated with remote cortical deactivation. This hypothesis not only suggests an alternative mechanism for dementia, but may also have therapeutic implications. If cortical deactivation is responsible for dementia and is neurotransmitter dependent, then receptor or replacement therapies may be a rational pharmacologic approach for certain forms of vascular dementia