Neuronal Alterations in Secondary Thalamic Degeneration Due to Cerebral Infarction: A 11C-Flumazenil Positron Emission Tomography Study

Abstract

Background: Studies using animal experiments have shown secondary neuronal degeneration in the thalamus after cerebral infarction. Neuroimaging studies in humans have revealed changes in imaging parameters in the thalamus, remote to the infarction. However, few studies have directly demonstrated neuronal changes in the thalamus in vivo. The purpose of this study was to determine whether secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease.

Methods: We retrospectively analyzed the data of 140 patients with unilateral cerebral infarction ipsilateral to internal carotid artery or middle cerebral artery disease. All patients had quantitative measurements of ¹¹C-flumazenil binding potential (FMZ-BP), cerebral blood flow, and cerebral metabolic rate of oxygen using positron emission tomography in the chronic stage. Region of interest analysis was performed using NeuroFlexer-an automated region of interest analysis software using NEUROSTAT.

Results: In the thalamus ipsilateral to the infarcts, the values of FMZ-BP, cerebral blood flow, and cerebral metabolic rate of oxygen were significantly lower than those in the contralateral thalamus. Significant correlations were found between the ipsilateral-to-contralateral ratio of FMZ-BP and the ipsilateral-to-contralateral ratio of cerebral blood flow or cerebral metabolic rate of oxygen in the thalamus. Patients with corona radiata infarcts and striatocapsular infarcts had significantly decreased ipsilateral-to-contralateral FMZ-BP ratio in the thalamus compared with those without. The ipsilateral-to-contralateral ratio of FMZ-BP in the thalamus was significantly correlated with the ipsilateral-to-contralateral cerebral metabolic rate of oxygen ratio in the frontal cortex and showed a significant negative correlation with the number of perseverative errors on the Wisconsin Card Sorting Test.

Conclusions: Secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease, which may be associated with frontal lobe dysfunction.

Keywords: cerebral infarction; cerebrovascular disorders; positron emission tomography; receptors, GABA-A; thalamus.

Figure 1.

Regions of interest in the thalamus on flumazenil positron emission tomography images in a normal volunteer. L indicates left; and R, right.

Figure 2.

Examples of positron emission tomography (PET) images in a patient with left (L) middle cerebral artery occlusion (MRA). Magnetic resonance imaging (MRI), 0.5 mo after stroke, showed corona radiata infarction (blue arrow) without ischemic lesions or apparent atrophy in the thalamus (yellow arrow). PET, 0.8 mo after stroke, showed a decrease in flumazenil binding potential (FMZ-BP), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂) in the thalamus (white arrows) ipsilateral to infarction. The ipsilateral-to-contralateral ratios for FMZ-BP, CBF, and CMRO₂ were 0.56, 0.76, and 0.61, respectively. R indicates right.

Figure 3.

The relationships between thalamic neuronal damage and other variables. Scatter plots of the ipsilateral-to-contralateral ratios for flumazenil binding potential (FMZ-BP) and those for cerebral blood flow (CBF; A) or cerebral metabolic rate of oxygen (CMRO₂; B) in the thalamus, the ipsilateral-to-contralateral ratios for FMZ-BP in the thalamus and those for CMRO₂ in the frontal cortex (C), the ipsilateral-to-contralateral ratios for FMZ-BP in the thalamus and the numbers of perseverative errors of Wisconsin Card Sorting Test (D), the ipsilateral-to-contralateral ratios for FMZ-BP in the thalamus and the volume of infarcts (E), and the ipsilateral-to-contralateral ratios for FMZ-BP and those for the area in the thalamus (F).