Factors behind poor cognitive outcome following a thalamic stroke

Abstract

Background: Thalamic strokes produce neurological, cognitive, and behavioral symptoms depending on the thalamic nuclei involved. While traditionally associated with severe cognitive deficits, recent studies suggest more modest impairments. This study aims to identify the factors that influence the severity of cognitive impairment following thalamic stroke.

Methods: We recruited 40 patients (mean age 51.1) with chronic isolated thalamic stroke and 45 healthy subjects (mean age 48.5) who underwent neuroimaging and neuropsychological assessment. Cluster and principal component analyses were used to discriminate patients from healthy subjects based on cognitive tasks. Disconnectome maps and cortical thickness were analyzed to understand the distant impact of thalamic strokes.

Results: Two cognitive profiles emerged from the cluster analysis. Cluster 1 included mostly healthy subjects (n = 43) and patients with no or minor deficits (n = 20). Cluster 2 included patients (n = 19) and two healthy subjects with severe deficits in verbal memory, executive functions, and attention. Cluster 1 encompassed all patients with right thalamic stroke, while Cluster 2 included all patients with bilateral stroke or mammillothalamic tract interruption. Patients with left-sided stroke were equally divided between clusters. Significant differences between clusters included age, education, interthalamic adhesion disruption, lesion volume, and location. Patients with left-sided stroke in Cluster 2 had more lateral thalamic lesions and greater disruption of the anterior thalamic projection.

Conclusions: Contrary to common expectations, our findings suggest that many patients with thalamic stroke have relatively good cognitive outcomes. In contrast, we identified the factors behind poor outcomes that will help clinicians.

Keywords: Cognition; MRI; Outcomes; Stroke; Thalamus.

Fig. 1

A Distribution of patient ages at the time of infarct. B Percentages of thalamic stroke etiologies, including congenital atrial septum anomalies like atrial septal defect ostium secondum, Patent Foramen Ovale (PFO), and/or atrial septal aneurysm (data missing for five patients). C Percentages of patients by categories of initial stroke symptoms. D Symptom prevalence comparison based on infarct laterality: B (Bilateral), L (Left), R (Right)

Fig. 2

A Comparison of neuropsychological test z-scores between patients and healthy subjects across both clusters. Solid dots show the median, bars indicate 95% confidence intervals, and each dot represents an individual's performance. Clusters differ significantly across all cognitive functions (Mann–Whitney, p < 0.001). B PCA plot: Larger dots represent cluster means with 95% confidence intervals. Subjects are color-coded by cluster (from panel A), and patient dots have an “x” (only in panel B for clarity). Individuals are projected on the x or y axes, showing how each component distinguishes the clusters

Fig. 3

Mean z-score in each cognitive function by groups of patients depending on the laterality of their infarct

Fig. 4

A Overlapping normalized lesions on an MNI152 slice showing the most affected voxels of Cluster 1 patients with left (n = 14) or right (n = 6) lesions, and Cluster 2 patients with left (n = 13) or bilateral lesions (n = 6). Cluster 1's left infarcts primarily affected the median thalamus, while Cluster 2's were mainly lateral. B Nuclei distribution (top) and percentage of lesioned nuclear groups for left-lesioned patients from both Clusters, segmented with HIPS-THOMAS (bottom). C Mean disconnectome maps by Cluster and infarct laterality, along with Brodmann atlas projections in the MNI152 space (right inset). Left anterior thalamic radiations were the most commonly disconnected tract, with Cluster 2's left infarcts showing stronger disconnection. When mapped onto the Brodmann atlas, these disrupted radiations projected to areas 11 and 47, linked to the orbitofrontal cortex and inferior frontal gyrus. A anterior, S superior, L left. Color bars show the number of patients with overlapping lesioned voxels