Shape alterations in the striatum in chorea-acanthocytosis

Abstract

Chorea-acanthocytosis (ChAc) is an uncommon autosomal recessive disorder due to mutations of the VPS13A gene, which encodes for the membrane protein chorein. ChAc presents with progressive limb and orobuccal chorea, but there is often a marked dysexecutive syndrome. ChAc may first present with neuropsychiatric disturbance such as obsessive-compulsive disorder (OCD), suggesting a particular role for disruption to striatal structures involved in non-motor frontostriatal loops, such as the head of the caudate nucleus. Two previous studies have suggested a marked reduction in volume in the caudate nucleus and putamen, but did not examine morphometric change. We investigated morphometric change in 13 patients with genetically or biochemically confirmed ChAc and 26 age- and gender-matched controls. Subjects underwent magnetic resonance imaging and manual segmentation of the caudate nucleus and putamen, and shape analysis using a non-parametric spherical harmonic technique. Both structures showed significant and marked reductions in volume compared with controls, with reduction greatest in the caudate nucleus. Both structures showed significant shape differences, particularly in the head of the caudate nucleus. No significant correlation was shown between duration of illness and striatal volume or shape, suggesting that much structural change may have already taken place at the time of symptom onset. Our results suggest that striatal neuron loss may occur early in the disease process, and follows a dorsal-ventral gradient that may correlate with early neuropsychiatric and cognitive presentations of the disease.

Figure 1

Representation of orientation of caudate (red) and putamen (blue) shapes on coronal, sagittal and horizontal view of a healthy control brain.

Figure 2

Scatter-plot of left and right caudate volumes (left) and Z-scores (right) according to group, showing significant separation of diagnostic groups and tight relationship between contralateral volumes.

Figure 2

Scatter-plot of left and right caudate volumes (left) and Z-scores (right) according to group, showing significant separation of diagnostic groups and tight relationship between contralateral volumes.

Figure 3

Scatter plot of left and right putaminal volumes (left) and Z-scores (right) according to group, showing significant separation, but greater left-right variation in the control group.

Figure 3

Scatter plot of left and right putaminal volumes (left) and Z-scores (right) according to group, showing significant separation, but greater left-right variation in the control group.

Figure 4

Left (top) and right (bottom) caudate changes, showing differences between ChAc patients and controls. On left, uncorrected raw p-value map; middle, FDR-corrected p-value map; right, between-group displacement map. Legend to p-value map shows that regions with p>0.05 are coloured blue, with significant values on a spectrum from green (p=0.05) to red (p=0). Legend to displacement map shows displacement of ChAc group from control group in mm.

Figure 5

Left (top) and right (bottom) putamen changes, showing differences between ChAc patients and controls.

Figure 6

Significance maps of correlations between duration of illness and shape of left (top) and right (bottom) caudates, showing uncorrected p-value maps (left), with FDR-corrected maps (middle) and Spearman’s r map (right). Legend to p-value map shows that regions with p>0.05 are coloured blue, with significant values on a spectrum from green (p=0.05) to red (p=0).

Figure 7

Significance maps of correlations between duration of illness and shape of left (top) and right (bottom) putamen, showing uncorrected p-value maps (left), with FDR-corrected maps (middle) and Spearman’s r map (right). Legend to p-value map shows that regions with p>0.05 are coloured blue, with significant values on a spectrum from green (p=0.05) to red (p=0).