Basilar artery diameter as neuroimaging biomarker in Chinese Fabry disease patients

Abstract

Background: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from mutations of α-galactosidase A gene, and has been emphasized as one of the etiologies of young stroke and leukoencephalopathy. Vertebrobasilar dolichoectasia (VBD) is a highlighted finding in FD. We aim to examine the utility of VBD in Chinese FD by comparing the differences in basilar artery (BA) diameter of Chinese FD patients against age-matched controls with and without stroke.

Methods: This was a matched case-control study involving 37 Chinese FD patients. The BA diameters were evaluated on axial T2-weighted magnetic resonance imaging and compared to two age-and-gender matched control groups, one with stroke and one without. The association between BA diameter and stroke occurrences and white matter hyperintensities (WMH) were analyzed among all FD patients.

Results: Patients with FD had significantly increased BA diameter compared to controls with and without stroke (p < 0.001). A BA diameter of 4.16 mm could distinguish FD from controls in the stroke subgroup (ROC AUC 0.870, p = 0.001, sensitivity 80% specificity 100%), and with a cut-off of 3.21 mm in the non-stroke subgroup (ROC AUC 0.846, p < 0.001, sensitivity 77.8% specificity 88.9%). Larger BA diameter had more stroke occurrences and was moderately associated with heavier WMH load in terms of higher total FAZEKAS scores. (Spearman's rho = 0.423, p = 0.011).

Conclusion: VBD was also present in Chinese FD patients. BA diameter has high diagnostic utility in identifying FD from a mixed cohort of stroke and normal controls, and carried predictive value in evaluating neurological complications of FD.

Keywords: Basilar artery; Chinese; Fabry disease; IVS4; Vertebrobasilar dolichoectasia.

Fig. 1

Differences in BA diameter among FD patients. (A) Boxplots showing no significant BA diameter differences between genders. (B) Larger BA diameter in FD stroke patients compared with those without stroke. (C) No significant BA diameter differences between classical and non-classical genotypes

Fig. 2

Comparison of BA diameter. Significantly enlarged BA diameter was observed when comparing FD patients against controls in both stroke and non-stroke subgroups. (p < 0.001)

Fig. 3

Receiver operating curves (ROC) analysis of BA diameters. ROC data showing high sensitivity and specificity of BA diameter comparing (A) FD patients (N = 10) versus controls (N = 20) in stroke subgroup. (B) FD patients (N = 27) versus controls (N = 54) in non-stroke subgroup

Fig. 4

66-year-old FD female patient who suffered from recurrent ischaemic strokes. (A) Initial CT Brain showing prominent BA. (B) BA diameter measuring 5.3mm on axial T2-weighted MRI imaging. Recurrent ischaemic strokes (C) left parietal infarct in left middle cerebral artery territory (D) left occipital infarct in left posterior cerebral artery territory. Intracranial arterial dolichoectasia was appreciated on CT angiography in PA view (E) and lateral view (F). Both anterior and posterior vessels were elongated, tortuous and ecstatic

Fig. 5

A 54-year-old IVS4 FD patient without hypertension suffering from advanced FD leukoencephalopathy. Serial axial FLAIR images demonstrated heavy white matter burden at periventricular and deep white matter regions. Large areas of patchy and confluent T2/FLAIR hyperintense signals were appreciated

Fig. 6

Relationship between BA diameter and CWML burden in FAZEKAS visual rating score. Scatter plot graph showing moderate correlation between BA diameter and FAZEKAS total score (Spearman’s rho correlation 0.423, p = 0.011). Larger BA diameter was associated with higher WML burden and leukoencephalopathy