Increased Intracranial Arterial Pulsatility and Microvascular Brain Damage in Pseudoxanthoma Elasticum

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FIG 1.
Clinical example of vascular and brain disease in PXE. Carotid siphon calcification on CT (A, red circles) and small-vessel disease on 3T MR imaging (B). The blue arrow shows a lacunar infarction; the orange arrows show WML.
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FIG 2.
Correlation between carotid siphon calcification and the PI in patients with PXE. Carotid siphon calcification was correlated with the intracranial PI (R = 0.51, P < .01, regression line; 95% CI, gray band). This association remained significant after multivariate adjustment for age and sex (β = 0.10; 95% CI, 0.02–0.18*) and age, sex, and hypertension (β = 0.10; 95% CI, 0.01–0.18*). Carotid siphon calcification was analyzed as ¹⁰log (1+carotid siphon calcification). P < .05 was statistically significant. A single asterisk indicates P < .05.
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FIG 3.
Arterial calcification, pulsatility, and microvascular brain damage in PXE. Carotid siphon calcification as a measure of intracranial arterial calcification is associated with increased flow pulsatility in PXE. The subsequent pulse pressure–induced microvascular damage, including lacunar infarctions and WML, might contribute to cognitive decline.

Table 1:

Clinical characteristics of 50 patients with PXE and 40 controls^a

Characteristics	PXE (n = 50)	Controls (n = 40)	P Value
Clinical
Age (yr)	57 (SD, 12)	58 (SD, 11)	.49
Male sex (No.)	24 (48)	20 (50)	.85
BMI (kg/m²)	26 (SD, 4)	26 (SD, 4)	.74
Current smokers (No.)	6 (12)	5 (13)	.86
Systolic blood pressure (mm Hg)	136 (SD, 21)	133 (SD, 15)	.49
Diastolic blood pressure (mm Hg)	77 (SD, 12)	79 (SD, 10)	.41
Hypertension (No.)	22 (44)	18 (45)	.92
Hypercholesterolemia (No.)	43 (86)	37 (93)	.33
Medication
Glucose-lowering medication (No.)	1 (2)	0 (0)	.38
Antihypertensive medication (No.)	13 (26)	7 (18)	.40
Cholesterol-lowering medication (No.)	26 (52)	5 (13)	<.01
Laboratory
Calcium (mmol/L)	2.38 (SD, 0.09)	2.39 (SD, 0.09)	.61
Phosphate (mmol/L)	1.02 (SD, 0.16)	0.98 (SD, 0.16)	.25
Estimated glomerular filtration rate (mL/min/1.73m²)	90 (82–90)	88 (75–90)	.17
LDL-cholesterol (mmol/L)	2.8 (SD, 0.9)	3.6 (SD, 0.8)	<.01
25-OH vitamin D (nmol/L)	74 (SD, 36)	61 (SD, 20)	.04

Note:—BMI indicates body mass index; 25-OH vitamin D = 25-hydroxy vitamin D.
^aData are presented as mean (SD), median (interquartile range), or No. (%) when appropriate. Data were analyzed using the Student t test, Mann Whitney U test, or χ² test when appropriate. A P value < .05 was statistically significant.

Table 2:

Imaging findings in patients with PXE compared with controls^{^a}

Note:—The en dash indicates that data on calcification mass are not available for controls.
↵a Data are presented as mean (SD), median (interquartile range), or No. (%) when appropriate. Data were analyzed using the Student t test, Mann-Whitney U test, or χ² test when appropriate. All infarctions include lacunar infarctions, 3 subcortical and 8 cortical infarctions in patients with PXE, and 6 cortical infarctions in controls. P < .05 was statistically significant.
↵b P < .05.
↵c P < .01.

Table 3:

Associations of carotid siphon calcification with brain MR imaging findings^{^a}

	Carotid Siphon Calcification in PXE
	Age- and Sex-Adjusted (n = 50)	Multivariable-Adjusted (n = 50)
MR imaging volumes (β [95% CI])
GM (mL)	–17.3 [–39.9–5.2]	–16.8 [–39.9–6.4]
WM (mL)	–3. 6 [–27.3–20.2]	–4.2 [–28.4–20.0]
CSF (mL)	74.7 [25.5–123.9]^{^c}	67.1 [18.7–115.5]^{^c}
Cortical thickness (µm)	–39.8 [–89.9–10.1]	–40.5 [–91.6–10.7]
WML (mL)	6.4 [1.9–11.0]^{^c}	6.2– [1.6–10.9]^{^b}
Brain infarctions (RR [95% CI])
Lacunar infarctions	2.5 [0.98–6.4]	2.3– [0.9–6.1]
All infarctions	3.1 [1.3–7.5]^{^b}	2.8– [1.1–7.0]^{^b}

↵a Carotid siphon calcifications are analyzed as ¹⁰log 1+ carotid siphon calcification. For carotid siphon calcification, MR imaging volumes and infarctions are adjusted for age and sex (model 1) and age, sex, and hypertension (model 2). P < .05 was statistically significant.
↵b P < .05.
↵c P < .01.

Table 4:

Associations of pulsatility with brain MR imaging findings^a

a For pulsatility, MR imaging volumes and infarctions are adjusted for age and sex (model 1) and age, sex, and hypertension (model 2). P < .05 was statistically significant.
b P < .05.
c P < .01.