Brain white matter hyperintensities in Kawasaki disease: A case-control study

Abstract

Background: Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke.

Purpose: To investigate whether childhood KD is associated with WMHs and other cerebrovascular findings later in adulthood.

Materials and methods: In this case-control study, patients diagnosed with KD (cases) at our tertiary hospital between 1978 and 1995 were invited to brain magnetic resonance (MRI) between 2016 and 2017. Migraine patients (controls) with available brain MRI were matched with cases (ratio 4:1) by age (±2 years) and sex. Two blinded neuroradiologists evaluated independently cerebrovascular findings from the brain MRI scans. Modified Scheltens' visual rating scale was used to evaluate WMH burden and the total WMH volume was measured using manual segmentation.

Results: Mean age [years, (SD)] at the time of brain MRI was 33.3 (3.8) and 32.8 (4.0) for cases (n = 40) and controls (n = 160), respectively (P = 0.53). Mean follow-up time for cases was 29.5 years (4.3). Total volume of WMHs (median) was 0.26 cm³ (IQR 0.34) for cases and 0.065 cm³ (IQR 0.075) for controls, P = 0.039. Cases had higher total WMH burden (P = 0.003), deep WMH burden (P = 0.003), and more periventricular WMHs (prevalence 7.5 vs. 0%, P = 0.008) than controls. Cases had greater risk of having total Scheltens' score ≥2 vs. < 2 (odds ratio, 6.88; 95% CI: 1.84-25.72, P = 0.0041) and ≥3 vs. < 3 (odds ratio, 22.71; 95% CI: 2.57-200.53, P = 0.0049). Diabetes type 1/type 2, hypertension, smoking status or hypercholesterolemia were not risk factors for WMH burden, p > 0.1. Myocarditis at the acute phase of KD increased the risk for periventricular WMHs (P < 0.05). Three cases (7.5%) and three controls (1.9%) had lacune of presumed vascular origin (P = 0.0096).

Conclusion: History of KD could be associated with an increased WMH burden. More studies are needed to confirm our results.

Keywords: Kawasaki disease; brain MRI; cerebrovascular abnormalities; follow up; white matter hyperintensities.

Figure 1

White matter hyperintensity scores (WMH) assesed by Scheltens' visual rating scale in 40 cases (Kawasaki disease) and 160 controls (migraine patients).

Figure 2

Brain MRI (T2-flair) of the white matter hyperintensities in four cases (Kawasaki disease). (A1–A4) a case (Kawasaki disease) with a total Scheltens' score of 8. (A1) Periventricular WMH > 5 mm in the right occipital horn (yellow arrow; Scheltens' score = 2) and in the deep occipital lobe WMH < 3 mm (white arrow; Scheltens' score = 1). (A2) Periventricular WMH > 5 mm in the right frontal horn (yellow arrow; Scheltens' score 2). (A3) Periventricular WMH > 5 mm in the left ventricle (yellow arrow; no score, because already score has been given from this area). (A4) deep WMH 4–10 mm in the left frontal lobe (white arrow; Scheltens' = score 3). (B1–B4) a case (Kawasaki disease) with a total Schelten score of 6. (B1) deep WMH 4–10 mm in the left temporal lobe (white arrow; Scheltens' score = 3). (B2–B5) multiple deep WMH in the both frontal lobes (white arrows), in the (B2) (left white arrow) and (B4) (white arrow) the size of the largest WMHs are 4–10 mm (Scheltens' score = 3). (C1–C7) a case (Kawasaki disease) with a total Schelten score of 6. (C1,C5,C7) multiple deep WMH < 3 mm in the frontal lobes (white arrows; Scheltens' score = 1). (C2) periventricular WMH ≤ 5 mm in the right frontal horn (yellow arrow; Scheltens' score = 1). (C3) deep WMH < 3mm in the right occipital lobe (white arrow; Scheltens' score = 1). (C4) (white arrow), (C5) (yellow arrow) and (C6) (yellow arrows): deep WMHs in the right parietal lobe, in the (C4) (white arrow) size of WMH is 4–10 mm (Scheltens' score = 1). (D1–D5) a case (Kawasaki disease) with a total Schelten score of 5. (D1,D2,D4,D5) Deep WMHs in the frontal lobes (white arrows). In the (D5) (white arrow) the size of the WMH is 4–10 mm (Scheltens' score = 3). (D3) periventricular WMH size > 5 mm next to left frontal horn (yellow arrow; Scheltens' score = 2).