Aicardi-Goutieres syndrome: neuroradiologic findings and follow-up

Abstract

Background and purpose: To date, few studies have focused specifically on imaging findings in Aicardi-Goutières syndrome (AGS). We set out to evaluate retrospectively neuroradiologic data from a large sample of patients with AGS, focusing on the pattern of white matter abnormalities and the temporal evolution of the cerebral involvement to establish the radiologic natural history of the disease.

Materials and methods: Thirty-six patients, 18 girls and 18 boys, were included. All had a clinical diagnosis of AGS, genetically confirmed in 31 of them. For every subject, we reviewed at least 1 CT and 1 MR imaging study; 19 (52.7%) had multiple examinations. In all, we reviewed 109 examinations. Clinical-neuroradiologic comparisons were analyzed by using the chi(2) test.

Results: Calcifications were found in all subjects, mainly in the basal ganglia, lobar white matter, and dentate nuclei. Abnormal white matter was present in all the subjects, showing 2 patterns of distribution: diffuse in 18 (50%) and an anteroposterior gradient in 18 (50%). Cystic areas were observed in the temporal and/or frontal lobes in 12/36 patients (33.3%). A correlation was found between early age at onset and severity of the leukoencephalopathy in the frontal (P = .024) and temporal (P = .034) regions. A significant degree of cerebral atrophy was found in 31/36 subjects (86.1%). The neuroradiologic presentation remained substantially stable with time.

Conclusions: The different neuroradiologic presentations of AGS are here outlined for the first time in a large sample of patients. These findings may facilitate more precise and earlier diagnosis of this rare but probably underdiagnosed syndrome.

Fig 1.

Leukoencephalopathy. A, Case 19. Axial spin-echo T2-weighted (1.5T, TR = 2554 ms, TE = 100 ms) MR image shows a faint T2 hyperintensity involving the cerebral white matter in a diffuse pattern. Calcifications are seen in the lobar white matter as focal hypointensities (arrows). B and C, Axial T2- (1.5T, turbo spin-echo, TR = 5022 ms, TE = 100 ms) (B) and T1-weighted images (1.5T, inversion recovery, TR = 3430 ms, TE = 15 ms, TI = 400 ms) (C), with the same parameters in case 10, demonstrate extensive cerebral white matter abnormalities, showing an anteroposterior gradient. The T1-weighted images better highlight areas of cavities in the frontal lobes, whereas the signal-intensity properties of the involved white matter are almost identical to those of the liquoral spaces (arrows).

Fig 2.

Cerebral calcifications. A, Axial nonenhanced CT image of case 1 shows numerous punctuate calcifications within the basal ganglia and the cerebral white matter, a pattern typical in patients with AGS. B, Contrast-enhanced CT scan (case 19) shows large calcifications in the white matter. Although the CT examination was performed in the acute phase of the disease, no signs of contrast enhancement are seen. Atrophy, microcephaly, and areas of hypoattenuation in the periventricular white matter are also evident.

Fig 3.

Coronal fast spin-echo T2-weighted MR image (1.5T, TR = 5022 ms, TE = 100 ms) of case 10 shows a diffuse signal-intensity abnormality of the cerebral lobar white matter. Note that the cerebellar white matter and the optic radiations (arrows) are spared, whereas the subcortical U-fibers are involved. The cortex shows an even thickness. Severe cerebral atrophy is evident.

Fig 4.

Correlation between age at onset and the severity of leukoencephalopathy involving the frontal and temporal lobes (leukoencephalopathy score: 1 = mild; 2 = moderate; 3 = severe; 4 = presence of cystic degeneration). Mths indicate months.