Neuroradiologic patterns and novel imaging findings in Aicardi-Goutières syndrome

Abstract

Objective: To perform an updated characterization of the neuroradiologic features of Aicardi-Goutières syndrome (AGS).

Methods: The neuroradiologic data of 121 subjects with AGS were collected. The CT and MRI data were analyzed with a systematic approach. Moreover, we evaluated if an association exists between the neuroradiologic findings, clinical features, and genotype.

Results: Brain calcifications were present in 110 subjects (90.9%). Severe calcification was associated with TREX1 mutations and early age at onset. Cerebral atrophy was documented in 111 subjects (91.8%). Leukoencephalopathy was present in 120 children (99.2%), with 3 main patterns: frontotemporal, diffuse, and periventricular. White matter rarefaction was found in 54 subjects (50.0%), strongly associated with mutations in TREX1 and an early age at onset. Other novel radiologic features were identified: deep white matter cysts, associated with TREX1 mutations, and delayed myelination, associated with RNASEH2B mutations and early age at onset.

Conclusions: We demonstrate that the AGS neuroradiologic phenotype is expanding by adding new patterns and findings to the classic criteria. The heterogeneity of neuroradiologic patterns is partly explained by the timing of the disease onset and reflects the complexity of the pathogenic mechanisms.

Figure 1. Calcifications in our sample of patients with Aicardi-Goutières syndrome

Calcium deposits could be visualized on axial T1-weighted (A) and T2-weighted gradient-echo images (B). (C) Spot-like calcifications located in the lentiform nuclei and left posterior white matter. (D) Severe confluent calcifications. (E) Linear pattern. (F) Calcifications limited to the putamina in a patient with ADAR1 mutations.

Figure 2. MRI patterns of white matter involvement

(A, B) Axial T2-weighted image shows frontotemporal predominance in a 21-month-old patient. (C) Axial T2-weighted fluid-attenuated inversion recovery image shows bilateral white matter rarefaction at the level of the temporal poles in the same patient reported in A and B. (D) Axial T2-weighted image shows diffuse pattern and swollen frontal poles in a 4-month-old patient. (E) Axial T2-weighted image shows periventricular predominance in a 12-month-old patient. (F, G) Axial T2-weighted images show periventricular white matter involvement and loss of substance in a 3-year-old patient. (H, I) Axial T2-weighted images show improved atrophy and myelination in a patient at 3 months (H) and 5 years of age (I).

Figure 3. Novel neuroradiologic findings in Aicardi-Goutières syndrome

(A) Axial T2-weighted fluid-attenuated inversion recovery shows deep frontal white matter cystic lesions in a 4-month-old patient. (B) CT scan shows calcifications along the walls of the cysts. (C) Axial T1-weighted and (D) T2-weighted images show inadequate myelination in an 8-month-old patient with mild white matter involvement. (E, F) Axial T2-weighted images performed in a patient at age 4 and 7 years show involvement of the transverse pontine fibers.