Neuroimaging aspects of Aicardi syndrome

Abstract

Aicardi syndrome is a rare neurodevelopmental disorder characterized by congenital chorioretinal lacunae, corpus callosum dysgenesis, seizures, polymicrogyria, cerebral heterotopias, intracranial cysts, and costovertebral defects. Cerebellar abnormalities have been described occasionally. Aicardi syndrome is sporadic and has been observed only in females and 47,XXY males. Therefore, it is thought to result from a mutation in an X-linked gene. Improved definition of the clinical phenotype should focus the selection of functional candidate genes for mutation analysis. Because central nervous system abnormalities are the most prominent component of the phenotype, we performed a detailed characterization of abnormalities identified on magnetic resonance neuroimaging studies from 23 girls with Aicardi syndrome, the largest cohort to undergo such review by a single group of investigators. All patients had polymicrogyria that was predominantly frontal and perisylvian and often associated with underopercularization. Periventricular nodular heterotopias, present in all patients, were more frequent than previously reported; 10 had single and 11 had multiple intracranial cysts. Posterior fossa abnormalities were also more frequent than previously described. Cerebellar abnormalities were noted in 95% of studies where they could be evaluated. As a novel finding, we noted tectal enlargement in 10 patients. Since mildly affected girls with variable callosal dysgenesis have now been reported, the constellation of frontal-dominant and perisylvian polymicrogyria, periventricular nodular heterotopias, intracranial cysts, and posterior fossa abnormalities, including tectal enlargement, should prompt consideration of the diagnosis of Aicardi syndrome. We further propose that improved characterization of the neurological phenotype will benefit the selection of candidate genes for mutation analysis.

(c) 2008 Wiley-Liss, Inc.

Figures

Figure 1. T2-weighted axial images from six girls with Aicardi syndrome

All have gross cerebral asymmetry. Dashed circles indicate areas of polymicrogyria (PMG): 1A-C: perisylvian PMG with most extensive involvement in 1B; 1A and 1C show frontal PMG. The solid white arrows in 1A, 1C, and 1D point to single, nodular, periventricular heterotopias. The round marker in 1C points to confluent rows of periventricular heterotopias. Arrowheads point to subcortical heterotopias in the cerebellum (1E) and in the frontal regions (1F). Underdevelopment of the operculum is seen in figures 1A, 1B, and 1C. Asterisks point to a large posterior fossa cyst in 1B; a midline interhemispheric cyst in 1C and a left-occipital intraparenchymal cyst in 1F.

Figure 2. T2 weighted axial image showing thalamic heterotopia

Bilateral thalamic heterotopia are indicated by black arrowheads. This image also demonstrates right sided underopercularization with bilateral perisylvian polymicrogyria, left frontal polymicrogyria, left lateral ventricle nodular heterotopia, ventriculomegaly, and gross cerebral hemispheric asymmetry.

Figure 3. T1 weighted axial, sagittal, and coronal images from five girls with Aicardi syndrome

3A and 3A1 (from the same individual) show a multiloculated contrast-enhancing hyperintense cyst in the right lateral ventricle, resembling cysts associated with choroid plexus papillomas. 3B and 3C each illustrate a round hyperintense cyst in the right lateral ventricle and a midline/interhemispheric cyst with contrast enchancement in 3B (3C was a study without contrast). 3D shows a large interhemispheric cyst. 3E illustrates an extra-axial cyst in the posterior fossa (also seen in 1B) and an intraparenchymal cyst in the right cerebellar hemisphere.

Figure 4. Cerebellar and tectal abnormalities in Aicardi syndrome

All panels demonstrate inferior vermis hypoplasia. 4A and 4B show superior foliar prominence, 4B and 4C show large cisternae magnae. 4A illustrates a normal sized tectum measuring 13 mm in length and 0.4 mm in width and 4B and 4C show tectal enlargement (3B = 16 mm × 7 mm and 3C = 15 mm × 6 mm).