Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome

Abstract

Objective: Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed.

Methods: Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed.

Results: Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported).

Conclusion: The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome.

Classification of evidence: This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.

Figure 1. Corpus Callosum (CC) Malformations

T1-weighted sagittal MRI shows complete (A) or partial (B, C) agenesis of the CC; absence of the posterior part of the body and of the splenium and rostrum (B) or only of the genu and the rostrum (C); and complete but diffusely hypoplastic CC (D).

Figure 2. Cysts

T1-weighted axial images (A, D) show single unilocular interhemispheric supratentorial arachnoid cysts (white arrow), with CSF-like signal (type 2d according to the Barcovich classification); in (D), associated with an infratentorial arachnoid cyst (*). T1-weighted axial images (B, C) show multilocular (black arrow, B) and unilocular (dashed white arrow, C) supratentorial interhemispheric cysts with hyperintense to CSF signal (type 2b according to the Barcovich classification), probably glioependymal cysts. T2-weighted axial images (E, F) show choroid plexus cysts (asterisk, E) and papillomas (asterisk, F).

Figure 3. Cortical Malformations

Cortical dysplasia: T2-weighted axial images show different distributions of cortical dysplasia: focal (arrow, A), multifocal (C, D, E), and diffuse (B), in most cases with a polymicrogyric pattern (asterisk, C, D, E), mostly with an anterior-to-posterior gradient (C, D). Nodular heterotopias: T2-weighted axial images (F, H, I) and inversion recovery T1 axial image (G) show the presence of periventricular heterotopias. The nodules could be numerous and spread asymmetrically around the lateral ventricles (F), and could be single (arrow, H), confluent (arrow, G), or both (F). A single case of subependymal heterotopia of the IV ventricle was detected (asterisk, I).

Figure 4. Posterior Fossa and Basal Ganglia Dysmorphisms

Posterior fossa dysmorphisms: T2-weighted axial (A, B, C) and coronal (D) MRI show (A) complex posterior fossa malformation with rhomboencephalosynapsis and hemispheric schizencephaly, (B) left cerebellar cortical dysplasia and inferior vermis hypoplasia, and (C) right cerebellar cortical dysplasia and fusion with the vermis, likely representing incomplete rhomboencephalosynapsis. (D) Cortical dysplasia of the right cerebellar hemisphere (left and superior aspects) and vermis. Basal ganglia dysmorphisms: T2-weighted axial images show a stubby and globular appearance or slight hypoplasia of the striatum with an irregular and straight lateral profile of the putamen (white arrow, E, F, G, H), variably associated with microcysts along the irregular profile of the putamen (asterisk, G, H, I)—likely small dilated perivascular spaces—and internal capsule anterior limb agenesis (black arrow, E ,F, G, H). (I) Association with thalamic adhesion can also be observed.