Abstract
BACKGROUND AND PURPOSE
Arg179His mutations in ACTA2 are associated with a distinctive neurovascular phenotype characterized by a straight course of intracranial arteries, absent basal Moyamoya collaterals, dilation of the proximal internal carotid arteries, and occlusive disease of the terminal internal carotid arteries. We now add to the distinctive neuroimaging features in these patients by describing their unique constellation of brain malformative findings that could flag the diagnosis in cases in which targeted cerebrovascular imaging has not been performed.
MATERIALS AND METHODS
Neuroimaging studies from 13 patients with heterozygous Arg179His mutations in ACTA2 and 1 patient with pathognomonic clinicoradiologic findings for ACTA2 mutation were retrospectively reviewed. The presence and localization of brain malformations and other abnormal brain MR imaging findings are reported.
RESULTS
Characteristics bending and hypoplasia of the anterior corpus callosum, apparent absence of the anterior gyrus cinguli, and radial frontal gyration were present in 100% of the patients; flattening of the pons on the midline and multiple indentations in the lateral surface of the pons were demonstrated in 93% of the patients; and apparent “squeezing” of the cerebral peduncles in 85% of the patients.
CONCLUSIONS
Because α-actin is not expressed in the brain parenchyma, only in vascular tissue, we speculate that rather than a true malformative process, these findings represent a deformation of the brain during development related to the mechanical interaction with rigid arteries during the embryogenesis.
The cerebral arteriopathy associated with Arg179His mutations in ACTA2 is a prototypical example of nonatherosclerotic cerebral arteriopathies, some of which are Mendelian disorders.1 Patients with the ACTA2 mutation have distinctive clinical (multisystem smooth-muscle involvement) and angiographic features2—specifically, a combination of ectasia and stenosis, a straight arterial course, absence of basal collaterals, and more widespread cerebrovascular involvement in comparison with Moyamoya disease.2 The diagnosis is suggested by these imaging features and has important implications for the management of the patient (increased risks associated with arterial instrumentation) and other family members, but it also provides important mechanistic insights that may be more generalizable.1 Previously, the imaging phenotype associated with ACTA2 mutations had been confined to cerebrovascular abnormalities and associated leukoencephalopathy,3 apart from a single case report of a patient with a dysmorphic corpus callosum.4
Here we expand the neuroimaging phenotype and describe characteristic brain parenchymal abnormalities that could flag the diagnosis when targeted cerebrovascular imaging has not been performed.
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Fellows’ Journal Club
Patients with the ACTA2 mutation have distinctive clinical and angiographic features—specifically, a combination of ectasia and stenosis, a straight arterial course, absence of basal collaterals, and more widespread cerebrovascular involvement in comparison with Moyamoya disease. Neuroimaging studies from 13 patients with heterozygous Arg179His mutations in ACTA2 and 1 patient with pathognomonic clinicoradiologic findings for ACTA2 mutation were retrospectively reviewed. Characteristic bending and hypoplasia of the anterior corpus callosum, apparent absence of the anterior gyrus cinguli, and radial frontal gyration were present in 100% of the patients; flattening of the pons on the midline and multiple indentations in the lateral surface of the pons were demonstrated in 93% of the patients.