Cervical and Intracranial Arterial Anomalies in 70 Patients with PHACE Syndrome

Abstract

BACKGROUND AND PURPOSE Cerebral and cervical arterial abnormalities are the most common non-cutaneous anomaly in PHACE syndrome, but the location and type of arterial lesions that occur have not been systematically assessed in a large cohort. Our aim was to characterize the phenotypic spectrum of arteriopathy, assess the frequency with which different arteries are involved, and evaluate spatial relationships between arteriopathy, brain structural lesions, and hemangiomas in PHACE syndrome. MATERIALS AND METHODS Intracranial MRA and/or CTA images from 70 children and accompanying brain MR images in 59 patients with arteriopathy and PHACE syndrome were reviewed to identify the type and location of arterial lesions and brain abnormalities. Five categories of arteriopathy were identified and used for classification: dysgenesis, narrowing, nonvisualization, primitive embryonic carotid-vertebrobasilar connections, and anomalous arterial course or origin. Univariate logistic regression analyses were performed to test for associations between arteriopathy location, hemangiomas, and brain abnormalities. RESULTS By study design, all patients had arterial abnormalities, and 57% had >1 form of arteriopathy. Dysgenesis was the most common abnormality (56%), followed by anomalous course and/or origin (47%), narrowing (39%), and nonvisualization (20%). Primitive embryonic carotid-vertebrobasilar connections were present in 20% of children. Hemangiomas were ipsilateral to arteriopathy in all but 1 case. The frontotemporal and/or mandibular facial segments were involved in 97% of cases, but no other specific associations between arteriopathy location and hemangioma sites were detected. All cases with posterior fossa anomalies had either ICA anomalies or persistent embryonic carotid-basilar connections. CONCLUSIONS The arteriopathy of PHACE syndrome commonly involves the ICA and its embryonic branches, ipsilateral to the cutaneous hemangioma, with dysgenesis and abnormal arterial course the most commonly noted abnormalities. Brain abnormalities are also typically ipsilateral.

Diagnosis and Management of Infantile Hemangioma

“…PHACE syndrome-associated IHs most commonly affect facial segments 1 and/or 3, which also confers a particularly high risk of associated central nervous system involvement. 84,119 PHACE syndrome is not exceedingly rare, and probably even more common than Sturge-Weber syndrome. 121 The segmental IH associated with PHACE is sometimes confused with the port wine stain associated with SturgeWeber syndrome, especially in the newborn period before significant IH proliferation or in cases of "minimal growth" IH in which there is an absence of significant proliferation.…”

“…More than 90% of infants with PHACE syndrome exhibit more than 1 extracutaneous anomaly, although very few manifest the complete spectrum. 119 In contrast to nonsyndromic IH, PHACE syndrome…”

“…84 The most common arterial abnormality in PHACE syndrome is dysgenesis of the anterior circulation, particularly within the internal carotid artery. 119 The neuroanatomic and cerebrovascular anomalies observed in PHACE may lead to a number of neurologic sequelae, including motor and speech delays, seizures, migraine-like headaches, and rarely, arterial ischemic stroke. 121 Hearing loss (conductive or sensorineural) has also been reported in PHACE syndrome, particularly when the IH involves the ear and periauricular scalp, which can be related to the presence of ipsilateral intracranial IH involving auditory structures.…”

Stroke in Children With Posterior Fossa Brain Malformations, Hemangiomas, Arterial Anomalies, Coarctation of the Aorta and Cardiac Defects, and Eye Abnormalities (PHACE) Syndrome

“…More than 59% had nonvisualization of a major cerebral artery compared with 20% of the Hess cohort of 70 patients with PHACE with arterial anomalies. 15 It is possible that the higher proportion of patients with these imaging findings is biased by the inherent pathophysiology of stroke with arterial narrowing or occlusion at the time of symptoms reflecting intravascular thrombus and/or the acute changes in blood flow accompanying infarction. However, the extent of narrowing or nonvisualization, presence of moyamoya collaterals, and the frequent observation of these findings in an arterial territory not directly related to the patient's acute symptoms mitigate against this possibility.…”

Infantile Hemangioma

“…En sık kızlarda görülen PHACE sendromu'nun nedeni tam olarak bilinememektedir. Arteriyel ya da serebral anomalilerin İH ile aynı tarafta görülmesi 20 , lokal hipoksiye bağlı oluşabileceğini düşündürmektedir. İH'den farklı olarak hastalar termde doğmuş ve normal doğum kilosuna sahiptir 21 .…”