Fetal neuroimaging findings in PHACE syndrome: case report and review of the literature

Death from cerebrovascular infarction in a patient with PHACES syndrome

Dandy-Walker Malformation

PHACE syndrome: Association with Persistent Fetal Vasculature and coloboma-like iris defect

Magnetic resonance imaging examination of the fetal brain

Large facial hemangiomas can have associated central nervous system malformations, particularly the Dandy-Walker posterior fossa malformations. Abnormal arteries, especially those of the central nervous system, coarctation of the aorta, cardiac defects, and unusual ophthalmologic abnormalities can also occur. We describe two patients with large facial hemangioma, congenital cataracts, and structural arterial abnormalities, particularly of the central nervous system vasculature. One of these infants also had a Dandy-Walker malformation detected on prenatal ultrasound at 12 weeks' gestation, suggesting that this syndrome had its origin during the first trimester of pregnancy. This infant also had a lingual thyroid and developed symptomatic hypothyroidism, possible induced by interferon alfa therapy of her hemangioma. These cases are discussed, along with 41 previously reported cases with similar findings. Large facial hemangiomas may have a distinctive group of associated arterial, central nervous system, and ophthalmologic anomalies. We propose the acronym PHACE syndrome to emphasize the characteristic findings of this neurocutaneous syndrome: posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities.

Aortic Coarctation: The Fetal Cardiologist's Achilles Heel.

To report the rate of additional central nervous system (CNS) anomalies detected exclusively on prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with isolated mild or moderate ventriculomegaly (VM) on ultrasound, according to the type of ultrasound protocol adopted (dedicated neurosonography vs standard assessment of the fetal brain), and to explore whether the diagnostic performance of fetal MRI in detecting such anomalies is affected by gestational age at examination and laterality and degree of ventricular dilatation. MEDLINE, EMBASE, CINAHL and Clinicaltrials.gov were searched for studies reporting on the prenatal MRI assessment of fetuses diagnosed with isolated mild or moderate VM (ventricular dilatation of 10-15 mm) on ultrasound. Additional anomalies detected only on MRI were classified as callosal, septal, posterior fossa, white matter, intraventricular hemorrhage, cortical, periventricular heterotopia, periventricular cysts or complex malformations. The rate of additional anomalies was compared between fetuses diagnosed on dedicated neurosonography, defined as a detailed assessment of the fetal brain, according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines, and those diagnosed on standard fetal brain assessment. The rate of additional CNS anomalies missed on prenatal MRI and detected only at birth was calculated and compared between fetuses that had early (at or before 24 weeks' gestation) and those that had late (after 24 weeks) MRI. Subanalysis was performed according to the laterality (uni- vs bilateral) and degree (mild vs moderate, defined as ventricular dilatation of 10-12 and 13-15 mm, respectively) of ventricular dilatation. Whether MRI assessment led to a significant change in prenatal management was explored. Random-effects meta-analysis of proportions was used. Sixteen studies (1159 fetuses) were included in the systematic review. Overall, MRI detected an anomaly not identified on ultrasound in 10.0% (95% CI, 6.2-14.5%) of fetuses. However, when stratifying the analysis according to the type of ultrasound assessment, the rate of associated anomalies detected only on MRI was 5.0% (95% CI, 3.0-7.0%) when dedicated neurosonography was performed compared with 16.8% (95% CI, 8.3-27.6%) in cases that underwent a standard assessment of the fetal brain in the axial plane. The overall rate of an additional anomaly detected only at birth and missed on prenatal MRI was 0.9% (95% CI, 0.04-1.5%) (I2 , 0%). There was no difference in the rate of an associated anomaly detected only after birth when fetal MRI was carried out before, compared with after, 24 weeks of gestation (P = 0.265). The risk of detecting an associated CNS abnormality on MRI was higher in fetuses with moderate than in those with mild VM (odds ratio, 8.1 (95% CI, 2.3-29.0); P = 0.001), while there was no difference in those presenting with bilateral, compared with unilateral, dilatation (P = 0.333). Finally, a significant change in perinatal management, mainly termination of pregnancy owing to parental request, following MRI detection of an associated anomaly, was observed in 2.9% (95% CI, 0.01-9.8%) of fetuses undergoing dedicated neurosonography compared with 5.1% (95% CI, 3.2-7.5%) of those having standard assessment. In fetuses undergoing dedicated neurosonography, the rate of a CNS anomaly detected exclusively on MRI is lower than that reported previously. Early MRI has an excellent diagnostic performance in identifying additional CNS anomalies, although the findings from this review suggest that MRI performed in the third trimester may be associated with a better detection rate for some types of anomaly, such as cortical, white matter and intracranial hemorrhagic anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

To assess the diagnostic and prognostic value of fetal cerebral magnetic resonance (MR) imaging of congenital cytomegalovirus (CMV) infection in comparison with that of level II ultrasonography (US). Institutional review board approval and informed consent for fetal MR imaging and data collection were obtained. Thirty-eight fetuses with CMV infection, examined by using serial level II US, underwent fetal MR imaging (mean gestational age, 25 weeks; age range at first fetal MR examination, 20-34 weeks). The frequency of pathologic findings at US (29 cases with transabdominal examination and nine cases with both transabdominal and transvaginal examination) and MR imaging was calculated, and a comparison between techniques by considering number (paired Student t test) and type (McNemar test) of finding was made. A comparison (paired Student t test) in cases of repeated fetal (nine of 38) and/or postnatal (14 of 38) MR imaging was obtained. Diagnostic and prognostic sensitivity was calculated for both techniques. US and MR imaging findings were both normal in 47% of cases (18 of 38). Abnormal studies were reported in 26% (10 of 38) of US and 53% (20 of 38) of MR imaging cases. In 47% of cases (18 of 38), MR imaging provided additional information (P = .0002). MR imaging had better results than US in detecting polar temporal lesions (P = .0001), microencephaly (P = .03), and cortical anomalies (P = .06). In 44.5% of cases (four of nine), the second fetal MR examination results showed new findings (P = .05). In 79% of cases, postnatal MR imaging results confirmed prenatal findings (P = .08). MR imaging had higher sensitivity than US in detecting brain anomalies (92% vs 38%) and in predicting symptomatic infection (83% vs 33%). US and MR imaging revealed low positive predictive values (29% vs 36%). Fetal MR imaging results can show abnormalities in the fetal brain after CMV infection, even when US results are normal. The early detection of some brain abnormalities, such as microencephaly and cortical anomalies, may substantially influence the prognosis of fetal infection.

PHACE (posterior fossa defects, haemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities) syndrome describes a constellation of abnormalities that can occur in association with segmental craniofacial infantile haemangioma. To report the spectrum of clinical and imaging abnormalities seen in a cohort of children. A retrospective review of the clinical and imaging records of all patients diagnosed with PHACE syndrome between 1998 and 2009 was performed. Information sought included patient demographics, craniofacial segments involved, imaging findings and other extracutaneous abnormalities. Twelve patients were diagnosed with PHACE syndrome over 11 years. All patients had a segmental craniofacial haemangioma. Involved facial segments, in order of frequency, were frontotemporal (12), maxillary (8), mandibular (5) and frontonasal (1). The most common extracutaneous abnormalities were neurovascular anomalies (10), with many patients having multiple anomalies. The spectrum of arterial anomalies ranged from hypoplasia (9) to ectasia (3), anomalous origin/course (2) and persistent fetal anastomosis (2). Other anomalies found included cardiac anomalies (3), coarctation of the aorta (2), posterior fossa malformations (1) and sternal region anomalies (1). Intracranial anomalies are the most common extracutaneous feature of PHACE syndrome. The contribution of the radiologist in the recognition of such anomalies is important for the diagnosis of PHACE syndrome.

Moyamoya Vasculopathy in PHACE Syndrome: Six New Cases and Review of the Literature.

Response of infantile airway and facial hemangiomas to propranolol in a patient with PHACE syndrome

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study

PHACE syndrome describes a spectrum of anomalies associated with large facial infantile hemangiomas and characterized by posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. With improved recognition and imaging practices of infants with PHACE syndrome, additional associations have been identified. To our knowledge, the potential association of ipsilateral hearing loss and PHACE syndrome has not been previously emphasized. We describe 6 patients, 4 with definite and 2 with probable PHACE syndrome, according to the new diagnostic criteria, and associated auditory deficiencies. One patient had isolated conductive hearing loss; 2 patients had isolated sensorineural hearing loss; 1 patient had mixed hearing loss (both conductive and sensorineural components); and 1 patient had hearing loss that was inconclusive at the time. Also, 1 patient had conductive loss and auditory neuropathy and auditory dyssynchrony. Four of the 6 patients had magnetic resonance imaging features of lesions consistent with intracranial hemangiomas involving auditory structures. All 6 patients had facial hemangiomas in a nearly identical distribution ipsilateral to the ear with the hearing loss, with involvement of the proposed facial segments S1 and S3, the affected ear, the periauricular region, and the midoccipital area of the scalp. There is an underrecognized risk of hearing loss in patients with PHACE syndrome, although the exact nature of such deficiencies can vary. Patients with PHACE syndrome who have cutaneous hemangiomas involving the ear should be evaluated for intracranial hemangiomas and monitored for hearing loss. Early detection and therapy of intracranial hemangiomas may slow or stop tumor growth, resultant hearing loss, and structural damage.

To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0-11.9 mm) or moderate (ventricular atrial diameter, 12.0-14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8-7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7-0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6-13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1-15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

We investigated whether prenatal magnetic resonance imaging (MRI) within 26weeks of gestation (GW) may predict the fate of isolated upward rotation of the cerebellar vermis (URCV). This retrospective multicentre observational study included foetuses diagnosed with isolated URCV in prenatal MRI performed within 26 GW. Isolated URCV was defined by a brainstem-vermis angle (BVA) ≥ 12° in the MR midline sagittal view without abnormalities of the supratentorial structures, brainstem, or cerebellum hemispheres. The assessments included the BVA, clival-supraoccipital angle, transverse diameter of the posterior cranial fossa, tentorial angle, width of the cisterna magna (WCM), ventricular width, vermian diameters, hypointense stripes, and cerebellar tail sign. Late prenatal or postnatal MRI was used as a reference standard to assess the final vermian fate (rotated/de-rotated). Forty-five foetuses (mean GW at prenatal MRI = 21.5 ± 1.4weeks) were included. In the reference standard, the vermis was de-rotated in 26 cases (57.7%). At least two of the following criteria were used to predict the persistence of URCV at imaging follow-up: BVA ≥ 23°, WCM ≥ 9mm, and the cerebellar tail sign. The results were a sensitivity of 84.21% (95% CI, 60.4-96.6%), specificity of 80.8% (95% CI, 60.6-93.4%), positive predictive value of 76% (95% CI, 58.7-87.8%), and negative predictive value of 87.5% (95% CI, 70.9-95.2%). MRI within 26 GW on foetuses diagnosed with isolated URCV may predict delayed cerebellar vermis de-rotation, which is associated with good neurodevelopmental outcome in most cases. • Foetal MRI is a valuable tool in predicting the fate of isolated upward-rotated cerebellar vermis. • A wider angle between the brainstem and vermis is associated with higher risk of persistence of vermian rotation. • The presence of ≥ 2 factors among a brainstem-to-vermis angle ≥ 23°, width of the cisterna magna ≥ 9mm, and the presence of the "cerebellar tail sign" has a sensitivity of 84.21% (95% CI, 60.4-96.6%) and specificity of 80.8% (95% CI, 60.6-93.4%) in predicting the persistence of the vermian rotation at imaging follow-up.