PHACE(S) SYNDROME - EARLY DIAGNOSTICS IN THE MAXILLOFACIAL AREA.

OBJECTIVE: The aim: To determine the minimum criteria for early diagnosing PHACE(S) syndrome in neonates and infants with infantile hemangioma (IH) in the max¬illofacial area. PATIENTS AND METHODS: Materials and methods: A total of 26 asymptomatic children from 20 days to six months of aged with IH of more than 5 cm² in the maxillofacial area were included in this study. A medical record of patients clinical examination, Holter monitoring, echocardiographic ultrasound and magnetic resonance imaging (MRI) were analysed. The IH treatment with ß-blockers was carried out. RESULTS: Results: IH localization was diagnosed: 62% with a lesion of a part facial segment, 23% in one segment, 15% in several segments (p=0.018), and 12% with other parts of the body lesion (p=1.000). The patent foramen ovale was diagnosed in 35% of children. Central nervous system disorders were observed in 12% over two years of age. The indices of Holter monitoring and blood glucose changed in age norm range during treatment. Cardiovascular (the aortic coarctation (p=0.003) and brain (the Dandy-Walker malformation) (p=0.031) abnormalities were determined in two cases (8%) according to the MRI only. We diagnosed PHACE(S) syndrome in both these cases of children, only aged 12 months and 2.5 years old. CONCLUSION: Conclusions: Early diagnosis of PHACE(S) syndrome is possible on a contrast-enhanced MRI performed in asymptomatic neonates and infants with the facial several segmental IH with / without ulceration (p=0.018, p=0.046; p < 0.05) for recognition of presymptomatic cardiovascular and brain abnormalities.

Long-term follow-up of patients with extensive segmental infantile hemangioma of the cervical or facial region: A French single-center prospective study.

BACKGROUND: Infantile hemangiomas (IHs) can be part of PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies) syndrome when they are segmental, extensive, and located on the face or neck. The initial assessment is codified and well known, but there are no recommendations for the follow-up of these patients. The aim of this study was to assess the long-term prevalence of different associated abnormalities. METHODS: Patients with a history of large segmental IHs of the face or neck. diagnosed between 2011 and 2016 were included in the study. Each patient underwent an ophthalmological, dental, ENT (ear, nose, and throat), dermatological, neuro-pediatric, and radiological assessment at inclusion. Eight patients including five with PHACE syndrome were prospectively evaluated. RESULTS: After a mean follow-up of 8.5 years, three patients presented with an angiomatous aspect of the oral mucosa, two with hearing loss, and two with otoscopic abnormalities. No patients developed ophthalmological abnormalities. The neurological examination was altered in three cases. Brain magnetic resonance imaging follow-up was unchanged in three out four patients and revealed atrophy of the cerebellar vermis in 1 patient. Neurodevelopmental disorders were found in five of the patients and learning difficulties were observed in five patients. The S1 location appears to be associated with a higher risk of neurodevelopmental disorders and cerebellar malformations, while the S3 location was associated with more progressive complications, including neurovascular, cardiovascular, and ENT abnormalities. CONCLUSION: Our study reported late complications in patients with a large segmental IH of the face or neck, whether associated with PHACE syndrome or not, and we proposed an algorithm to optimize the long-term follow-up.

Histologic and morphologic character of pediatric abdominal aortic developmental coarctation and hypoplasia.

OBJECTIVES: Abdominal aortic coarctation and hypoplasia are uncommon diseases, recognized most often in pediatric-aged individuals. Comprehensive studies regarding the pathologic spectrum of these aortopathies are nonexistent. This investigation was undertaken to better define the histologic and morphologic character of abdominal aortic narrowings affecting children and assess its potential relevance to contemporary clinical practice. METHODS: Aortic specimens obtained during open operations in children being treated for symptomatic, noninflammatory abdominal aortic narrowings at the University of Michigan were subjected to histologic study after hematoxylin and eosin, Movat, Verhoeff Van Gieson, and Masson's trichrome preparations. Microscopic findings were correlated with the anatomic aortic images. In addition, a detailed review was completed of all prior reports in the English literature that included images depicting the histologic character of noninflammatory abdominal aortic narrowings in children. RESULTS: Among a series of 67 pediatric-aged individuals undergoing open surgical interventions for abdominal aortic narrowings, eight children ranging in age from 9 months to 18 years, had adequate aortic tissue available for study. The loci of the specimens paralleled the anatomic sites of segmental coarctations observed in the entire series, with involvement of the suprarenal abdominal aorta (n = 3), intrarenal aorta (n = 2), and infrarenal aorta (n = 1). Diffusely hypoplastic abdominal aortas (n = 2) included one case of a de facto aortic duplication, represented by a channel that paralleled the narrow native aorta and gave origin to celiac artery branches, as well as the superior mesenteric and renal arteries. Concentric or eccentric intimal fibroplasia was observed in every aorta, often with internal elastic fragmentation and duplication (n = 4). Media abnormalities included elastic tissue disorganization (n = 3) and focal medial fibrosis (n = 1). Organizing luminal thrombus occurred in two infants. Coexistent ostial stenoses of the celiac, superior mesenteric, or renal arteries were observed in all but the only child who had an infrarenal aortic coarctation. Neurofibromatosis type 1 affected one child whose histologic findings were indistinguishable from those of the other children. A review of prior published histologic images of abdominal aortic coarctation and hypoplasia affecting children from other centers revealed a total of 14 separate reports, each limited to single case photomicrographs, of which 11 exhibited intimal fibroplasia. CONCLUSIONS: Intimal fibroplasia is a common accompaniment of developmental abdominal aortic coarctation and hypoplasia. It is posited that intimal fibroplasia, which is likely progressive in instances of abnormal shear stresses in these diminutive vessels, may contribute to less salutary outcomes after endovascular and certain open reconstructions of pediatric abdominal aortic narrowings.

Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

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PHACES Syndrome and Associated Anomalies: Risk Associated With Small and Large Facial Hemangiomas.

OBJECTIVE. PHACES syndrome includes posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal defect with or without supraumbilical raphe. Usually, brain imaging is performed when facial hemangiomas are larger than 5 cm. Data on associated anomalies regardless of hemangioma size are sparse. The objective of this study was to determine, first, the prevalence of PHACES-like associated anomalies in a large sample of infants with all sizes of segmental facial or periorbital focal infantile hemangioma and, second, whether the cutaneous localization of the hemangioma correlates with the type of anomalies present. MATERIALS AND METHODS. The records of all patients of a vascular anomalies practice who had a diagnosis of segmental facial or periorbital focal infantile hemangioma and who had clinical photographs and brain MRI available were reviewed. The clinical photographs were reviewed to determine the localization by segment and lateralization. MRI was reviewed by two experienced pediatric radiologists. If present, cardiovascular anomalies, sternal defects, and eye anomalies were recorded. The criteria for definite and possible PHACES were used. RESULTS. The study included 122 children (90 girls, 32 boys; mean age, 16.6 months). Forty-five (36.9%) children had a facial infantile hemangioma larger than 5 cm. Twenty-two patients (18.0%) had PHACES or possible PHACES syndrome. Cerebrovascular structural anomalies were seen in 14 of 22 and brain anomalies in 6 of 22 patients with PHACES syndrome but in none and one of the patients in the group without PHACES (p < .001). Cardiovascular anomalies were seen in six patients and ocular anomalies in eight patients. All but one of them had PHACES syndrome. CONCLUSION. Clinical concern about associated extracutaneous anomalies is warranted for all children with facial segmental or periorbital focal infantile hemangiomas, including those with small hemangiomas. Further studies are needed to correlate cerebrovascular anomalies with the clinical evolution of hemangiomas and their effects on cerebral perfusion.

Intravascular Ultrasound for Assessment of Residual Coarctation of the Aorta after Balloon Angioplasty in Infants.

Intravascular ultrasound (IVUS) has been introduced as an accurate and minimally invasive diagnostic technique for the assessment of vascular anatomy and its abnormalities. We believe that IVUS can be used for clarifying the reasons for failure of balloon angiography in infantile coarctation of the aorta (CoA), because post-balloon angioplasty tearing, intimal flap, thrombosis and pseudoaneurysm of the aorta can be evaluated by IVUS with greater sensitivity and specificity. We aimed to assess the outcome of balloon angioplasty of CoA using angiography as the gold standard and IVUS as a new method in infants, comparing the two techniques for the evaluation of the diameter and area of CoA segment pre- and post-procedure. This cross-sectional study was performed on 18 infants hospitalized with a final diagnosis of CoA. All the infants underwent angiography and were also assessed by IVUS to measure the preoperative and postoperative diameter of the narrow segment in the two anterior-posterior and lateral views. In assessment by IVUS, the mean diameter of the coarctation site increased from 2.10 ± 0.30 mm to 4.50 ± 0.94 mm (P < 0.001). Similarly, the average minimum area of the coarctation level increased from 5.26 ± 1.50 mm2 to 13.77 ± 3.48 mm2 after angioplasty (P < 0.001). Comparing these findings, angiography and IVUS showed a high level of agreement. In the assessment of a dissection flap, there was a high level of agreement between angioplasty and IVUS before the procedure, but IVUS had higher accuracy after the procedure. Our study showed that IVUS was more reliable than angiography in the assessment of residual coarctation. IVUS yielded high sensitivity (58.3%) and specificity (100%) for discriminating the presence and absence of residual coarctation as well as the need for repeating the procedure. The assessment of coarctation before and after angioplasty procedures in children is possible using the IVUS method, with high accuracy. IVUS can offer greater accuracy than angiography in the evaluation of the coarctation area, detecting tears, dissection and flaps, and assessment of residual coarctation.

Arterial Spin-Labeling Perfusion for PHACE Syndrome.

BACKGROUND AND PURPOSE: Arterial stroke is a rare-but-reported complication in patients with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome. Currently, stroke risk is inferred by the severity of arterial anomalies identified on MRA, though no evidenced-based data exist. The purpose of our study was to determine whether arterial spin-labeling MR imaging perfusion can detect alterations in CBF in patients with PHACE syndrome. MATERIALS AND METHODS: Records were reviewed from 3 institutions for all patients with PHACE syndrome who underwent arterial spin-labeling from 2000 to 2019. CBF was qualitatively investigated with arterial spin-labeling to determine whether there was decreased or normal perfusion. Arterial anomalies were characterized on MRA imaging, and parenchymal brain findings were evaluated on conventional MR imaging sequences. RESULTS: Forty-one patients with PHACE syndrome had arterial spin-labeling imaging. There were 30 females and 11 males (age range, 7 days to 15 years). Of the 41 patients, 10 (24%) had decreased CBF signal corresponding to a major arterial territory. Ten of 10 patients had decreased CBF signal in the anterior circulation, 2/10 had decreased anterior and posterior circulation CBF signal, 2/10 had decreased bilateral anterior circulation CBF signal, and 1/10 had globally decreased CBF signal. Forty of 41 (97.5%) patients had at least 1 arteriopathy, and in those with decreased CBF signal, the arteriopathy corresponded to the CBF signal alteration in 10/10 patients. CONCLUSIONS: Arterial spin-labeling can potentially characterize hemodynamic changes in patients with PHACE syndrome.

Infantile and congenital hemangiomas.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy. They typically appear after birth and undergo a period of rapid growth, followed by a gradual period of involution. Although the majority of IHs do not requirement treatment, oral propranolol is the first-line therapy for lesions that are at risk for life-threatening complications, functional impairment, ulceration, or permanent disfigurement. Rarely, IHs can be associated with structural anomalies. Congenital hemangiomas (CHs) are a distinct clinical entity, caused by a point mutation in GNAQ or GNA11. These lesions are typically present at birth and display a wide spectrum of clinical presentations. CHs can be distinguished from IHs by their unique histologic and radiographic features. Given the high-flow vascularity of CHs, surgical excision may be indicated due to the high risk of bleeding.

Blood pressure changes PVAT function and transcriptome: use of the mid-thoracic aorta coarcted rat.

Perivascular adipose tissue (PVAT) modifies the contractile function of the vessel it surrounds (outside-in signaling). Little work points to the vessel actively affecting its surrounding PVAT. We hypothesized that inside-out arterial signaling to PVAT would be evidenced by the response of PVAT to changes in tangential vascular wall stress. Rats coarcted in the mid-thoracic aorta created PVAT tissues that would exemplify pressure-dependent changes (above vs. below coarctation); a sham rat was used as a control. Radiotelemetry revealed a ∼20 mmHg systolic pressure gradient across the coarctation 4 wk after surgery. Four measures (histochemical, adipocyte progenitor proliferation and differentiation, isometric tone, and bulk mRNA sequencing) were used to compare PVAT above versus below the ligature in sham and coarcted rats. Neither aortic collagen deposition in PVAT nor arterial media/radius ratio above coarctation was increased versus below segments. However, differentiated adipocytes derived from PVAT above the coarctation accumulated substantially less triglycerides versus those below; their relative proliferation rate as adipogenic precursors was not different. Functionally, the ability of PVAT to assist stress relaxation of isolated aorta was reduced in rings above versus below the coarctation. Transcriptomic analyses revealed that the coarctation resulted in more differentially expressed genes (DEGs) between PVAT above versus below when compared with sham samples from the same locations. A majority of DEGs were in PVAT below the coarctation and were enriched in neuronal/synaptic terms. These findings provide initial evidence that signaling from the vascular wall, as stimulated by a pressure change, influences the function and transcriptional profile of its PVAT.NEW & NOTEWORTHY A mid-thoracic aorta coarcted rat was created to generate a stable pressure difference above versus below the coarctation ligature. This study determined that the PVAT around the thoracic aorta exposed to a higher pressure has a significantly reduced ability to assist stress relaxation versus that below the ligature and appears to retain the ability to be anticontractile. At the same time, the PVAT around the thoracic aorta exposed to higher pressure had a reduced adipogenic potential versus that below the ligature. Transcriptomics analyses indicated that PVAT below the coarctation showed the greatest number of DEGs with an increased profile of the synaptic neurotransmitter gene network.

How often is coarctation of aorta correctly diagnosed antemortem in children with fatal illnesses? A retrospective review of medical and autopsy records.

This retrospective study analyzed the level of concordance between clinical and autopsy diagnosis of coarctation of aorta over 10 years. Utilizing the Goldmann classification, the concordance rate was found to be 16%. Major discrepancies (Class I and II) were found in 56% cases and minor discrepancies (Class III and IV) in 28% cases.

Management of PHACES syndrome: Risk of stroke and its prevention from a neurosurgical perspective.

BACKGROUND AND OBJECTIVES: A multidisciplinary approach for PHACES is essential. A meticulous diagnostic and treatment protocol for PHACES patients with cerebrovascular anomalies within the intermediate and high risk strata for ischemic stroke is presented. We also differentiate the vasculopathy associated with PHACES syndrome from moyamoya angiopathy. METHODS: Medical records and radiological imaging were reviewed. After initial magnetic resonance imaging/angiography (MRI/MRA), H215O-PET scan (baseline and Acetazolamide challenge) was performed in three patients and 6-vessel cerebral angiography was performed in two patients. Two patients with significant intracranial cerebrovascular anomalies underwent cerebral revascularization. RESULTS: Each patient presented with a facial hemangioma at birth and additional cerebrovascular anomalies ranging from hypoplasia to steno-occlusive changes of intracranial cerebral arteries. Additional involvement of the cardiovascular system was observed in two patients. Additional to MRI/MRA, a H215O-PET helped stratify the three patients into intermediate (n=1) and high risk groups (n=2). The high-risk group patients underwent individualized cerebral revascularization for future stroke prevention. The patient in intermediate risk group will be followed. Cerebrovascular angiopathy seen in all patients was typical for PHACES without moyamoya and was not progressive at follow-up. CONCLUSIONS: Patients within the intermediate and high-risk strata for ischemic stroke must undergo a 6-vessel cerebral angiography and further hemodynamic evaluation to indicate need for cerebral revascularization to prevent ischemic stroke. Non-progressive vasculopathy associated with PHACES can itself be hemodynamically relevant for neurosurgical intervention. This vasculopathy is distinct from moyamoya angiopathy, which can occur in conjunction with PHACES, resulting in concurrent progressive vasculopathy that would otherwise be absent.

Impact of valve morphology, hypertension and age on aortic wall properties in patients with coarctation: a two-centre cross-sectional study.

OBJECTIVE: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation. DESIGN: Cross-sectional study. SETTING: The study was conducted at two university medical centres, located in Berlin and London. PARTICIPANTS: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements. OUTCOME MEASURES: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines. RESULTS: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment. CONCLUSION: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation.

Early Postnatal Echocardiography in Neonates with a Prenatal Suspicion of Coarctation of the Aorta.

Coarctation of the aorta (COA) is suspected prenatally when there is ventricular asymmetry, arterial disproportion, and hypoplasia of the aortic arch/isthmus. The presence of fetal shunts creates difficulty in prenatal confirmation of the diagnosis so serial echocardiography after birth is necessary to confirm or refute the diagnosis. The first neonatal echocardiogram in prenatally suspected cases of COA was assessed for prediction of neonatal COA repair (NCOAR). This included morphological assessment, measurement of the aortic arch and calculation of the distal arch index (DAI = distance between left common carotid and left subclavian artery/diameter of the distal arch). NCOAR was undertaken in 23/60 (38%) cases. Transverse arch, aortic isthmus z-score, and DAI had an area under the receiver operator curve of 0.88 (95% CI 0.77-0.98), 0.86 (95% CI 0.75-0.96), and 0.84 (95% CI 0.74-0.95), respectively for the prediction of NCOAR. Using transverse arch z-score threshold < - 3 gave sensitivity 100%, NPV: 100%, specificity 76%; aortic isthmus z-score < - 3: NPV 92%, specificity 62% and DAI > 1.4: NPV 88%, specificity 78%. The size of the distal aortic arch in infants with a common origin of the innominate artery and left common carotid artery who did not require COA repair was similar to the NCOAR cases (p = 0.22). The early postnatal assessment of the size and morphology of the aortic arch can assist in risk stratification for development of neonatal COA. The branching pattern of the head/neck vessels impacts on the size of the distal aortic arch adding to the complexity of predicting COA based on vessel size.

Hamartomas and midline anomalies in association with infantile hemangiomas, PHACE, and LUMBAR syndromes.

BACKGROUND/OBJECTIVE: The pathogenesis of infantile hemangiomas (IH), PHACE, and LUMBAR syndromes remains unknown. We aim to describe histopathologic features of midline anomalies associated with IH, including patients with PHACE and LUMBAR syndromes. METHODS: A multicenter retrospective chart review was performed to identify patients with IH, PHACE, and LUMBAR syndrome with histopathologic specimens from sternal or midline anomalies. A total of 18 midline lesions from 13 patients were included. Out of 18, 14 midline lesions underwent both histopathologic and clinical review. Three hamartoma-like chin plaques and one supraumbilical raphe underwent only clinical review. RESULTS: All 13 patients had midline lesions and IH. Histopathologic diagnoses were as follows: rhabdomyomatous mesenchymal hamartoma (3), folliculosebaceous cystic hamartoma (1), fibroepithelial polyp (1), verrucous epidermal hyperplasia with vascular proliferation and fibroplasia (1), congenital midline cervical cleft (1), pericardium with fibrosis (1), fibrous components with increased collagen (1), atrophic skin/membrane (3), angiolipomatous mass with neural components (1), and lipomatous mass (1). Due to the retrospective nature of this study, it was not possible to obtain pathology slides for all midline lesions that had previously been biopsied or resected. We show clinically and histopathologically a new association between PHACE syndrome and rhabdomyomatous mesenchymal hamartoma (RMH), in addition to demonstrating the association between PHACE syndrome and chin hamartomas. We also display histopathologic findings seen in midline lesions resected from LUMBAR patients. CONCLUSION: Rhabdomyomatous mesenchymal hamartoma is thought to be related to aberrations of mesenchymal cells during development; therefore, this may provide clues to the pathogenesis of IH and related syndromes.

Recoarctation of the aorta after the Norwood procedure may be treated during the second stage of the surgical palliation.

OBJECTIVES: Recoarctation of the aorta (re-CoA) after the Norwood procedure is traditionally treated during catheter-based aortoplasty (CB-A) performed as a separate procedure preceding stage II surgical palliation (S II SP). Our goal was to determine the efficacy of the protocol according to which re-CoA after the Norwood procedure in patients with hypoplastic left heart syndrome is treated during S II SP using hybrid catheter-based aortoplasty. METHODS: We compared 2 groups of infants who developed re-CoA after the Norwood procedure and were treated at the same institution: In group I (n = 18), CB-A was traditionally performed before S II SP; in group II (n = 15), CB-A was performed during S II SP using a hybrid procedure (catheter access was through an aortic cannula routinely used for cardiopulmonary bypass). The right ventricular fractional area change was analysed. RESULTS: The CB-A was performed effectively in both groups. S II SP was performed at a younger age in group II (5.4 ± 0.3 vs 6.0 ± 0.4 months; P = 0.003), with lower body weight (5.6 ± 0.5 vs 6.0 ± 0.4; P = 0.03, respectively). The duration of hospital stay did not differ between the groups (10.6 ± 6.2 vs 11.6 ± 6.4 days; P = 0.91). The right ventricular fractional area change measured before S II SP was higher in group I (39.7 ± 4.2% vs 36.8 ± 3.6%, respectively; P = 0.009), but the difference was not seen 1 month after S II SP (41.0 ± 5.6 vs 39.8 ± 4.1; P > 0.05). The total radiation dose was significantly lower in group II. CONCLUSIONS: re-CoA after the Norwood procedure in patients with hypoplastic left heart syndrome can be treated effectively during S II SP using a hybrid procedure. The strategy allows for reduction of the total radiation dose and of the number of procedures and does not prolong the postoperative course, even in patients with decreased right ventricular systolic function.

A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions.

Background PHACE syndrome is a rare vascular neurocutaneous disorder characterized by posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies. Growth hormone deficiency (GHD) has been infrequently described. Case presentation We report a girl with PHACE syndrome. Endocrine abnormalities including abnormal thyroid functions and GHD have recently been described in similar cases. Conclusions This case suggests the necessity to screen pituitary functions in all patients with PHACE syndrome with abnormal hypothalamus and pituitary (HP) anatomy. Likewise, growth parameters and thyroid function test (TFT) should be monitored in all patients with PHACE syndrome at regular intervals.