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Propranolol use in PHACE syndrome with cervical and intracranial arterial anomalies: collective experience in 32 infants.

ABSTRACT: The objective of this retrospective study of patients evaluated between July 2008 and October 2011 in seven pediatric dermatology centers was to combine collective clinical experience using oral propranolol therapy in 32 infants with PHACE syndrome (Posterior fossa [brain malformations present at birth], Hemangioma [usually covering a large area of the skin of the head or neck >5 cm]; Arterial lesions [abnormalities of the blood vessels in the neck or head]; Cardiac abnormalities or aortic coarctation [abnormalities of the heart or blood vessels that are attached to the heart]; Eye abnormalities) with cervical or intracranial arterial anomalies. Patients were given an average daily dose of oral propranolol of 1.8 mg/kg divided two or three times per day for an average duration of 12.3 months. The main outcome measure was adverse neurologic events. Seven (22%) patients were categorized as being at higher risk for stroke, defined on magnetic resonance imaging as severe, long-segment narrowing or nonvisualization of major cerebral or cervical vessels without anatomic evidence of collateral circulation, often in the presence of concomitant cardiovascular comorbidities. Only one patient developed a change in neurologic status during propranolol treatment: mild right hemiparesis that remained static and improved while propranolol was continued. An additional three patients had worsening hemangioma ulceration or tissue necrosis during therapy. This is the largest report thus far of patients with PHACE syndrome treated with propranolol. Although no catastrophic neurologic events occurred, serious complications, particularly severe ulcerations, were seen in a minority of patients, and given the sample size, we cannot exclude the possibility that propranolol could augment the risk of stroke in this population. We propose radiologic criteria that may prove useful in defining PHACE patients as being at high or standard risk for stroke. We continue to advise caution in using systemic beta-blockers, particularly for children with vascular anomalies at higher risk for stroke. Use of the lowest possible dosage, slow dosage titration, three times per day dosing to minimize abrupt changes in blood pressure, and close follow-up, including neurologic consultation as needed, are recommended.

SUBMITTER: Metry D

PROVIDER: S-EPMC4995066 | biostudies-literature | 2013 Jan-Feb

REPOSITORIES: biostudies-literature

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Propranolol use in PHACE syndrome with cervical and intracranial arterial anomalies: collective experience in 32 infants.

Metry Denise D Frieden Ilona J IJ Hess Christopher C Siegel Dawn D Maheshwari Mohit M Baselga Eulalia E Chamlin Sarah S Garzon Maria M Mancini Anthony J AJ Powell Julie J Drolet Beth A BA

Pediatric dermatology 20120920 1

The objective of this retrospective study of patients evaluated between July 2008 and October 2011 in seven pediatric dermatology centers was to combine collective clinical experience using oral propranolol therapy in 32 infants with PHACE syndrome (Posterior fossa [brain malformations present at birth], Hemangioma [usually covering a large area of the skin of the head or neck >5 cm]; Arterial lesions [abnormalities of the blood vessels in the neck or head]; Cardiac abnormalities or aortic coarc ...[more]

PMID: 22994362

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Project description:Background and purposeCerebral 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 methodsIntracranial 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.ResultsBy 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.ConclusionsThe 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.

Project description:ImportanceOral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke.ObjectiveTo assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma.Design, setting, and participantsThis multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed.ExposuresPatients received oral propranolol, 0.3 mg/kg/dose or more.Main outcomes and measuresThe main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher.ResultsA total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%]).Conclusions and relevanceThis study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.

Project description:This review summarizes recent therapeutic advances in cervical (CeAD) and intracranial artery dissection (IAD) research. Despite unproven benefits, but in the absence of any signal of harm, in patients, with acute ischemic stroke attributable to CeAD, intravenous thrombolysis and, in case of large-vessel occlusion, endovascular revascularization should be considered. Future research will clarify which patients benefit most from either treatment modality. For stroke prevention, the recently published randomized controlled TREAT-CAD study showed that, against the initial hypothesis, aspirin was not shown non-inferior to anticoagulation with vitamin K antagonists (VKAs). With the results of two randomized controlled trials (CADISS and TREAT-CAD) available now, the evidence to consider aspirin as the standard therapy of CeAD is weak. Further analyses might clarify whether the assumption supports, in particular, that patients presenting with cerebral ischemia, clinical or subclinical with magnetic resonance imaging surrogates, might benefit most from VKA treatment. In turn, it remains to be shown, whether in CeAD patients presenting with pure local symptoms and without hemodynamic compromise, antiplatelets are sufficient, and whether a dual antiplatelet therapy during the first weeks of treatment is recommendable. The observation that ischemic strokes occurred (or recurred) very early after CeAD diagnosis, consistently across randomized and observational studies, supports the recommendation to start antithrombotic treatment immediately, whatever antithrombotic agent is chosen in each individual case. The lack of a license for the use in CeAD patients and the paucity of data are still arguments against the use of direct oral anticoagulants in CeAD. Nevertheless, due to their beneficial safety and efficacy profile proven in atrial fibrillation, these agents are a worthwhile treatment option to be tested in further CeAD treatment trials. In IAD, the experience with the use of antithrombotic agents is limited. As the risk of suffering intracranial hemorrhage is higher in IAD than in CeAD, the use of antithrombotic therapy in IAD remains controversial.

Project description:OBJECTIVES:Supraventricular tachycardia is the most common arrhythmia in infants, and antiarrhythmic medications are frequently used for prophylaxis. The optimal prophylactic antiarrhythmic medication is unknown, and prior randomized trials have been underpowered. We used data from a large clinical registry to compare efficacy and safety of digoxin and propranolol for infant supraventricular tachycardia prophylaxis. We hypothesized that supraventricular tachycardia recurrence is less common on digoxin when compared with propranolol. DESIGN:Retrospective cohort study. SETTING:Pediatrix Medical Group neonatal ICUs. PATIENTS:Infants discharged from 1998 to 2012 with supraventricular tachycardia who were treated with digoxin or propranolol. We excluded infants discharged before completing 2 days of therapy, those with Wolff-Parkinson-White syndrome, structural heart defects (except atrial/ventricular septal defects and patent ductus arteriosus), and those started on multidrug therapy. MEASUREMENTS AND MAIN RESULTS:We used Cox proportional hazards to evaluate supraventricular tachycardia recurrence, defined as need for adenosine or electrical cardioversion while exposed to digoxin versus propranolol, controlling for infant characteristics, inotropic support, supplemental oxygen, and presence of a central line. We identified 342 infants exposed to digoxin and 142 infants exposed to propranolol. The incidence rate of treatment failure was 6.7/1,000 infant-days of exposure to digoxin and 15.4/1,000 infant-days of exposure to propranolol. On multivariable analysis, treatment failure was higher on propranolol when compared with that on digoxin (hazard ratio, 1.97; 95% CI, 1.05-3.71). Hypotension was more frequent during exposure to digoxin versus propranolol (39.4 vs 11.1/1,000 infant-days; p < 0.001). There was no difference in frequency of other clinical adverse events. CONCLUSIONS:Digoxin was associated with fewer episodes of supraventricular tachycardia recurrence but more frequent hypotension in hospitalized infants relative to propranolol.

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Propranolol use in PHACE syndrome with cervical and intracranial arterial anomalies: collective experience in 32 infants.

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Propranolol use in PHACE syndrome with cervical and intracranial arterial anomalies: collective experience in 32 infants.

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