Propranolol Use in PHACE Syndrome with Cervical and Intracranial Arterial Anomalies: Collective Experience in 32 Infants

Abstract

1. Objective Combine collective clinical experience using oral propranolol therapy in PHACE syndrome infants with cerebrovascular anomalies. 2. Design Retrospective study of patients evaluated between July 2008 and October 2011. 3. Setting Seven pediatric dermatology centers. 4. Patients 32 infants with definite PHACE syndrome and cervical and/or intracranial arterial anomalies. 5. Intervention Oral propranolol: average dose of 1.8 mg/kg/day divided t.i.d. or b.i.d., for an average duration of 12.3 months. 6. Main Outcome Measure Adverse neurologic events. 7. Results 7/32 (22%) patients were categorized as higher-risk for stroke, defined on MRA as severe, long-segment narrowing or non-visualization of major cerebral or cervical vessels without anatomic evidence for collateral circulation, often in the presence of concomitant cardiovascular comorbidities. Only 1 patient developed a change in neurologic status during propranolol treatment: a mild right hemiparesis that remained static and improved while propranolol was continued. An additional 3 patients had worsening hemangioma ulceration and/or tissue necrosis during therapy. 8. Conclusions This is the largest report thus far of PHACE patients treated with propranolol. While no catastrophic neurologic events occurred, serious complications, particularly severe ulcerations were seen in a minority of patients, and given the sample size we cannot negate the possibility that propranolol could augment the risk of stroke in this population. 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, and t.i.d. dosing in order to minimize abrupt changes in blood pressure and close follow-up, including neurologic consultation as needed, are recommended.

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

“…When we look at the final outcome from the responses of the cells to propranolol, we can argue that both apoptotic and antiapoptotic, tumor suppressor, prosurvival, and also inflammatory genes are activated via propranolol treatment, but the expression of antiapoptotic and tumor suppressor genes may eliminate the effects of the other genes. On the other hand, propranolol has been well studied in adults and infants (Metry et al 2012). The most common serious adverse effects of propranolol are bradycardia and hypotension (Metry et al 2012;Zusman et al 1987).…”

“…On the other hand, propranolol has been well studied in adults and infants (Metry et al 2012). The most common serious adverse effects of propranolol are bradycardia and hypotension (Metry et al 2012;Zusman et al 1987). Propranolol can be used in high doses but even these concentrations do not have serious adverse effects (Zusman et al 1987).…”

Treatment of infantile haemangiomas: recommendations of a European expert group

“…Children with PHACE syndrome are at risk of having associated cardiovascular anomalies. Long-segment narrowing of major cerebral or cervical vessels without collateral circulation represents an indication of increased risk of stroke [47]. It is therefore strongly recommended to observe several precautions in children with segmental haemangioma before propranolol treatment is started:…”

“…Pretreatment evaluation-Preferentially, MRI angiography and echocardiography should be performed before initiation of propranolol therapy [18,47].…”

Propranolol for Infantile Hemangiomas: A Review

“…One of 32 patients developed a change in neurologic status. Recommendations were to use the lowest possible dosage of propranolol, slow titration, tid dosing to minimize abrupt changes in BP, and close patient follow-up [30]. PHACE syndrome is not an absolute contraindication to propranolol use, but must be considered and monitored carefully, particularly if the child has aberrant cerebrovasculature.…”