Case Report: Propranolol Therapy for Infantile Tremor Syndrome in a Child With Vitamin B12 Deficiency

Vitamin B12 deficiency in childhood presents with a wide variety of symptoms including anemia, failure to thrive and developmental delays. It is a diagnostic consideration in children who are exclusively breastfed or have minimal solid intake, especially if their mother is vegetarian or has underlying vitamin B12 deficiency. Infantile tremor syndrome (ITS) has been associated with vitamin B12 deficiency. ITS presents with neurological symptoms such as developmental delays and tremors. The tremors seen in ITS can be profound and interfere with daily functioning. Different therapies have been tried for those tremors without much evidence or information regarding their efficacy and dosing regimens. We present the case of a 13-month-old girl with vitamin B12 deficiency who developed ITS with significant tremors after initiation of vitamin B12 therapy. She was treated with propranolol which resulted in significant improvement in her tremors. This case highlights the efficacy and safety of propranolol for the treatment of ITS in the context of vitamin B12 deficiency.

Results of Infantile Hemangioma Laser Therapy in Children with Persistent Residual Signs after Systemic Propranolol Therapy: Clinical Cases

Background. Infantile hemangiomas are revealed in 1-3% of newborns and 10-12% of infants. There are only anecdotal reports on the laser therapy efficacy in this pathology management. However, there is no common approach to the use of this method in the complex treatment of infantile hemangioma in infants. Clinical Cases Description. Two clinical cases of infantile hemangioma are presented. Patients underwent complex treatment: systemic propranolol and laser therapy via pulsed dye laser. Laser exposure modes ware selected individually: laser spot sizes were 10 and 12 mm, energy levels were 5-10 J/cm2, burst duration was short (0.45 ms) or long (10-20 ms), procedure duration was from 15 to 40 minutes, number of procedures varied from 1 to 8. Laser therapy has shown its efficacy in treatment of superficial infantile hemangioma. Conclusion. The indication for using laser therapy in management of infants with hemangiomas is especially persistent residual signs such as telangiectasias and erythema after spontaneous or drug involution phase. Laser therapy allows us to avoid aggressive methods and improves the quality of life of our patients according to this article.

HOW TOPICAL BETA-BLOCKER DID WONDER IN THE MANAGEMENT OF RESIDUAL HEMANGIOMA AFTER PROPRANOLOL THERAPY

Background: To determine the role of topical β- blocker in the management of residual hemangioma after propranolol therapy. Method: A retrospective study of all pediatric patients presenting with hemangioma from April 2014 to March 2019 was performed. Topical timolol gel was applied over the residual hemangioma which persisted even after one year of propranolol therapy. Result: Out of 68 patients included in this study 45 (70.3%), patients had complete resolution by one year using the treatment with propranolol. In 14 patients (21.8%) had residual lesion even after 1 year of treatment, upon which we applied topical timolol 0.5% gel for further 4 to 6 months. (Mean 5.35 months). At the end of the treatment, hemangioma was almost resolved. Conclusion: Timolol is a safer alternative to propranolol for residual hemangioma as a sequential treatment. It augments the regression of residual hemangioma with minimal side effects.

Propranolol for Treatment of Infantile Hemangioma: Efficacy and Effect on Pediatric Growth and Development

Purpose. Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH. Method. Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z -scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum from a small representative cohort of age-matched children with IH treated and not treated with propranolol was collected. Results. A total of 185 children receiving propranolol therapy between 2008 and 2013 for IH were assigned to this study. The children were divided into two cohorts based on the presence of comorbidities or risk factors that may affect growth and development ( n = 142 no comorbidities, n = 43 with comorbidities). Neither cohort demonstrated deviation from normal weight in comparison to WHO normative data. There was a significant deviation for BMI-for-age and weight-for-age z -scores in our population, especially in patients on propranolol for more than 7 months. Based on data from participants, via either completed questionnaires or chart results, most children met their developmental milestones at or before target ages, regardless of the presence of comorbidities. Eighty percent of guardians noticed clinical improvement of the IH, with 91% either happy about or neutral to using the medication. hGH levels were higher in patients receiving propranolol therapy, but not significantly different. Conclusion. Propranolol therapy is effective and well tolerated in the treatment of infantile hemangiomas. This study suggests that propranolol does not impair growth and has no impact on normal pediatric development.

Ultrasound and MRI findings as predictors of propranolol therapy response in patients with infantile hemangioma

Objectives To evaluate the prognostic value of ultrasound and MRI findings in patients with infantile hemangioma undergoing propranolol therapy. Methods This study was based on retrospective interpretation of prospectively acquired data. Thirty-eight consecutive patients (28 females and 10 males; mean age ± standard deviation, 3.2 ± 2.2 months) who underwent propranolol treatment for infantile hemangioma were included. Pre-treatment ultrasound images were assessed in terms of echogenicity, lesion height and vascularity. Presence of prominent intratumoral fat, non-fat septa, and enhancement pattern on MRI were retrospectively evaluated. Mann-Whitney test, chi-square, and Fisher’s exact tests were used to compare imaging parameters between patients with treatment success and failure. Results All patients underwent ultrasound and 15 patients underwent MRI. A total of 24 patients showed successful treatment. Between patients with treatment success and failure, there were significant differences in increased vascularity on pre-treatment ultrasound (19/24 vs. 6/14, p = 0.025), decreased vascularity on post-treatment ultrasound (21/24 vs. 5/14, p = 0.001), and prominent intratumoral fat on MRI (1/8 vs. 5/7 p = 0.033). There were no significant differences in echogenicity, lesion height on ultrasound, non-fat septa and MR enhancement pattern. Conclusions Increased vascularity on pre-treatment ultrasound was significantly associated with successful treatment for propranolol therapy in patients with infantile hemangioma, whereas prominent fat component on MRI was significantly associated with treatment failure.

Clinical Significance of Screening Electrocardiograms for the Administration of Propranolol for Problematic Infantile Hemangiomas

Objective. Low-dose nonselective β blockade is an effective treatment for problematic infantile hemangioma (PIH). Screening electrocardiograms (ECG) are performed prior to the initiation of propranolol to minimize the risk of exacerbating undiagnosed heart block. How ECG results affect subsequent propranolol usage and patient management remains unclear. We examined the value of ECG prior to propranolol therapy in a quaternary pediatric hospital. Methods. A retrospective chart review was performed on all infants who received propranolol (2 mg/kg/day divided three times daily) to treat PIH at Arkansas Children’s Hospital from Sept. 2008 to Sept. 2015. All available demographic, historical, and clinical data were obtained. ECGs and echocardiographic data were reviewed and summarized. A pediatric cardiologist read all ECGs. Results. A total of 333 patients (75% female) received propranolol therapy. ECG information was available for 317 (95%). Abnormal findings were present on 44/317 (13.9%) of study ECGs. The most common abnormal finding was “voltage criteria for ventricular hypertrophy” ( n = 35 , 76.1%). Two patients had abnormal rhythms; one had first-degree atrioventricular (AV) block, and one had occasional premature atrial contractions. Of the 31 patients who underwent echocardiograms, 20 (35%) were abnormal. 2.9% of infants with PIH treated with propranolol required a follow-up with a cardiologist. No patient was precluded from taking propranolol due to the findings on screening ECG. Conclusions. Screening ECGs prior to propranolol therapy are abnormal in nearly 14% of patients with PIH but are unlikely to preclude therapy. In the absence of prior cardiac history, this cohort offers further evidence suggesting that screening ECGs may be of limited value in determining the safety of propranolol in otherwise healthy infants with PIH.

Pharmacoeconomic feasibility of using the drug Hemangiol (propranolol, oral solution) in the treatment of proliferating infantile hemangioma requiring systemic therapy

Aim. The study aimed to evaluate the pharmacoeconomic feasibility of propranolol application in the dosage form of the oral solution in the treatment of proliferating infantile hemangioma requiring systemic therapy.Materials and methods. The study design was a retrospective analysis of the published data. The methods of pharmacoeconomic analysis included a clinical-economic analysis (cost-effectiveness analysis) with a sensitivity analysis; and a "budget impact" analysis with a sensitivity analysis. The authors compared the pharmacoeconomic effectiveness of pharmacotherapy for infant hemangiomas with propranolol and surgical methods of treatment.Results. The efficacy of propranolol therapy was 39% higher than surgical methods of treatment. The relative increase in the efficacy of propranolol therapy compared to surgical treatments was 68.4%. At the same time, the cost of propranolol therapy was lower than the cost of surgical treatments by 31.7% or 56,486,07 RUR per patient per year. The application of propranolol in the treatment for proliferating infantile hemangioma allowed reducing the burden on the budget of the state guarantee program in comparison with surgical methods of treatment for 3 years by 1,562.0 million RUR with a proportion of 12% of patients with infant hemangiomas requiring systemic therapy (9,694 patients per year). The sensitivity analysis of the cost and effectiveness of the compared medical technologies showed that the obtained results are resistant to the fluctuations in these parameters in the range from − 20% to + 20%.Conclusion. The application of propranolol preparation in a dosage form of oral solution for the treatment of patients with proliferating infantile hemangioma will significantly increase the efficiency of therapy and reduce costs associated with the application of surgical methods of treatment.