Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study.

OBJECTIVE: To determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior. STUDY DESIGN: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with the NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx - DNAmpre-tx) and NNNS summary scores (NNNSpost-tx - NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. RESULTS: DNAm was significantly decreased from pretreatment to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS. CONCLUSIONS: Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

Botulinum toxin type A (Botox) for the neuromuscular correction of excessive gingival display on smiling (gummy smile).

INTRODUCTION: Previously, botulinum toxin type A (BTX-A) (Botox; Allergan, Irvine, Calif) was shown to be effective in reducing excessive gingival display in 5 patients with gummy smiles. This study was conducted to determine whether the doses and the primary injection sites used in the pilot study for the correction of gummy smiles provide consistent, statistically significant, and esthetically pleasing results. METHODS: Thirty patients received BTX-A injections to reduce excessive gingival display. Gingival display was defined as the difference between the lower margin of the upper lip and the superior margin of the right incisor. Patients were followed at 2, 4, 8, 12, 16, 20, and 24 weeks postinjection, with changes documented by photographs and videos. At week 2, the patients rated the effects of BTX-A. A group of specialty clinicians also evaluated the effects of BTX-A. RESULTS: Preinjection gingival display averaged 5.2 +/- 1.4 mm in the 30 patients. At 2 weeks postinjection, mean gingival display had declined to 0.09 mm (+/- 1.06 mm) in 30 patients (t = 26.01, P <.00001). The average lip-drop at 2 weeks was 5.1 mm for 30 patients. Gingival display gradually increased from 2 weeks postinjection through 24 weeks, but, at 24 weeks, average gingival display had not returned to baseline values. Based on predictions from a third-order polynomial equation, the baseline average of 5.2 mm would not be reached until 30 to 32 weeks postinjection. Patients and specialty evaluators rated the effects of BTX-A as highly favorable. CONCLUSIONS: BTX-A injections for the neuromuscular correction of gummy smiles caused by hyperfunctional upper lip elevator muscles was effective and statistically superior to baseline smiles, although the effect is transitory.

New indications for botulinum toxin type a in cosmetics: mouth and neck.

Botulinum toxin type A is frequently used to smooth hyperkinetic lines in the periocular and forehead areas of the upper face, but it has been used less frequently for indications in the lower face and neck. This study was designed to determine whether botulinum toxin treatment of the mouth and neck areas is as clinically successful as the treatment of the upper face. This was a retrospective study of patients who were treated with botulinum toxin type A (Botox) to soften hyperkinetic facial wrinkles. Of 100 patients randomly selected from a single clinical practice, 91 met the inclusion criteria and were divided into two groups for analysis. The 56 patients in group 1 did not receive treatment in the mouth and neck areas, whereas the 35 patients in group 2 were treated at least once in the mouth and neck areas. Patients were surveyed for periods ranging from 7 to 49 months. Most patients in each group had a single botulinum procedure during this period. Both groups of patients had comparable improvement of wrinkles both at the evaluation immediately after the neuromuscular blockade and during follow-up. In comparison with patients whose treatment was confined to the upper face, patients who received global treatment with botulinum toxin type A, including injections in the mouth and neck areas, were injected in more sites per procedure and had more procedures in combination with other therapies. Patient satisfaction with botulinum toxin treatment and outcomes was high in both groups. Botulinum toxin type A is an important tool within the therapeutic spectrum for the treatment of hyperkinetic facial wrinkles, including those in the areas of the mouth and neck.

Botulinum toxin A in management of cerebral palsy.

The efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in children with cerebral palsy was studied in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. Fifteen children with cerebral palsy (mean age: 6 years, 8 months) were included in the study. All had limb deformities associated with non-fixed joint contractures that had not responded to physical therapy. Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while bare-footed. The study provides evidence that the intramuscular injection of botulinum toxin A in selected skeletal muscles decreases muscle tone and contractures, and increases range of motion and motor function.