Outcomes of Botulinum Toxin Injection for Shoulder Internal Rotation Contractures in Infants with Brachial Plexus Birth Injury.

PURPOSE: Shoulder internal rotation contractures (IRC) are common sequela of brachial plexus birth injuries (BPBI). Botulinum toxin A (BTX-A) injection into targeted muscles has been described to facilitate functional improvement at the shoulder joint and prevent glenohumeral dysplasia. The purpose of this study was to assess the outcomes of BTX-A injections on shoulder IRC in children with BPBI. METHODS: We conducted a retrospective analysis of 47 children with shoulder IRC due to BPBI, who were treated with BTX-A. Shoulder passive external rotation in adduction and Active Movement Scale external rotation scores were recorded before and after BTX-A injection. We also recorded the number of children who underwent secondary surgical balancing procedures to improve shoulder motion after BTX-A injection. RESULTS: Mean age at the time of injection was 12 months (range, 5-23 months). Subjects demonstrated a significant increase in passive external rotation of 46° (range, 10° to 90) at 4 months; an average improvement of 18° (range, -30° to 80°) persisted at 11 months after injection. A total of 28 patients (60%) underwent subsequent external rotation tendon transfer. At 5-year follow-up, 7 patients (15%) had adequate functional shoulder range of motion and did not undergo external rotation tendon transfer. CONCLUSIONS: Botulinum toxin A injections result in improvement in IRC due to BPBI, which is sustained beyond the expected half-life of 3 months. As many as 15% of patients who have this treatment avoid external rotation tendon transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Combination histamine and serotonin treatment after simulated childbirth injury improves stress urinary incontinence.

AIMS: Histamine and serotonin-related pharmaceuticals have the potential to modulate micturition and continence. The aim of this study was to determine if treatment with histamine and/or serotonin improves stress urinary incontinence (SUI) in female rats. METHODS: Twenty-six age-matched female rats underwent pudendal nerve crush and vaginal distension (PNC + VD), to produce SUI. One week after injury, rats were treated subcutaneously with saline, histamine (1.1 µg), serotonin (2µg), or the combination of both twice daily for another week. A sham injured group received sham PNC + VD and were treated with saline (n = 7). Leak point pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography (EMG) was conducted 2 weeks after injury. The urethra was harvested for qualitative and quantitative histology. Data were analyzed with a one-way ANOVA and Student-Newman-Keuls posthoc test with P < 0.05 indicating statistically significant differences between groups. RESULTS: Combination treatment significantly increased LPP after PNC + VD compared to injured sham treatment and treatment with either histamine or serotonin alone. Compared to injured sham treated rats, all three treatments significantly increased EUS EMG amplitude at both baseline and peak pressure and EUS EMG firing rate at peak pressure during LPP testing. There were more consistent urethral striated muscle fibers and thicker smooth and striated muscle with combination and histamine treatment. There was a statistically significant shift to a greater proportion of thicker collagen fibers in the urethra in serotonin and combination treated rats compared with injured sham treated rats. CONCLUSIONS: Combination treatment was the most effective and may provide an effective therapy for SUI. Neurourol. Urodynam. 35:703-710, 2016. © 2015 Wiley Periodicals, Inc.

Botulinum toxin for the treatment of motor imbalance in obstetrical brachial plexus palsy.

BACKGROUND: Residual muscle imbalance is a common problem affecting obstetrical brachial plexus palsy patients. The goal of this study was to examine the efficacy of botulinum toxin type A (Botox) in improving this muscle imbalance. METHODS: The authors retrospectively reviewed obstetrical brachial plexus palsy patients treated with Botox for muscle imbalance as an isolated procedure. Outcomes were the change in Active Movement Scale scores from pre-Botox scores to scores at 1 month after Botox and 1 year after Botox. RESULTS: Twenty-seven patients were included, 19 treated for shoulder imbalance and eight treated for elbow imbalance. Active Movement Scale scores (mean±SD) for shoulder external rotation improved from 0.6±1.0 before Botox to 2.6±2.14 (p<0.01) at 1 month after Botox, and declined to 1.3±1.2 (p<0.01) at 1 year after Botox. Scores for elbow flexion were 3.3±2.1 before Botox, unchanged at 4.4±1.8 (p=0.07) 1 month after Botox, and improved to 5.8±0.5 (p<0.01) at 1 year after Botox. Scores for elbow supination were 2.9±1.7 before Botox and 3.4±1.5 (p=0.2) at 1 month after Botox, and improved to 3.9±2.0 (p<0.01) at 1 year after Botox. CONCLUSIONS: Botox for shoulder movement imbalance produces improvement in external rotation that is not sufficiently sustained over time to be of clinical benefit. However, Botox for elbow movement imbalance produces a sustained and clinically useful improvement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Indications and effects of botulinum toxin A for obstetric brachial plexus injury: a systematic literature review.

AIM: To give an overview of indications for the use of botulinum toxin A (BoNT-A) treatment for children with obstetric brachial plexus injury (OBPI), and to present the best available evidence of the effectiveness of this treatment. METHOD: Searches were performed in Cinahl, Cochrane Library, Embase, PubMed, and Web of Science, using the keywords 'botulinum' and 'plexus', to identify articles reporting on the use of BoNT-A as a treatment for children with OBPI. Studies found through the references of related articles were also selected. RESULTS: Ten full-text papers and six congress abstracts were included, involving 343 children. Four groups of indications could be identified: internal rotation/adduction contracture of the shoulder, limited active elbow flexion, limited active elbow extension, and pronation contracture of the lower arm. Overall, positive results were reported for all except the indication for limited active elbow extension. However, only one study was comparative in nature; all others were classified as having a low level of evidence. There was a large variation in outcome measures. INTERPRETATION: To provide better evidence for the already partly promising results of BoNT-A treatment for children with OBPI, multicentre randomized controlled trials are needed.

Traumatic bleeding at birth treated with Factor VII.

We report 36 week gestation twins born following a traumatic delivery. Twin 2 had profuse haemorrhage where haemostasis was achieved with recombinant Factor VIIa (rFVIIa - NovoSeven;Novo Nordisk A/S, Bagsvaerd, Denmark).

Mast cell stabilization limits hypoxic-ischemic brain damage in the immature rat.

Perinatal hypoxic-ischemic (HI) brain damage is a major cause of mortality and neurological morbidity in infants and children. Using an established model of unilateral hypoxia-ischemia in neonatal rats, the present study focused on mast cells (MCs), important regulators of inflammatory processes, as potential contributors to HI damage. MCs are present in the pia of the neonatal rat, entering the central nervous system (CNS) during cerebral development along penetrating blood vessels. Following hypoxia-ischemia, MC numbers increased dramatically in the ipsilateral (ischemic) hemisphere (p < 0.01). In animals exposed to hypoxia only, the numbers of MCs were elevated in both hemispheres to an extent equal to that observed in the contralateral hemisphere of HI animals (p < 0.05 vs. control). Within damaged areas (ipsilateral only), MCs were observed in regions of activated microglia and astroglia that characterize the ischemic hemisphere. Using a triple-label paradigm, MCs were observed along elongating blood vessels, some of which express the GLUT1 isoform of the glucose transporter protein, indicative of blood-brain barrier vessels. To determine whether MC activation has a role in HI brain damage, rat pups were treated with the MCs stabilizer, disodium cromoglycate (cromolyn), prior to and/or following hypoxia-ischemia. The cromolyn treatment inhibited MC migration into the CNS (p < 0.05) and limited brain damage more than 50% (p < 0.01) vs. saline controls. These data support the hypothesis that MCs are key contributors to the extent of brain damage due to hypoxia-ischemia in the immature animal.

Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury.

A previous study from our lab has shown that the polyphenol-rich pomegranate juice can protect the neonatal mouse brain against hypoxic-ischemic (H-I) injury when given to mothers in their drinking water. To test the hypothesis that this protection is due to the polyphenols in the juice, we studied the effects of the pomegranate polyphenol extract in the same neonatal H-I model. To further explore the role of a specific polyphenol in neonatal H-I we investigated the effects of resveratrol. The neuroprotective effects of resveratrol have been demonstrated in adult models of stroke, but had not previously been examined in neonates. We show that pomegranate polyphenols and resveratrol reduce caspase-3 activation following neonatal H-I. Resveratrol reduced caspase-3 activation when given before the injury but not when given 3 h after the injury. In addition to preventing caspase-3 activation, resveratrol also reduced calpain activation. Finally, we show that resveratrol can protect against tissue loss measured at 7 days after the injury. These and other recent findings suggest that polyphenols should be further investigated as a potential treatment to decrease brain injury due to neonatal H-I.

Gender-dependent pathways of hypoxia-ischemia-induced cell death and neuroprotection in the immature P3 rat.

Previously, we demonstrated neuroprotection with 2-iminobiotin (2-IB) after cerebral hypoxia-ischemia (HI) in female, but not in male P7 rats. Given the different patterns of brain injury in more immature rats, we examined whether these gender differences could also be observed in P3 rats. HI was induced by unilateral carotid ligation and FiO2 reduction, followed by 2-IB administration. HSP70 protein expression and cytochrome c release from the mitochondria, markers of short-term outcome, were induced by HI to the same extent in male and female animals. However, reduction in HSP70 production and cytochrome c release by 2-IB was seen in female rats only. Long-term cerebral injury after HI, assessed with histology, was similar in male and female P3 rats, but long-term neuroprotection by 2-IB was observed in female rats only. In conclusion, 2-IB provides neuroprotection after cerebral HI in female, but not in male immature P3 rats.

Delayed peripheral administration of a GPE analogue induces astrogliosis and angiogenesis and reduces inflammation and brain injury following hypoxia-ischemia in the neonatal rat.

Glycine 2-methyl proline glutamate (G-2mPE) is a proline-modified analogue to the naturally existing N-terminal tripeptide glycine-proline-glutamate that is a cleaved product from insulin-like growth factor-1. G-2mPE is designed to be more enzymatically resistant than glycine-proline-glutamate and to increase its bioavailability. The current study has investigated the protective effects of G-2mPE following hypoxic-ischemic brain injury in the neonatal brain. On postnatal day 7, Wistar rats were exposed to hypoxia-ischemia (HI). HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (7.7% O2, 36 degrees C) for 60 min. The drug treatment started 2 h after the insult, and the pups were given either 1.2 mg/kg (bolus), 1.2 mg/ml once a day for 7 days, or vehicle. The degree of brain damage was determined histochemically by thionin/acid fuchsin staining. G-2mPE's anti-inflammatory properties were investigated by IL-1beta, IL-6, and IL-18 ELISA, and effects on apoptosis by caspase 3 activity. Vascularization was determined immunohistochemically by the total length of isolectin-positive blood vessels. Effect on astrocytosis was also determined in the hippocampus. Animals treated with multiple doses of G-2mPE demonstrated reduced overall brain injury 7 days after HI, particularly in the hippocampus and thalamus compared to vehicle-treated rats. The expression of IL-6 was decreased in G-2mPE-treated animals compared to vehicle-treated pups, and both the capillary length and astrogliosis were increased in the drug-treated animals. There was no effect on caspase 3 activity. This study indicates that peripheral administration of G-2mPE, starting 2 h after a hypoxic-ischemic insult, reduces the degree of brain injury in the immature rat brain. The normalization of IL-6 levels and the promotion of both neovascularization and reactive astrocytosis may be potential mechanisms that underlie its protective effects.

The role of botulinum toxin in the neuro-rehabilitation of young patients with brachial plexus birth palsy.

PURPOSE: To favour the active movements of the shoulder abductor/external rotator, elbow extensor and supinator muscles, through the partial inhibition of the uninvolved antagonistic muscles, in the Brachial Plexus birth Palsy (BPP). METHODS: The type A Botulinum Neuro Toxin (BNT-Dysport, Ipsen) was injected in 50 outpatients (mean age: 4.7 +/- 3.4 years) with BPP according to the criteria: early and current neuro-rehabilitation (Reflex Locomotion-RL), age <14 years, no cognitive impairment. Repeat injections (1.9 +/- 0.8) were performed in 30 patients. RESULTS: The range of active movements increased at the maximal benefit phase, compared to the baseline values (p < 0.05-0.01). The gain of shoulder's abduction was directly related to the youngest age (r = 0.6). An expanded compliance of the injected muscles and a faster response to the RL, in respect to that experienced in the pre-BNT sessions, was detected. The Global Clinical Rating Scale disclosed the temporal profile of the clinical outcome, with step-like increases of the function in 70% of the patients, and a 'plateau' trait in the remaining ones (+29.8 +/- 10.5%). The video-taped recordings showed an improvement in the global movements. CONCLUSIONS: The employment of BNT in the management of young patients with BPP has beneficial effects in the integration of the bodily scheme.

Botulinum toxin treatment of cocontractions after birth-related brachial plexus lesions.

The authors studied botulinum toxin type A therapy of severe biceps-triceps cocontractions after nerve regeneration following birth-related brachial plexus lesions. Six children (age, 2 to 4 years) were treated two to three times over a period of 8 to 12 months with 40 mouse units of botulinum toxin at two sites of the triceps muscle. Elbow range of motion improved from 0 to 25 to 50 deg to 0 to 25 to 100 deg (p < 0.05), and muscle force of elbow flexion increased from a mean of Medical Research Council classification 1.7 to 3.7 (p < 0.05). After a 1-year follow-up, there was no clinical recurrence.

[A trial of the use of the multivitamin Multitabs in the combined treatment of patients with a perinatal brain lesion]. / Opyt primeneniia mul'tivitamina "Mul'titabs" v kompleksnom lechenii bol'nykh s preinatal'nym porazheniem mozga.

Pediatric patients in early childhood presenting with perinatal affection of the nervous system benefit much from incorporation into their combined treatment of multivitamins "Multitabs", as evidenced by improvement in their general health, as well as in the red blood parameters and immunity status. Thus, use of the above multivitamins for children presenting with perinatal cerebral pathology is considered liable to be of benefit making for optimization of the process of treatment.

Recién nacido con trombosis venosa del miembro superior / Newborn with venous thrombosis of the upper limb

Se presenta el caso de trombosis venosa del miembro superior en un recién nacido del sexo masculino, producida por la permanencia de la extremidad superior en la vagina durante 29 horas, lo que determinó la realización de césarea. Se informa que el tratamiento médico se basó en anticoagulantes por vía endovenosa en infusión constante, espasmolíticos, diuréticos y antibióticos. Se señala que para la realización del diagnóstico se tuvo en cuenta el cuadro clínico y la evolución; el niño no presentó secuelas. Se revisa la literatura médica de los años 1978 a 1983 y no se encuentra ningún caso publicado al repecto