Botulinum Toxin Type A Injections Impact Hamstring Muscles and Gait Parameters in Children with Flexed Knee Gait.

The aim of this study was to determine if botulinum toxin type A (BoNT-A) injection into the medial hamstring can improve gait kinematics and muscle-tendon length in spastic cerebral palsy (CP) with a flexed knee gait (FKG). Twenty-nine children with spastic CP (Gross Motor Function Classification System I-III) with FKG were recruited for this prospective study. BoNT-A was injected into the semitendinosus and semimembranosus (SM) muscles under ultrasonography guidance. Assessments included Gross Motor Function Measure (GMFM), Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), 3-dimensional computerized gait analysis, calculated SM muscle-tendon length and lengthening velocity during gait using musculoskeletal modeling at baseline, 4 and 16 weeks after the injection. Compared to baseline data, significant improvements in GMFM, MAS, and MTS were demonstrated at weeks 4 and 16, and also a significant increase in maximum knee extension during the stance phase was observed at week 4. In addition, the mean lengthening velocity during the swing phase was increased at week 16 without a change in the SM muscle length. Furthermore, there was a significant increase in anterior pelvic tilt at week 4, compared to baseline data. The significant decrease in hip internal rotation after injection was observed only in children with excessive hip internal rotation at initial contact before injection. BoNT-A injection into hamstrings leads to a significant increase in knee extension and anterior pelvic tilt with an increase in lengthening velocity of SM in spastic CP with FKG.

Change in Pulmonary Function after Incentive Spirometer Exercise in Children with Spastic Cerebral Palsy: A Randomized Controlled Study.

PURPOSE: The aim of this study was to investigate the effect of incentive spirometer exercise (ISE) on pulmonary function and maximal phonation time (MPT) in children with spastic cerebral palsy (CP). MATERIALS AND METHODS: Fifty children with CP were randomly assigned to two groups: the experimental group and the control group. Both groups underwent comprehensive rehabilitation therapy. The experimental group underwent additional ISE. The forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), and MPT were assessed as outcome measures before and after 4 weeks of training. RESULTS: There were significant improvements in FVC, FEV1, PEF, and MPT in the experimental group, but not in the control group. In addition, the improvements in FVC, FEV1, and MPT were significantly greater in the experimental group than in the control group. CONCLUSION: The results of this randomized controlled study support the use of ISE for enhancing pulmonary function and breath control for speech production in children with CP.

Substitution at rt269 in Hepatitis B Virus Polymerase Is a Compensatory Mutation Associated with Multi-Drug Resistance.

The emergence of compensatory mutations in the polymerase gene of drug resistant hepatitis B virus (HBV) is associated with treatment failure. We previously identified a multi-drug resistant HBV mutant, which displayed resistance towards lamivudine (LMV), clevudine (CLV), and entecavir (ETV), along with a strong replication capacity. The aim of this study was to identify the previously unknown compensatory mutations, and to determine the clinical relevance of this mutation during antiviral therapy. In vitro mutagenesis, drug susceptibility assay, and molecular modeling studies were performed. The rtL269I substitution conferred 2- to 7-fold higher replication capacity in the wild-type (WT) or YMDD mutation backbone, regardless of drug treatment. The rtL269I substitution alone did not confer resistance to LMV, ETV, adefovir (ADV), or tenofovir (TDF). However, upon combination with YMDD mutation, the replication capacity under LMV or ETV treatment was enhanced by several folds. Molecular modeling studies suggested that the rtL269I substitution affects template binding, which may eventually lead to the enhanced activity of rtI269-HBV polymerase in both WT virus and YMDD mutant. The clinical relevance of the rtL269I substitution was validated by its emergence in association with YMDD mutation in chronic hepatitis B (CHB) patients with sub-optimal response or treatment failure to LMV or CLV. Our study suggests that substitution at rt269 in HBV polymerase is associated with multi-drug resistance, which may serve as a novel compensatory mutation for replication-defective multi-drug resistant HBV.

Effects of hippotherapy on gross motor function and functional performance of children with cerebral palsy.

PURPOSE: The purpose of our study was to investigate the effects of hippotherapy on gross motor function and functional performance in children with spastic cerebral palsy (CP). MATERIALS AND METHODS: We recruited 34 children (M:F=15:19, age: 3-12 years) with spastic CP who underwent hippotherapy for 45 minutes twice a week for 8 weeks. Twenty-one children with spastic CP were recruited for control group. The distribution of gross motor function classification system level and mean age were not significantly different between the two groups. Outcome measures, including the Gross Motor Function Measure (GMFM)-66, GMFM-88 and the Pediatric Evaluation of Disability Inventory: Functional Skills Scale (PEDI-FSS), were assessed before therapy and after the 8-weeks intervention as outcome measures. RESULTS: There were no significant differences between intervention and control groups in mean baseline total scores of GMFM-66, GMFM-88 or PEDI-FSS. After the 8-weeks intervention, mean GMFM-66 and GMFM-88 scores were significantly improved in both groups. However, the hippotherapy group had significantly greater improvement in dimension E and GMFM-66 total score than the control group. The total PEDI-FSS score and the sub-scores of its 3 domains were significantly improved in the hippotherapy group, but not in the control group. CONCLUSION: The results of our study demonstrate the beneficial effects of hippotherapy on gross motor function and functional performance in children with CP compared to control group. The significant improvement in PEDI-FSS scores suggests that hippotherapy may be useful to maximize the functional performance of children with CP.

Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.

OBJECTIVES: To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. DESIGN: A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. SETTING: Human gait analysis laboratory. SUBJECTS: Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). INTERVENTIONS: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. MAIN MEASURES: Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. RESULTS: Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). CONCLUSIONS: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.

Changes in gait patterns with rhythmic auditory stimulation in adults with cerebral palsy.

The objective is to evaluate the changes in gait patterns with rhythmic auditory stimulation (RAS) in adults with cerebral palsy (CP). Fourteen CP with bilateral spasticity participated in this study. A repeated-measures analysis of gait was performed in the presence and absence of RAS. Thirty healthy controls were also recruited. Each subject walked 10 m at their comfortable walking speed. Temporospatial data and kinematic parameters of gait were analyzed without RAS and with RAS. RAS was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard playing. Kinematic parameters, gait deviation index (GDI) as a measure of overall gait pathology, and asymmetry of temporospatial data were assessed. Gait analysis revealed that anterior tilt of pelvis and hip flexion during a gait cycle was significantly changed with RAS (p < 0.05), whereas there were no statistical differences in knee, ankle, and foot kinematic parameters. Additionally, the GDI exhibited a modest, but a statistically significant, improvement with RAS (p < 0.05). Based on ambulatory status, household ambulators showed that side-to-side asymmetry of step length as well as the GDI was significantly attenuated with RAS (p < 0.05). Walking with RAS resulted in kinematic changes of the pelvic and hip movement in spastic CP. Especially, the application of RAS immediately ameliorated overall gait pathology as well as temporospatial asymmetry in household ambulators. Therefore, RAS may be one of the therapeutic tools for gait training in adults with CP.

Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients.

Clevudine (CLV) is a nucleoside analog with potent antiviral activity against chronic hepatitis B virus (HBV) infection. Viral resistance to CLV in patients receiving CLV therapy has not been reported. The aim of this study was to characterize CLV-resistant HBV in patients with viral breakthrough (BT) during long-term CLV therapy. The gene encoding HBV reverse transcriptase (RT) was analyzed from chronic hepatitis B patients with viral BT during CLV therapy. Sera collected from the patients at baseline and at the time of viral BT were studied. To characterize the mutations of HBV isolated from the patients, we subjected the HBV mutants to in vitro drug susceptibility assays. Several conserved mutations were identified in the RT domain during viral BT, with M204I being the most common. In vitro phenotypic analysis showed that the mutation M204I was predominantly associated with CLV resistance, whereas L229V was a compensatory mutation for the impaired replication of the M204I mutant. A quadruple mutant (L129M, V173L, M204I, and H337N) was identified that conferred greater replicative ability and strong resistance to both CLV and lamivudine. All of the CLV-resistant clones were lamivudine resistant. They were susceptible to adefovir, entecavir, and tenofovir, except for one mutant clone. In conclusion, the mutation M204I in HBV RT plays a major role in CLV resistance and leads to viral BT during long-term CLV treatment. Several conserved mutations may have a compensatory role in replication. Drug susceptibility assays reveal that adefovir and tenofovir are the most effective compounds against CLV-resistant mutants. These data may provide additional therapeutic options for CLV-resistant patients.

The neuroradiological findings of children with developmental language disorder.

PURPOSE: To investigate the general characteristics of glucose metabolism distribution and the functional deficit in the brain of children with developmental language delay (DLD), we compared functional neuroradiological studies such as positron emission tomography (PET) of a patient group of DLD children and a control group of attention- deficit hyperactivity disorder (ADHD) children. PATIENTS AND METHODS: Seventeen DLD children and 10 ADHD children under 10 years of age were recruited and divided into separate groups consisting of children less than 5 years of age or between 5 and 10 years of age. The PET findings of 4 DLD children and 6 control children whose ages ranged from 5 to 10 years were compared by Statistical Parametric Mapping (SPM) analysis. RESULTS: All of the DLD children revealed grossly normal findings in brain MRIs, however, 87.5% of them showed grossly abnormal findings in their PET studies. Abnormal findings were most frequent in the thalamus. The patient group showed significantly decreased glucose metabolism in both frontal, temporal and right parietal areas (p < 0.005) and significantly increased metabolism in both occipital areas (p < 0.05) as compared to the control group. CONCLUSION: This study reveals that DLD children may show abnormal findings on functional neuroradiological studies, even though structural neuroradiological studies such as a brain MRI do not show any abnormal findings. Frequent abnormal findings on functional neuroradiological studies of DLD children, especially in the subcortical area, suggests that further research with quantitative assessments of functional neuroradiological studies recruiting more DLD children and age-matched normal controls could be helpful for understanding the pathophysiology of DLD and other disorders confined to the developmental disorder spectrum.

[Pain relieving effect of yakson therapy for infants].

PURPOSE: The purpose of this study was to identify the effects of Yakson therapy as a pain management tool on the physiologic and behavioral responses of infants with a painful heelstick procedure. METHOD: Infants were randomly assigned to a group that underwent a series of Yakson therapy and a control that received nothing before a heelstick. Heart rate, oxygen saturation, and NIPS were compared between the experimental (n=16) and control (n=16) infants during an undisturbed baseline and after a standard heelstick procedure. Yakson therapy consisted of laying a hand on the back, and caressing the abdomen by hand for 5 minutes. RESULT: The pain scores of the Yakson group were lower than the control group. For oxygen saturation, there were statistically significant differences between groups. For heart rate, there were no statistically significant differences between groups. CONCLUSION: This data suggests that Yakson therapy had a pain relief effect in behavior responses and SaO2. Accordingly, Yakson therapy should be used as a nursing intervention for simple pain management for a heel prick.