Joint and muscle assessments of the separate effects of Botulinum NeuroToxin-A and lower-leg casting in children with cerebral palsy

Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 +/- 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon levels were performed using Spearman correlation coefficients (p < 0.05). Increased joint resistance, measured during slow ankle rotations, was not significantly reduced after either treatment. Additional joint resistance assessed during fast rotations only reduced in the BoNT-A group (-37.6%, p = 0.013, effect size = 0.47), accompanied by a reduction in MG stretch reflexes (-70.7%, p = 0.003, effect size = 0.56). BoNT-A increased the muscle length measured at the resting ankle angle (6.9%, p = 0.013, effect size = 0.53). Joint angles shifted toward greater dorsiflexion after casting (32.4%, p = 0.004, effect size = 0.56), accompanied by increases in tendon length (5.7%, p = 0.039, effect size = 0.57; r = 0.40). No associations between the changes in muscle or tendon lengths and the changes in the stretch reflexes were found. We conclude that intramuscular BoNT-A injections reduced stretch reflexes in the MG accompanied by an increase in resting muscle belly length, whereas casting resulted in increased dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle

Reliability of Processing 3-D Freehand Ultrasound Data to Define Muscle Volume and Echo-intensity in Pediatric Lower Limb Muscles with Typical Development or with Spasticity

This investigation assessed the processer reliability of estimating muscle volume and echo-intensity of the rectus femoris, tibialis anterior and semitendinosus. The muscles of 10 typically developing children (8.15 [1.40] y) and 15 children with spastic cerebral palsy (7.67 [3.80] y; Gross Motor Function Classification System I = 5, II = 5, III = 5) were scanned with 3-D freehand ultrasonography. For the intra-processer analysis, the intra-class correlations coefficients (ICCs) for muscle volume ranged from 0.943–0.997, with relative standard errors of measurement (SEM%) ranging from 1.24%–8.97%. For the inter-processer analysis, these values were 0.853 to 0.988 and 3.47% to 14.02%, respectively. Echo-intensity had ICCs >0.947 and relative SEMs <4% for both analyses. Muscle volume and echo-intensity can be reliably extracted for the rectus femoris, semitendinosus and tibialis anterior in typically developing children and children with cerebral palsy. The need for a single processer to analyze all data is dependent on the size of the expected changes or differences

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

<p>Abstract</p> <p>Background</p> <p>In recent years there has been an increasing interest in MRI as a non-invasive diagnostic modality for the work-up of suspicious breast lesions. The additional value of Breast MRI lies mainly in its capacity to detect multicentric and multifocal disease, to detect invasive components in ductal carcinoma in situ lesions and to depict the tumor in a 3-dimensional image. Breast MRI therefore has the potential to improve the diagnosis and provide better preoperative staging and possibly surgical care in patients with breast cancer. The aim of our study is to assess whether performing contrast enhanced Breast MRI can reduce the number of surgical procedures due to better preoperative staging and whether a subgroup of women with suspicious nonpalpable breast lesions can be identified in which the combination of mammography, ultrasound and state-of-the-art contrast-enhanced Breast MRI can provide a definite diagnosis.</p> <p>Methods/Design</p> <p>The MONET – study (<b><it>M</it></b>R mammography <b><it>O</it></b>f <b><it>N</it></b>onpalpable Br<b><it>E</it></b>ast <b><it>T</it></b>umors) is a randomized controlled trial with diagnostic and therapeutic endpoints. We aim to include 500 patients with nonpalpable suspicious breast lesions who are referred for biopsy. With this number of patients, the expected 12% reduction in surgical procedures due to more accurate preoperative staging with Breast MRI can be detected with a high power (90%). The secondary outcome is the positive and negative predictive value of contrast enhanced Breast MRI. If the predictive values are deemed sufficiently close to those for large core biopsy then the latter, invasive, procedure could possibly be avoided in some women. The rationale, study design and the baseline characteristics of the first 100 included patients are described.</p> <p>Trial registration</p> <p>Study protocol number NCT00302120</p

Threshold things that think: usable authorization for resharing

People start carrying around more and more mobile devices that can contain sensitive data. To protect these devices, Desmedt et al. [1] proposed a threshold security architecture for Things That Think. In this architecture, security is the result of the cooperation of at least the threshold number of personal devices. Personal devices are devices that are frequently in the user’s proximity and able to interact with each other. For threshold security each personal device possesses a share of the key material. When at least the threshold number of these devices cooperate, this key material can be used to, for instance place signatures or decrypt encrypted information. The advantages of deploying a threshold cryptography scheme are : a user does not need all his personal devices (e.g. dead battery, device left at home) to access the necessary key material; an adversary does not gain any knowledge of the key material when he does not compromise the threshold number of devices. For a threshold security architecture on Things That Think to be practical, a mechanism allowing the user to add or remove devices from the set of personal devices is essential. Refreshing key material enhances security. Adding a device, removing a device and refreshing key material are essentially the same in terms of the underlying protocol, resharing. One example of a protocol for resharing can be found in [6]. However, little attention has been paid to the problem of authorisation for resharing. Proper authorisation is necessary to prevent an adversary from altering the set of personal devices in such a way that he would be able to break the scheme. Moreover authorisation should not enable the adversary to succeed in a Denial of Service (DoS) attack and prevent the genuine user from signing and/or decrypting. The authors developed a protocol to manually authorise resharing in [4]. This paper focuses on the usability aspect of this protocol, which was an essential part of development. Although the proposed manual authorisation protocol is studied in the context of resharing, it could also be used to authorise signing and for bootstrapping. An overview of related work on usability and pairing of two devices is given by Saxena et al. [5].status: publishe

Quantifying the separate effects of Botulinum toxin-A and lower leg casting on ankle joint hyper-resistance in children with cerebral palsy

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Progressive resistance training for children with cerebral palsy : a randomized controlled trial evaluating the effects on muscle strength and morphology

Children with spastic cerebral palsy often present with muscle weakness, resulting from neural impairments and muscular alterations. While progressive resistance training (PRT) improves muscle weakness, the effects on muscle morphology remain inconclusive. This investigation evaluated the effects of a PRT program on lower limb muscle strength, morphology and gross motor function. Forty-nine children with spastic cerebral palsy were randomized by minimization. The intervention group (n participants = 26,age: 8.3 +/- 2.0 years, Gross Motor Function Classification System [GMFCS]level I/II/III: 17/5/4, n legs = 41) received a 12-week PRT program, consisting of 3-4 sessions per week, with exercises performed in 3 sets of 10 repetitions, aiming at 60%-80% of the 1-repetition maximum. Training sessions were performed under supervision with the physiotherapist and at home. The control group (n participants = 22, age: 8.5 +/- 2.1 year, GMFCS level I/II/III:14/5/3, n legs = 36) continued usual care including regular physiotherapy and use of orthotics. We assessed pre- and post-training knee extension, knee flexion and plantarflexion isometric strength, rectus femoris, semitendinosus and medial gastrocnemius muscle morphology, as well as functional strength, gross motor function and walking capacity. Data processing was performed blinded. Linear mixed models were applied to evaluate the difference in evolution over time between the control and intervention group(interaction-effect) and within each group (time-effect). The alpha-level was set at p= 0.01. Knee flexion strength and unilateral heel raises showed a significant interaction-effect (p <= 0.008), with improvements in the intervention group (p <= 0.001). Moreover, significant time-effects were seen for knee extension and plantarflexion isometric strength, rectus femoris and medial gastrocnemius MV, sit-to-stand and lateral step-up in the intervention group (p <= 0.004). Echo-intensity, muscle lengths and gross motor function showed limited to no changes. PRT improved strength and MV in the intervention group, where by strength parameters significantly or close to significantly differed from the control group. Although, relative improvements in strength were larger than improvements in MV, important effects were seen on the maintenance of muscle size relative to skeletal growth. In conclusion, this study proved the effectiveness of a home-based, physiotherapy supervised, PRT program to improve isometric and functional muscle strength in children with SCP without negative effects on muscle properties or any serious adverse events

Muscle characteristics in pediatric hereditary spastic paraplegia vs. bilateral spastic cerebral palsy : an exploratory study

Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9–17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP (p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass (p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups

Morphological Medial Gastrocnemius Muscle Growth in Ambulant Children with Spastic Cerebral Palsy: A Prospective Longitudinal Study

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of gross motor functional limitations on altered muscle growth remains unclear. This prospective longitudinal study modelled morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III = 47/22/18). Ultrasound assessments were performed during 2-year follow-up and repeated for a minimal interval of 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I and GMFCS-II&III. MV and CSA growth trajectories showed a piecewise model with two breakpoints, with the highest growth before 2 years and negative growth rates after 6–9 years. Before 2 years, children with GMFCS-II&III already showed lower growth rates compared to GMFCS-I. From 2 to 9 years, the growth rates did not differ between GMFCS levels. After 9 years, a more pronounced reduction in normalized CSA was observed in GMFCS-II&III. Different trajectories in ML growth were shown between the GMFCS level subgroups. These longitudinal trajectories highlight monitoring of SCP muscle pathology from early ages and related to motor mobility. Treatment planning and goals should stimulate muscle growth