Steffen Berweck

Robotic-assisted treadmill therapy improves walking and standing performance in children and adolescents with cerebral palsy

OBJECTIVE Task-specific body-weight-supported treadmill therapy improves walking performance in children with central gait impairment. The aim of the study was to investigate the effect of robotic-assisted treadmill therapy on standing and walking performance in children and adolescents with cerebral palsy and to determine parameters influencing outcome. METHODS 20 Patients (mean age 11.0 ± 5.1, 10 males and 10 females) with cerebral palsy underwent 12 sessions of robotic-assisted treadmill therapy using the driven gait orthosis Lokomat. Outcome measures were the dimensions D (standing) and E (walking) of the Gross Motor Function Measure (GMFM). RESULTS Significant improvements in dimension D by 5.9% (± 5.2, p=0.001) and dimension E by 5.3% (± 5.6, p<0.001) of the GMFM were achieved. Improvements in the GMFM D and E were significantly greater in the mildly affected cohort (GMFCS I and II) compared to the more severely affected cohort (GMFCS III and IV). Improvement of the dimension E but not of D correlated positively with the total distance and time walked during the trial (r(s)=0.748, p<0.001). CONCLUSIONS Children and adolescents with bilateral spastic cerebral palsy showed improvements in the functional tasks of standing and walking after a 3-week trial of robotic-assisted treadmill therapy. The severity of motor impairment affects the amount of the achieved improvement.

Treatment of adductor spasticity with BTX-A in children with CP: a randomized, double-blind, placebo-controlled study

Adductor spasticity in children with cerebral palsy (CP) impairs motor function and development. In a placebo‐controlled, double‐blind, randomized multicentre study, we evaluated the effects of botulinum toxin A(BTX‐A) in 61 children (37 males, 24 females; mean age 6 years 1 month [SD 3y 1mo]) with CP (leg‐dominated tetraparesis, n=39; tetraparesis, n=22; GMFCS level I, n=3; II, n=6; III, n=17; IV, n=29; V, n=6). Four weeks after treatment, a significant superiority of BTX‐A was observed in the primary outcome measure (knee‐knee distance ‘fast catch’, p=0.002), the Ash worth scale (p=0.001), and the Goal Attainment Scale (p=0.037).

Improved Gait Parameters After Robotic-Assisted Locomotor Treadmill Therapy in a 6-Year-Old Child with Cerebral Palsy

Task‐specific body‐weight‐supported treadmill therapy improves walking performance in children with central gait impairment. Modulation of spinal networks and improvement of muscle energy consumption are thought to contribute to this effect. Robotic‐assisted treadmill therapy enabled by a driven gait orthosis (DGO) has been established for adults and shown to provide significant improvements in individuals with spinal cord injury and stroke. Recently a pediatric DGO has been developed. Here, we report the results of a 3‐week trial of robotic‐assisted treadmill therapy of a 6‐year‐old boy with bilateral spastic cerebral palsy. The boy tolerated the trial very well and showed improved function, speed, and endurance of walking. Introducing methods of robotic medicine to pediatrics may help children with central gait impairment to regain motor function.

Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia--report of six patients and literature-based analysis of predictive outcomes variables.

INTRODUCTION Primary generalized dystonia is a rare movement disorder. Medical treatment rarely relieves symptoms. The aim of this study was to investigate the efficacy and safety of bilateral pallidal stimulation in 6 children and adolescents with primary generalized dystonia. In addition, we strived to find predictors for treatment outcome by review and analysis of previously published studies. METHODS Six patients with primary generalized dystonia underwent chronic bilateral stimulation of the globus pallidus internus. A PubMed and MEDLINE search was performed in order to identify children and adolescents who underwent deep brain stimulation for primary generalized dystonia. The primary efficacy endpoint was the relative change of the Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) after surgery. RESULTS Forty-four patients were found to meet the inclusion criteria. The mean age at onset of the disease was 7.8+/-2.8years and the mean age at surgery was 14.2+/-3.5years. The mean Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) was 56.9+/-22.7 before surgery and 23.7+/-23.2 at a mean follow up of 13.0+/-4.8months (p<0.001). The improvement in the DYT1-positive group was significantly higher compared to the DYT1-negative group (77%+/-24% and 44%+/-30%, respectively, p<0.001). A positive correlation between the movement score before and after surgery was found in both the DYT1-positive and DYT1-negative cohort (rs=0.624, p<0.001 and rs=0.734, p<0.001, respectively). CONCLUSION DBS is an effective treatment in children and adolescents with primary generalized dystonia. Predictive factors for a better treatment outcome are DYT1-positive status and minor motor impairment before surgery.

Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study

Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise‐induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but ‘healthy’ contralateral motor projections (contra).

Muscle biopsy substantiates long-term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers†

Despite numerous clinical and experimental studies on botulinum toxin type A (BoNT/A), long‐term alterations of muscle texture and fine structure following BoNT/A treatment have thus far not been studied in normal human skeletal muscle. After obtaining institutional review board approval, we performed a prospective, placebo‐controlled, double‐blinded follow‐up study on two healthy adults using magnetic resonance imaging (MRI) and muscle biopsy to visualize long‐term alterations after a single BoNT/A injection into the lateral head of the gastrocnemius muscle. MRI disclosed a high‐signal‐intensity pattern in short tau inversion recovery sequences, and a reduction of the cross‐sectional area in the BoNT/A‐injected, but not in the saline‐injected contralateral control muscle (at 6 to 9 months in volunteer A: 73%, in B: 62%; at 12 months in A: 88%, and in B: 78%). Enzyme histochemistry, 12 months after injection, confirmed neurogenic atrophy of muscle fibers only in the BoNT/A‐injected muscle. Electron microscopy revealed additional degenerative changes at the neuromuscular junction. The data confirm that MRI is a suitable tool to monitor the long‐term effect of BoNT/A on skeletal muscle. Neurogenic muscle atrophy following a single BoNT/A injection should be taken into consideration when repeated BoNT/A injections into the same muscles are proposed.

Clinical impact of antibody formation to botulinum toxin A in children

We studied the clinical impact of neutralizing antibodies to botulinum toxin A that occurred during long‐term treatment of children between 1993 and 2001. Antibodies were found in high titers in 35 of 110 (31.8%) samples from individual patients. Antibody formation correlated with secondary nonresponse (p < 0.001). The most significant risk factors for antibody formation were the frequency of treatments (p = 0.0001) and the injection of a higher weight‐adapted maximum dose per treatment (p = 0.001).

Motor Cortex Plasticity in Ischemic Perinatal Stroke: A Transcranial Magnetic Stimulation and Functional MRI Study

To assess motor cortex plasticity after constraint-induced movement therapy in patients with ischemic perinatal stroke, functional MRI and transcranial magnetic stimulation were applied. Seven hemiparetic patients with ischemic perinatal stroke of the middle cerebral artery and preserved crossed corticospinal projections to the paretic hand were studied before and after 12 days of constraint-induced movement therapy. After therapy, all patients demonstrated improved manual motor function. Transcranial magnetic stimulation of the motor cortex of the affected hemisphere revealed a significant increase of motor-evoked potential amplitude recorded from the paretic hand, whereas no significant change was detected in the nonparetic hand after transcranial magnetic stimulation of the contralesional hemisphere. Functional MRI revealed increased activation of the contralateral central region (including primary sensorimotor cortex) and supplementary motor area during active movement of the paretic hand. No change in functional MRI activation was detected during passive movement of the paretic hand or during active and passive movement of the nonparetic hand. In ischemic perinatal stroke with crossed corticospinal projections, constraint-induced movement therapy induces neuroplastic changes on the synaptic level, detected as increased excitability (transcranial magnetic stimulation) and increased task-related brain activation (functional MRI) in the primary motor cortex of the lesioned hemisphere.

Botulinum toxin treatment of children with cerebral palsy — a short review of different injection techniques

The intramuscular application of botulinum toxin type A (BoNT/A) has emerged to be an established treatment option to reduce muscular hyperactivity due to spasticity in children with cerebral palsy. Accurate injection is a prerequisite for efficient and safe treatment with BoNT/A. So far, treatment procedures have not been standardized. This paper is a short review of different injection techniques, i.e., manual needle placement as well as guidance by electromyography, electrical stimulation, and ultrasound. Advantages and disadvantages of the different injection techniques are discussed with a focus on needle positioning within the targeted muscle, injection close to the neuromuscular junction and diffusion of BoNT/A within the target muscles and through fascia. The additional information gained by each injection technique is weighed in terms of the clinical impact for children with cerebral palsy.

Use of botulinum toxin in pediatric spasticity (cerebral palsy).

Local injection of botulinum toxin (BT) is a well‐established treatment option for spastic movement disorders in children. BT blocks the release of acetylcholine from the axon terminal into the synaptic cleft of the motor endplate resulting in paresis of the injected musculature. Such localised, temporary chemodenervation of affected muscles can lead to functional gains and may improve the childs daily routine and rehabilitative care. We summarise state‐of‐the‐art treatment of spasticity in children with BT type A, addressing critical issues and introducing recent advances, such as sonography‐guided injection of BT and the distal injection of the psoas muscle without the need for general anaesthesia. First‐hand experience with BT type B in children is presented.