Mark Belokopytov

Comparison of efficacy of Adeli suit and neurodevelopmental treatments in children with cerebral palsy

This study compared the efficacy of Adeli suit treatment (AST) with neurodevelopmental treatment (NDT) in children with cerebral palsy (CP). Twenty‐four children with CP, Levels II to IV according to the Gross Motor Function Classification System (GMFCS), were matched by age and functional status and randomly assigned to the AST or NDT treatment groups. In the AST group (n=12; eight males, four females; mean age 8.3y [SD 2.0]), six children had spastic/ataxic diplegia, one triplegia and five spastic/mixed quadriplegia. In the NDT group (n=12; nine males, three females; mean age 8.1y [SD 2.2]), five children had spastic diplegia and seven had spastic/mixed quadriplegia. Both groups were treated for 4 weeks (2 hours daily, 5 days per week, 20 sessions). To compare treatments, the Gross Motor Function Measure (GMFM‐66) and the mechanical efficiency index (EIHB) during stair‐climbing were measured at baseline, immediately after 1 month of treatment, and 10 months after baseline. The small but significant time effects for GMFM‐66 and EIHB that were noted after 1 month of both intensive physiotherapy courses were greater than expected from natural maturation of children with CP at this age. Improvements in motor skills and their retention 9 months after treatment were not significantly different between the two treatment modes. Post hoc analysis indicated a greater increase in EIHB after 1 month (p=0.16) and 10 months (p=0.004) in AST than that in NDT, predominantly in the children with higher motor function (GMFCS Levels II and III). The results suggest that AST might improve mechanical efficiency without a corresponding gain in gross motor skills, especially in children with higher levels of motor function.

Effectiveness of motor learning coaching in children with cerebral palsy: a randomized controlled trial

Objective: To evaluate effectiveness of motor learning coaching on retention and transfer of gross motor function in children with cerebral palsy. Design: Block randomized trial, matched for age and gross motor function. Setting: Coordinated, multinational study (Israel, Jordan and Palestinian Authority) in schools and rehabilitation centers. Subjects: 78 children with spastic cerebral palsy, gross motor functional levels II and III, aged 66 to 146 months. Interventions: 1 hr/day, 3 days/week for 3 months treatment with motor learning coaching or neurodevelopmental treatment: two groups. Main measures: Gross motor function Measure (GMFM-66), stair-climbing mechanical efficiency (ME) and parent questionnaire rating their child’s mobility. Immediate treatment effects were assessed after 3 months and retention determined from follow-up measurements 6 months after treatment. Results: GMFM-66, ME and parent questionnaires were obtained from 65, 31 and 64 subjects, respectively. Although both groups increased GMFM-66 score over 3 months, measurements 6 months later indicated retention was significantly superior by 2.7 in the motor learning coaching children of level-II. Similar retention trend was evident for ME, increasing 6 months after motor learning coaching by 1.1% and declining 0.3% after neurodevelopmental treatment. Mobility performance in the outdoors and community environment increased 13% from 3 to 9 months after motor learning coaching and decreased 12% after neurodevelopmental treatment. Minor group differences occurred in children of level-III. Conclusions: In higher functioning children with cerebral palsy, the motor learning coaching treatment resulted in significantly greater retention of gross motor function and transfer of mobility performance to unstructured environments than neurodevelopmental treatment.

Neuroprotective vaccination with copolymer-1 decreases laser-induced retinal damage

The retinal damage induced by laser photocoagulation increases manifold by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1) in adjuvant was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions. The present study tested the neuroprotective ability of Cop-1 to reduce the spread of laser-induced retinal damage. Standard argon laser lesions were created in 72 DA pigmented rats divided into four groups: two Cop-1 treated groups (animals treated seven days before or immediately after the laser session) and two control groups treated respectively by saline or the effective but toxic neuroprotective compound MK-801. The histological and morphological evaluations of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss of the retinas of the pre-immunized animals. Cop-1 given after the laser injury did not prevent cell loss significantly, while the neuroprotective effect of MK-801 was observed only on the third day after the laser injury. The results show that pre-immunization with Cop-1 is neuroprotective in unmyelinated (gray matter) neural tissue such as the retina. This approach may be of clinical significance in ameliorating laser-induced retinal injuries in humans.

Repeatability of Net Mechanical Efficiency During Stair Climbing in Children with Cerebral Palsy

Purpose: To determine the smallest significant change in mechanical efficiency (MEnet) measured by a stair-climbing test. Methods: Duplicate stair-climbing tests (T1 and T2), with more than a 30-minute rest between, were performed by 51 children with diplegic cerebral palsy (CP) at levels II and III of Gross Motor Function Classification System (GMFCS) and 9 children with typical development, aged 5.5 to 13.0 years. Results: The T2 versus T1 slope values of MEnet for CP and typical development did not significantly differ from 1.00. MEnet was significantly higher for GMFCS level II (7.0%) than level III (1.2%). The mean percentage of difference was 7.8% (T2 > T1) for the children with CP, with a 95% confidence interval of −39% to +54%. The 95% confidence interval for MEnet scores computed from the standard error of the mean (SEM) of the percentage of differences was 4.0 to 4.5 for CP. Conclusions: An increase of >13.4% in MEnet score (eg, mean increase from 4.0% to 4.5%) can indicate improved motor status resulting from interventions.

Training to walk amid uncertainty with Re-Step: measurements and changes with perturbation training for hemiparesis and cerebral palsy.

Abstract Purpose: To describe Re-Step™, a novel mechatronic shoe system that measures center of pressure (COP) gait parameters and complexity of COP dispersion while walking, and to demonstrate these measurements in healthy controls and individuals with hemiparesis and cerebral palsy (CP) before and after perturbation training. Method: The Re-Step™ was used to induce programmed chaotic perturbations to the feet while walking for 30u2009min for 36 sessions over 12-weeks of training in two subjects with hemiparesis and two with CP. Results: Baseline measurements of complexity indices (fractal dimension and approximate entropy) tended to be higher in controls than in those with disabilities, while COP variability, mean and variability of step time and COP dispersion were lower. After training the disabled subjects these measurement values tended toward those of the controls, along with a decrease in step time, 10u2009m walk time, average step time, percentage of double support and increased Berg balance score. Conclusions: This pilot trial reveals the feasibility and applicability of this unique measurement and perturbation system for evaluating functional disabilities and changes with interventions to improve walking. Implication for Rehabilitation Walking, of individuals with cerebral palsy and hemiparesis following stroke, can be viewed in terms of a rigid motor behavior that prevents adaptation to changing environmental conditions. Re-Step system (a) measures and records linear and non-linear gait parameters during free walking to provide a detailed evaluation of walking disabilities, (b) is an intervention training modality that applies unexpected perturbations during walking. This perturbation intervention may improve gait and motor functions of individuals with hemiparesis and cerebral plasy.

Copolymer-1 vaccination regimens for neuroprotection in laser-induced retinal injuries

The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1, Copaxone) in adjuvant against laser-induced retinal damage was previously reported. The present study quantitatively compares various regimens of this vaccination for reducing the spread of laser-induced retinal damage and investigates the cellular mechanism of Cop-1 activity. Standard argon laser lesions were created in 78 DA pigmented rats divided into five groups: three Cop-1 single treatment groups (treated 7 days before, immediately after, or 24 hours after the injury), one group treated twice (7 days before and 20 days after injury), and a control group treated with adjuvant 7 days before the injury. The retinal lesions were evaluated 3, 20, and 60 days after the injury. Immunostaining of the retinas of the pretreated and control group animals 3 days after the laser injury was performed for T-cell detection. Cop-1 pre-immunization reduced photoreceptor loss at all time points as measured over the central zone of the lesion and 3 and 20 days after lasing as measured over the whole damaged area. Lesion diameter was reduced only 60 days after laser injury in pre-treated animals. Cop-1 given immediately after injury reduced cell loss as measured 20 and 60 days later in the whole lesion and 20 days after the laser irradiation, when measured in the center of lesion. It had no effect on lesion diameter. Late treatment reduced only the lesion diameter at all time points. Repeated treatment enhanced the neuroprotective effect, decreasing the cell loss in the center of lesion and reducing the diameter of lesion. T-cells were detected in the retinal lesions of pre-immunized animals and not in non-treated group, demonstrating the cellular immune mechanism of Cop-1. Immunization with Cop-1 is neuroprotective against laser-induced retinal injuries, and repeating the treatment enhances this effect. Cellular immune action of Cop-1 of was detected.

The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (P<0.01). The shorter HBO treatment was less effective, showing an increase only in nuclei density at the central area of lesion (P< 0.01). Hyperbaric oxygen seems to exert a neuroprotective effect on laser-induced retinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.