Action observation treatment: a novel tool in neurorehabilitation

This review focuses on a novel rehabilitation approach known as action observation treatment (AOT). It is now a well-accepted notion in neurophysiology that the observation of actions performed by others activates in the perceiver the same neural structures responsible for the actual execution of those same actions. Areas endowed with this action observation–action execution matching mechanism are defined as the mirror neuron system. AOT exploits this neurophysiological mechanism for the recovery of motor impairment. During one typical session, patients observe a daily action and afterwards execute it in context. So far, this approach has been successfully applied in the rehabilitation of upper limb motor functions in chronic stroke patients, in motor recovery of Parkinson''s disease patients, including those presenting with freezing of gait, and in children with cerebral palsy. Interestingly, this approach also improved lower limb motor functions in post-surgical orthopaedic patients. AOT is well grounded in basic neuroscience, thus representing a valid model of translational medicine in the field of neurorehabilitation. Moreover, the results concerning its effectiveness have been collected in randomized controlled studies, thus being an example of evidence-based clinical practice.     

Young children with autism spectrum disorder use predictive eye movements in action observation

Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others’ actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand–object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS.     

Frequency and topography in monkey electroencephalogram during action observation: possible neural correlates of the mirror neuron system

The observation of actions executed by others results in desynchronization of electroencephalogram (EEG) in the alpha and beta frequency bands recorded from the central regions in humans. On the other hand, mirror neurons, which are thought to be responsible for this effect, have been studied only in macaque monkeys, using single-cell recordings. Here, as a first step in a research programme aimed at understanding the parallels between human and monkey mirror neuron systems (MNS), we recorded EEG from the scalp of two monkeys during action observation. The monkeys were trained to fixate on the face of a human agent and subsequently to fixate on a target upon which the agent performed a grasping action. We found that action observation produced desynchronization in the 19–25 Hz band that was strongest over anterior and central electrodes. These results are in line with human data showing that specific frequency bands within the power spectrum of the ongoing EEG may be modulated by observation of actions and therefore might be a specific marker of MNS activity.     

Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study

Background aimsPre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders.MethodsAfter providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age.ResultsThe score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation.ConclusionsAutologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function.     

Mechanobiological prediction of proximal femoral deformities in children with cerebral palsy

Children with cerebral palsy (CP) walk with altered gait and frequently exhibit proximal femoral deformities, such as anteversion and coxa valga. The objective of this research was to investigate the effect of specific gait patterns on the femoral morphology in CP.

In this study, the mechanobiological principles were implemented on a 3D finite element (FE) model of the proximal femur in order to predict changes in morphology over time in healthy and CP children. This model relies on the assumption that cyclic octahedral shear stress promotes growth and cyclic hydrostatic compressive stress inhibits growth. Growth was simulated over 16 iterations, representing approximately 5 months of growth.

The FE model predicts an increase in the femoral anteversion and coxa valga for CP loading conditions when compared with healthy ones. Understanding the role of loading in skeletal morphogenesis may help prevent bone deformities and improve function in children with gait abnormalities.     

The morphology of the medial gastrocnemius in typically developing children and children with spastic hemiplegic cerebral palsy

We collected 3D ultrasound images of the medial gastrocnemius muscle belly (MG) in 16 children with spastic hemiplegic cerebral palsy (SHCP) (mean age: 7.8 years; range: 4–12) and 15 typically-developing (TD) children (mean age: 9.5 years; range: 4–13). All children with SHCP had limited passive dorsiflexion range on the affected side with the knee extended (mean ± 1SD: −9.3° ± 11.8). Scans were taken of both legs with the ankle joint at its resting angle (RA) and at maximum passive dorsiflexion (MD), with the knee extended. RA and MD were more plantar flexed (p < 0.05) in children with SHCP than in TD children.

We measured the volumes and lengths of the MG bellies. We also measured the length of muscle fascicles in the mid-portion of the muscle belly and the angle that the fascicles made with the deep aponeurosis of the muscle. Volumes were normalised to the subject’s body mass; muscle lengths and fascicle lengths were normalised to the length of the fibula.

Normalised MG belly lengths in the paretic limb were shorter than the non-paretic side at MD (p = 0.0001) and RA (p = 0.0236). Normalised muscle lengths of the paretic limb were shorter than those in TD children at both angles (p = 0.0004; p = 0.0003). However, normalised fascicle lengths in the non-paretic and paretic limbs were similar to those measured in TD children (p > 0.05). When compared to the non-paretic limb, muscle volume was reduced in the paretic limb (p < 0.0001), by an average of 28%, and normalised muscle volume in the paretic limb was smaller than in the TD group (p < 0.0001).

The MG is short and small in the paretic limb of children with SHCP. The altered morphology is not due to a decrease in fascicle length. We suggest that MG deformity in SHCP is caused by lack of cross-sectional growth.     

A new child-friendly 3D bimanual protocol to assess upper limb movement in children with unilateral cerebral palsy: Development and validation

Unilateral cerebral palsy (uCP) causes upper limb movement disorders that impact on daily activities, especially in bimanual condition. However, a few studies have proposed bimanual tasks for 3D motion analysis. The aim of this study was to validate the new version of a child-friendly, 3D, bimanual protocol for the measurement of joint angles and movement quality variables. Twenty children with uCP and 20 typically developing children (TDC) performed the five-task protocol integrated into a game scenario. Each task specifically targeted one or two upper limb degrees of freedom. Joint angles, smoothness and trajectory straightness were calculated. Elbow extension, supination, wrist extension and adduction amplitudes were reduced; hand trajectories were less smooth and straight in children with uCP compared to TDC. Correlations between the performance-based score and kinematic variables were strong. High within and between-session reliability was found for most joint angle variables and lower reliability was found for smoothness and straightness in most tasks. The results therefore demonstrated the validity and reliability of the new protocol for the objective assessment of bimanual function in children with uCP. The evaluation of both joint angles and movement quality variables should increase understanding of pathological movement patterns and help clinicians to optimize treatment.ClinicalTrials.gov identifier: NCT03888443.     

Efficacy of transcutaneous electrical nerve stimulation combined with therapeutic exercise on hand function in children with hemiplegic cerebral palsy

Purpose: Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological method used to reduce spasticity. It was also assumed that TENS reduces pain and therefore improves limb function. Most of the previous studies about the effect of TENS were done in the lower limb and in stroke patients. There is a lack of enough literature about the direct and indirect effects of TENS in the upper limb. Hence, our study aimed to determine whether TENS combined with therapeutic exercises helps to improves hand function by reducing spasticity in children with hemiplegic cerebral palsy (CP).

Materials and methods: Twenty-nine children with hemiplegic CP were randomly assigned to the TENS group (n?=?15) or the control group (n?=?14). The TENS group received traditional physical therapy with the adjunct application of conventional TENS for 30?minutes (pulse duration, 250 µs; pulse rate, 100?Hz) on the wrist extensors, once daily, 3?days a week, for 8?weeks, while the control group received traditional physical therapy.

Results: The results showed a significant intergroup difference in handgrip strength over the 8-week period. The time to accomplish the Jebsen Taylor Hand Function Test (JTHFT) task decreased by 48% and the ABILHAND-Kids questionnaire scores improved by 23% in the TENS group.

Conclusions: The use of TENS in combination with therapeutic exercise may improve strength and hand function.     

脑瘫伴癫痫儿童肠道菌群变化

目的 探讨脑瘫伴癫痫儿童肠道菌群的变化。方法 选择龙岗区社会福利中心诊断为脑瘫伴癫痫的31例患儿作为疾病组;另外选取同龄健康儿童30例作为健康组。留取受试者的粪便标本,提取总DNA,并对16S rRNA基因的V3‒V4可变区进行扩增,并在Illumina MiSeq平台进行高通量测序。结果 与健康儿童相比,疾病组儿童肠道内微生物多样性出现明显差异。在门水平优势菌群中,疾病组儿童放线菌的相对丰度明显高于健康组（32.87% vs 3.56%）,而拟杆菌的相对丰度明显低于健康组（22.66% vs 53.59%）。在属水平优势菌群中,疾病组儿童双歧杆菌属、副拟杆菌属的相对丰度均明显高于健康组（26.94% vs 2.61%,5.72% vs 1.90%）,其中肠杆菌属的相对丰度达6.00%,而拟杆菌属、粪杆菌属的相对丰度明显低于健康组（11.38% vs 45.16%,0.63% vs 12.78%）,普雷沃菌属的相对丰度也低于健康组（3.11% vs 5.30%）。结论 与同龄健康儿童相比,脑瘫伴癫痫儿童肠道菌群改变明显,菌群门水平和属水平均有明显差异。     

Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial

Background aimsCerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion.MethodsIn this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow–derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733).ResultsA median of 13.12 × 10⁸ TNCs (range, 4.83–53.87) including 10.02 × 10⁶ CD34+ cells (range, 1.02–29.9) in a volume of 7 mL (range, 4–10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10⁸ TNCs (range, 1.36–17.85), with 3.39 × 10⁶ cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found.ConclusionsSubarachnoid placement of autologous bone marrow–derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.     

Altered corticomuscular coherence elicited by paced isotonic contractions in individuals with cerebral palsy: A case-control study

The purpose of the study was to analyze corticomuscular coherence during planning and execution of simple hand movements in individuals with cerebral palsy (CP) and healthy controls (HC).Fourteen individuals with CP and 15 HC performed voluntary paced movements (opening and closing the fist) in response to a warning signal. Simultaneous scalp EEG and surface EMG of extensor carpi radialis brevis were recorded during 15 isotonic contractions. Time–frequency corticomuscular coherence (EMG-C3/C4) before and during muscular contraction, as well as EMG intensity, onset latency and duration were analyzed.Although EMG intensity was similar in both groups, individuals with CP exhibited longer onset latency and increased duration of the muscular contraction than HC. CP also showed higher corticomuscular coherence in beta EEG band during both planning and execution of muscular contraction, as well as lower corticomuscular coherence in gamma EEG band at the beginning of the contraction as compared with HC.In conclusion, our results suggest that individuals with CP are characterized by an altered functional coupling between primary motor cortex and effector muscles during planning and execution of isotonic contractions. In addition, the usefulness of corticomuscular coherence as a research tool for exploring deficits in motor central processing in persons with early brain damage is discussed.     

Stiffness of hip adductor myofibrils is decreased in children with spastic cerebral palsy

Cerebral palsy (CP) is the result of a static brain lesion which causes spasticity and muscle contracture. The source of the increased passive stiffness in patients is not understood and while whole muscle down to single muscle fibres have been investigated, the smallest functional unit of muscle (the sarcomere) has not been. Muscle biopsies (adductor longus and gracilis) from pediatric patients were obtained (CP n = 9 and control n = 2) and analyzed for mechanical stiffness, in-vivo sarcomere length and titin isoforms. Adductor longus muscle was the focus of this study and the results for sarcomere length showed a significant increase in length for CP (3.6 µm) compared to controls (2.6 µm). Passive stress at the same sarcomere length for CP compared to control was significantly lower in CP and the elastic modulus for the physiological range of muscle was lower in CP compared to control (98.2 kPa and 166.1 kPa, respectively). Our results show that CP muscle at its most reduced level (the myofibril) is more compliant compared to normal, which is completely opposite to what is observed at higher structural levels (single fibres, muscle fibre bundles and whole muscle). It is noteworthy that at the in vivo sarcomere length in CP, the passive forces are greater than normal, purely as a functional of these more compliant sarcomeres operating at long lengths. Titin isoforms were not different between CP and non-CP adductor longus but titin:nebulin was reduced in CP muscle, which may be due to titin loss or an over-expression of nebulin in CP muscles.     

Effects of seat surface inclination on respiration and speech production in children with spastic cerebral palsy

Background

Respiratory and speech problems are commonly observed in children with cerebral palsy (CP). The purpose of this study was to identify if inclination of seat surface could influence respiratory ability and speech production in children with spastic diplegic CP.

Methods

Sixteen children with spastic diplegic CP, ages 6 to 12 years old, participated in this study. The subjects’ respiratory ability (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximum phonation time (MPT)) were measured in three sitting conditions: a seat surface inclined 0°, anterior 15°, and posterior 15°.

Results

FVC was significantly different across three inclinations of seat surface, F(2, 45) = 3.81, P = 0.03. In particular, the subjects’ FVC at a seat surface inclined anterior 15° was significantly greater than at a seat surface inclined posterior 15° (P < 0.05). However, FEV1, PEF, and MPT were not significantly affected by seat surface inclination (P > 0.05).

Conclusions

The results suggest that anterior inclination of seat surface may provide a positive effect on respiratory function in children with spastic diplegic CP.     

The severity of chewing disorders is related to gross motor function and trunk control in children with cerebral palsy

Abstract

Purpose: The frequency of chewing disorders increases with decreasing level of gross motor function in children with cerebral palsy (CP). Besides its frequency, the severity of chewing disorders is also important. The aim of this study was to determine the relationship between chewing performance level and gross motor function, and trunk postural control in children with CP.

Materials and methods: The study included 119 children with CP (age 2–10 years). Chewing performance level was determined by the Karaduman Chewing Performance Scale (KCPS). The Gross Motor Function Classification System (GMFCS) was used to determine the level of gross motor function. Segmental Assessment of Trunk Control (SATCo) was used to measure trunk control.

Results: Children with spastic CP with a median age of 4?years were evaluated, of which 50.4% were male. The percentages of patients classified to GMFCS levels I to V were 43.7%, 6.7%, 9.2%, 5.0%, and 35.3%, respectively. The median KCPS score was 3 (min?=?0, max?=?4). A good correlation was found between KCPS and GMFCS (p?<?.001, r?=?0.70). Negative, excellent correlations between KCPS and SATCo static, SATCo active, and SATCo reactive postural controls were found (p?<?.001, r?=?–0.75, r?=?–0.77, r?=?–0.79; respectively).

Conclusions: The severity of chewing disorders is related to the level of gross motor function and trunk postural control in children with CP.

Clinical trial number: NCT03241160     

Vitamin D deficiency in children with cerebral palsy: A narrative review of epidemiology,contributing factors,clinical consequences and interventions

Sufficient vitamin D levels are necessary, not only for mineralization, normal growth and development of bones, but also for the prevention of fatal chronic diseases like diabetes mellitus, metabolic syndrome and cancer. This is of particular importance in children with neuro- and musculoskeletal disorders, especially cerebral palsy (CP). CP is a heterogeneous group of childhood developmental disability disorders described by uncharacteristic posture, balance, and movement. Patients with CP are at an increased risk of vitamin D deficiency and as a result reduced bone mineral density, bone fragility, osteopenia, and rickets. The present review aims to combine and summarize available evidence, regarding the epidemiology, underlying contributing factors, clinical consequences, and treatment interventions of vitamin D deficiency in children with CP.     

Congenital facial palsy and emotion processing: The case of Moebius syndrome

According to the Darwinian perspective, facial expressions of emotions evolved to quickly communicate emotional states and would serve adaptive functions that promote social interactions. Embodied cognition theories suggest that we understand others' emotions by reproducing the perceived expression in our own facial musculature (facial mimicry) and the mere observation of a facial expression can evoke the corresponding emotion in the perceivers. Consequently, the inability to form facial expressions would affect the experience of emotional understanding. In this review, we aimed at providing account on the link between the lack of emotion production and the mechanisms of emotion processing. We address this issue by taking into account Moebius syndrome, a rare neurological disorder that primarily affects the muscles controlling facial expressions. Individuals with Moebius syndrome are born with facial paralysis and inability to form facial expressions. This makes them the ideal population to study whether facial mimicry is necessary for emotion understanding. Here, we discuss behavioral ambiguous/mixed results on emotion recognition deficits in Moebius syndrome suggesting the need to investigate further aspects of emotional processing such as the physiological responses associated with the emotional experience during developmental age.     

The role of co-activation in strength and force modulation in the elbow of children with unilateral cerebral palsy

To study the role of coactivation in strength and force modulation in the elbow joint of children and adolescents with cerebral palsy (CP), we investigated the affected and contralateral arm of 21 persons (age 8-18) with spastic unilateral CP in three tasks: maximal voluntary isokinetic concentric contraction and passive isokinetic movement during elbow flexion and extension, and sub-maximal isometric force tracing during elbow flexion. Elbow flexion-extension torque and surface electromyography (EMG) of the biceps brachii (BB) and triceps brachii (TB) muscles were recorded. During the maximal contractions, the affected arm was weaker, had decreased agonist and similar antagonist EMG amplitudes, and thus increased antagonist co-activation (% of maximal activity as agonist) during both elbow flexion and extension, with higher coactivation levels of the TB than the BB. During passive elbow extension, the BB of the affected arm showed increased resistance torque and indication of reflex, and thus spastic, activity. No difference between the two arms was found in the ability to modulate force, despite increased TB coactivation in the affected arm. The results indicate that coactivation plays a minor role in muscle weakness in CP, and does not limit force modulation. Moreover, spasticity seems particularly to increase coactivation in the muscle antagonistic to the spastic one, possibly in order to increase stability.     

Hearing function and auditory evoked potentials in children with spastic forms of cerebral palsy

We studied auditory short-latency brainstem and long-latency cortical evoked potentials (EP)in 62 healthy children and 126 children with spastic forms of childrens cerebral palsy, CP (spastic tetraparesis, spastic diplegia, and left-and right-side hemiplegias). An increase in the thresholds of audibility (independently of the CP form) was the most typical disturbance of the function of hearing revealed by the analysis of EP recorded in children suffering from CP. Disturbances in transmission of afferent impulsation in the brain-stem structures of the auditory system and disorders in the perception of different tones within the speech frequency range were also rather frequent. Modifications of the brainstem and cortical auditory EP typical of different CP forms, in particular hemiplegias, are described. It is demonstrated that recording and analysis of EP allow one to diagnose in children with CP those disorders in the hearing function that, in many cases, are of a subclinical nature. This technique allows clinicians to examine the youngest children (when verbal contact with the child is difficult or impossible), to study brainstem EP, and to obtain more objective data; these are significant advantages, as compared with subjective audiometry.Neirofiziologiya/Neurophysiology, Vol.36, No.4, pp.306–312, July-August, 2004.