In utero arsenic exposure and early childhood motor development in the New Hampshire Birth Cohort Study.

Introduction: High-level prenatal and childhood arsenic (As) exposure characteristic of several regions in Asia (e.g., Bangladesh), may impact motor function. However, the relationship between lower-level arsenic exposure (characteristic of other regions) and motor development is largely unstudied, despite the potential for deficient motor skills in childhood to have adverse long-term consequences. Thus, we sought to investigate the association between prenatal As exposure and motor function among 395 children in the New Hampshire Birth Cohort Study, a rural cohort from northern New England. Methods: Prenatal exposure was estimated by measuring maternal urine speciated As at 24-28 weeks of gestation using high-performance liquid chromatography (HPLC) inductively coupled plasma mass spectrometry (ICP-MS) and summing inorganic As, monomethylarsonic acid, and dimethylarsinic acid to obtain total urinary As (tAs). Motor function was assessed with the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2) at a mean (SD) age of 5.5 (0.4) years. Results: Children who completed this exam were largely reported as white race (97%), born to married mothers (86%) with a college degree or higher (67%). The median (IQR) gestational urine tAs concentration was 4.0 (5.0) µg/L. Mean (SD) BOT-2 scores were 48.6 (8.4) for overall motor proficiency and 48.2 (9.6) for fine manual control [standard score = 50 (10)], and were 16.3 (5.1) for fine motor integration and 12.5 (4.1) for fine motor precision [standard score = 15 (5)]. We found evidence of a non-linear dose response relationship and used a change-point model to assess the association of tAs with overall motor proficiency and indices of fine motor integration, fine motor precision, and their composite, fine manual control, adjusted for age and sex. In models adjusted for potential confounders, each doubling of urine tAs decreased overall motor proficiency by -3.3 points (95% CI: -6.1, -0.4) for tAs concentrations greater than the change point of 9.5 µg/L and decreased fine motor integration by -4.3 points (95% CI: -8.0, -0.6) for tAs concentrations greater than the change point of 17.0 µg/L. Discussion: In summary, we found that levels of prenatal As exposure above an empirically-derived threshold (i.e., the change point) were associated with decrements in childhood motor development in a US population.

Peer review at the Ministry of Silly Walks.

BACKGROUND: Fifty years ago, the groundbreaking British sketch series Monty Python's Flying Circus premiered on BBC One and forever changed the world of comedy. The humour transcended mere absurdity by poking a subversive finger in the eye of buttoned-up British society. Here, we commemorate this cultural milestone and simultaneously call attention to an emerging concept in the health sciences, termed simplified peer review. The union of these disparate subjects motivates a formal gait analysis based on one of the troupe's most iconic sketches, "The Ministry of Silly Walks", a satire of bureaucratic inefficiency. RESEARCH QUESTION: The sketch portrays peer review as exceedingly efficient, lasting all of 20 s. But was it fair? The answer depends on how one measures silliness. If silly walking can be defined as deviations from typical walking, then it can be quantified using video-based gait analysis. METHODS: To assess the quality of peer review at the Ministry of Silly Walks, we measured knee flexion in the sagittal plane of motion and calculated the Gait Variable Score (GVS) for three gait cycles, those of the Minister (n = 2) and Mr. Pudey (n = 1), an applicant for a Research Fellowship. RESULTS: For the Minister, we found large deviations from typical walking across two gait cycles (GVSknee(1) = 33.6, GVSknee(2) = 23.3), whereas the gait of Mr Pudey produced an intermediate score (GVSknee = 16.3). By this measure, Mr Pudney's walk is 3.3 times more variable than typical walking, whereas an exemplary silly walk is 6.7 and 4.7 times more variable, respectively, than typical walking. SIGNIFICANCE: Our analysis corroborates the Minister's assessment: Mr Pudey is a promising applicant and deserving of a Research Fellowship to advance his silly walk. We suggest that the sketch holds special resonance and uncanny prescience for researchers in the health sciences today.

Reorganization of the somatosensory cortex in hemiplegic cerebral palsy associated with impaired sensory tracts.

Functional neuroimaging studies argue that sensory deficits in hemiplegic cerebral palsy (HCP) are related to deviant somatosensory processing in the ipsilesional primary somatosensory cortex (S1). A separate body of structural neuroimaging literature argues that these deficits are due to structural damage of the ascending sensory tracts (AST). The relationship between the functional and structural integrity of the somatosensory system and the sensory performance is largely unknown in HCP. To address this relationship, we combined findings from magnetoencephalography (MEG) and probabilistic diffusion tractography (PDT) in 10 children with HCP and 13 typically developing (TD) children. With MEG, we mapped the functionally active regions in the contralateral S1 during tactile stimulation of the thumb, middle, and little fingers of both hands. Using these MEG-defined functional active regions as regions of interest for PDT, we estimated the diffusion parameters of the AST. Somatosensory function was assessed via two-point discrimination tests. Our MEG data showed: (i) an abnormal somatotopic organization in all children with HCP in either one or both of their hemispheres; (ii) longer Euclidean distances between the digit maps in the S1 of children with HCP compared to TD children; (iii) suppressed gamma responses at early latencies for both hemispheres of children with HCP; and (iv) a positive correlation between the Euclidean distances and the sensory tests for the more affected hemisphere of children with HCP. Our MEG-guided PDT data showed: (i) higher mean and radian diffusivity of the AST in children with HCP; (ii) a positive correlation between the axial diffusivity of the AST with the sensory tests for the more affected hemisphere; and (iii) a negative correlation between the gamma power change and the AD of the AST for the MA hemisphere. Our findings associate for the first time bilateral cortical functional reorganization in the S1 of HCP children with abnormalities in the structural integrity of the AST, and correlate these abnormalities with behaviorally-assessed sensory deficits.

Artificial Walking Technologies to Improve Gait in Cerebral Palsy: Multichannel Neuromuscular Stimulation.

Cerebral palsy (CP) is the most common childhood motor disability and often results in debilitating walking abnormalities, such as flexed-knee and stiff-knee gait. Current medical and surgical treatments are only partially effective in improving gait abnormalities and may cause significant muscle weakness. However, emerging artificial walking technologies, such as step-initiated, multichannel neuromuscular electrical stimulation (NMES), can substantially improve gait patterns and promote muscle strength in children with spastic CP. NMES may also be applied to specific lumbar-sacral sensory roots to reduce spasticity. Development of tablet computer-based multichannel NMES can leverage lightweight, wearable wireless stimulators, advanced control design, and surface electrodes to activate lower-limb muscles. Musculoskeletal models have been used to characterize muscle contributions to unimpaired gait and identify high muscle demands, which can help guide multichannel NMES-assisted gait protocols. In addition, patient-specific NMES-assisted gait protocols based on 3D gait analysis can facilitate the appropriate activation of lower-limb muscles to achieve a more functional gait: stance-phase hip and knee extension and swing-phase sequence of hip and knee flexion followed by rapid knee extension. NMES-assisted gait treatment can be conducted as either clinic-based or home-based programs. Rigorous testing of multichannel NMES-assisted gait training protocols will determine optimal treatment dosage for future clinical trials. Evidence-based outcome evaluation using 3D kinematics or temporal-spatial gait parameters will help determine immediate neuroprosthetic effects and longer term neurotherapeutic effects of step-initiated, multichannel NMES-assisted gait in children with spastic CP. Multichannel NMES is a promising assistive technology to help children with spastic CP achieve a more upright, functional gait.

Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment.

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP.

Clinical motion analyses over eight consecutive years in a child with crouch gait: a case report.

BACKGROUND: This case report provides a unique look at the progression of crouch gait in a child with cerebral palsy over an 8-year time period, through annual physical examinations, three-dimensional gait analyses, and evaluation of postural balance. Our patient received regular botulinum toxin-A injections, casting, and physical therapy but no surgical interventions. CASE PRESENTATION: A white American boy with spastic diplegic cerebral palsy was evaluated annually by clinical motion analyses, including physical examination, joint kinematics, electromyography, energy expenditure, and standing postural balance tests, from 6 to 13 years of age. These analyses revealed that the biomechanical factors contributing to our patient's crouch gait were weak plantar flexors, short and spastic hamstrings, moderately short hip flexors, and external rotation of the tibiae. Despite annual recommendations for surgical lengthening of the hamstrings, the family opted for non-surgical treatment through botulinum toxin-A injections, casting, and exercise. Our patient's crouch gait improved between ages 6 and 9, then worsened at age 10, concurrent with his greatest body mass index, increased plantar flexor weakness, increased standing postural sway, slowest normalized walking speed, and greatest walking energy expenditure. Although our patient's maximum knee extension in stance improved by 14 degrees at 13 years of age compared to 6 years of age, peak knee flexion in swing declined, his ankles became more dorsiflexed, his hips became more internally rotated, and his tibiae became more externally rotated. From 6 to 9 years of age, our patient's minimum stance-phase knee flexion varied in an inverse relationship with his body mass index; from 10 to 13 years of age, changes in his minimum stance-phase knee flexion paralleled changes in his body mass index. CONCLUSIONS: The motor deficits of weakness, spasticity, shortened muscle-tendon lengths, and impaired selective motor control were highlighted by our patient's clinical motion analyses. Overall, our patient's crouch gait improved mildly with aggressive non-operative management and a supportive family dedicated to regular home exercise. The annual clinical motion analyses identified changes in motor deficits that were associated with changes in the child's walking pattern, suggesting that these analyses can serve to track the progression of children with spastic cerebral palsy.

Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here.

The pediatric upper limb motion index and a temporal-spatial logistic regression: quantitative analysis of upper limb movement disorders during the Reach & Grasp Cycle.

This study describes a novel pediatric upper limb motion index (PULMI) for children with cerebral palsy (CP). The PULMI is based on three-dimensional kinematics and provides quantitative information about upper limb motion during the Reach & Grasp Cycle. We also report key temporal-spatial parameters for children with spastic, dyskinetic, and ataxic CP. Participants included 30 typically-developing (TD) children (age=10.9±4.1 years) and 25 children with CP and upper limb involvement (age=12.3±3.7 years), Manual Ability Classification System (MACS) levels I-IV. The PULMI is calculated from the root-mean-square difference for eight kinematic variables between each child with CP and the average TD values, and scaled such that the TD PULMI is 100±10. The PULMI was significantly lower among children with CP compared to TD children (Wilcoxon Z=-5.06, p<.0001). PULMI scores were significantly lower among children with dyskinetic CP compared to spastic CP (Z=-2.47, p<.0135). There was a strong negative correlation between PULMI and MACS among children with CP (Spearman's rho=-.78, p<.0001). Temporal-spatial values were significantly different between CP and TD children: movement time (Z=4.06, p<.0001), index of curvature during reach (Z=3.68, p=.0002), number of movement units (Z=3.72, p=.0002), angular velocity of elbow extension during reach (Z=-3.96, p<.0001), and transport(1):reach peak velocities (Z=-2.48, p=.0129). A logistic regression of four temporal-spatial parameters, the Pediatric Upper Limb Temporal-Spatial Equation (PULTSE), correctly predicted 19/22 movement disorder subtypes (spastic versus dyskinetic CP). The PULMI, PULTSE, and key temporal-spatial parameters of the Reach & Grasp Cycle offer a quantitative approach to analyzing upper limb function in children with CP.

Rotational biomechanics of the elite golf swing: benchmarks for amateurs.

The purpose of this study was to determine biomechanical factors that may influence golf swing power generation. Three-dimensional kinematics and kinetics were examined in 10 professional and 5 amateur male golfers. Upper-torso rotation, pelvic rotation, X-factor (relative hip-shoulder rotation), O-factor (pelvic obliquity), S-factor (shoulder obliquity), and normalized free moment were assessed in relation to clubhead speed at impact (CSI). Among professional golfers, results revealed that peak free moment per kilogram, peak X-factor, and peak S-factor were highly consistent, with coefficients of variation of 6.8%, 7.4%, and 8.4%, respectively. Downswing was initiated by reversal of pelvic rotation, followed by reversal of upper-torso rotation. Peak X-factor preceded peak free moment in all swings for all golfers, and occurred during initial downswing. Peak free moment per kilogram, X-factor at impact, peak X-factor, and peak upper-torso rotation were highly correlated to CSI (median correlation coefficients of 0.943, 0.943, 0.900, and 0.900, respectively). Benchmark curves revealed kinematic and kinetic temporal and spatial differences of amateurs compared with professional golfers. For amateurs, the number of factors that fell outside 1-2 standard deviations of professional means increased with handicap. This study identified biomechanical factors highly correlated to golf swing power generation and may provide a basis for strategic training and injury prevention.

Definition and classification of hyperkinetic movements in childhood.

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials.

Temporal-spatial parameters of the upper limb during a Reach & Grasp Cycle for children.

The objective of this study was to characterize normal temporal-spatial patterns during the Reach & Grasp Cycle and to identify upper limb motor deficits in children with cerebral palsy (CP). The Reach & Grasp Cycle encompasses six sequential tasks: reach, grasp cylinder, transport to self (T(1)), transport back to table (T(2)), release cylinder, and return to initial position. Three-dimensional motion data were recorded from 25 typically developing children (11 males, 14 females; ages 5-18 years) and 12 children with hemiplegic CP (2 males, 10 females; ages 5-17 years). Within-day and between-day coefficients of variation for the control group ranged from 0 to 0.19, indicating good repeatability of all parameters. The mean duration of the Cycle for children with CP was nearly twice as long as controls, 9.5±4.3s versus 5.1±1.2s (U=37.0, P=.002), partly due to prolonged grasp and release durations. Peak hand velocity occurred at approximately 40% of each phase and was greater during the transport (T(1), T(2)) than non-transport phases (reach, return) in controls (P<.001). Index of curvature was lower during transport versus non-transport phases for all children. Children with CP demonstrated an increased index of curvature during reach (U=46.0, P=.0074) and an increased total number of movement units (U=16.5, P<.0001) compared to controls, indicating less efficient and less smooth movements. Total duration of the Reach & Grasp Cycle (rho=.957, P<.0001), index of curvature during reach and T(1) (rho=.873, P=.0002 and rho=.778, P=.0028), and total number of movement units (rho=.907, P<.0001) correlated strongly with MACS score. The consistent normative data and the substantial differences between children with CP and controls reflect utility of the Reach & Grasp Cycle for quantitative evaluation of upper limb motor deficits.

Three-dimensional kinematics of the upper limb during a Reach and Grasp Cycle for children.

The ability to reach, grasp, transport, and release objects is essential for activities of daily living. The objective of this study was to develop a quantitative method to assess upper limb motor deficits in children with cerebral palsy (CP) using three-dimensional motion analysis. We report kinematic data from 25 typically developing (TD) children (11 males, 14 females; ages 5-18 years) and 2 children with spastic hemiplegic CP (2 females, ages 14 and 15 years) during the Reach and Grasp Cycle. The Cycle includes six sequential tasks: reach, grasp cylinder, transport to mouth (T(1)), transport back to table (T(2)), release cylinder, and return to initial position. It was designed to represent a functional activity that was challenging yet feasible for children with CP. For example, maximum elbow extension was 43+/-11 degrees flexion in the TD group. Consistent kinematic patterns emerged for the trunk and upper limb: coefficients of variation at point of task achievement for reach, T(1), and T(2) for trunk flexion-extension were (.11, .11, .11), trunk axial rotation (.06, .06, .06), shoulder elevation (.13, .11, .13), elbow flexion-extension (.25, .06, .23), forearm pronation-supination (.08, .10, .11), and wrist flexion-extension (.25, .21, .22). The children with CP demonstrated reduced elbow extension, increased wrist flexion and trunk motion, with an increased tendency to actively externally rotate the shoulder and supinate the forearm during T(1) compared to the TD children. The consistent normative data and clinically significant differences in joint motion between the CP and TD children suggest the Reach and Grasp Cycle is a repeatable protocol for objective clinical evaluation of functional upper limb motor performance.

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.

Neonatal microstructural development of the internal capsule on diffusion tensor imaging correlates with severity of gait and motor deficits.

Neonatal microstructural development in the posterior limbs of the internal capsule (PLIC) was assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA) in 24 very-low-birthweight preterm infants at 37 weeks' gestational age and compared with the children's gait and motor deficits at 4 years of age. There were 14 participants with normal neonatal FA values (seven females, seven males; born at 27.6 weeks [SD 2.3] gestational age; birthweight 1027g [SD 229]) and 10 participants with low FA values in the PLIC (four females, six males; born at 28.4 weeks [SD 2.0] gestational age; birthweight 1041g [SD 322]). Seven of the 10 children with low FA and none of the children with normal FA had been diagnosed with CP by the time of gait testing. Among children with low neonatal FA, there was a strong negative correlation between FA of the combined left and right side PLIC and log NI (r=-0.89, p=0.001) and between FA and GMFCS (r=-0.65, p=0.04) at 4 years of age. There was no correlation between FA and gait NI or GMFCS at 4 years of age among children with normal neonatal FA. This preliminary study suggests neonatal DTI may be an important predictor of the severity of future gait and motor deficits.

Postural equilibrium during pregnancy: decreased stability with an increased reliance on visual cues.

OBJECTIVE: The purpose of this study was to determine whether there are changes in postural equilibrium during pregnancy and to examine whether the incidence of falls increases during pregnancy. STUDY DESIGN: Static postural balance measures were collected from 12 pregnant women at 11 to 14, 19 to 22, and 36 to 39 weeks gestation and at 6 to 8 weeks after delivery and from 12 nulligravid control subjects who were matched for age, height, weight, and body mass index. Subjects were asked to stand quietly on a stable force platform for 30 seconds with eyes open and closed. Path length and average radial displacement were computed on the basis of the average of 3 trials for each condition. The women were asked at each session if they had sustained a fall in the previous 3 months. RESULTS: Postural stability remained relatively stable during the first trimester; however, second and third trimester and postpartum values for path length and average radial displacement with eyes open and closed were increased significantly compared with the control subjects, which indicates diminished postural balance. The difference between the eyes open and closed values of path length increased as pregnancy progressed. Although 25% of pregnant women sustained falls, none of the control subjects had fallen in the past year. CONCLUSION: These data suggest that postural stability declines during pregnancy and remains diminished at 6 to 8 weeks after delivery. The study also indicates that there is an increased reliance on visual cues to maintain balance during pregnancy.