Mary P. Galea

Gait and balance impairment in early multiple sclerosis in the absence of clinical disability

This study evaluated the gait and balance performance of two clinically distinct groups of recently diagnosed and minimally impaired multiple sclerosis (MS) patients (Expanded Disability Status Scale range 0- 2.5), compared to control subjects. Ten MS patients with mild pyramidal signs (Pyramidal Functional Systems 1.0), 10 MS patients with no pyramidal signs (Pyramidal Functional Systems 0) and 20 age- and gender-matched control subjects were assessed using laboratory-based gait analysis and clinical balance measures. Both MS groups demonstrated reduced speed and stride length (P < 0.001), and prolonged double limb support (P<0.02), compared to the control group, along with alterations in the timing of ankle muscle activity, and the pattern of ankle motion during walking, which occurred independent of gait speed. The pyramidal MS group walked with reduced speed (P=0.03) and stride length (P=0.04), and prolonged double limb support (P=0.01), compared to the non-pyramidal group. Both MS groups demonstrated concomitant balance impairment, performing poorly on the Functional Reach Test compared to the control group (P<0.05). The identification of incipient gait and balance impairment in MS patients with recent disease onset suggests that motor function may begin to deteriorate in the early stages of the disease, even in the absence of clinical signs of pyramidal dysfunction.

Reorganization of the motor cortex is associated with postural control deficits in recurrent low back pain

Many people with recurrent low back pain (LBP) have deficits in postural control of the trunk muscles and this may contribute to the recurrence of pain episodes. However, the neural changes that underlie these motor deficits remain unclear. As the motor cortex contributes to control of postural adjustments, the current study investigated the excitability and organization of the motor cortical inputs to the trunk muscles in 11 individuals with and without recurrent LBP. EMG activity of the deep abdominal muscle, transversus abdominis (TrA), was recorded bilaterally using intramuscular fine-wire electrodes. Postural control was assessed as onset of TrA EMG during single rapid arm flexion and extension tasks. Motor thresholds (MTs) for transcranial magnetic stimulation (TMS) were determined for responses contralateral and ipsilateral to the stimulated cortex. In addition, responses of TrA to TMS over the contralateral cortex were mapped during voluntary contractions at 10% of maximum. MTs and map parameters [centre of gravity (CoG) and volume] were compared between healthy and LBP groups. The CoG of the motor cortical map of TrA in the healthy group was approximately 2 cm anterior and lateral to the vertex, but was more posterior and lateral in the LBP group. The location of the CoG and the map volume were correlated with onset of TrA EMG during rapid arm movements. Furthermore, the MT needed to evoke ipsilateral responses was lower in the LBP group, but only on the less excitable hemisphere. These findings provide preliminary evidence of reorganization of trunk muscle representation at the motor cortex in individuals with recurrent LBP, and suggest this reorganization is associated with deficits in postural control.

Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice

Spinal cord injury usually results in permanent paralysis because of lack of regrowth of damaged neurons. Here we demonstrate that adult mice lacking EphA4 (-/-), a molecule essential for correct guidance of spinal cord axons during development, exhibit axonal regeneration and functional recovery after spinal cord hemisection. Anterograde and retrograde tracing showed that axons from multiple pathways, including corticospinal and rubrospinal tracts, crossed the lesion site. EphA4-/- mice recovered stride length, the ability to walk on and climb a grid, and the ability to grasp with the affected hindpaw within 1-3 months of injury. EphA4 expression was upregulated on astrocytes at the lesion site in wild-type mice, whereas astrocytic gliosis and the glial scar were greatly reduced in lesioned EphA4-/- spinal cords. EphA4-/- astrocytes failed to respond to the inflammatory cytokines, interferon-γ or leukemia inhibitory factor, in vitro. Neurons grown on wild-type astrocytes extended shorter neurites than on EphA4-/- astrocytes, but longer neurites when the astrocyte EphA4 was blocked by monomeric EphrinA5-Fc. Thus, EphA4 regulates two important features of spinal cord injury, axonal inhibition, and astrocytic gliosis.

Sagittal gait patterns in spastic diplegia

Classifications of gait patterns in spastic diplegia have been either qualitative, based on clinical recognition, or quantitative, based on cluster analysis of kinematic data. Qualitative classifications have been much more widely used but concerns have been raised about the validity of classifications, which are not based on quantitative data. We have carried out a cross-sectional study of 187 children with spastic diplegia who attended our gait laboratory and devised a simple classification of sagittal gait patterns based on a combination of pattern recognition and kinematic data. We then studied the evolution of gait patterns in a longitudinal study of 34 children who were followed for more than one year and demonstrated the reliability of our classification.

Muscle spindle distribution, morphology, and density in longus colli and multifidus muscles of the cervical spine.

Study Design. Tissue blocks comprising muscle and bone from C5 to C7 segments were harvested at autopsy from 16 individuals ranging in age from 4 to 77 years. The prevertebral longus colli and postvertebral multifidus muscle pairs from one side in each individual were randomly selected for this study of muscle spindles. Objectives. To determine muscle spindle distribution, morphology, and density for the longus colli and multifidus in caudal segments of the human cervical spine, and to assess whether changes are evident from infancy to old age. Summary of Background Data. Age-related changes to the osteoligamentous framework of the cervical spine have been well documented. Postural modification accompanies these structural alterations, but there have been limited attempts to document whether muscle sustains a comparable level of morphologic alteration. Previous studies have examined muscle spindles in the neck muscles of various animal models and in a variety of isolated human muscles. However, most of these studies incurred bias through sampling and methodologic assumptions. Methods. The longus colli and multifidus were resected between C5 and C7, and between left and right pairs selected randomly for spindle analysis. These vertebral segments were selected deliberately because they form the apex of the cervical lordosis and the site at which the greatest age-related modification occurs. The tissue was processed in paraffin, sectioned, and then stained by Masson’s trichrome. Spindle characteristics were examined using light microscopy and analyzed by unbiased stereologic methods. A one-sample paired t test was used to ascertain whether the differences in spindle density between the two muscles were statistically significant. Results. The longus colli has a high density of muscle spindles, which appear clustered and concentrated anterolaterally, away from the vertebral body. The multifidus has a low density of muscle spindles, which are found predominantly as single units concentrated closely to the vertebral lamina. No change in spindle distribution, morphology, and density were observed with age. Conclusions. The current study examined spindle characteristics for an intrinsic neck muscle pair whose coactivation contributes to segmental stability of the cervical spine. The distribution and morphology of muscle spindles differ between the longus colli and the multifidus. In addition, these muscles have significant differences in terms of mean spindle density. Spindle characteristics represent one of many factors that govern proprioceptive regulation in skeletal muscle, and in neck muscles, the central connectivity of these receptors remains undefined. Therefore, although there are anatomic differences between the neck flexor and extensor, the functional implications of these differences are not clear. It is also of interest that spindle characteristics remain unchanged in these intrinsic muscles whose underlying segments are subject to age-related osteoligamentous changes.

Measures of muscle and joint performance in the lower limb of children with cerebral palsy

The aim of this study was to determine the reliability and magnitude of error of three lower‐limb clinical measures for children with cerebral palsy (CP): the Modified Ashworth Scale of Spasticity (MAS), passive range of movement (PROM) and the modified Tardieu scale (MTS). Six physiotherapists measured 11 females and seven males (mean age 6 years 4 months, SD 2 years 4 months; age range 2 years 4 months to 10 years) on two occasions using a repeated measures design, collecting all data over 6 days. The severity of CP spanned all five levels of the Gross Motor Function Classification System and all children demonstrated varying degrees of spasticity. Exclusion criteria included botulinum toxin injections, inhibitory plasters, and orthopaedic surgery within the 6 months before study entry. For PROM and the MTS interrater reliability was acceptable with an intraclass correlation coefficient of 0.7, but results for MAS were lower. Standard error of measurement for repeated measures of PROM and MTS was about five degrees, but 95% confidence interval ranges were considerably higher. Test‐retest results varied widely, particularly for the MAS. These measurement tools should be used with caution when evaluating changes in young children with CP.

Correction of severe crouch gait in patients with spastic diplegia with use of multilevel orthopaedic surgery.

BACKGROUND Severe crouch gait in patients with spastic diplegia causes excessive loading of the patellofemoral joint and may result in anterior knee pain, gait deterioration, and progressive loss of function. Multilevel orthopaedic surgery has been used to correct severe crouch gait, but no cohort studies or long-term results have been reported, to our knowledge. METHODS In order to be eligible for the present retrospective cohort study, a patient had to have a severe crouch gait, as defined by sagittal plane kinematic data, that had been treated with multilevel orthopaedic surgery as well as a complete clinical, radiographic, and instrumented gait analysis assessment. The surgical intervention consisted of lengthening of contracted muscle-tendon units and correction of osseous deformities, followed by the use of ground-reaction ankle-foot orthoses until stable biomechanical realignment of the lower limbs during gait was achieved. Outcome at one and five years after surgery was determined with use of selected sagittal plane kinematic and kinetic parameters and valid and reliable scales of functional mobility. Knee pain was recorded with use of a Likert scale, and all patients had radiographic examination of the knees. RESULTS Ten subjects with severe crouch gait and a mean age of 12.0 years at the time of surgery were studied. After surgery, the patients walked in a more extended posture, with increased extension at the hip and knee and reduced dorsiflexion at the ankle. Pelvic tilt increased, and normalized walking speed was unaltered. Knee pain was diminished, and patellar fractures and avulsion injuries healed. Improvements in functional mobility were found, and, at the time of the five-year follow-up, fewer patients required the use of wheelchairs or crutches in the community than had been the case prior to intervention. CONCLUSIONS Multilevel orthopaedic surgery for older children and adolescents with severe crouch gait is effective for relieving stress on the knee extensor mechanism, reducing knee pain, and improving function and independence.

A Systematic Review of Motor and Cognitive Outcomes After Early Surgery for Congenital Heart Disease

CONTEXT: Brain injury is the most common long-term complication of congenital heart disease requiring surgery during infancy. It is clear that the youngest patients undergoing cardiac surgery, primarily neonates and young infants, are at the greatest risk for brain injury. Developmental anomalies sustained early in life have lifelong repercussions. OBJECTIVE: We conducted a systematic review to examine longitudinal studies of cognitive and/or motor outcome after cardiac surgery during early infancy. METHODS: Electronic searches were performed in Medline, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and Embase (1998–2008). The search strategy yielded 327 articles, of which 65 were reviewed. Eight cohorts provided prospective data regarding the cognitive and/or motor outcome of infants who had undergone surgery for congenital heart disease before 6 months of age. Two authors, Ms Snookes and Dr Gunn, independently extracted data and presented results according to 3 subgroups for age of follow-up: early development (1 to <3 years); preschool age (3–5 years); and school age (>5 to 17 years). Weighted analysis was undertaken to pool the results of studies when appropriate. RESULTS: All of the identified studies reported results of the Bayley Scales of Infant Development for children younger than the age of 3. Outcome data as reported by the Bayley Scales were combined for infants assessed at 1 year of age, revealing a weighted mean Mental Development Index of 90.3 (95% confidence interval: 88.9–91.6) and Psychomotor Development Index of 78.1 (95% confidence interval: 76.4–79.7). Additional analysis was limited by a lack of data at preschool and school age. CONCLUSIONS: With this review we identified a limited number of prospective studies that systematically addressed outcome in patients at the highest risk. These studies consistently revealed cognitive and motor delay in children after cardiac surgery during early infancy. Additional investigation is required to ascertain the consequences of such impairment during later childhood and into adult life.

Driving plasticity in the motor cortex in recurrent low back pain

The sensory and motor systems can reorganise following injury and learning of new motor skills. Recently we observed adaptive changes in motor cortical organisation in patients with recurrent low back pain (LBP), which are linked to altered motor coordination. Although changes in motor coordination can be trained and are associated with improved symptoms and function, it remains unclear whether these training‐induced changes are related to reorganisation of the motor cortex. This was investigated using the model of a delay in postural activation of the deep abdominal muscle, transversus abdominis (TrA) in 20 individuals with recurrent LBP. Subjects were allocated to either motor skill training that involved isolated voluntary contractions of TrA, or a control intervention of self‐paced walking exercise for 2 weeks. Electromyographic (EMG) activity was recorded from TrA bilaterally using intramuscular fine‐wire electrodes. Motor cortical organisation using transcranial magnetic stimulation (TMS) and postural activation associated with single rapid arm movements were investigated before and after training. Motor skill training induced an anterior and medial shift in motor cortical representation of TrA, towards that observed in healthy individuals from our previous study. This shift was associated with earlier postural activation of TrA. Changes were not observed following unskilled walking exercise. This is the first observation that motor training can reverse reorganisation of neuronal networks of the motor cortex in people with recurrent pain. The observed relationship between cortical reorganisation and changes in motor coordination following motor training provides unique insight into potential mechanisms that underlie recovery.

Investigation of the timed‘Up & Go’test in children

The timed‘Up & Go’test (TUG) is a test of basic or functional mobility in adults which has rarely been used in children. Functional mobility was defined for this study as an individuals ability to manoeuvre his or her body capably and independently to accomplish everyday tasks. Reliability and validity of TUG scores were examined in 176 children without physical disabilities (94 males, 82 females; mean age 5y 9mo [SD 1y 8mo]; range 3 to 9y) and in 41 young people with physical disabilities due to cerebral palsy or spina bifida (20 males, 21 females; mean age 8y 11mo [SD 4y 3mo], range 3 to 19y). Mean TUG score for children without physical disability was 5.9s (SD 1.3). Reliability of the TUG test was high, with intraclass correlation coefficients (ICC) of 0.89 within session, and 0.83 for test‐retest reliability. Mean score of the group aged 3 to 5 years was significantly higher (6.7s SD 1.2) than that of the older group (5.1s, SD 0.8;p=0.001). Scores in the younger group reduced significantly over a 5‐month follow‐up period (p=0.001), indicating that the TUG was responsive to change. Within‐session reliability of the TUG in young people with disabilities was very high (ICC=0.99). There were significant differences in TUG scores between children classified at levels I, II, and III of the Gross Motor Function Classification System (p=0.001). TUG scores showed a moderate negative correlation with scores on the Standing and Walking dimensions of the Gross Motor Function Measure (n=22, rho=‐0.52,p=0.012). There was no significant difference in TUG scores between typically developing male and female children. The TUG can be used reliably in children as young as 3 years using the protocol described in this paper. It is a meaningful, quick, and practical objective measure of functional mobility. With further investigation, the TUG is potentially useful as a screening test, an outcome measure in intervention studies for young people with disabilities, a measure of disability, and as a measure of change in functional mobility over time.