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.

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.

Spinal cord injury usually results in permanent paralysis because of lack of regrowth of damaged neurons. Here we demonstrate that adult mice lacking EphA4 (Ϫ/Ϫ), 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. EphA4Ϫ/Ϫ 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 EphA4Ϫ/Ϫ spinal cords. EphA4Ϫ/Ϫ astrocytes failed to respond to the inflammatory cytokines, interferon-␥ or leukemia inhibitory factor, in vitro. Neurons grown on wild-type astrocytes extended shorter neurites than on EphA4Ϫ/Ϫ 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.

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.

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 individual's 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.

Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.

In primates, multiple corticospinal projections from the sensorimotor cortex operate in concert to regulate voluntary action. We examined the soma distributions of all those corticospinal neuron populations projecting to different zones in the cervical and more caudal spinal segments in the macaque that are labeled with retrogradely transported fluorescent tracers; 2-4 differentiable dyes were injected into different sites in the cervical spinal cord of each of 11 monkeys. Lamina V of the cerebral cortex, in which all corticospinal neuron somas were located, was unfolded with computer assistance to form a flat surface, and local soma densities were displayed on this plane as contour and 3-D maps. At least nine discrete, somatotopically organized corticospinal projections were identified. Three separate corticospinal projections originated in frontal cortex. The first projected mostly from area 4 (approximately 35% of the total contralateral neuron population), but also from the adjacent dorsolateral area 6a alpha (approximately 6% of total). The second large corticospinal projection (approximately 15% of total) originated in the supplementary motor area and a third small projection (approximately 2.6% of total) projected from the "postarcuate" cortex. Two separate corticospinal neuron populations were identified in areas 24 (approximately 6% of total) and 23 (approximately 4% of total) of the cingulate cortex. Thus, nearly 70% of the contralateral corticospinal projection originated in frontal and cingulate cortex. At the boundary between the primary motor and somatosensory cortex there was a sharp change in the pattern of projections. Only approximately 2.2% of the contralateral corticospinal projection originated in area 3a, rising to approximately 9% in areas 3b/1, and approximately 13% in areas 2/5. The projections from SII and insula totaled 3.4%. Ipsilateral and contralateral corticospinal projection patterns were similar, but the ipsilateral projection was only approximately 8.1% of that from the contralateral cortex. Each corticospinal neuron population had terminals in the intermediate zone of all spinal segments; additionally, there were ventral horn projections from the primary motor and cingulate cortex, and dorsal horn projections from the somatosensory cortex. Recognizing a number of separate populations of corticospinal neurons in the frontal, parietal, and insular cortex, each with unique thalamic and cortical inputs, and each of which has continuous access to all spinal motoneuron populations, underlines the importance of cortical and spinal connections linking them and coordinating their action. No coherent model of the cortical control of limb movements that incorporates this functional anatomy yet exists.

Reliability of digital muscle testing was very good in sitting and good in the other three positions. vaginal resting pressure demonstrated very good reliability in all four positions for maximum voluntary contraction, but was unreliable for endurance testing. Vaginal resting pressure was not reliable in upright positions. Both measurement tools are reliable in certain positions, with manometry demonstrating higher reliability coefficients.