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 ∼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.

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.

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.

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. 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. 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. 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. 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. 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.

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.