Mary C. Verrier

Gait Asymmetry in Community-Ambulating Stroke Survivors

OBJECTIVES To determine the prevalence and severity of asymmetry among independently ambulating stroke survivors and to establish the association between velocity and asymmetry. DESIGN Descriptive analysis. SETTING Research gait laboratory in a Canadian hospital. PARTICIPANTS Community-dwelling, independently ambulating participants (N=54) with chronic stroke. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Overground gait velocity, symmetry ratios for temporal and spatial step parameters, and motor impairment of the foot and leg. Spatiotemporal parameters were collected with a pressure-sensitive mat. Motor impairment was measured clinically with the Chedoke-McMaster Stroke Assessment. RESULTS Thirty (55.5%) participants showed statistically significant temporal asymmetry and 18 (33.3%) exhibited statistically significant spatial asymmetry. Preferred velocity was negatively associated with temporal asymmetry (r=-.583, df=52, P<.001) but not spatial asymmetry (r=-.146, df=52, P=.29). Temporal asymmetry was also associated with motor recovery of the leg (r=-.644, df=35, P<.001) and foot (r=-.628, df=35, P<.001). CONCLUSIONS The results of the current study illustrate that temporal asymmetry can be found in many independently ambulating stroke patients. The work highlights the need for a standard assessment of poststroke gait symmetry in light of the complex relationship with motor impairment and velocity.

Sensorimotor Cortical Plasticity During Recovery Following Spinal Cord Injury: A Longitudinal fMRI Study

Background. Although the consequences of spinal cord injury (SCI) within the spinal cord and peripheral nervous system have been studied extensively, the influence of SCI on supraspinal structures during recovery remains largely unexplored. Objective. To assess temporal changes in cortical sensorimotor representations beginning in the subacute phase following SCI and determine if an association exists between the plastic changes within cortical sensorimotor areas and recovery of movement postinjury. Methods. Functional magnetic resonance imaging (fMRI) was used to study 6 SCI patients for 1 year, beginning shortly postinjury, and 10 healthy control individuals. During fMRI, individuals performed a simple self-paced wrist extension motor task. Recovery of movement was assessed using the American Spinal Injury Association (ASIA) Standard Neurological Classification of SCI. Results. In the subacute period post-SCI, during impaired movement, little task-related activation within the primary motor cortex (M1) was present, whereas activation in associated cortical sensorimotor areas was more extensive than in controls. During motor recovery, a progressive enlargement in the volume of movement-related M1 activation and decreased activation in associated cortical sensorimotor areas was seen. When movement was performed with little to no impairment, the overall pattern of cortical activation was similar to that observed in control individuals. Conclusions . This study provides the first report of the temporal progression of cortical sensorimotor representational plasticity during recovery following traumatic SCI in humans and suggests an association between movement-related fMRI activation and motor recovery postinjury. These findings have implications on current and future rehabilitative interventions for patients with SCI.

The Community Balance and Mobility Scale-a balance measure for individuals with traumatic brain injury

Objective: To provide evidence for the validity and reliability of a new outcome measure of balance, the Community Balance and Mobility Scale, developed for the ambulatory individual with traumatic brain injury. Design: A validity and reliability study. Setting: Acute care, in- and outpatient rehabilitation and day hospital settings. Subjects: Two convenience samples (n=36, 32) of ambulatory patients with traumatic brain injury. Main measures: The content and construct validity, test-retest, inter- and intra-rater reliability and internal consistency of the Community Balance and Mobility Scale. Results: Content validity was demonstrated by the involvement of patients with traumatic brain injury (n=7) and clinicians (n=17) in the process of item generation and by physical therapists’ ratings of item relevance. Further support is the correlation of the Community Balance and Mobility Scale scores with physical therapists’ global balance ratings of the patient (r=0.62). Construct validity was supported by the ability of the measure to differentiate between patients along the continuum of care and also by comparisons with maximal walking velocity (r=0.64). Patients who scored greater than or less than 50 on the balance measure demonstrated significantly different Community Integration Questionnaire scores (P=0.004). The Community Balance and Mobility Scale demonstrated intraclass correlation coefficients (ICCs) of 0.977, 0.977, 0.975 and Cronbach’s alpha of 0.96 for intra-, inter-, test-retest reliability and internal consistency, respectively. Conclusion: The Community Balance and Mobility Scale is a valid and reliable outcome measure for the ambulatory individual with traumatic brain injury.

MPTP produces reversible disappearance of tyrosine hydroxylase-containing retinal amacrine cells.

To determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) alters the tyrosine hydroxylase (TH) immunoreactivity of murine dopaminergic retinal amacrine cells, 8-10-week-old C57BL/6J mice were treated with i.p. with saline or cumulative doses of MPTP ranging from 10 to 300 mg/kg. Paraformaldehyde-fixed retinal whole mounts and cross sections were examined using immunochemistry with a tyrosine hydroxylase (TH) or a choline acetyltransferase (ChAT) polyclonal antibody and an avidin-biotin peroxidase reaction. Both TH+ amacrines and ChAT+ retinal neurons showed somal and process morphology and distributions that were commensurate with previous studies of the same or several related species. At 20 days following the MPTP treatment, there was a loss of TH+ amacrines according to a logarithmic relationship relative to MPTP dosage. The loss ranged from 18 to 87% for the dosage range without any decrease in the numbers of ChAT+ neurons. The TH+ amacrines were deleted randomly from the retinas without any peripheral-central predilection. By 273 days after MPTP treatment, the number of TH+ amacrines had returned to values found for age-matched controls demonstrating that the loss of TH immunoreactivity was reversible and occurred without destruction of TH+ amacrines. Computer densitometry revealed that the MPTP-treated TH+ amacrines were divided into two distinct populations: one with normal TH immunodensity levels and a second with TH immunodensity levels below our detection capability. Increasing the MPTP dosage increased the proportion of TH amacrines in the second population. The transient and completely reversible disappearance in the number of TH+ amacrines: (1) appears to form the basis for the decreased concentrations of dopamine and the loss of catecholamine fluorescent neurons previously described for MPTP-treated mouse retinae; (2) may underlie the defects in the electroretinograms of MPTP-treated monkeys, and (3) may result as a response to neurite damage similarly to the alterations in protein synthesis in other central neurons following axonal damage.

Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study

Study design:A multicenter Canadian cohort study.Objectives:The objective of this study is to evaluate the impact of early versus late surgical decompression on motor neurological recovery after traumatic spinal cord injury (SCI).Setting:Canadian acute care and SCI rehabilitation facilities.Methods:A prospective cohort study of patients within the Ontario Spinal Cord Injury Registry program was performed. We considered SCI patients with an admission American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade of A through D, with magnetic resonance imaging-confirmed spinal cord compression. Grouped analysis was performed comparing the cohort of patients who received early surgery (<24 h after SCI) to those receiving delayed surgery (⩾24 h after SCI). The primary outcome was the change in ASIA motor score (AMS) occurring between hospital admission and rehabilitation discharge.Results:A total of 35 (41.7%) patients underwent early surgery and 49 (58.3%) underwent late surgery. At admission, there was a greater proportion of patients within the early surgery group with more severe AIS grade A injuries. Of the 55 patients with neurological exam available at rehabilitation discharge, a greater proportion had at least a two-grade AIS improvement in the early-surgery group (P=0.01). The mean improvement in AMS at rehabilitation discharge was 20 points amongst early-surgery patients and 15 points amongst late-surgery patients (P=0.46). In the analysis investigating AMS improvement, adjusted for preoperative status and neurological level, there was a positive effect estimate for early surgical therapy that was statistically significant (P=0.01).Conclusion:The results here add weight to the growing body of literature, which supports the principle of early intervention in the setting of spinal trauma and SCI.

Adaptation in the motor cortex following cervical spinal cord injury

BackgroundThe nature of the adaptive changes that occur in the cerebral cortex following injury to the cervical spinal cord are largely unknown. ObjectiveTo investigate these adaptive changes by examining the relationship between the motor cortical representation of the paretic right upper extremity compared with that of the tongue. The tongue was selected because the spinal cord injury (SCI) does not affect its movement and the cortical representation of the tongue is adjacent to that of the paretic upper extremity. MethodsFMRI was used to map cortical representations associated with simple motor tasks of the right upper extremity and tongue in 14 control subjects and 9 patients with remote (>5.5 months) cervical SCI. ResultsThe mean value for the site of maximum cortical activation during upper limb movement was identical between the two groups. The site of maximum left hemispheric cortical activation during tongue movement was 12.8 mm (p < 0.01) medial and superior to that of control subjects, indicating the presence of a shift in cortical activation. ConclusionThe findings indicate that the adult motor cortex does indeed adapt following cervical SCI. The nature of the adaptation and the underlying biological mechanisms responsible for this change require further investigation.

The Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity.

With the advent of new interventions targeted at both acute and chronic spinal cord injury (SCI), it is critical that techniques and protocols are developed that reliably evaluate changes in upper limb impairment/function. The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) protocol, which includes five subtests, is a quantitative clinical upper limb impairment measure designed for use in acute and chronic cervical SCI. The objectives of this study were to: (1) establish the inter-rater and test-retest reliability, and (2) establish the construct and concurrent validity with the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), Spinal Cord Independence Measure II (SCIM), and the Capabilities of Upper Extremity Questionnaire (CUE). The study protocol included repeated administration of the GRASSP to a cross-section of individuals with tetraplegia who were neurologically stable (n=72). ISNCSCI, CUE, and SCIM assessments were also administered. Two assessors examined the individuals over a 7-day period. Reliability was tested with intra-class correlation coefficients; construct validity was established with agreement/discordance analysis between the GRASSP and ISNCSCI sensory and motor items; and concurrent validity was tested with Spearman correlation coefficients. Inter-rater and test-retest reliability for all subtests within the GRASSP were above the hypothesized value of 0.80 (0.84-0.96 and 0.86-0.98, respectively). The GRASSP is about 50% more sensitive (construct validity) than the ISNCSCI when defining sensory and motor integrity of the upper limb; the subtests showed concurrence with the SCIM, SCIM self-care subscale, and CUE. The strongest concurrence to impairment was with self-perception of function (CUE) (0.57-0.83, p<0.0001). The GRASSP was found to demonstrate reliability, construct validity, and concurrent validity for use as a standardized upper limb impairment measure for individuals with tetraplegia.

Somatosensory cortical atrophy after spinal cord injury: A voxel-based morphometry study

The authors used voxel-based morphometry to compare sensorimotor cortical gray and white matter volume on structural MR images of a group of 17 individuals with cervical spinal cord injury (SCI) and a group of 17 healthy subjects. SCI subjects had reduced gray matter volume bilaterally in primary somatosensory cortex (p < 0.001). These findings suggest that the somatosensory cortex of the human brain atrophies after SCI.

Development of the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific to the upper limb in tetraplegia

OBJECT Primary outcome measures for the upper limb in trials concerning human spinal cord injury (SCI) need to distinguish between functional and neurological changes and require satisfying psychometric properties for clinical application. METHODS The Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) was developed by the International GRASSP Research and Design Team as a clinical outcome measure specific to the upper limbs for individuals with complete and incomplete tetraplegia (that is, paralysis or paresis). It can be administered across the continuum of recovery after acute cervical SCI. An international multicenter study (involving centers in North America and Europe) was conducted to apply the measure internationally and examine its applicability. RESULTS The GRASSP is a multimodal test comprising 5 subtests for each upper limb: dorsal sensation, palmar sensation (tested with Semmes-Weinstein monofilaments), strength (tested with motor grading of 10 muscles), and prehension (distinguishes scores for qualitative and quantitative grasping). Thus, administration of the GRASSP results in 5 numerical scores that provide a comprehensive profile of upper-limb function. The established interrater and test-retest reliability for all subtests within the GRASSP range from 0.84 to 0.96 and from 0.86 to 0.98, respectively. The GRASSP is approximately 50% more sensitive (construct validity) than the International Standards of Neurological Classification of SCI (ISNCSCI) in defining sensory and motor integrity of the upper limb. The subtests show concurrence with the Spinal Cord Independence Measure (SCIM), SCIM self-care subscales, and Capabilities of Upper Extremity Questionnaire (CUE) (the strongest concurrence to impairment is with self-perception of function [CUE], 0.57-0.83, p < 0.0001). CONCLUSIONS The GRASSP was found to demonstrate reliability, construct validity, and concurrent validity for use as a standardized upper-limb impairment measure for individuals with complete or incomplete tetraplegia. Responsiveness (follow-up from onset to 1 year postinjury) is currently being tested in international studies (in North America and Europe). The GRASSP can be administered early after injury, thus making it a tool that can be administered in acute care (in the ICU), rehabilitation, and outpatient clinics.

Different rates of age-related loss for four murine monoaminergic neuronal populations

The age-related loss of locus coeruleus (LC) noradrenergic neurons, substantia nigra compacta (SNc) dopaminergic neurons, dopaminergic retinal amacrine (rAm) neurons and raphe serotonergic neurons, identified using antibodies against tyrosine hydroxylase (TH) and serotonin (5HT) was investigated in C57B1 mice aged 8 to 104 weeks. The neuronal somata were counted and their locations three-dimensionally reconstructed from serial sections alternately immunoreacted or Nissl stained. Nonlinear estimation analysis showed that decaying exponential equations best fitted the plots of neuronal numbers versus age and each subtype was lost according to different exponential constants of -0.015, -0.013, -0.004 and -0.001 for LC TH+, SNc TH+, rAm TH+ and raphe 5HT+ neurons, respectively. Neurons were lost from all different subregions within the nuclei or the retinae. Counts of immediately adjacent TH-immunoreacted and Nissl-stained sections through the LC at different ages indicate that the neuronal loss was due to neuronal death rather than loss of TH immunoreactivity. The markedly different rates of age-related neuronal loss for the four monoaminergic subtypes offer a model to study the underlying molecular and cellular mechanisms.