Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery.
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ABSTRACT:
SUBMITTER: Sinke MRT
PROVIDER: S-EPMC8593321 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Damage to the corticospinal tract (CST) in stroke patients has been associated with functional reorganization in the ipsilesional and contralesional sensorimotor cortices. However, it is unknown whether a quantitative relationship exists between the extent of structural damage to the CST and functional reorganization in stroke patients. The purpose of the current study was to examine the relationship between structural CST damage and motor task-related cortical activity in chronic hemiparetic stroke patients. In 10 chronic hemiparetic stroke patients with heterogeneous lesions, CST damage was quantified using conventional structural magnetic resonance imaging and tractography based on diffusion tensor imaging. Cortical activity was measured using functional magnetic resonance imaging during repetitive flexion/extension movements of the digits. We found that the two measures of CST damage were strongly correlated. Moreover, greater CST damage was significantly and linearly correlated with increased activation during affected hand movement in the hand area of the contralesional primary sensorimotor cortex (M1/S1) and in the ipsilesional M1/S1 ventral to the hand area. To our knowledge, this is the first demonstration of a quantitative relationship between the extent of structural damage to the CST and functional reorganization in stroke patients. This relationship was observed in stroke patients with heterogeneous lesions, suggesting that CST damage is a factor relevant to the variation in functional reorganization in the clinical population.
| S-EPMC2259387 | biostudies-literature
Project description:Background and Purpose- Injury to the corticospinal tract (CST) has been shown to have a major effect on upper extremity motor recovery after stroke. This study aimed to examine how well CST injury, measured from neuroimaging acquired during the acute stroke workup, predicts upper extremity motor recovery. Methods- Patients with upper extremity weakness after ischemic stroke were assessed using the upper extremity Fugl-Meyer during the acute stroke hospitalization and again at 3-month follow-up. CST injury was quantified and compared, using 4 different methods, from images obtained as part of the stroke standard-of-care workup. Logistic and linear regression were performed using CST injury to predict ΔFugl-Meyer. Injury to primary motor and premotor cortices were included as potential modifiers of the effect of CST injury on recovery. Results- N=48 patients were enrolled 4.2±2.7 days poststroke and completed 3-month follow-up (median 90-day modified Rankin Scale score, 3; interquartile range, 1.5). CST injury distinguished patients who reached their recovery potential (as predicted from initial impairment) from those who did not, with area under the curve values ranging from 0.70 to 0.8. In addition, CST injury explained ≈20% of the variance in the magnitude of upper extremity recovery, even after controlling for the severity of initial impairment. Results were consistent when comparing 4 different methods of measuring CST injury. Extent of injury to primary motor and premotor cortices did not significantly influence the predictive value that CST injury had for recovery. Conclusions- Structural injury to the CST, as estimated from standard-of-care imaging available during the acute stroke hospitalization, is a robust way to distinguish patients who achieve their predicted recovery potential and explains a significant amount of the variance in poststroke upper extremity motor recovery.
| S-EPMC6878199 | biostudies-literature
Project description:To elucidate how the motor pathways rewire the denervated tissue after stroke, we investigated remodeling of the corticospinal tract (CST) in transgenic mice with yellow fluorescent protein CST labeling in conjunction with transsynaptic pseudorabies virus retrograde tracing.Adult male CST-yellow fluorescent protein mice were subjected to permanent right middle cerebral artery occlusion (n=8/group). Foot-fault test was performed to monitor functional deficit and recovery. Pseudorabies virus tracer was injected into the left forelimb muscles at 1 or 4 weeks after middle cerebral artery occlusion (4 days before euthanasia), respectively. A third group of CST-yellow fluorescent protein mice without middle cerebral artery occlusion was used for normal control (n=6). The yellow fluorescent protein labeling of CST in the cervical cord and pseudorabies virus labeling of pyramidal neurons in the bilateral cortices were measured on vibratome sections using a confocal imaging system.Compared with normal animals, axonal density in the stroke-affected side of the cervical cord was significantly decreased at 11 days (P<0.001) and significantly increased at 32 days after stroke compared with the Day 11 values (P<0.05). Pseudorabies virus labeling was significantly decreased in the ischemic hemisphere 11 days after middle cerebral artery occlusion (P<0.001). In contrast, a significant increase was observed in pseudorabies virus labeling of bilateral cortices 32 days after stroke compared with 11 days (P<0.05). The CST axonal density in the denervated spinal cord and pyramidal neuron labeling in the bilateral cortices were significantly correlated with behavioral recovery (P<0.05).Spontaneous functional recovery after stroke may, at least in part, be attributed to neuronal remodeling in the corticospinal system.
| S-EPMC2704262 | biostudies-literature
Project description:Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.
| S-EPMC4549385 | biostudies-literature
Project description:ObjectiveDiffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders. The relationship between these two measures was explored.MethodsCSF and serum NfL concentrations and DTI acquired at 3 Tesla on the same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between NfL and DTI measures of microstructural integrity in major white matter tracts (CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were performed using tract-based spatial statistics.ResultsNfL levels were higher in patients compared to controls. CSF levels correlated with clinical upper motor neuron burden and rate of disease progression. Higher NfL levels were significantly associated with lower DTI fractional anisotropy and increased radial diffusivity in the CSTs of ALS patients, but not in controls.InterpretationElevated CSF and serum NfL is, in part, a result of CST degeneration in ALS. This highlights the wider potential for combining neurochemical and neuroimaging-based biomarkers in neurological disease.
| S-EPMC4531057 | biostudies-literature
Project description:Remote ischemic conditioning (RIC) is a noninvasive procedure whereby several periods of ischemia are induced in a limb. Although there is growing interest in using RIC to improve stroke recovery, preclinical RIC research has focused exclusively on neuroprotection, using male animals and the intraluminal suture stroke model, and delivered RIC at times not relevant to either brain repair or behavioral recovery. In alignment with the Stroke Recovery and Rehabilitation Roundtable, we address these shortcomings. First, a standardized session (5-minute inflation/deflation, 4 repetitions) of RIC was delivered using a cuff on the contralesional hindlimb in both male and female Sprague-Dawley rats. Using the endothelin-1 stroke model, RIC was delivered once either prestroke (18 hours before, pre-RIC) or poststroke (4 hours after, post-RIC), and infarct volume was assessed at 24 hours poststroke using magnetic resonance imaging. RIC was delivered at these times to mimic the day before a surgery where clots are possible or as a treatment similar to tissue plasminogen activator, respectively. Pre-RIC reduced infarct volume by 41% compared with 29% with post-RIC. RIC was neuroprotective in both sexes, but males had a 46% reduction of infarct volume compared with 23% in females. After confirming the acute efficacy of RIC, we applied it chronically for 4 weeks, beginning 5 days poststroke. This delayed RIC failed to enhance poststroke behavioral recovery. Based on these findings, the most promising application of RIC is during the hyperacute and early acute phases of stroke, a time when other interventions such as exercise may be contraindicated.
| S-EPMC8135236 | biostudies-literature
Project description:BackgroundPrognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine.ObjectiveOur primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume.MethodsIn all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured.ResultsAcute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures.ConclusionsLoss in acute CST AD and subacute CST FA are strong prognostic indicators of future motor functions of the upper limb for stroke patients with substantial initial motor impairment. DTI-derived measure of CST injury early after stroke may have utility in health care planning and in design of acute stroke clinical trials.
| S-EPMC4128905 | biostudies-literature
Project description:BACKGROUND:The purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST-WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging. METHODS AND RESULTS:Consecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST-WD on diffusion-weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor-NIHSS. Twenty-seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST-WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST-WD changes evolved into T2-hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST-WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor-NIHSS (5 versus 1, P=0.001) at 3 months. CONCLUSIONS:Wallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST-WD is associated with poor motor and functional recovery after ICH.
| S-EPMC3828779 | biostudies-other
Project description:The purpose of this study was to investigate whether textures computed from T1-weighted (T1W) images of the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS) are associated with degenerative changes evaluated by diffusion tensor imaging (DTI). Nineteen patients with ALS and 14 controls were prospectively recruited and underwent T1W and diffusion-weighted magnetic resonance imaging. Three-dimensional texture maps were computed from T1W images and correlated with the DTI metrics within the CST. Significantly correlated textures were selected and compared within the CST for group differences between patients and controls using voxel-wise analysis. Textures were correlated with the patients' clinical upper motor neuron (UMN) signs and their diagnostic accuracy was evaluated. Voxel-wise analysis of textures and their diagnostic performance were then assessed in an independent cohort with 26 patients and 13 controls. Results showed that textures autocorrelation, energy, and inverse difference normalized significantly correlated with DTI metrics (p <?.05) and these textures were selected for further analyses. The textures demonstrated significant voxel-wise differences between patients and controls in the centrum semiovale and the posterior limb of the internal capsule bilaterally (p <?.05). Autocorrelation and energy significantly correlated with UMN burden in patients (p <?.05) and classified patients and controls with 97% accuracy (100% sensitivity, 92.9% specificity). In the independent cohort, the selected textures demonstrated similar regional differences between patients and controls and classified participants with 94.9% accuracy. These results provide evidence that T1-based textures are associated with degenerative changes in the CST.
| S-EPMC6865626 | biostudies-literature
Project description:Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A-D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration. We aimed to assess the severity of corticospinal tract degeneration in a large cohort of cases with type C (n = 31). Pathological analysis included semi-quantitation of myelin loss of fibres of the corticospinal tract and associated macrophage burden, as well as axonal loss, at the level of the medullary pyramids. We also assessed for motor cortex degeneration and fibre loss of the medial lemniscus/olivocerebellar tract. All cases were subdivided into three groups based on the degree of corticospinal tract degeneration: (i) no corticospinal tract degeneration; (ii) equivocal corticospinal tract degeneration; and (iii) moderate to very severe corticospinal tract degeneration. Clinical, genetic, pathological and imaging comparisons were performed across groups. Eight cases had no corticospinal tract degeneration, and 14 cases had equivocal to mild corticospinal tract degeneration. Nine cases, however, had moderate to very severe corticospinal tract degeneration with myelin and axonal loss. In these nine cases, there was degeneration of the motor cortex without lower motor neuron degeneration or involvement of other brainstem tracts. These cases most commonly presented as semantic dementia, and they had longer disease duration (mean: 15.3 years) compared with the other two groups (10.8 and 9.9 years; P = 0.03). After adjusting for disease duration, severity of corticospinal tract degeneration remained significantly different across groups. Only one case, without corticospinal tract degeneration, was found to have a hexanucleotide repeat expansion in the C9ORF72 gene. All three groups were associated with anterior temporal lobe atrophy on MRI; however, the cases with moderate to severe corticospinal tract degeneration showed right-sided temporal lobe asymmetry and greater involvement of the right temporal lobe and superior motor cortices than the other groups. In contrast, the cases with no or equivocal corticospinal tract degeneration were more likely to show left-sided temporal lobe asymmetry. For comparison, the corticospinal tract was assessed in 86 type A and B cases, and only two cases showed evidence of corticospinal tract degeneration without lower motor neuron degeneration. These findings confirm that there exists a unique association between frontotemporal lobar degeneration with type C pathology and corticospinal tract degeneration, with this entity showing a predilection to involve the right temporal lobe.
| S-EPMC3572926 | biostudies-literature