A review of motor recovery mechanisms in patients with stroke

Elucidation of the motor recovery mechanisms in stroke patients is important because such information could provide the scientific basis for stroke rehabilitation. The motor recovery mechanism after stroke, however, has not yet been clearly elucidated, but several suggested mechanisms have been proposed. These include the ipsilateral motor pathway from the unaffected motor cortex to the affected hand, peri-lesional reorganization, the recovery of a damaged lateral corticospinal tract, and contribution of the secondary motor area. Additionally, little is known about the motor recovery mechanism for patients with intracerebral hemorrhage, for locomotor recovery, and for damage at the subcortical level. Therefore, we suggest that further research should be focused on the elucidation of motor recovery mechanisms in relation to the above topics. In the current study, we tried to review the literatures about the motor recovery mechanisms of the patients with stroke.     

Diffusion tensor imaging studies on corticospinal tract injury following traumatic brain injury: a review

The corticospinal tract (CST) is the most important neural tract for motor function in the human brain. Therefore, clarification of CST injury would be an important topic in traumatic brain injury (TBI) rehabilitation. In this review, I reviewed diffusion tensor imaging (DTI) studies on CST injuries in terms of etiology and recovery in patients with TBI. Although DTI has several unique advantages for research on CST injury in TBI, only a dozen DTI studies on this topic have been reported: etiology of CST injury (9 studies), recovery of CST injury (3 studies). As for the etiology of CST injury in TBI, the previous studies have demonstrated the usefulness of DTI in diagnosis of CST injury in cases of diffuse axonal injury, transtentorial herniation, cerebral hemorrhage, and cortical contusion; moreover, according to the severity of TBI. The three studies on recovery of CST injury focused on recovery of a CST injured by diffuse axonal injury. In the future, we suggest an increase in the total number of DTI studies on this topic. In particular, research on recovery of CST injury should be encouraged. Moreover, studies of the various recovery mechanisms related to the CST are necessary.     

脑卒中患者病灶周围运动功能的重组

Perilesional reorganization is an important recovery mechanism for stroke patients because it yields good motor outcomes. However, perilesional reorganization remains poorly understood. The scientific basis for stroke rehabilitation can be established when detailed mechanisms of recovery are clarified. In addition, studies at the subcortical level remain in the early stages. Therefore, the present study suggested that additional investigations should focus on perilesional reorganization at the subcortical level, identifying the critical period for this mechanism and determining treatment strategies and modalities to facilitate development. The present study reviews literature focused on perilesional reorganization in stroke patients with regard to demonstration, clinical characteristics, and rehabilitative aspects, as well as previous studies of perilesional reorganization at cortical and subcortical levels.     

Microstructural status of ipsilesional and contralesional corticospinal tract correlates with motor skill in chronic stroke patients

Greater loss in structural integrity of the ipsilesional corticospinal tract (CST) is associated with poorer motor outcome in patients with hemiparetic stroke. Animal models of stroke have demonstrated that structural remodeling of white matter in the ipsilesional and contralesional hemispheres is associated with improved motor recovery. Accordingly, motor recovery in patients with stroke may relate to the relative strength of CST degeneration and remodeling. This study examined the relationship between microstructural status of brain white matter tracts, indexed by the fractional anisotropy (FA) metric derived from diffusion tensor imaging (DTI) data, and motor skill of the stroke‐affected hand in patients with chronic stroke. Voxelwise analysis revealed that motor skill significantly and positively correlated with FA of the ipsilesional and contralesional CST in the patients. Additional voxelwise analyses showed that patients with poorer motor skill had reduced FA of bilateral CST compared to normal control subjects, whereas patients with better motor skill had elevated FA of bilateral CST compared to controls. These findings were confirmed using a DTI‐tractography method applied to the CST in both hemispheres. The results of this study suggest that the level of motor skill recovery achieved in patients with hemiparetic stroke relates to microstructural status of the CST in both the ipsilesional and contralesional hemispheres, which may reflect the net effect of degeneration and remodeling of bilateral CST. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Diffusion tensor imaging of pyramidal tract reorganization after pediatric stroke

Background

Plasticity of the developing motor tracts is a contributor to recovery of motor function after pediatric stroke. The mechanism of these plastic changes may be functional and/or structural in nature. The corticospinal tract (CST) represents the major pathway responsible for voluntary movement. Stroke-induced damage to the CST as well as to other motor tracts leads to motor deficits which may show favorable functional recovery particularly in the pediatric population.

Methods

We report the case of a 3-year-old girl demonstrating reorganization of the pyramidal tracts after an extensive left MCA territory stroke secondary to head trauma. Reorganization is characterized using serial diffusion tensor imaging (DTI) of the pyramidal tracts which contain the CST.

Results

Imaging shows decreased ipsi-lesional fractional anisotropy (FA) suggestive of Wallerian degeneration and increased contralesional FA.

Conclusions

These results point to plastic reorganization of the pyramidal tract post-stroke and the utility of DTI in recognizing these changes.     

Reorganization of Intact Descending Motor Circuits to Replace Lost Connections After Injury

Neurons have a limited capacity to regenerate in the adult central nervous system (CNS). The inability of damaged axons to re-establish original circuits results in permanent functional impairment after spinal cord injury (SCI). Despite abortive regeneration of axotomized CNS neurons, limited spontaneous recovery of motor function emerges after partial SCI in humans and experimental rodent models of SCI. It is hypothesized that this spontaneous functional recovery is the result of the reorganization of descending motor pathways spared by the injury, suggesting that plasticity of intact circuits is a potent alternative conduit to enhance functional recovery after SCI. In support of this hypothesis, several studies have shown that after unilateral corticospinal tract (CST) lesion (unilateral pyramidotomy), the intact CST functionally sprouts into the denervated side of the spinal cord. Furthermore, pharmacologic and genetic methods that enhance the intrinsic growth capacity of adult neurons or block extracellular growth inhibitors are effective at significantly enhancing intact CST reorganization and recovery of motor function. Owing to its importance in controlling fine motor behavior in primates, the CST is the most widely studied descending motor pathway; however, additional studies in rodents have shown that plasticity within other spared descending motor pathways, including the rubrospinal tract, raphespinal tract, and reticulospinal tract, can also result in restoration of function after incomplete SCI. Identifying the molecular mechanisms that drive plasticity within intact circuits is crucial in developing novel, potent, and specific therapeutics to restore function after SCI. In this review we discuss the evidence supporting a focus on exploring the capacity of intact motor circuits to functionally repair the damaged CNS after SCI.     

Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish between ALS phenotypes

Patients with amyotrophic lateral sclerosis (ALS) can present with varying degrees of upper motor neuron (UMN) and lower motor neuron dysfunction. Previous diffusion tensor imaging (DTI) studies, in which ALS patients were not separated by the degree of UMN dysfunction, have resulted in conflicting or inconclusive results. We hypothesized that (1) categorizing ALS patients by their clinical phenotype can reveal differences in DTI abnormalities along the corticospinal tract (CST), and (2) data obtained from routine clinical DTI scans can provide this type of information. Clinical DTI scans were obtained at 1.5T in 87 ALS patients (categorized into four subgroups based on clinical phenotype) and in 12 neurologic controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity values from the CST were compared between ALS subgroups and controls. Significantly reduced FA and elevated MD values were observed in ALS patients compared to controls at the subcortical motor cortex level. Significant differences in AD values were not only seen between control and ALS patients but also between the ALS subgroups, suggesting divergent pathologies in these ALS patients. Classifying ALS patients by phenotype reveals differences in CST abnormalities between subgroups and may provide novel insights into disease mechanisms. The close similarity of our results from routine clinical scans with published research studies suggests wider accessibility to useful DTI metrics.     

Recovery mechanisms of somatosensory function in stroke patients: implications of brain imaging studies

Somatosensory dysfunction is associated with a high incidence of functional impairment and safety in patients with stroke. With developments in brain mapping techniques, many studies have addressed the recovery of various functions in such patients. However, relatively little is known about the mechanisms of recovery of somatosensory function. Based on the previous human studies, a review of 11 relevant studies on the mechanisms underlying the recovery of somatosensory function in stroke patients was conducted based on the following topics: (1) recovery of an injured somatosensory pathway, (2) peri-lesional reorganization, (3) contribution of the unaffected somatosensory cortex, (4) contribution of the secondary somatosensory cortex, and (5) mechanisms of recovery in patients with thalamic lesions. We believe that further studies in this field using combinations of diffusion tensor imaging, functional neuroimaging, and magnetoencephalography are needed. In addition, the clinical significance, critical period, and facilitatory strategies for each recovery mechanism should be clarified.     

Prediction of motor outcome for hemiparetic stroke patients using diffusion tensor imaging: A review

We reviewed relevant diffusion tensor imaging (DTI) studies on prediction of motor outcome in hemiparetic stroke patients in order to evaluate the following objectives: characteristics of DTI for prediction of motor outcome in stroke patients, previous DTI studies, and future direction. DTI offers the unique advantage of visualization and estimation of the corticospinal tract, which is the most important neural tract for motor function. Although prediction of motor outcome is a very important topic for clinicians, only about a dozen DTI studies have been reported on this topic. These studies can be classified into two groups: 1) studies for adoption of DTI parameters as a potential marker for prediction of motor outcome in stroke patients, and 2) studies for analysis of the integrity of the corticospinal tract in prediction of motor outcome. In order to increase the predictability of motor outcome, studies according to the somatotopy and studies combined with transcranial magnetic stimulation are necessary. Other additional studies on optimal DTI scanning time for motor prediction will also be required.     

The functional role of beta‐oscillations in the supplementary motor area during reaching and grasping after stroke: A question of structural damage to the corticospinal tract

Hand motor function is often severely affected in stroke patients. Non‐satisfying recovery limits reintegration into normal daily life. Understanding stroke‐related network changes and identifying common principles that might underlie recovered motor function is a prerequisite for the development of interventional therapies to support recovery. Here, we combine the evaluation of functional activity (multichannel electroencephalography) and structural integrity (diffusion tensor imaging) in order to explain the degree of residual motor function in chronic stroke patients. By recording neural activity during a reaching and grasping task that mimics activities of daily living, the study focuses on deficit‐related neural activation patterns. The study showed that the functional role of movement‐related beta desynchronization in the supplementary motor area (SMA) for residual hand motor function in stroke patients depends on the microstructural integrity of the corticospinal tract (CST). In particular, in patients with damaged CST, stronger task‐related activity in the SMA was associated with worse residual motor function. Neither CST damage nor functional brain activity alone sufficiently explained residual hand motor function. The findings suggest a central role of the SMA in the motor network during reaching and grasping in stroke patients, the degree of functional relevance of the SMA is depending on CST integrity.     

磁共振弥散张量成像在基底节区高血压脑出血致皮质脊髓束损伤中的应用研究

目的 探讨磁共振弥散张量成像(DTI)技术评价基底节区高血压脑出血(HICH)患者皮质脊髓束(CST)受损程度的意义及其与肌力恢复的关系.方法 徐州医学院附属医院神经外科自2006年11月至2009年5月行小骨窗开颅血肿清除术治疗单侧基底节区HICH患者35例,术后10 d应用3.0T磁共振DTI技术检测患者和10例健康志愿者CST,应用Functool软件进行图像分析观察CST损伤程度,HICH患者康复治疗2月后采用Brunnstrom标准进行肢体肌力检查,分析CST损伤程度与肢体肌力的相关性.结果 10例健康志愿者CST显示清晰.35例HICH患者CST受损的模式有3种:纤维束显示达正常侧的2/3或相仿(11例),患者肢体肌力恢复最好;纤维束显示小于正常侧的2/3(18例),患者肢体肌力恢复较好;纤维柬显示小于正常侧的1/3(6例),患者肢体肌力恢复最差.CST受损患者患侧的FA值均较健侧降低,差异有统计学意义(P<0.05).3种模式CST损伤患者患侧的FA值、肢体肌力不同,差异均有统计学意义(P=0.000).患者CST损伤程度与肌力恢复水平存在负相关关系(r=0.931,P=0.000).结论 应用磁共振DTI技术可显示脑内白质纤维束的走形及分布,能够早期检测HICH患者CST的损伤程度,对患者肢体运动功能损伤的评估、判断预后有重要的临床意义.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Functional Reorganization and Recovery After Constraint-Induced Movement Therapy in Subacute Stroke: Case Reports

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke.     

Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke.     

Motor outcome after subcortical stroke correlates with the degree of cortical reorganization.

OBJECTIVE: The contribution of cortical reorganization to motor recovery after a subcortical stroke is uncertain. The purpose of the study was to investigate the relationship between changes in motor cortex organization, and the degree of motor function after a subcortical stroke. METHODS: Transcranial magnetic stimulation mapping of the corticomotor projection to the hand was performed in 27 patients who had suffered a subcortical ischemic stroke resulting in an upper limb motor deficit up to 23 years previously. Corticospinal conduction was assessed by measurements of motor evoked potential latency, amplitude and threshold. Motor function in the upper limb was assessed using the Motor Assessment Scale for Stroke and measurements of grip strength. RESULTS: Motor maps for the hand were displaced on the affected side relative to the unaffected side in 17 patients. In 10 of these patients in whom corticospinal conduction had normalized, there was a strong positive correlation between the magnitude of the map shift and grip strength in the affected hand (r=0.79; P=0.006). In the other seven patients with a map shift, in whom corticospinal conduction was still impaired, there was a tendency for a larger map area to be associated with better motor function, and in the group as a whole there was a correlation between map area and grip strength (r=0.52; P=0.005). CONCLUSIONS: The present findings provide evidence that the cortical plasticity and reorganization that occurs after a subcortical stroke is functionally significant and contributes to motor outcome.     

Dynamic brain structural changes after left hemisphere subcortical stroke

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High‐resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel‐based morphometry technique, and dynamic changes in GMV were evaluated using a mixed‐effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these “healthy” brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive‐related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive‐related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Motor outcome and motor recovery mechanisms in pontine infarct: a review

Characteristics of motor recovery mechanisms are known to be linked with motor outcome in stroke. Detailed knowledge of motor outcome and recovery mechanisms in stroke allow for prediction of prognosis and provide the basis for establishment of scientific rehabilitation strategies. Thirteen previous studies with regard to motor outcome (8 studies) and the motor recovery mechanisms (5 studies) in pontine infarct were reviewed. Several motor recovery mechanisms have been reported in pontine infarct: peri-lesional reorganization, and other possible recovery mechanisms (aberrant pyramidal tract, ipsilateral motor pathway, and motor recovery via spared corticospinal tract). Previous studies on motor outcome in pontine infarct have reported generally good outcome. This good motor outcome appears to be related to the characteristics of the motor recovery mechanisms recovered by the lateral corticospinal tract. We think that further studies on motor outcome and recovery mechanisms should be performed for clarification of various motor tracts including non-corticospinal tract, which can affect the motor outcome and recovery mechanisms in pontine infarct. In addition, the effect of rehabilitation on these topics should also be elucidated.     

Reorganization of sensory and motor systems in hemiplegic stroke patients. A positron emission tomography study.

BACKGROUND AND PURPOSE: Cortical reorganization of motor systems has been found in recovered stroke patients. Reorganization in nonrecovered hemiplegic stroke patients early after stroke, however, is less well described. We used positron emission tomography to study the functional reorganization of motor and sensory systems in hemiplegic stroke patients before motor recovery. METHODS: Regional cerebral blood flow (rCBF) was measured in 6 hemiplegic stroke patients with a single, subcortical infarct and 3 normal subjects with the [(15)O]H(2)O injection technique. Brain activation was achieved by passive elbow movements driven by a torque motor. Increases of rCBF comparing passive movements and rest were assessed with statistical parametric mapping. Significant differences were defined at P<0.01. RESULTS: In normal subjects, significant increases of rCBF were found in the contralateral sensorimotor cortex, supplementary motor area, cingulate cortex, and bilaterally in the inferior parietal cortex. In stroke patients, significant activation was observed bilaterally in the inferior parietal cortex and in the contralateral sensorimotor cortex, ipsilateral prefrontal cortex, supplementary motor area, and cingulate cortex. Significantly larger increases of rCBF in patients compared with normal subjects were found bilaterally in the sensorimotor cortex, stronger in the ipsilateral, unaffected hemisphere, and in both parietal lobes, including the ipsilateral precuneus. CONCLUSIONS: Passive movements in hemiplegic stroke patients before clinical recovery elicit some of the brain activation patterns that have been described during active movements after substantial motor recovery. Changes of cerebral activation in sensory and motor systems occur early after stroke and may be a first step toward restoration of motor function after stroke.     

Motor outcome after subcortical stroke: MEPs correlate with hand strength but not dexterity.

OBJECTIVE: Motor evoked potential (MEP) amplitude and threshold are predictors of functional outcome in the early stages after stroke, and improvement in these parameters usually accompanies motor recovery. The aim of this study in patients with subcortical stroke was to determine whether there is a correlation between MEP amplitude and threshold and the degree of recovery of strength and dexterity in the affected hand. METHODS: MEP amplitude and threshold were measured on the affected and unaffected sides in 23 patients who had suffered a subcortical ischaemic stroke up to 23 years previously. Grip strength was measured using a hand-held dynamometer and dexterity was assessed using a modification of the McCarron test battery. RESULTS: Grip strength correlated with both MEP amplitude and threshold (r=0.49 and r=-0.54, respectively, P<0.05), whereas the McCarron score for motor dexterity did not correlate significantly with either of these MEP parameters. CONCLUSIONS: Grip strength and dexterity correlate differentially with MEP parameters of excitability and conduction in the corticospinal pathway after recovery in patients with subcortical stroke. Grip strength is dependent on restoration of corticospinal excitability and conduction whereas additional factors such as cortical reorganization may underlie recovery of motor dexterity.