Brain lesion size and location: Effects on motor recovery and functional outcome in stroke patients

doi:10.1053/mr.2000.3837

Archives of Physical Medicine and Rehabilitation

Volume 81, Issue 4, April 2000, Pages 447-452

https://doi.org/10.1053/mr.2000.3837 Get rights and content

Abstract

Chen C-L, Tang F-T, Chen H-C, Chung C-Y, Wong M-K. Brain lesion size and location: effects on motor recovery and functional outcome in stroke patients. Arch Phys Med Rehabil 2000;81:447-52. Objective: To investigate effects of brain lesion profiles that combined sizes and locations on motor recovery and functional outcome after stroke in hemiplegic patients. Design: Delimiting sizes (a threshold lesion size) of 5 primary locations were identified to establish brain lesion profiles based on magnetic resonance imaging findings 1 month after stroke. Motor and functional outcome were correlated with brain lesion profiles and other brain lesion factors to identify the most dominant factor. Setting: Medical center, rehabilitation department. Participants: Fifty-five hemiplegic patients. Main Outcome Measures: Brunnström's stages and Functional Independence Measure (FIM) scores were assessed 1 and 6 months after stroke. Results: With delimiting sizes for the cortical, corona radiata, internal capsule, putaminal, and thalamic regions set at 75, 4,.75, 22, and 12cm³, respectively, brain lesion profiles play a dominant role in determining final Brunnström's stages (Spearman's ρ =.861, p <.01) and FIM score (Spearman's ρ =.571, p <.01). Brunnström's and FIM scores had no or only weak negative relationship with either absolute or relative lesion size. Conclusions: These findings may suggest that motor and functional outcomes after stroke correlate with brain lesion profiles (a combination of delimiting sizes and primary locations) more than with absolute or relative lesion sizes only. Delimiting sizes in determining final outcomes varied markedly according to the primary lesion locations. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Section snippets

Methods

From November 1995 to March 1997, hemiplegic stroke patients in stable condition who were transferred to the rehabilitation department about 1 month after stroke were recruited for this study. Patients who met the following entry were included: (1) first-ever stroke; (2) hemiplegia; (3) unilateral hemispheric lesions proved by MRI about 1 month after stroke; (4) age older than 40 years; (5) not a cerebellar or brain stem stroke; (6) no significant communication disturbances (able to understand,

Results

The delimiting sizes of brain lesions used to classify BLPs as good or poor varied according to the location: 75cm³ for cortical, 4cm³ for CR,.75cm³ for IC, 22cm³ for putaminal, and 12cm³ for thalamic lesions. The sensitivities of all BLPs were 100%, and the specificities were 75%, 100%, 100%, 93%, and 100% for cortical, CR, IC, putaminal, and thalamic subgroups, respectively (fig 2).

. Delimiting sizes of five primary brain lesion locations determined with boxplots.

The delimiting size chosen for

Discussion

We found that motor recovery and functional outcome after stroke correlated more with BLPs, while they had no or only a weak relationship with either the absolute or relative lesion size. When the delimiting sizes were set at 75cm³ for cortical, 4cm³ for CR, 0.75cm³ for IC, 22cm³ for putaminal, and 12cm³ for thalamic lesions, BLPs could determine motor and functional outcomes. These findings may imply that motor recovery and functional outcome after stroke correlate with BLPs that combined the

Conclusions

In summary, motor recovery and functional outcome after stroke correlated more with BLPs, while they had no or only a weak relationship with either the absolute or relative lesion size. These findings may suggest that motor and functional outcomes after stroke correlated with BLPs (a combination of delimiting sizes and primary locations) more than with the absolute and relative lesion size only. Delimiting sizes in determining final outcomes varied markedly according to the primary locations of

Acknowledgements

The authors thank Y.Y. Wai for her instruction in the interpretation of MR images, W.H. Hong for preparing the computer graphics, and S.W. Chou for reviewing this work.

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Despite great advances in acute care and rehabilitation, stroke remains the leading cause of motor impairment in the industrialized world. We have developed a deep brain stimulation (DBS)-based approach for post-stroke rehabilitation that has shown reproducible effects in rodent models and has been recently translated to humans. Mechanisms underlying the rehabilitative effects of this novel therapy have been largely focused on the ipsilesional cortex, including cortical reorganization, synaptogenesis, neurogenesis and greater expression of markers of long-term potentiation. The role of subcortical structures on its therapeutic benefits, particularly the striatum, remain unclear. In this study, we compared the motor rehabilitative effects of deep cerebellar stimulation in two rodent models of cerebral ischemia: a) cortical ischemia; and b) combined striatal and cortical ischemia. All animals underwent the same procedures, including implantation of the electrodes and tethered connections for stimulation. Both experimental groups received four weeks of continuous lateral cerebellar nucleus (LCN) DBS and each was paired with a no stimulation, sham, group. Fine motor function was indexed using the pasta matrix task. Brain tissue was harvested for histology and immunohistochemical analyses. In the cortical-only ischemia, the average pasta matrix performance of both sham and stimulated groups reduced from 19 to 24 pieces to 7—8 pieces following the stroke induction. At the end of the four-week treatment, the performance of stimulated group was significantly greater than that of sham group (14 pieces vs 7 pieces, p < 0.0001). Similarly, in the combined cortical and striatal ischemia, the performance of both sham and stimulated groups reduced from 29 to 30 pieces to 7–11 pieces following the stroke induction. However, at the end of the four-week treatment, the performance of stimulated group was not significantly greater than that of sham group (15 pieces vs 11 pieces, p = 0.452). In the post-mortem analysis, the number of cells expressing CaMKIIα at the perilesional cortical and striatum of the LCN DBS treated animals receiving cortical-only stroke elevated but not those receiving cortical+striatal stroke. The current findings suggested that the observed, LCN DBS-enhanced motor recovery and perilesional plasticity may involve striatal mechanisms.
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Cyclic glycyl-proline (cGP) exerts neuroprotective effects against ischemic stroke and may promote neural plasticity or network remodeling. We sought to determine to what extent oral administration of cGP could facilitate task learning in rats with ischemic lesions. We trained rats to perform a choice reaction time task using their forepaws. One week after changing the food to pellets containing cGP (no cGP: 0 mg/kg; low cGP: 25 mg/kg; and high cGP: 75 mg/kg), we made a focal ischemic lesion on the left or right forepaw area of the sensorimotor cortex. After recovery of task performance, we altered the correct-response side of the task, and then analyzed the number of training days required for the rat to reach a learning criterion (error rate < 15%) and the regulation of adult neurogenesis in the subventricular zones (SVZs), taking lesion size into account. The low-cGP group required fewer training days for task learning than the no-cGP group. Unexpectedly, rats with larger lesions required fewer training days in the no-cGP and low-cGP groups, but more training days in the high-cGP group. The number of Ki67-immunopositive cells (indicating proliferative cells) in ipsilesional SVZ increased more rapidly in the low-cGP and high-cGP groups than in the no-cGP group. However, lesion size had only a small effect on required training days and the number of Ki67-immunopositive cells. We conclude that oral administration of cGP can facilitate task learning in rats with focal ischemic infarction through neural plasticity and network remodeling, even with minimal neuroprotective effects.
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Citation Excerpt :
To illustrate, prior investigations among stroke patients have reported that the extent of CST damage and not infarct size per se are crucial determinants of post-stroke motor ability (Sterr et al., 2010; Zhu et al., 2010). Similarly, Chen et al. (2000) examined the impact of brain lesion factors on motor measures in hemiplegic stroke patients and documented that patients with poorer brain lesion profiles had worse motor recovery regardless of lesion location, possibly due to the involvement and destruction of the CST due to Wallerian degeneration. Building on such evidence about the key prognostic value of white matter degeneration, our method can provide a comprehensive set of affected voxels along modelled fibers for finding correlations with behavioral symptoms.
Secondary white matter degeneration is a common occurrence after ischemic stroke, as identified by Diffusion Tensor Imaging (DTI). However, despite recent advances, the time course of the process is not completely understood. The primary aim of this study was to assess secondary degeneration using an approach whereby we create a patient-specific model of damaged fibers based on the volumetric characteristics of lesions. We also examined the effects of secondary degeneration along the modelled streamlines at different distances from the primary infarction using DTI. Eleven patients who presented with upper limb motor deficits at the time of a first-ever ischemic stroke were included. They underwent scanning at weeks 6 and 29 post-stroke. The fractional anisotropy (FA), mean diffusivity (MD), primary eigenvalue (λ₁), and transverse eigenvalue (λ₂₃) were measured. Using regions of interest based on the simulation output, the differences between the modelled fibers and matched contralateral areas were analyzed. The longitudinal change between the two time points and across five distances from the primary lesion was also assessed using the ratios of diffusion quantities (rFA, rMD, rλ₁, and rλ₂₃) between the ipsilesional and contralesional hemisphere. At week 6 post-stroke, significantly decreased λ₁ was found along the ipsilesional corticospinal tract (CST) with a trend towards lower FA, reduced MD and λ₂₃. At week 29 post-stroke, significantly decreased FA was shown relative to the non-lesioned side, with a trend towards lower λ₁, unchanged MD, and higher λ₂₃. Along the ipsilesional tract, the rFA diminished, whereas the rMD, rλ₁, and rλ₂₃ significantly increased over time. No significant variations in the time progressive effect with distance were demonstrated. The findings support previously described mechanisms of secondary degeneration and suggest that it spreads along the entire length of a damaged tract. Future investigations using higher-order tractography techniques can further explain the intravoxel alterations caused by ischemic injury.
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Compensatory increase in ipsilesional supplementary motor area and premotor connectivity is associated with greater gait impairments: a personalized fMRI analysis in chronic stroke
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^☆☆: Reprint requests to May-Kuen Wong, MD, Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan 333, Taiwan.

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ArticlesBrain lesion size and location: Effects on motor recovery and functional outcome in stroke patients☆,☆☆,★

Abstract

Section snippets

Methods

Results

Discussion

Conclusions

Acknowledgements

Lancet

Arch Phys Med Rehabil

Pediatr Neurol

Recovery of voluntary movement in hemiplegic patients

Brain

The pattern of motor deficit in relation to the site of stroke lesions

Eur Neurol

The importance of brain infarct size and location in predicting outcome after stroke

Age Ageing

Computerized tomography head scans as predictors of functional outcome of stroke patients

Arch Phys Med Rehabil

Diffusion-weighted magnetic resonance imaging in acute stroke

Stroke

Computed tomography: its potential as a predictor of functional recovery following stroke

Arch Phys Meds Rehabil

Measurement of infarct size using MRI predicts prognosis in middle cerebral artery infarction

Stroke

Motor recovery after stroke: morphological and functional brain alterations

Brain

Patients with stroke confined to basal ganglia have diminished response to rehabilitation efforts

Neurology

Functional outcome for patients with hemiparesis, hemihypesthesia, and hemianopsia: does lesion location matter?

Stroke

Impact of thalamic hematoma on six-month mortality and motor and cognitive functional outcome

Stroke

Predicting the outcome of acute stroke: a prognostic score

J Neurol Neurosurg Psychiatry

Articles
Brain lesion size and location: Effects on motor recovery and functional outcome in stroke patients☆,☆☆,★