Size Doesn't Matter: Cortical Stroke Lesion Volume Is Not Associated With Upper Extremity Motor Impairment and Function in Mild, Chronic Hemiparesis

doi:10.1016/j.apmr.2013.01.010

Archives of Physical Medicine and Rehabilitation

Volume 94, Issue 5, May 2013, Pages 817-821

https://doi.org/10.1016/j.apmr.2013.01.010 Get rights and content

Abstract

Objectives

To determine (1) the relationship between lesion volume and upper extremity (UE) motor impairment using the UE section of the Fugl-Meyer (FM) assessment; and (2) the relationship between lesion volume and UE functional outcomes using the Arm Motor Ability Test (AMAT) Functional Ability (FA) and Time scales.

Design

Secondary retrospective analysis of randomized controlled trial data.

Setting

Outpatient rehabilitation clinic.

Participants

Subjects with chronic stroke (N=139, 83 men; mean age ± SD of all subjects, 56.7±11.2y; mean time ± SD since stroke onset, 59.6±65.6mo; 90 subjects with right hemiparesis) and stable, active, distal UE movement.

Intervention

Data were collected related to subjects' lesion volume and UE movement before their participation in a multicenter, randomized controlled trial.

Main Outcome Measures

FM and AMAT.

Results

Neither age nor lesion volume was related to FM performance. The P value for the regression coefficient of lesion volume was .045 in the AMAT FA model and .016 in the AMAT Time model. Lesion volume accounted for only an additional 1.7% (AMAT FA) to 3.1% (AMAT Time) of the variability in motor function and was not clinically meaningful.

Conclusions

Data suggest no relationship between lesion volume and UE impairment, and a small, clinically insignificant relationship between lesion volume and UE motor function. Stroke causes metabolic changes in intact regions and diffuse structural loss in anatomically remote regions from the infarction. These other factors may account for variance in motor outcomes after stroke.

Section snippets

Study design

This study was a secondary analysis of data from the Everest randomized controlled trial of implanted cortical stimulation for UE movement in chronic stroke.¹⁶ Outcome measures had been administered before and after intervention as part of the above trial. However, the current study focused solely on lesion volume and values obtained on the FM and AMAT before randomization or before any interventions had taken place. The study had been approved by all participating centers' institutional review

Outcomes of correlation analyses

Multivariate tests of significance of independent linear combinations of the outcome variables were performed to assess the response variables that were related to predictor variables. Lesion volume was not related to FM performance (P=.77).

Age and lesion volume were significantly related to performance on the AMAT FA and the AMAT Time scales. Their combined influence was small, however, accounting for only 6% of the variance in AMAT FA and AMAT Time (R²=.07, adjusted R²=.06) (see table 2).

Discussion

UE hemiparesis remains one of the most common and disabling stroke sequelae. Yet, while association between lesion volume and general neurologic (eg, NIHSS) or functional (eg, FIM) status has been examined, no large studies have determined the relationships between lesion volume and functional UE motor outcomes using stroke-specific, validated functional measures and a large, well-defined cohort of stroke survivors. This study addressed these limitations by examining associations between

Conclusions

To the best of our knowledge, this is the first study to determine whether lesion volume is significantly associated with UE motor status in a well-defined, sizable cohort of chronic stroke survivors. Data suggest a small, clinically insignificant relationship between lesion volume and UE impairment and motor function.

Supplier

a.
SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.

References (33)

American Heart Association
Heart disease and stroke statistics—2011 update
(2011)
S.L. Wolf et al.
Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial
JAMA
(2006)
S.J. Page et al.
Effects of mental practice on affected limb use and function in chronic stroke
Arch Phys Med Rehabil
(2005)
S.J. Page et al.
Modified constraint-induced therapy in chronic stroke: results of a single-blinded randomized controlled trial
Phys Ther
(2008)
B. Caplan et al.
Stroke
H.O. Karnath et al.
Posterior thalamic hemorrhage induces “pusher syndrome.”
Neurology
(2005)
J. Fridriksson et al.
Aphasia severity: association with cerebral perfusion and diffusion
Aphasiology
(2002)
C. Exner et al.
Implicit and explicit memory after focal thalamic lesions
Neurology
(2001)
K.O. Lovblad et al.
Ischemic lesion volume in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome
Ann Neurol
(1997)
F. Binkofski et al.
Recovery of motor functions following hemiparetic stroke: a clinical and magnetic resonance morphometric study
Cerebrovasc Dis
(2001)

K.R. Crafton et al.

Improved understanding of cortical injury by incorporating measures of functional anatomy

Brain

(2003)

M.A. Naeser et al.

Visible changes in lesion borders on CT scan after five years poststroke, and long-term recovery in aphasia

Brain Lang

(1998)

A. Sterr et al.

The role of corticospinal tract damage in chronic motor recovery and neurorehabilitation: a pilot study

Neurorehabil Neural Repair

(2010)

J.D. Riley et al.

Anatomy of stroke injury predicts gains from therapy

Stroke

(2011)

V. Mark et al.

MRI infarction load and CI therapy outcomes for chronic post-stroke hemiparesis

Restor Neurol Neurosci

(2008)

R. Harvey et al.

Design for the Everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke

Neurorehabil Neural Repair

(2009)

Cited by (32)

Changes in ultrasonic vocalizations after unilateral cerebral ischemia in a rat stroke model
2023, Behavioural Brain Research
Citation Excerpt :
Compared to the sham-controls, stroke was associated with shorter calls and smaller bandwidths, yet within the stroke group there was a negative correlation between simple call duration and bandwidth, with larger strokes associated with shorter calls and larger bandwidths. Correlations between functional outcomes and infarct size are often not strong as larger infarct volumes increase the likelihood that relevant brain areas are damaged, but any sized infarct could spare or damage the individual brain regions that control the function of interest [62]. We also explored the relationship between lingual weakness and the stroke-associated USV changes in simple calls because the clinical association between lingual weakness and dysarthria is well established [63–65].
Stroke frequently results in communication impairments that negatively impact quality of life and overall recovery, yet the biological mechanisms underlying these changes are not well understood. Ultrasonic vocalizations (USVs) in rodent models of disease and aging have been used to improve our understanding of the biological mechanisms that underlie vocal deficits and their response to interventions. Changes in USVs after middle cerebral artery occlusion (MCAO) in mice have been reported, yet rat models have significant anatomical and behavioral advantages over mice, including the ability to vocally train rats with an established paradigm. We sought to determine whether a unilateral MCAO rat stroke model provides a biologically and behaviorally relevant way to study post stroke vocalization deficits. We hypothesized that left MCAO would be associated with changes in USVs. Six weeks after MCAO or sham-control surgery, USVs were recorded in rats using an established mating paradigm. Stroke was associated with differences in USV acoustics including more frequent use of simple calls characterized by shorter durations and restricted bandwidths. These parameters were also found to correlate with post stroke lingual weakness. This is the first study to describe changes to rat USVs using a stroke model. These results suggest the unilateral MCAO rat stroke model is a biologically and behaviorally relevant model to understand how stroke affects vocal behaviors.
Investigating the neuroanatomy underlying proprioception using a stroke model
2021, Journal of the Neurological Sciences
Neuroanatomical investigations have associated cortical areas, beyond Primary Somatosensory Cortex (S1), with impaired proprioception. Cortical regions have included temporoparietal (TP) regions (supramarginal gyrus, superior temporal gyrus, Heschl's gyrus) and insula. Previous approaches have struggled to account for concurrent damage across multiple brain regions. Here, we used a targeted lesion analysis approach to examine the impact of specific combinations of cortical and sub-cortical lesions and quantified the prevalence of proprioceptive impairments when different regions are damaged or spared.
Seventy-seven individuals with stroke (49 male; 28 female) were identified meeting prespecified lesion criteria based on MRI/CT imaging: 1) TP lesions without S1, 2) TP lesions with S1, 3) isolated S1 lesions, 4) isolated insula lesions, and 5) lesions not impacting these regions (other regions group). Initially, participants meeting these criteria (1–4) were grouped together into right or left lesion groups and compared to each other, and the other regions group (5), on a robotic Arm Position Matching (APM) task and a Kinesthesia (KIN) task. We then examined the behaviour of individuals that met each specific criteria (groups 1–5).
Proprioceptive impairments were more prevalent following right hemisphere lesions than left hemisphere lesions. The extent of damage to TP regions correlated with performance on both robotic tasks. Even without concurrent S1 lesions, TP and insular lesions were associated with impairments on the APM and KIN tasks. Finally, lesions not impacting these regions were much less likely to result in impairments.
This study highlights the critical importance of TP and insular regions for accurate proprioception.
This work advances our understanding of the neuroanatomy of human proprioception. We validate the importance of regions, beyond the dorsal column medial lemniscal pathway and S1, for proprioception. Further, we provide additional evidence of the importance of the right hemisphere for human proprioception. Improved knowledge on the neuroanatomy of proprioception is crucial for advancing therapeutic approaches which target individuals with proprioceptive impairments following neurological injury or with neurological disorders.
Grey and white matter network disruption is associated with sensory deficits after stroke
2021, NeuroImage: Clinical
Citation Excerpt :
Larger infarct volumes are associated with greater somatosensory deficits (Hawe et al., 2018). However, lesion size only partly determines the clinical severity of ischaemic stroke (Page et al., 2013). Additional information is contained in the anatomical location of the lesion and its consequent disruption of cortical areas associated with specific neurological functions or white matter tracts that allow for distributed processing of brain functions (Wu et al., 2015).
Somatosensory deficits after ischaemic stroke are common and can occur in patients with lesions in the anterior parietal cortex and subcortical nuclei. It is less clear to what extent damage to white matter tracts within the somatosensory system may contribute to somatosensory deficits after stroke. We compared the roles of cortical damage and disruption of subcortical white matter tracts as correlates of somatosensory deficit after ischaemic stroke.
Clinical and imaging data were assessed in incident stroke patients. Somatosensory deficits were measured using a standardized somatosensory test. Remote effects were quantified by projecting the MRI-based segmented stroke lesions onto a predefined atlas of white matter connectivity. Direct ischaemic damage to grey matter was computed by lesion overlap with grey matter areas. The association between lesion impact scores and sensory deficit was assessed statistically.
In 101 patients, median sensory score was 188/193 (97.4%). Lesion volume was associated with somatosensory deficit, explaining 23.3% of variance. Beyond this, the stroke-induced grey and white matter disruption within a subnetwork of the postcentral, supramarginal, and transverse temporal gyri explained an additional 14% of the somatosensory outcome variability. On mutual comparison, white matter network disruption was a stronger predictor than grey matter damage.
Ischaemic damage to both grey and white matter are structural correlates of acute somatosensory disturbance after ischaemic stroke. Our data suggest that white matter integrity of a somatosensory network of primary and secondary cortex is a prerequisite for normal processing of somatosensory inputs and might be considered as an additional parameter for stroke outcome prediction in the future.
Changes in mu and beta amplitude of the EEG during upper limb movement correlate with motor impairment and structural damage in subacute stroke
2019, Clinical Neurophysiology
Citation Excerpt :
However, in our study, the overall extent of damage, and more specifically, the amount of injury to capsual-putaminal structures, did correlate with the magnitude of movement-related attenuation of the MU and beta bands in the affected hemisphere, which in turn correlated with residual functional ability of the hemiparetic upper limb and with the EMG amplitude in the wrist-extensor muscles of that limb. It should be noted that Page et al (Page et al., 2013) looked only at moderately affected patients in the chronic stage (i.e., at a stage where lesion impact is already largely modulated by the effects of natural and treatment-induced plasticity), while our study investigated patients with severe to moderate hemiparesis in the sub-acute stage of the disease. It remains to be shown whether spontaneous or treatment-related improvement in hemiparesis is also associated with corresponding increments in ERD magnitude.
Mu and beta EEG oscillations show typical desynchronization patterns during movement. The aim of the current study was to assess whether in sub-acute stroke patients the magnitude of movement-related desynchronization reflects the extent of residual motor ability in the paretic upper limb.
EEG and EMG data were recorded from 14 first-event stroke patients during repeated wrist extension movements of the paretic upper limb. Residual motor ability was assessed by the Fugl Meyer and Box and Blocks standardized clinical tests. Normalized lesion data was analyzed using the MEDx software.
The magnitude of event-related de-synchronization (ERD) of the high-mu and low-beta bands of the EEG, measured over the affected hemisphere, correlated significantly with (a) residual motor function in the paretic upper limb as measured by standard clinical tests; (b) the magnitude of EMG recorded from the paretic upper limb during wrist extension; and (c) the total hemispheric volume loss (negative correlation).
The magnitude of high-mu and low-beta ERD recorded from the lesioned hemisphere of subacute stroke patients correlates with residual motor ability in the paretic upper limb.
Measures derived from quantitative EEG analysis may play an important role in neurorehabilitation clinical practice.
Vision of the upper limb fails to compensate for kinesthetic impairments in subacute stroke
2018, Cortex
Citation Excerpt :
We found that lesion size for subjects with deficits in both conditions (−NV/−V) was significantly larger than lesion size for subjects with no deficits in either condition (+NV/+V). We suggest that larger lesions affecting areas of parietal cortex may be more likely to negatively impact kinesthetic processing and the ability to use visuospatial information to correct for sensory errors (Chen, Tang, Chen, & Chung, 2000; Page, Gauthier, & White, 2013). Ideally, to mitigate this issue, we would need to match our analyses for lesion size, but that is difficult in a heterogenous stroke sample, such as ours.
Kinesthesia is an essential component of proprioception allowing for perception of movement. Due to neural injury, such as stroke, kinesthesia can be significantly impaired. Throughout neurorehabilitation, clinicians may encourage use of vision to guide limb movement to retrain impaired kinesthesia. However, little evidence exists that vision improves kinesthetic performance after stroke. We examined behavioral and neuroanatomical characteristics of kinesthesia post-stroke to determine if these impairments improve with vision.
Stroke subjects (N = 281) performed a robotic kinesthetic matching task (KIN) without and with vision at ∼10 days post-stroke. A robotic exoskeleton moved the stroke-affected arm while subjects mirror-matched the movement with the opposite arm. Performance was compared to 160 controls. Spatial and temporal parameters were used to quantify kinesthetic performance. A Kinesthetic Task Score was calculated to determine overall performance on KIN without and with vision. Acute stroke imaging (N = 236) was collected to determine commonalities in lesion characteristics amongst kinesthetic impairment groups.
Forty-eight percent (N = 135) of subjects had post-stroke impairment in kinesthesia both without and with vision. Only 19% (N = 52) improved to control-level performance with vision. Of the 48% of subjects that failed to improve with vision, many (N = 77, 57%) had neglect and/or field deficits. Notably 58 subjects (43%) did not have these deficits and still failed to improve with vision. Subjects who failed to improve with vision often had lesions affecting corticospinal tracts, insula, and parietal cortex, specifically the supramarginal gyrus and inferior parietal lobule.
Many individuals could not use vision of the limb to correct for impaired kinesthesia after stroke. Subjects that failed to improve kinesthesia with vision had lesions affecting known sensorimotor integration areas. Our results suggest that integration of spatial information is impaired in many individuals post-stroke, particularly after parietal cortex damage. The result is a disconnect between kinesthetic and visuomotor processing necessary for visual limb guidance.
Quantitative microstructural deficits in chronic phase of stroke with small volume infarcts: A diffusion tensor 3-D tractographic analysis
2016, Magnetic Resonance Imaging
Citation Excerpt :
Therefore, the small volume of infarcted tissue, poses a particular challenge, such that the abnormalities in non-infarct zone may potentially be sub-threshold on conventional imaging techniques such as FLAIR and T2w images. Additionally, evidence suggests that lesion volume itself does not explain variance in functional recovery and it is plausible that the variability in the integrity of non-infarct zone white matter may have additive values in predicting functional profile [7]. By virtue of small size, the extent of gliosis and encephalomalacia at the site of primary infarct is often minimal and there are virtually no overt stigmata of wallerian degeneration on routine imaging.
Non-infarct zone white matter wallerian degeneration is well-documented in large volume territorial infarctions. However to what extent these abnormalities exist in small volume infarction is not known, particularly since routine T2/FLAIR MR images show minimal changes in such cases. We therefore utilized DTI based quantitative 3D tractography for quantitative assessment of white matter integrity in chronic phase of small volume anterior circulation infarcts.
Eleven chronic stroke subjects with small anterior circulation large vessel infarcts (≤ 10 cm³ volume of primary infarct) were compared with 8 age matched controls. These infarcts had negligible to mild gliosis and encephalomalacia in the primary infarct territory without obvious wallerian degeneration on conventional MRI. Quantitative Diffusion Tensor 3-D tractography was performed for CST, genu and splenium of corpus callosum. Tract based Trace and fractional anisotropy (FA) were compared with age matched controls.
On univariate analysis, Chronic stroke subjects had significant elevation in Trace measurement in genu of corpus callosum (GCC), ipsilesional and contralesional CST, (p < 0.05), compared to controls. After adjusting for smoking, hypertension (HTN) and non-specific white matter hyperintensities, (WMHs), there was significant elevation in trace within the ipsilesional CST (p = 0.05). Contralesional CST FA correlated significantly with walking speed, r = 0.67, p = 0.03.
Stroke subjects with small volume infarcts demonstrate significant quantitative microstructural white matter abnormalities in chronic phase, which are otherwise subthreshold for detection on routine imaging. Ability to quantify these changes provides an important marker for assessing non-infarct zone neuroaxonal integrity in the chronic phase even in the setting of small infarction.

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: Supported in part by Northstar Neuroscience and the National Institutes of Health (grant no. R01AT004454-04).

: No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

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Original articleSize Doesn't Matter: Cortical Stroke Lesion Volume Is Not Associated With Upper Extremity Motor Impairment and Function in Mild, Chronic Hemiparesis

Abstract

Objectives

Design

Setting

Participants

Intervention

Main Outcome Measures

Results

Conclusions

Section snippets

Study design

Outcomes of correlation analyses

Discussion

Conclusions

Supplier

Heart disease and stroke statistics—2011 update

Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial

JAMA

Effects of mental practice on affected limb use and function in chronic stroke

Arch Phys Med Rehabil

Modified constraint-induced therapy in chronic stroke: results of a single-blinded randomized controlled trial

Phys Ther

Stroke

Posterior thalamic hemorrhage induces “pusher syndrome.”

Neurology

Aphasia severity: association with cerebral perfusion and diffusion

Aphasiology

Implicit and explicit memory after focal thalamic lesions

Neurology

Ischemic lesion volume in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome

Ann Neurol

Recovery of motor functions following hemiparetic stroke: a clinical and magnetic resonance morphometric study

Cerebrovasc Dis

Improved understanding of cortical injury by incorporating measures of functional anatomy

Brain

Visible changes in lesion borders on CT scan after five years poststroke, and long-term recovery in aphasia

Brain Lang

The role of corticospinal tract damage in chronic motor recovery and neurorehabilitation: a pilot study

Neurorehabil Neural Repair

Anatomy of stroke injury predicts gains from therapy

Stroke

MRI infarction load and CI therapy outcomes for chronic post-stroke hemiparesis

Restor Neurol Neurosci

Design for the Everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke

Neurorehabil Neural Repair

Original article
Size Doesn't Matter: Cortical Stroke Lesion Volume Is Not Associated With Upper Extremity Motor Impairment and Function in Mild, Chronic Hemiparesis