Gordon et al. BMC Neurology 2012, 12:53
http://www.biomedcentral.com/1471-2377/12/53

CASE REPORT

Open Access

Corticospinal tract integrity and motor function
following neonatal stroke: a case study
Anne L Gordon1,2, Amanda Wood2,4, Jacques Donald Tournier5,6 and Rod W Hunt2,3,7*

Abstract
Background: New MRI techniques enable visualisation of corticospinal tracts and cortical motor activity. The
objective of this case study was to describe the magnetic resonance evidence of corticospinal pathway
reorganisation following neonatal stroke.
Case presentation: An 11 year old boy with a neonatal right middle cerebral artery territory ischaemic stroke was
studied. Functional MRI was undertaken with a whole hand squeezing task, comparing areas of cortical activation
between hands. White matter tracts, seeded from the area of peak activation in the cortex, were visualised using a
diffusion weighted imaging probabilistic tractography method. Standardised evaluations of unilateral and bilateral
motor function were undertaken. Clinically, the child presented with a left hemiparesis. Functional MRI
demonstrated that movement of the hemiparetic hand resulted in activation in the ipsi-lesional (right) hemisphere
only. Diffusion tractography revealed pathways in the right (lesioned) hemisphere tracked perilesionally to the
cortical area identified by functional MRI.
Conclusion: Our case demonstrates that neonatal stroke is associated with maintenance of organization of
corticospinal pathways sufficient to maintain some degree of hand function in the affected hemisphere. Functional
MRI and diffusion weighted imaging tractography may inform our understanding of recovery, organisation and
reorganisation and have the potential to monitor responses to intervention following neonatal stroke.
Keywords: Stroke, Children, Plasticity, Functional imaging, Motor outcome

Background
Neonatal arterial ischaemic stroke (AIS) is an important
cause of cerebral palsy. The middle cerebral artery is the
most common vascular territory affected. Functional
consequences are diverse, and may emerge over time.
Hemiparesis is less common in neonatal onset stroke
when compared with childhood onset [1]. It has been
postulated that the developmental stage of the brain at
the time of injury may influence recovery from brain injury in children. A number of mechanisms may be responsible for cerebral recovery including formation of
new synaptic connections, change of function of neurones in response to injury, and utilisation of pathways
contralateral to the injury site [2].
Magnetic resonance imaging (MRI) techniques enable
visualisation of corticospinal tracts (using diffusion* Correspondence: rod.hunt@rch.org.au
2
Murdoch Children’s Research Institute, Melbourne, Australia
3
Department of Paediatrics, University of Melbourne, Melbourne, Australia
Full list of author information is available at the end of the article

weighted imaging (DWI)) and cortical motor activity
(using functional MRI (fMRI)). This information has the
potential to be used to explore mechanisms of recovery
and reorganisation and to measure response to interventions aimed at improving outcome. The aim of this study
was to investigate whether there was evidence of relocation of cortical motor activity and reorganisation of
motor pathways in a school- aged child who had a unilateral perinatal AIS affecting the motor cortex with residual hemiparesis.

Case presentation
Method

The subject, an 11 year old boy, sustained an AIS affecting the right middle cerebral artery territory diagnosed
radiologically during the perinatal period. Perinatal MR
imaging had previously been obtained on a 1.5-Tesla
General Electric LX Echospeed system (version 9.0).
Transverse T1 fast spin echo (TR/TE 1400/10, ETL 2,
BW +/− 20 kHz, FOV 20 cm, slice thickness 3.5 mm;

© 2012 Gordon et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Gordon et al. BMC Neurology 2012, 12:53
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256 × 224 matrix, 2 averages) and transverse fast spin
echo T2 (TR/TE 3600/16, ETL 18, BW +/− 20.83 kHz,
FOV 18 cm, slice thickness 3.0 mm, 256 × 224 matrix, 3
averages), epi-DWI (3-directions, b = 1 ms/μm2, TR/TE
10000/104, BW +/− 100 kHz, FOV 25 cm, slice thickness 4.0 mm,192 × 128 matrix, 2 averages) were
obtained.). Ethics approval for the current study was
obtained. Clinical evaluation was undertaken by an
experienced paediatric occupational therapist (AG) and
included the Bruininks-Oseretsky Test of Motor Proficiency 2 (BOT2) [3], Assisting Hand Assessment (v4.1)
(AHA) [4] and Pediatric Stroke Outcome Measure
(PSOM) [5]. The BOT2 provides standard scores for
overall motor function based on age-matched peers
(mean 100, sd 15). The AHA enables calculation of the
effectiveness of use of the assisting hand and arm in bimanual activities and scores are expressed as percentage
score out of maximum of 100. The PSOM is a standardised neurological examination expressing neurological
impairment across domains as a total on a scale of 1–10.
Motor abilities were further classified using the Manual
Ability Classification System (MACS) [6] and Gross
Motor Functional Classification System (Expanded &
Revised) (GMFCS) [7] both 5 point scales of motor function. Motor outcome measures were scored in relation
to normative data (BOT2) or reported descriptively.
The imaging protocol undertaken included T1weighted imaging of the whole brain (3D high resolution
(3D MPRAGE)) and T2-weighted imaging (turbo spin
echo and T2 FLAIR imaging). DWI was obtained with
60 directions (b-value = 3000 s/mm2, 2.3 × 2.3 × 2.3 mm3
voxel size). fMRI consisted of multi-slice 2D echo planar
imaging, with a whole-hand ball squeezing task in a
block design with five epochs. Five cycles of task (hand
squeeze) and rest (no movement) were performed per
epoch. fMRI data were processed using Statistical Parametric Mapping (v5) [8]. The realignment was processed
using FLIRT, and mean fMRI co-registered to the
b = 0 s/mm2 image using the default metric. Peak activation coordinates were transformed to the DWI space by
applying the transform to the native coordinates. Data
was smoothed to 11 mm, and statistics were family-wise
error corrected at p < 0.05. Areas of peak activation for
each hand were identified by coordinates, which were
then used to seed diffusion weighted tractography
(DWT) of the corticospinal tracts, comparing left and
right hands. The DWT was undertaken using a probabilistic streamlines approach capable of tracking through
crossing fibre regions [9-11] as implemented in the
MRtrix software package (http://www.brain.org.au/software). Tracking was from a 3 mm radius sphere centered on peak fMRI activation (more on that below) for
each side, down to a 10 mm radius sphere centered on
the medulla oblongata, located immediately inferior to

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the pons on the sagittal image. The tracks generated
were then resampled at 2 mm intervals in the inferiorsuperior direction.
Results

The subject presented with a MACS level 2 and GMFCS
level 2 left hemiparesis, and a PSOM score of 1. He was
able to achieve an inferior pincer grip but not reliably,
with his left (affected) hand. The left arm and hand were
used to assist in bilateral activities by holding with a
restricted repertoire of movements. Consistent with this
functional picture, his AHA score was 65 % and BOT2
total composite standard score was 33 (below average).
On structural MRI, the site of the brain injury was
identified in the right perisylvian region with cystic leukoencephalomalacia involving posterior right frontal,
right parietal pre- and post-central gyri and superior
temporal lobe. Comparison of cortical activation between left and right hemispheres using fMRI demonstrated that movement of the affected left hand resulted
in activation in the ipsi-lesional hemisphere only, anterior to the lesion within the motor cortex. In comparison,
movement of the right hand resulted in expected activation of the motor cortex. DWT revealed pathways in the
right (lesioned) hemisphere tracked perilesionally to the
cortical area identified by fMRI. The right hand motor
task resulted in expected and more robust motor cortical
activation with the expected contralateral hemisphere
and corticospinal tracts when compared to left (see
Figures 1, 2). DWT was seeded from areas of maximal fMRI activation to the pons (Figure 3). Sampling
of FA values sequentially along the corticospinal tracts

Figure 1 Motor fMRI Findings. Coronal view. fMRI activation in R
cortical region with left (affected) hand motor task. (R side of brain
appears on L side of image).

Gordon et al. BMC Neurology 2012, 12:53
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Figure 2 Motor fMRI Findings. Coronal view. fMRI activation in L
cortical region with right hand motor task (R side of brain appears
on L side of image).

(Figures 4, 5) shows reduced FA in the ipsilesional
tracts when compared to the contralesional side.

Conclusion
The DWT results described in this case show that the
region identified by fMRI as supporting hemiparetic
hand use has the necessary white matter connections to
perform this function. The underlying white matter may
not be sufficiently preserved to allow a full recovery of
function, but partial recovery is evident. The reduced FA

Figure 3 DWI Tractography Findings. DWI tractography seeded
from coordinates of maximal activation on fMRI to the brainstem (R
side of brain appears on L side of image).

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Figure 4 DWI Tractography Findings. Fractional anisotropy values
were calculated at 2 mm intervals, resampled from the pons to the
centrum semiovale. (R side of brain appears on L side of image).

within the ipsilesional cortico-spinal tract compared to
the contralesional side may be explained by a number of
factors. These include absence of myelin; compromised
axonal membranes; reduced axonal density; and
increased extra-cellular water [12]. In this case however,
it is unlikely given the child’s medical history that the
observed FA changes are due to demyelination or compromised axonal membranes. Given the nature of the
brain insult, it may however be expected that there
would be loss of axonal density, and corresponding

Figure 5 FA Values Along Corticospinal Tracts. FA values at 2
mm intervals (displayed in Figure 4) shown numerically, showing
reduced FA in the cortico-spinal tracts in inferior regions on lesioned
right side compared to left. X axis: FA values from inferior (lower end
of axis) to superior structures (upper end). Right hemisphere
(lesioned side) tracts green, left hemisphere tracts blue.

Gordon et al. BMC Neurology 2012, 12:53
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increase in extra-cellular water, due to loss of some projections to/from the site of injury.
Our findings suggest that chronic functional motor
deficits following neonatal AIS may be associated with
limited preservation of organisation to ipsilesional
regions of the cortex, and there was reduced pathway
density in regions of the tracts distal to the site of injury.
The underlying mechanisms for these processes remain
unknown. Wallerian degeneration of the descending corticospinal tracts has been associated with poor motor
outcome in both acute and chronic paediatric stroke
[13,14].
In this case, despite unilateral damage to the motor
cortex, the child developed useful functional ability of
the impaired upper limb, as a non-dominant limb. DWT
suggests intact perilesional motor pathways were associated with the use of the child’s impaired hand. fMRI
and DWI of structures associated with motor outcome
may improve our ability to predict outcome following
paediatric stroke. In paediatric clinical practice a number
of approaches have shown potential to improve motor
function including transcranial magnetic stimulation
[15], modified constraint induced movement therapy,
and bimanual training [16]. It is possible that activitydependent synaptic plasticity and reorganisation of
motor and sensory maps is influenced by lesion, age and
intervention characteristics. Prospective magnetic resonance studies imaging motor tracts longitudinally in relation to functional recovery may assist in identifying
targets for motor rehabilitation intervention. Future
studies are indicated to explore the impact of intervention on axonal density in the corticospinal tracts and
functional outcome.

Summary
DWT enables visualisation and quantification of white
matter tracts and can inform our understanding of
mechanisms of recovery in early acquired damage to the
developing brain. Further studies are needed to explore
the relationship between white matter tracts (as characterised using DWT) and the degree of motor recovery.
This has the potential to underpin rehabilitation interventions aimed at improving motor function following
stroke in infancy.
Consent
Written informed consent was obtained from the
patient’s parents for publication of this Case report and
any accompanying images. A copy of the written consent
is available for review by the Series Editor of this
journal.
Abbreviations
MRI: Magnetic resonance imaging; fMRI: Functional MRI; DWT: Diffusion
weighted tractography; DWI: Diffusion-weighted imaging, AIS, Arterial

Page 4 of 5

ischaemic stroke (AIS, BOT2, Bruininks-Oseretsky Test of Motor Proficiency 2;
AHA: Assisting Hand Assessment v4.1, PSOM, Pediatric Stroke Outcome
Measure, MACS, Manual Ability Classification System; GMFCS: Gross Motor
Functional Classification System (Expanded & Revised).
Competing interests
The authors declare they have no competing interests.
Acknowledgements
Thanks to Professors Alan Connelly & Michael Ditchfield for assistance in
study design and Chris Adamson and Jian Chen for assistance with data
analysis. This study was funded by a Murdoch Childrens Research Institute
Critical Care & Neurosciences Theme small project grant. JDT is grateful to
the National Health and Medical Research Council (NHMRC) of Australia,
Austin Health, and the Victorian Government's Operational Infrastructure
Support Program for their support.
Author details
Evelina Children’s Hospital, Guys’ & St Thomas’ Hospital NHS Trust, London,
UK. 2Murdoch Children’s Research Institute, Melbourne, Australia.
3
Department of Paediatrics, University of Melbourne, Melbourne, Australia.
4
School of Psychology, University of Birmingham, Edgbaston, UK. 5Brain
Research Institute, Florey Neuroscience Institutes (Austin), Melbourne,
Australia. 6Department of Medicine, Austin Health and Northern Health,
University of Melbourne, Melbourne, Victoria, Australia. 7Department of
Neonatal Medicine, The Royal Children’s Hospital, Flemington Road, Parkville,
Victoria 3052, Australia.
1

Authors’ contributions
AG conceived of the study, undertook the clinical examinations, participated
in the imaging data acquisition and drafted the manuscript; JDT participated
in the design of the study, performed diffusion weighted imaging analysis
and data interpretation and helped draft the manuscript; AW participated in
the imaging protocol design, undertook functional imaging analysis and
interpretation and helped draft the manuscript; RH conceived of the study,
participated in its design and coordination, and drafting of the manuscript.
All authors read and approved the final manuscript.
Received: 27 February 2012 Accepted: 9 July 2012
Published: 9 July 2012
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doi:10.1186/1471-2377-12-53
Cite this article as: Gordon et al.: Corticospinal tract integrity and motor
function following neonatal stroke: a case study. BMC Neurology 2012
12:53.

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