MS: 2095915187305953
Title: Deterioration of pre-existing hemiparesis due to injury of the ipsilateral anterior
corticospinal tract
Reviewer's report 1
This case report describes deterioration of muscle weakness possibly caused by an ischemic
injury to uncrossed corticospinal tract (CST) at the pons. The authors attempt to show the
injury to the uncrossed CST by diffusion tensor tractography. I think this case report is of
interest, but some fallacies need to be fixed before acceptance for publication.
Major compulsory revision:
Point 1) I was wondering if the tractgram of the CST in the figure could be trustworthy,
because no pyramidal decussation was seemingly demonstrated. I guess the authors are going
too far with not-so-convincing tractography results. I think this report would be more reliable
if the authors could show regions of interest that they actually employed and rewrite the
interpretation of the tractography results in a more careful manner.
Answer: When we reconstruct the CST using DTT, we can not often observe the pyramidal
decussation of CST, but very rarely we can observe the pyramidal decussation of CST. That
seems to be related to the high angle of the pyramidal decussation of CST. So, we think there
was no error in our DTT results for the CST. We tried to reconstruct the whole and anterior
CST using giving regions of interest (ROIs) on the pons and upper medulla (anterior blue
color) and an additional ROI on the anterior funiculus of the upper cervical cord. So, as your
comments, we added the ROIs in the figure 1 and revised tractography results and figure
legends as follows.
Diffusion Tensor Tractography
The DTTs for whole CSTs of the right hemisphere in the patient and both hemispheres in
the control subjects originated from the primary sensori-motor cortex and descended
through the medullary pyramid along the known CST pathway. By contrast, the DTT for
left whole CST of the patient showed a Wallerian degeneration to the left pons with
discontinuation.
Figure Legends
Fig. 1. A) Brain MRI showing an old infarct in the left middle cerebral artery territory and a
new infarct in the right pontine basis (arrow). B) Regions of interest for the whole and
anterior corticospinal tract (CST)(yellow-lined circle) and results of diffusion tensor
tractography. The whole CST and the anterior CST were constructed in the patient and a
normal control subject (yellow: right whole CST, red: left whole CST, green: right anterior
CST, blue: left anterior CST).
Minor essential revision:
Point 2) In 6th line of the first paragraph of the discussion, “an infarct in the right MCA
territory” should be “left” instead of "right."
Answer: We are sorry for our mistake and corrected as follows
Discussion
In the current study, we evaluated the whole and anterior CSTs in a quadriparetic patient with
a new right pontine infarct and an old left MCA infarct. According to our results, it appeared
that the deterioration of the pre-existing right hemiparesis was ascribed to the injury of the
right anterior CST following the new right pontine infarct, for the following reasons. First,
the patient had been diagnosed with an infarct in the right MCA territory 7 years ago,
involving whole CST in the left corona radiata [18].
Discretionary revision:
Point 3) As is written above, the authors should show regions of interest they actually
employed in the figure.
Answer: we added the ROIs in the figure 1 and revised figure legends as follows.
Figure Legends
Fig. 1. A) Brain MRI showing an old infarct in the left middle cerebral artery territory and a
new infarct in the right pontine basis (arrow). B) Regions of interest for the whole and
anterior corticospinal tract (CST)(yellow-lined circle) and results of diffusion tensor
tractography. The whole CST and the anterior CST were constructed in the patient and a
normal control subject (yellow: right whole CST, red: left whole CST, green: right anterior
CST, blue: left anterior CST).
Reviewer's report 2
In this case report, the authors describe a patient with a pre-existing stroke in the left internal
carotid artery distribution and consequent right-sided hemiparesis who suffers a second
ischemic stroke, this time in the right ventral paramedian pons. The pontine stroke is
relatively small and causes mild to moderate left-sided hemiparesis, but in addition, the
chronic right-sided hemiparesis worsens to the point that all voluntary movement is abolished
on the right side. The authors propose that the right-sided anterior corticospinal tract (CST)
had taken over motor control of the right side of the body, and that lesion of this tract is
responsible for the deterioration of motor function on the right side. They show diffusion
tensor tractography (DTT) images that indeed illustrate that the right anterior CST is
interrupted at the level of the pontine stroke.
This article is well written and beautifully illustrates the large-scale reorganization of cerebral
function that takes place after a brain insult. This reorganization is responsible for the
alterations to the usual clinical-anatomical correlations (here, a right-sided injury aggravates
right-sided hemiparesis). The authors are appropriately cautious in generalizing from their
observation on a single case. This case will be of interest to a broad readership including
general neurologists, students and residents in neurology, stroke neurologists, and
rehabilitation medicine specialists.
1) Minor revisions
Point 1) I think that the authors should describe how spasticity evolved on the right side after
the right pontine stroke. Presumably the patient was spastic on the right side and had a rightsided extensor cutaneous plantar response from his previous left hemispheric stroke. It would
be interesting to know whether spasticity, hyperreflexia and the extensor cutaneous plantar
response were still present or whether they were abolished by the pontine stroke. This would
contribute to our understanding of the pathophysiology of spasticity (or the pyramidal
syndrome) and its anatomical pathways.
Answer: We are so sorry that we do not have detailed data on the spasticity at present,
especially the data for spasticity before the onset of right pontine infarct. So, unfortunately,
we are obliged to turn down the description about the change of spasticity.
2) Discretionary revisions
Point 2) In the first paragraph of the Introduction section, I suggest removing the “On the
other hand” that starts the last sentence of the paragraph.
Answer: We removed it and revised as follows.
Introduction
The corticospinal tract (CST) is the major neuronal pathway that mediates voluntary
movements in the human brain [1,2]. The CST is generally divided into the crossed lateral
CST and the uncrossed anterior CST. The anterior CST primarily innervates the musculature
of the trunk and proximal extremities [1,2]. The anterior CST is considered to be one of the
ipsilateral motor pathways from the unaffected motor cortex to the affected extremities,
which contribute to motor recovery following stroke incidents [3].
Point 3) In the first paragraph of the Diffusion tensor tractography section, there is a sentence
which reads “The whole CSTs, which were determined by selection of fibers passing through
two regions of interest (ROIs), were placed on the CST area of the pons and upper medulla
on the color maps.” I suggest rephrasing it to something like “The whole CSTs were
determined by selection of fibers passing through two regions of interest (ROIs), which were
placed on the CST area of the pons and upper medulla on the color maps.”
Answer: We revised as follows.
Diffusion Tensor Tractography
Fiber tracking was performed using the FACT algorithm implemented within the DTI task
card software [4,13]. The whole CSTs were determined by selection of fibers passing through
two regions of interest (ROIs), which were placed on the CST area of the pons and upper
medulla on the color maps [14,15]. By contrast, for reconstruction of the anterior CST, three
ROIs were placed on the CST area of the pons and upper medulla (anterior blue color) and an
additional ROI was placed on the anterior funiculus of the upper cervical cord on the color
maps [16].