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PEER REVIEW HISTORY
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reproduced where possible.
ARTICLE DETAILS
TITLE (PROVISIONAL)
AUTHORS
The role of corticofugal fibres involvement in motor deficit following
subcortical stroke
Phan, Thanh; de Voort, Sanne; chen, jian; Beare, Richard; Ma,
Henry; Clissold, Benjamin; Ly, John; Foster, Emma; Thong, Eleanor;
Srikanth, Velandai
VERSION 1 - REVIEW
REVIEWER
REVIEW RETURNED
THE STUDY
GENERAL COMMENTS
REVIEWER
REVIEW RETURNED
THE STUDY
Hyun Ah Kim, MD
Assistant professor, Department of Neurology, Keimyung University
School of Medicine,Republic of Korea
I declare no competing interest.
04-Jul-2013
1. In the abstract, it is needed a concise and clearly explained
description about method.
2. Is the examination time of motor deficit on admission equal to the
time of brain imaging? It might be important in investigating the
relationship between the degree of the motor deficit and the
imaging.
2. The style of the paper is rather poor across the whole manuscript
and some sentences are too long and not understandable.
The reviewer completed the checklist and provided a marked-up
copy which is available on request from the publisher
Francesco Arba, MD, PhD student
University of Florence
NEUROFARBA Department
Largo Brambilla, Florence, Italy
19-Jul-2013
1- Research question is not clear. Motor outcome is always affected
by integrity of corticofugal fibres. The authors state "We hypothesise
that motor deficit from subcortical stroke is associated with
involvement of corticofugal tracts", but this is not a hypothesis, this is
ALWAYS true. It should be better defined that authors aimed to
correlate motor deficit with one of the corticofugal tracts.
2- Patients: it should be better defined inclusion criteria and
exclusion criteria (age, range of severity of stroke, clinical and
radiological criteria to select subcortical stroke, anterior or posterior
stroke. I suggest to use OCSP classification).
3- Patients: it is not mentioned if any patient underwent any
thrombolytic treatment. This fact could affect motor outcome at three
months.
Moreover, it should be better defined baseline characteristics of
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patients.
4- Methods: it is not clear why authors perform MR image on normal
subjects. I suppose that they do this to better define corticofugal
tracts. It should be better defined in the text.
5- Methods: why authors adopted NIHSS instead of other scales (i.e.
Scandinavian Stroke Scale) to detect motor deficit? NIHSS is not so
sensitive to detect distal deficit in the arm (i.e. it does not consider
the hand). This fact should be explicitated in the text.
6- Characteristics of patients: authors should clearly explicitate
radiological profile of selected patients that may affect outcome. Did
any patients have leukoaraiosis (which is an independent predictor
of disability)? Did stroke damage other important corticofugal tracts
that may affect outcome?
7- Clinical outcomes: they should be better explicitated because
there are two different outcomes (NIHSS which is a pure clinical
outcome, and mRS, which is a disability scale).
1- Results should be better presented. I suggest to build a table to
correlate radiological data (i.e. tract volume involved in the stroke)
with clinical outcome in a clearer way. Data are usually easier to
read in tables.
2- The regression model is adjusted for which variables? It should
be clearly stated in the text.
3- In the discussion section authors state "this result may have
implications for interpretation of clinical images and extrapolation of
infarct location for prognostication on stroke recovery". It is not clear
which is the message, since they previously state and associations
between involvement of corticofugal fibres to stroke motor deficit and
disability were variable.
Interesting exploratory study, it may be good clinical applications,
particularly on patient stratification in order to define physiotherapy
after discharge.
It is not so clear what authors want to demonstrate. I suggest to be
more pragmatic in defining methods and in reporting results. They
have to be clear.
Good list of reference, even if there are many references of the
authors' group.
RESULTS & CONCLUSIONS
GENERAL COMMENTS
VERSION 1 – AUTHOR RESPONSE
Reviewer 1
1. In the abstract, it is needed a concise and clearly explained description about method.
The abstract has been re-written.
2. Is the examination time of motor deficit on admission equal to the time of brain imaging? It might be
important in investigating the relationship between the degree of the motor deficit and the imaging.
The time to MR imaging was not associated with outcome. This has been dicussed in the Results
section on page 11.
3. The style of the paper is rather poor across the whole manuscript and some sentences are too long
and not understandable.
The style has been revised. Long sentences have been removed.
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Reviewer 2
1- Research question is not clear. Motor outcome is always affected by integrity of corticofugal fibres.
The authors state "We hypothesise that motor deficit from subcortical stroke is associated with
involvement of corticofugal tracts", but this is not a hypothesis, this is ALWAYS true. It should be
better defined that authors aimed to correlate motor deficit with one of the corticofugal tracts.
This statement has been changed in the abstract and the last para of the introduction (page 4).
2- Patients: it should be better defined inclusion criteria and exclusion criteria (age, range of severity
of stroke, clinical and radiological criteria to select subcortical stroke, anterior or posterior stroke. I
suggest to use OCSP classification).
On page 5, we had defined the inclusion criteia as any patient who had subcortical infarct on MR
imaging. The OCSP classfication was not used because this classfication has poor correlation with
the location of infarct on MRI. This was described in Asdaghi’s paper in Stroke 2011; 42: 2143.
Age and severity of stroke was not used as these features do not impact on the location of infarct.
The key feature here is the presence of subcortical infarct as the corticofugal fibers traverse the white
matter.
The term subcortical infarct will be defined in the revised manuscript.
3- Patients: it is not mentioned if any patient underwent any thrombolytic treatment. This fact could
affect motor outcome at three months.Moreover, it should be better defined baseline characteristics of
patients.
The baseline characteristics is described on page 10 of the Results section. The number of patients
who had received tpa has been added. In our study, tpa was not associated with outcome as the
proportion of patients with no to mild disability was high (47/57).
4- Methods: it is not clear why authors perform MR image on normal subjects. I suppose that they do
this to better define corticofugal tracts. It should be better defined in the text.
The reason for performing MR imaging in normal subjects has now been added (page 6, Methods).
Further details are provided on page 16 in the Discussion under Limitations.
5- Methods: why authors adopted NIHSS instead of other scales (i.e. Scandinavian Stroke Scale) to
detect motor deficit? NIHSS is not so sensitive to detect distal deficit in the arm (i.e. it does not
consider the hand). This fact should be explicitated in the text.
The NIHSS is a standardised method for recording motor deficit and is used in many acute stroke
trials. Muir had published previous comparison study of this scale against other acute scales (Stroke
1996: 27: 1817). We had used this scale as it also record other neurological deficit such as neglect.
By contrast, the SSS does not have any item for neglect.
6- Characteristics of patients: authors should clearly explicitate radiological profile of selected patients
that may affect outcome. Did any patients have leukoaraiosis (which is an independent predictor of
disability)? Did stroke damage other important corticofugal tracts that may affect outcome?
The radiological profile is better defined. This has been added to both the Methods and Results
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section.
The issue of ‘leukoariosis’ had been looked at in the NINDS tpa trial by Demchuk et al.
Cerebrovascular Diseases 2008; 26:120. They did not observe a treatment effect with leukoariosis.
Similarly, we did not observe a relationship between leukoariosis and outcome. This is now described
in the Results (page 13) and Methods (page 7-8).
7- Clinical outcomes: they should be better explicitated because there are two different outcomes
(NIHSS which is a pure clinical outcome, and mRS, which is a disability scale).
The Rankin score is better defined on page 5 of the Methods section.
8- Results should be better presented. I suggest to build a table to correlate radiological data (i.e. tract
volume involved in the stroke) with clinical outcome in a clearer way. Data are usually easier to read
in tables.
The results have been moved to Table 1.
9- The regression model is adjusted for which variables? It should be clearly stated in the text.
The regression was adjusted for age only according to the criteria defined in the Methods. Only
variables with p<0.20 on univariable analysis were entered into multivariable models (page 10,
Methods)
10- In the discussion section authors state "this result may have implications for interpretation of
clinical images and extrapolation of infarct location for prognostication on stroke recovery". It is not
clear which is the message, since they previously state and associations between involvement of
corticofugal fibres to stroke motor deficit and disability were variable.
This statement is now been changed for clarification in the first para of Discussion.
11-Interesting exploratory study, it may be good clinical applications, particularly on patient
stratification in order to define physiotherapy after discharge.
It is not so clear what authors want to demonstrate. I suggest to be more pragmatic in defining
methods and in reporting results. They have to be clear.
We had tried to correlate motor deficit at 3 months with involvement of corticofugal fibers in patients
with subcortical infarcts. We agree with the reviewer that the results has implication for rehabilitation.
However, we had been careful with our conclusion and discussion because of the retrospective
nature of this study.
12-Good list of reference, even if there are many references of the authors' group.
Only reference 5 is from our group.
VERSION 2 – REVIEW
REVIEWER
Francesco Arba, MD
Downloaded from http://bmjopen.bmj.com/ on June 18, 2017 - Published by group.bmj.com
Neurologist
PhD student
University of Florence, Italy
REVIEW RETURNED
THE STUDY
I have no conflict of interest
16-Aug-2013
Not clear why authors choose p<0.2 as significative instead of
p<0.05, as usual.
The reviewer completed the checklist but made no further comments.
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Impact of corticofugal fibre involvement in
subcortical stroke
Thanh G Phan, Sanne van der Voort, Jian Chen, Richard Beare, Henry
Ma, Benjamin Clissold, John Ly, Emma Foster, Eleanor Thong and
Velandai Srikanth
BMJ Open 2013 3:
doi: 10.1136/bmjopen-2013-003318
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