Shape of the Central Sulcus and Disability After
Subcortical Stroke
A Motor Reserve Hypothesis
Eric Jouvent, MD, PhD; Zhong Yi Sun, PhD; François De Guio, PhD;
Edouard Duchesnay, PhD; Marco Duering, MD; Stefan Ropele, PhD; Martin Dichgans, MD;
Jean-François Mangin, PhD; Hugues Chabriat, MD, PhD
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Background and Purpose—Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases.
Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to
determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is
independently associated with disability in patients with a positive history of small subcortical ischemic stroke.
Methods—Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without
supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke
caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy),
a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used
to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and
sulcal shape.
Results—Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education
(proportional odds ratio =1.19, 95% confidence interval =1.06–1.35; P=0.002). Results remained significant after further
adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular
origin.
Conclusions—The severity of disability in patients with a positive history of small subcortical ischemic stroke caused
by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main
determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity
in patients with a positive history of small subcortical ischemic stroke. (Stroke. 2016;47:1023-1029. DOI: 10.1161/
STROKEAHA.115.012562.)
Key Words: CADASIL ◼ central sulcus ◼ cerebral cortex ◼ motor reserve ◼ stroke
I
n chronic neurological disorders, both brain and cognitive
reserves modulate the relationships between brain pathology and clinical symptomatology.1,2 After stroke, age, initial
clinical severity, treatment,3,4 and imaging characteristics of
the stroke lesion are associated with clinical outcomes,5 but
whether a motor reserve also modulates the relationships
between stroke and the severity of disability is unknown.
The shape of the central sulcus reflects the development of
underlying motor connections6,7 that might influence disability in stroke patients. Particularly, the prominent development
of the hand motor area shapes locally the central sulcus as an
inversed omega.8 Recent developments in magnetic resonance
imaging (MRI) postprocessing allowed comparing shapes of
central sulci among individuals without supervision.9 With
this approach, it was shown that the vertical position of the
hand motor area is the main source of variability regarding
shapes of central sulci among healthy individuals, and that
when the hand area is shifted upwards, its size decreases.9
To determine whether disability after stroke is related to the
shape of the central sulcus, as a marker of the development
of underlying motor connections, we studied a large cohort of
patients with a positive history of small subcortical ischemic stroke
caused by Cerebral Autosomal Dominant Arteriopathy With
Subcortical Infarcts and Leukoencephalopathy (CADASIL),
a severe monogenic cerebral small vessel disease characterized, after normal brain development, by the early occurrence
Received December 23, 2015; final revision received February 1, 2016; accepted February 10, 2016.
From the Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1161 INSERM, F-75205 Paris, France and AP-HP, Lariboisière Hospital, Department
of Neurology, F-75475 Paris, France, and DHU NeuroVasc Sorbonne Paris Cité, Paris, France (E.J., F.D.G., H.C.); UNATI, Neurospin, I2BM, CEA,
Saclay, France (Z.Y.S., E.D., J.-F.M.); CATI Multicenter Neuroimaging Platform, cati-neuroimaging.com, France (Z.Y.S., E.D., J.-F.M.); Institute for
Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M. Duering, M. Dichgans);
Munich Cluster of Systems Neurology (SyNergy), Munich, Germany (M. Duering, M. Dichgans); and Department of Neurology, Medical University
of Graz, Austria (S.R.).
Correspondence to Hugues Chabriat, MD, PhD, Service de Neurologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France. E-mail hugues.
[email protected]
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.012562
1023
1024 Stroke April 2016
of stroke and the development of highly variable levels of disability in young patients.10 The study of a monogenic disorder
responsible for small subcortical ischemic strokes in young
patients allows reducing the confounding effect of age and of
potentially associated prodromal neurodegenerative disorders
in the elderly. Additionally, the cerebral cortex is macroscopically largely spared in this disorder, allowing fine analyzes of
its morphology.11,12
Methods
Patients
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One hundred and ninety patients (123 from Paris and 67 from
Munich) with CADASIL (proven genetically) were included in the
present study between 2003 and 2009 and were evaluated every 18
months. At each visit, both clinical, biological, and MRI evaluations
were performed using harmonized protocols. The present analyses
are based on the initial assessment of MRI and clinical data. All
patients had a positive history of small subcortical ischemic stroke
caused by CADASIL and were aged >18 years. Small subcortical
ischemic strokes were defined as neurological deficits lasting more
that 24H linked to a recent small subcortical infarct identified on
imaging (computed tomographic scan or MRI). They participated
in a prospective cohort study of CADASIL at Lariboisière (Paris)
or Ludwig-Maximilians-Universität (Munich). Details of the protocol have been previously reported.12 Age, sex, and level of education
were collected among a large set of clinical and epidemiological data.
Disability was assessed using the modified Rankin scale (mRS), a
widely used scale heavily weighted toward motor disability, ranging from 0 (no symptom) to 5 (bedridden).13 An ethics committee
approved the study in both centers.
MRI Acquisition
MRI scans were obtained on 1.5-T systems (Siemens Magnetom
Vision [Munich] or General Electric Medical Systems Signa [Paris
and Munich]). 3DT1 sequences (Munich: repetition time/echo time
(TR/TE) =11.4/4.4 ms, slice thickness =1.2 mm, no interslice gap,
in-plane resolution =0.9×0.9 mm; Paris: TR/TE=9.1/2 ms, slice
thickness =0.8 mm, no gap, in-plane resolution =1.02×1.02 mm),
fluid-attenuated inversion recovery (Munich: repetition time/echo
time/inversion time (TR/TE/TI) =4284/110/1428 ms, slice thickness
=5 mm, no gap, in-plane resolution =0.98×0.98 mm; Paris: TR/TE/
TI =8402/161/2002 ms, slice thickness =5.5 mm, no gap, in-plane
resolution =0.94×0.94 mm), and T2*-weighted gradient echo imaging (Munich: TR/TE=1056/22 ms, slice thickness =5 mm, no gap,
in-plane resolution =0.98×0.98 mm; Paris: TR/TE=500/15 ms, slice
thickness =5.5 mm, no gap, in-plane resolution =0.98×0.98 mm)
were performed.
Image Processing
White matter hyperintensities and lacunes of presumed vascular origin as well as microbleeds were extracted using validated methods
detailed elsewhere from high-resolution fluid-attenuated inversion
recovery, 3DT1, and T2* MRI sequences, respectively,12 in agreement with the STRIVE (Standards for Reporting Vascular Changes
on Neuroimaging) criteria.14 Volume of white matter hyperintensities,
volume of lacunes, and number of microbleeds were measured as previously reported.12 In a second step, those variables were measured
specifically within pyramidal tracts after registration within the Johns
Hopkins University probabilistic atlas of major white matter tracts
in the Montreal Neurological Institute template.15 Given the skewed
distributions of the volumes of white matter hyperintensities both
globally, within and without pyramidal tracts, these variables were
log-transformed to obtain close to normal distributions. Brain parenchymal fraction, a recognized measure of brain atrophy, was defined
as the ratio of brain tissue volume to the intracranial cavity volume to
take into account differences in head size between patients, as previously detailed.16
Reconstruction and identification of cortical sulci were performed
using Brainvisa (http://brainvisa.info). Ordering of shapes of central
sulci was performed using previously validated methodology.9 Right
central sulci were first flipped relative to the interhemispheric plane to
allow comparison with left central sulci (Figure 1). Hence, all analyses included both left and right sulci of each patient. A pairwise shape
similarity matrix was computed across the whole set of sulci.9 The
similarity between 2 sulci was coded by the average quadratic distance between their 3-dimensional representations after alignment.
This pairwise registration was achieved using the iterative closest
point algorithm, which aligns one sulcus relative to the other through
successive rotations and translations. The shape similarity matrix was
built from all the pairwise comparisons, and manifold learning (using
the Isomap algorithm) was used to capture a 1-dimensional approximation of the high dimensional space spanned by central sulci.9 This
1-dimensional approximation provided a numeric index of sulcal
shape (I) for each sulcus relative to all the others (hence each subject
had an index for his right central sulcus IR and one for his left central
sulcus IL). For analyses, an index IRL was calculated for each patient
as the average of this numeric index on both sides (Figure 1).
Statistical Analyses
Statistical analyses were performed using the R software (http://
www.r-project.org/). To determine whether mRS is independently
related to IRL, we used ordinal logistic regression analyses to determine the regression coefficients on the log scale that were further
exponentiated to obtain proportional odds ratios (ORP) together with
their 95% confidence interval (95% CI). In model 1, univariate analysis was tested, with mRS as the dependent variable and IRL as the
independent variable. In model 2, IRL, age, sex, and level of education
were included as covariates. In model 3, IRL, age, sex, level of education, brain parenchymal fraction, volume of lacunes, volume of white
matter hyperintensities, and number of microbleeds were included as
covariates, those imaging variables being associated with disability in
cerebral small vessel disease in general and in CADASIL in particular.13 In model 4 (full model), the same covariates as model 3 were
included, but volume of lacunes, volume of white matter hyperintensities, and number of microbleeds were evaluated separately within
and outside pyramidal tracts and considered as different covariates.
The different models were compared by analysis of variance.
Results
Among 190 CADASIL patients with a positive history of
small subcortical ischemic stroke caused by CADASIL who
were recruited in the 2 centers, 6 were excluded from analyses
because they also had a large cortical infarct on MRI. Seven
had incomplete MRI data or MRI data of insufficient quality for image processing. For 11 patients, the reconstruction
of one or the other central sulcus failed for various technical
reasons, leaving 166 patients for analyses. Characteristics of
those 166 patients are given in Table 1. Fifty-three percent
of patients experienced ≥2 small subcortical ischemic strokes,
whereas 28% had ≥3.
We observed that the first source of variability regarding the
shape of central sulci among CADASIL patients was the vertical position of the hand knob along the central sulcus together
with a decrease of its size when shifted upward (Figure 1).
A scatterplot of the rough relationships between sulcal shape
(IRL) and mRS is presented Figure 2.
In univariate ordinal logistic regression analysis, mRS was
significantly associated with IRL (ORP=1.20, 95% CI =1.07–
1.35; P=0.002). In other words, for a 1-unit increase in IRL, the
odds to move from a low or intermediate mRS to a larger mRS
Jouvent et al Motor Reserve in Subcortical Stroke 1025
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Figure 1. Methodology. A, Native magnetic resonance imaging (MRI) axial slices illustrating the variability of shapes of central sulci
among 5 CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) patients with a positive history of subcortical ischemic stroke, particularly respective to the position and size of hand knobs (white stars). B, Central sulci
were reconstructed using BrainVisa (http://brainvisa.info). The right sulci were transformed by symmetry through the interhemispheric
plane to compare them to left sulci. Sulcal shapes are represented overlaid on meshes of underlying white matter. C, The whole sample
of central sulci of patients included in the present study is shown according to the ordering determined without supervision by the Isomap algorithm. Ten meshes representing the average shape of similar sulci are represented overlaid over the whole sample to highlight
the main source of variability. Importantly, this first and most important source of variability was the vertical position and size of the hand
knob, as reported previously in healthy subjects.9 An index was determined for each central sulcus respective to the whole sample of
central sulci. The IRL index for a subject was obtained by averaging right and left indexes.
increase by 20% (multiplied by a factor of 1.2), with upper
and smaller hand knobs being associated with larger mRS.
In model 2, including age, sex, and level of education
as covariates, mRS was significantly associated with IRL
(ORP=1.19, 95% CI =1.06–1.35; P=0.004), age (ORP=1.08,
95% CI =1.04–1.12; P<10–4), and level of education
(ORP=0.69, 95% CI =0.52–0.90; P=0.006), but not sex
(Table 2). Model 2 performed statistically significantly better
than model 1 (P<10–4).
In model 3, further including as covariates brain parenchymal fraction, volume of lacunes, volume of white matter hyperintensities, and number of microbleeds, mRS was
significantly related to IRL (ORP=1.19, 95% CI =1.05–1.35;
P=0.005), brain parenchymal fraction (ORP=0.88, 95% CI
=0.81–0.96; P<10–4), and level of education (ORP=0.73, 95%
CI =0.55–0.97; P=0.03), but not to age, sex, volume of lacunes, or of white matter hyperintensities or number of microbleeds. Model 3 performed statistically significantly better
than model 2 (P=0.0009).
In the full model (model 4) including volume of lacunes,
volume of white matter hyperintensities, and number of microbleeds evaluated separately outside and within pyramidal
tracts, mRS was significantly associated with IRL (ORP=1.23,
95% CI =1.09–1.41; P=0.002), the volume of lacunes measured within pyramidal tracts (ORP=1.01, 95% CI =1.00–1.01;
P=0.01), the number of microbleeds measured outside pyramidal tracts (ORP=1.11, 95% CI =1.02–1.22; P=0.009), brain
parenchymal fraction (ORP=0.86, 95% CI =0.79–0.94; P<10–4),
and level of education (ORP=0.74, 95% CI =0.55–0.98;
P=0.03). The full model performed statistically significantly
better than model 3 (P=0.003). The inclusion of center as a
fixed effect in the 4 different models did not alter the results.
Discussion
The results of the present study show that, in a large cohort
of young patients all affected by the same severe monogenic
cerebral small vessel disease responsible for small subcortical
ischemic strokes,17 the severity of disability is independently
associated with the shape of the central sulcus, mostly driven
by the vertical position and the size of the hand knob as in
healthy subjects. Our results suggest that the position of the
hand knob, a cortical marker that can be easily determined on
brain MRI before stroke, might predict the patient’s ability to
recover after stroke, providing an alternative explanation for
the various levels of disability observed in patients with similar subcortical ischemic lesions at the same age.
Our findings are in line with the widely recognized concepts of cognitive reserve (mostly related to the amount and
efficiency of brain networks, development of which would
take place during childhood18) and with that of brain reserve
1026 Stroke April 2016
Table 1. Clinical and MRI Data of the 166 Patients
Clinical Data
Age, mean±SD (range)
Male sex, count (%)
Level of education, count (%)
52.2±9.7 (31.4–77.5)
84/166 (51%)
Basic: 24 (14%)
Secondary: 109 (66%)
University: 27 (16%)
Number of subcortical ischemic strokes,
count (%)
1: 79 (47%)
2: 41 (25%)
≥3: 46 (28%)
Modified Rankin scale, median,
interquartile range, range
1, 2, 0–5
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Time elapsed in days between first stroke
and current study, median, interquartile
range, range
1203, 1675, 17–6655
Time elapsed in days between last stroke
and current study, median, interquartile
range, range
471, 993, 17–6258
Imaging data
Brain parenchymal fraction, %, mean±SD
(range)
84.2±6.1 (65.3–96.1)
Volume of lacunes, mm3, mean±SD
(range)
478±671 (0–3864)
Volume of white matter hyperintensities of
presumed vascular origin, mm3, mean±SD
(range)
113 140±68 273 (3796–
414 400)
Number of microbleeds, mean±SD (range)
3.7±12.7 (0–123)
motor cortex volume, offering higher probabilities to detect
intersubject differences.
Others and we have previously shown that the cortical
mantle can be altered secondary to subcortical lesions in
cerebral small vessel diseases.19,20 In the present study, we
cannot formally exclude that the observed cortex shape variations between patients are in fact the remote cortical consequences of subcortical strokes and lacunes on connected fiber
bundles.19 However, it is important to note that the pattern of
variations of shapes of central sulci detected by our unsupervised algorithm was very similar to that of healthy individuals.
This strongly argues against the hypothesis that the variations
observed in patients results from remote effects of subcortical lesions, but rather support the hypothesis that they actually represent a developmental marker independent of the
effects of the disease.9 In addition, by contrast to other MRI
measures, the shape of the central sulcus seems highly stable
during lifespan, also rendering less likely the possibility of
secondary alterations. In our cohort, >30 patients are being
followed using MRI acquisitions every 18 months since >12
years, and the shape of the central sulcus is largely unaltered
as illustrated by a typical case even when they develop disability (Figure 3).
After stroke, motor recovery seems highly variable among
individuals.21 Both structural and functional reorganization
occur not only locally but also remotely to the stroke lesion.22
Bilateral modulations of sensorimotor activations have been
consistently observed and may predict motor recovery after
stroke.23 The integrity of pyramidal tracts measured using various quantitative measures of diffusion and electrophysiological
MRI indicates magnetic resonance imaging.
(mostly related to available tissue resources and components)
that can modulate the clinical expression of brain pathologies both in young and older populations.1 Whether our findings are specific to CADASIL or can be generalized to other
types of cerebral small vessel diseases or to other stroke
populations will of course require further investigations. In
particular, although all the patients included in the present
study experienced at least one small subcortical ischemic
stroke, 53% of them experienced ≥2 small subcortical ischemic strokes. Moreover, in these patients, the whole burden
of lacunes, a large proportion of which did not lead to stroke,
is a major determinant of disability compared with other etiologies of stroke.13
Other metrics such as the volume of gyri or of primary
motor cortex might have also been of interest to evaluate the
motor aspects of the cerebral cortex. However, the analysis
of sulcal shape offers several advantages. First, the volume
of cortex structures, such as the primary motor area, is difficult to determine on a simple morphological MR scan,
and more elaborate acquisitions would be required to delineate its limits. Another major advantage is that shape is
invariant with respect to head size, whereas all other volumetric measures would need statistical adjustment for this
confounding effect. Finally, the variability of sulcal shape
among healthy subjects is far larger than that of primary
Figure 2. Relationships between sulcal shape and modified
Rankin scale. Scatter plot representing the rough relationships
between the index of sulcal shape and modified Rankin scale.
The line of best fit obtained with ordinary least square regression
is shown with its 95% confidence interval. The suggested link
was confirmed by ordinal regression analyses (see the results
section). Please note that a small amount of random noise was
added on the horizontal axis to allow a better visualization, particularly regarding scores 0 and 1 of modified Rankin scale for
which several points would have been otherwise overlaid onto
each other.
Jouvent et al Motor Reserve in Subcortical Stroke 1027
Table 2. Results of Ordinal Logistic Regression Models Testing the Associations Between
Modified Rankin Scale and Sulcal Shape According to Various Covariate Configurations
Proportional Odds Ratios
Model 1
Model 2
Model 3
Model 4
1.20 [1.07–1.35]*
1.19 [1.06–1.35]*
1.19 [1.05–1.35]*
1.23 [1.09–1.41]*
Age
1.08 [1.04–1.12]†
1.02 [0.97–1.07]
1.04 [0.99–1.09]
Sex
0.65 [0.34–1.32]
1.17 [0.54–2.54]
1.46 [0.64–3.37]
Level of education
0.69 [0.52–0.90]*
IRL
0.73 [0.55–0.97]‡
0.74 [0.55–0.98]‡
BPF
0.88 [0.81–0.96]†
0.86 [0.79–0.94]†
Volume of lacunes§
1.00 [0.99–1.00]
1.00 [1.00–1.00]
Volume of WHM§
1.77 [0.98–3.41]
2.58 [0.87–8.09]
Number of MB§
1.01 [0.96–1.07]
1.11 [1.02–1.22]*
Volume of lacunes in PT
1.01 [1.00–1.01]*
Volume of WMH in PT
0.60 [0.26–1.45]
Number of MB in PT
1.01 [0.91–1.11]
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Proportional odds ratios are provided with 95% confidence intervals. BPF indicates brain parenchymal fraction; IRL, index
of sulcal shape; MB, microbleeds; PT, pyramidal tracts; and WMH, white matter hyperintensities.
*Level of significance: <0.01.
†Level of significance: <0.001.
‡Level of significance: <0.05.
§Measured outside pyramidal tracts in model 4.
parameters was found promising to help predict motor recovery,24,25 although the yield of these techniques compared with
clinical data alone remains undetermined.26 Analysis of sulcal
morphology is independent from all these methods and may
provide additional information to better determine the patients
who will more likely benefit of neurorehabilitation.26 Whether
sulcal shape can help in predicting long-term disability in
patients having initially the same level of motor impairment
will require further investigations.
Our study has several limitations. We studied patients
with CADASIL, a rare monogenic disorder, thus questioning the generalizability of our results to other stroke populations. Also, we used mRS to assess disability while it is not
a direct measure of motor function but a general measure of
disability. Although in the present cohort we did not plan
to measure scores of motor function, pyramidal involvement was tested at each visit. We tested, using a logistic
regression model, whether pyramidal involvement was
Figure 3. Stability of sulcal shape over long periods of time. Example of a 46-year-old female CADASIL (Cerebral Autosomal Dominant
Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) patient, representative of our sample. After a 12-year-long follow-up period,
significant whole brain atrophy has developed, with major enlargement of ventricles (lateral, 3rd, 4th), whereas cortical sulci are wider and
less deep. By contrast, the global shape of the central sulcus appears stable both on magnetic resonance imaging (MRI) axial slices and on
3-dimensional reconstruction when overlaid on surfaces meshes (please note that MRI slices are conventionally flipped, but meshes are represented through a top-down view, with right hemisphere on right side). Meanwhile, significant disability has developed (mRS score from 0 to 2).
1028 Stroke April 2016
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associated with IRL. Results were significant both in univariate analyses and after adjustment for potential confounders.
Furthermore, adding pyramidal involvement as a covariate
in the different regression models led to lower and less significant effect of IRL as a predictor of mRS (data not shown).
Altogether, these additional results strongly support that the
link between IRL and mRS is actually mostly mediated by
motor involvement. Moreover, given the few values allowed
by this score (0–5), sampling variations may promote the
detection of significant results because of chance alone.
However, we found similar results with the Barthel Index,
another measure of disability largely independent from the
mRS, thus rendering this hypothesis unlikely. We studied
sulcal shape on both sides rather than through separated
analyses, which is questionable. However, this allowed
limiting the number of statistical tests, thus reducing the
probability to find significant results because of chance
alone. Moreover, given that most patients experienced several small subcortical strokes, separate analyses on both
sides would have been very difficult to perform and interpret. Additionally, we could not adjust our results for the
initial stroke severity because National Institutes of Health
Stroke Scale (NIHSS) at time of previous strokes was not
available for most patients. However, our results were left
unchanged when taking into account NIHSS at baseline
evaluation in the present study. As NIHSS at baseline may
not match NIHSS at time of stroke, we also checked that
the presence of motor symptoms at time of stroke, more
likely to be associated with larger NIHSS scores, did not
alter our results. Further adjustment for time elapsed since
last stroke did not either alter our results. Also, we did not
perform diffusion tensor analyses because the strong loss of
anisotropy in our cohort would have led to highly unreliable
estimates.27 Finally, although we have adjusted analyses for
most known factors associated with the severity of disability
in CADASIL, we cannot formally exclude that unidentified
confounders could be responsible for our results.
Our study also has important strengths. We have tested
our hypothesis in a homogeneous sample of patients who are
affected by the same monogenic disorder that is characterized
by a normal brain development followed by the occurrence of
stroke at a young age.10 In CADASIL, patients develop various degrees of disability at the same age, despite similar loads
of ischemic lesions in the brain, for reasons that are not all
well understood and while brain comorbidities are unlikely.10
Furthermore, our analyses were unsupervised, and the statistical strategy was straightforward, hierarchical with clear a
priori selection of covariates, and with limitation of the number of tests.
In summary, the results of the present study suggest that a
simple parameter visible at the surface of the cerebral cortex
might be a marker of a cerebral motor reserve modulating the
relationships between subcortical ischemic stroke and disability. Further studies are needed to determine whether these
results can be generalized to other stroke populations.
Acknowledgments
We acknowledge the CERVCO team for their strong involvement in
the follow-up of patients.
Sources of Funding
This work was supported by grants from the French Ministry
of Health (Regional and National PHRC AOR 02-001), an FP7
ERA-NET NEURON grant (01EW1207), and grants from the
Vascular Dementia Research Foundation and the Fondation Leducq
(Transatlantic Network of Excellence on the Pathogenesis of Small
Vessel Disease of the Brain) (http://fondationleducq.org).
Disclosures
None.
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Downloaded from http://stroke.ahajournals.org/ by guest on June 16, 2017
Shape of the Central Sulcus and Disability After Subcortical Stroke: A Motor Reserve
Hypothesis
Eric Jouvent, Zhong Yi Sun, François De Guio, Edouard Duchesnay, Marco Duering, Stefan
Ropele, Martin Dichgans, Jean-François Mangin and Hugues Chabriat
Downloaded from http://stroke.ahajournals.org/ by guest on June 16, 2017
Stroke. 2016;47:1023-1029; originally published online March 3, 2016;
doi: 10.1161/STROKEAHA.115.012562
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