RESEARCH ARTICLE

Recovery in cognitive motor dissociation after

severe brain injury: A cohort study
Jane Jöhr ID1*, Floriana Halimi1, Jérôme Pasquier ID2, Alessandro Pincherle1,
Nicholas Schiff3, Karin Diserens1
1 Department of Clinical Neurosciences, Neurology Service, Acute Neurorehabilitation Unit, University
Hospital Lausanne, Lausanne, Switzerland, 2 Center for Primary Care and Public Health, University of
Lausanne, Lausanne, Switzerland, 3 Feil Family Brain and Mind Research Institute, Weill Cornell Medicine,
New York, New York, United States of America

a1111111111 * [email protected]
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Abstract

Objective
To investigate the functional and cognitive outcomes during early intensive neurorehabilita-
OPEN ACCESS tion and to compare the recovery patterns of patients presenting with cognitive motor disso-
Citation: Jöhr J, Halimi F, Pasquier J, Pincherle A, ciation (CMD), disorders of consciousness (DOC) and non-DOC.
Schiff N, Diserens K (2020) Recovery in cognitive
motor dissociation after severe brain injury: A
Methods
cohort study. PLoS ONE 15(2): e0228474. https://
doi.org/10.1371/journal.pone.0228474 We conducted a single center observational cohort study of 141 patients with severe
Editor: Jose A. Muñoz-Moreno, Lluita contra la acquired brain injury, consecutively admitted to an acute neurorehabilitation unit. We divided
SIDA Foundation - Germans Trias i Pujol University patients into three groups according to initial neurobehavioral diagnosis at admission using
Hospital - Autònoma de Barcelona University, the Coma Recovery Scale-Revised (CRS-R) and the Motor Behavior Tool (MBT): potential
SPAIN
clinical CMD, [N = 105]; DOC [N = 19]; non-DOC [N = 17]). Functional and cognitive out-
Received: September 19, 2019 comes were assessed at admission and discharge using the Glasgow Outcome Scale, the
Accepted: January 16, 2020 Early Rehabilitation Barthel Index, the Disability Rating Scale, the Rancho Los Amigos Lev-
Published: February 5, 2020 els of Cognitive Functioning, the Functional Ambulation Classification Scale and the modified
Rankin Scale. Confirmed recovery of conscious awareness was based on CRS-R criteria.
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
process; therefore, we enable the publication of Results
all of the content of peer review and author CMD patients were significantly associated with better functional outcomes and potential for
responses alongside final, published articles. The
editorial history of this article is available here:
improvement than DOC. Furthermore, outcomes of CMD patients did not differ significantly
https://doi.org/10.1371/journal.pone.0228474 from those of non-DOC. Using the CRS-R scale only; approximatively 30% of CMD patients
did not recover consciousness at discharge.
Copyright: © 2020 Jöhr et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which Interpretation
permits unrestricted use, distribution, and
Our findings support the fact that patients presenting with CMD condition constitute a sepa-
reproduction in any medium, provided the original
author and source are credited. rate category, with different potential for improvement and functional outcomes than patients
suffering from DOC. This reinforces the need for CMD to be urgently recognized, as it may
Data Availability Statement: All relevant data are
within the paper and its Supporting Information directly affect patient care, influencing life-or-death decisions.
files.

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 Recovery in cognitive motor dissociation

Funding: The Gianni Biaggi de Blasys Foundation Introduction

provided support in the form of contribution to the
salary for author [JJ], but did not have any Severe brain damage entails multiple outcomes from brain death, disorders of consciousness
additional role in the study design, data collection (DOC), disability without alteration of consciousness, to complete recovery. Prognosticating
and analysis, decision to publish, or preparation of the degree of functional and cognitive impairment when treating brain-injured patients
the manuscript. depends on a number of critical factors that encompass the etiology of injury, the concomitant
Competing interests: The authors have declared medical complications and the duration of coma [1].
that no competing interests exist. Three ascending levels of DOC have been clinically identified using behavioral criteria:
coma [1], unresponsive wakefulness syndrome (UWS) [2] and minimally conscious state
(MCS) [3]. These states exist as a continuum through which patients may or may not transi-
tion sequentially. Comatose patients are unarousable and unresponsive. UWS patients reco-
ver arousal (i.e., eyes opening), but have no evidence of awareness. Patients in MCS show
minimal but definite behavioral signs of self and environmental awareness, yet lack the ability
to communicate functionally.
Over the past decade, supplementary approaches using neuroimaging and electrophysio-
logical techniques detected conscious awareness when behavioral examination suggested
absent or low-level responsiveness–a phenomenon whose proposed name is cognitive motor
dissociation (CMD) [4–6]. A recent systematic review and meta-analysis reported that approx-
imately 15% of patients clinically diagnosed with UWS demonstrated preserved cognitive
ability to follow commands [7].
Total or partial block of a patient’s intentional responses from underlying motor, verbal
or drive deficits could prevent detection of voluntary behavior, leading to erroneous quanti-
fication and interpretation of the patient’s state in the acute stage. Indeed, as the current
standard of neurobehavioral examination (i.e., the Coma Recovery Scale-Revised, CRS-R
[8]) has stringent criteria for defining consciousness, clinical underestimation of consci-
ous awareness may occur. In this context our group developed a new behavioral assessment
strategy, the Motor Behavior tool (MBT) [9] that we recently revised and validated as a
stand-alone form, MBT-r [10], to unveil subtle behavioral evidence of residual cognition
not detected by the CRS-R. Its simple design values any intentional motor signs, as well as
takes into account concomitant causal pathologies and patterns of motor abnormalities as
a reflection of extensive bilateral forebrain lesions [1]. This tool demonstrated its ability to
identify clinically patients with behavioral signs of potential CMD and distinguish them
from DOC patients [10].
Studies addressing the outcomes of DOC states documented different prognostic values.
Coma carries a grave prognosis [11]. Anoxic injuries have a far less optimistic prognosis than
traumatic injuries [12, 13]. A more favorable prognosis is associated with MCS (as opposed
to UWS) regarding recovery of consciousness [14, 15]. The potential for recovery of functional
independence in ambulation and activities of daily living in MCS appears crucial in the first
three months [16]. To date, no longitudinal study specifically characterized the pattern of func-
tional/cognitive recovery in patients presenting potential CMD using careful clinical assess-
ments in the acute rehabilitation setting.
In the present study, we investigated the functional and cognitive outcomes in early inten-
sive neurorehabilitation and compared the recovery patterns of patients with potential clinical
CMD detected using the MBT/MBT-r, DOC (i.e., coma, UWS, MCS) and non-DOC in the
acute phase. We hypothesized that patients with CMD will present noticeable and greater
gains in functional and cognitive status during inpatient rehabilitation, compared to the DOC
group.

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 Recovery in cognitive motor dissociation

Methods
Participants
In the period from November 2011 to August 2018, all consecutive patients admitted to the
acute neurorehabilitation unit of the University Hospital of Lausanne (CHUV, Lausanne,
Switzerland) were included. Inclusion criteria were: 1) age sixteen or older; 2) severe acquired
brain injury requiring an intermediate care structure; 3) Early Rehabilitation Barthel Index
(ERBI) [17] < 30. Brain injuries include traumatic brain injury (TBI) and non-traumatic brain
injury (non-TBI). Non-TBIs include vascular injuries, anoxia, encephalopathy and neoplasm.
We excluded subjects suffering from non-neurological disorders, neuromuscular disturbances
and diseases involving the peripheral nervous system such as Guillian-Barré Syndrome, critical
illness polyneuropathy or spinal muscular atrophy.
During the stay in the acute neurorehabilitation unit, patients underwent an individualized
intensive rehabilitation program of at least 3 hours daily, 5 days a week, according to their clin-
ical condition. The rehabilitation program included physical, occupational, neuropsychologi-
cal, outdoor [18] and speech therapies.
The Ethics Committee of Lausanne (CER-VD, Cantonal Commission on Ethics in Human
Research) approved the protocol of the study (142–09). According to the Declaration of Hel-
sinki, the patients’ legal representatives were informed and provided written consent for inclu-
sion in the study. The patient provided his or her informed consent if they had decisional
capacity.

Procedure
At admission and at weekly follow-up evaluations, patients were assessed neurobehaviorally by
experienced physicians and a neuropsychologist from the acute neurorehabilitation unit using
the French version of the Coma Recovery Scale-Revised (CRS-R) [19]. Just before admission
to the acute neurorehabilitation unit, or on entry, the assessment was complemented with the
MBT or MBT-r, according to the routine clinical diagnosis guidelines developed by the acute
neurorehabilitation unit for the admission procedure. MBT/MBT-r uses an easy dichotom-
ous scoring method to identify signs of residual cognition/conscious awareness as previously
described in details [10]. Based on CRS-R and MBT/MBT-r, we therefore categorized patients
as either suffering real alteration of consciousness (i.e., DOC, ranging from coma to UWS and
MCS) or as presenting with potential clinical CMD (i.e., patients whose conscious awareness is
preserved according to MBT/MBT-r yet not clinically identified using the CRS-R due to severe
motor defects). Patients able to interact adequately were categorized as non-DOC.

Outcome measurements
Functional and cognitive evaluation was ascertained by the Glasgow Outcome Scale (GOS)
[20], Early Rehabilitation Barthel Index (ERBI) [17], Disability Rating Scale (DRS) [21],
Rancho Los Amigos Levels of Cognitive Functioning (LCF) [22], Functional Ambulation
Classification Scale (FAC) [23] and modified Rankin Scale (mRS) [24] at admission and dis-
charge from the acute neurorehabilitation unit by a skilled neuropsychologist. For patients
admitted to the unit between November 2011 and May 2016, we retrospectively collected
data using the electronic medical records, interdisciplinary therapeutic reports and video-
recordings of the complete neurological status of each patient at admission and discharge.
Demographics, injury type, days from injury to unit admission, length of stay, diagnostic
imaging were extracted from the electronic medical records.

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 Recovery in cognitive motor dissociation

We documented recovery of consciousness based on CRS-R criteria of functional use of

objects and/or functional communication with correct answers to six simple questions by a
yes/non-verbal response or by a communication code.

Statistical analyses
Changes from admission to discharge. All scores at admission and discharge were
dichotomously categorized as poor or good according to literature. Good score/category
were considered as GOS >3, ERBI � -75, DRS � 11, LCF � 6, FAC � 2 and mRS � 3. For
each measurement, we compared improvement and decreased scores with a McNemar Chi
squared test. Moreover, we computed proportion of improvement among the poor scores at
admission.
Differences between the groups. For each response variable, we estimated the group
means of the values of the responses measured at discharge with a multivariable linear regr-
ession. Each regression was adjusted for the corresponding response variable measured at
admission and for age, sex and TBI or non-TBI. As the variable FAC scale is not measured
at admission, the regression for this variable was only adjusted for age, sex and TBI or not.
As an alternative analysis, we considered for each response variable, not the value at dis-
charge, but the difference between the latter and the value at the admission. In this case, only
age, sex and trauma variables are used as adjustment variables.
Sensitivity and specificity of the consciousness recovery diagnostic. Considering clini-
cal CMD as the positive issue between DOC and clinical CMD, we measured the sensitivity
and specificity of the consciousness recovery diagnostic based on functional CRS-R criteria.
We computed 95% Wilson’s confidence intervals for these proportions.

Results
One hundred and forty-one patients (87 males, mean age = 53.05±17.18 years) with severe
traumatic (n = 55), vascular (n = 63), anoxic (n = 12), various encephalopathies (n = 7) and
neoplasm (n = 4) fulfilled the inclusion criteria. Length of acute rehabilitation stay ranged
from seven to 77 days (mean length = 28.06 days) (Table 1).
Using the CRS-R only, we classified one hundred and twenty-four patients as DOC
(twenty-seven comatose, fifty-one UWS and forty-six MCS). Using the MBT/MBT-r in

Table 1. Means (and SD) or distribution of demographic, anamnestic and recovery of consciousness per groups designated using the Motor Behavior Tool in com-
plement to the Coma Recovery Scale-Revised.
Clinical CMD (N = 105) DOC (N = 19) Non-DOC (N = 17)
Age, y 54.4 (16.2) 40.6 (17.8) 58.2 (16.8)
Sex, F/M 66/39 11/8 4/13
Length of stay, d 29.6 (14.4) 29.3 (10.9) 20.8 (10.9)
Etiology TBI 41 11 3
Hemorrhagic 36 4 7
Ischemic 10 - 5
Anoxic 9 3 1
Toxic 5 1 1
Tumoral 4 - -
Time BI to unit admission, d 34.8 (106.5) 55.1 (18.8) 25.0 (19.3)
Recovery of consciousness (per CRS-R), Yes/No 75/30 1/18 na

CMD = cognitive motor dissociation; DOC = disorders of consciousness; TBI = traumatic brain injury; CRS-R = Coma Recovery Scale-Revised

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 Recovery in cognitive motor dissociation

complement, we categorized one hundred and five patients as presenting with clinical
CMD condition and only nineteen as real DOC state (seven comatose, ten as UWS, two
MCS). Seventeen were classified as non-DOC using both the CRS-R and the MBT/MBT-r
(Table 1).

Changes from admission to discharge

Outcome measurements at discharge for all groups are presented in details in Fig 1(A). A large
proportion of clinical CMD patients who presented scores considered as poor at admission,
had scores considered as good at discharge (26% to 73% according to the measurement). Addi-
tionally, no patient with a good score at admission dropped to a poor score at discharge. We
observed only improvement in the clinical CMD group and so the McNemar’s Chi-squared
test was highly significant for all measurements (all p<0.001, Table 2). Seventy-five (71.4%)
clinical CMD patients recovered consciousness according to CRS-R criteria during their reha-
bilitation stay (Fig 1B). From the thirty clinical CMD patients (28.6%) who did not recover
consciousness according to CRS-R criteria by discharge from acute rehabilitation, five (16.7%)
reached DRS scores �11 (corresponding to good outcome), two (6.7%) obtained a FAC score
of two (corresponding to good outcome) and one (3.3%) patient obtained an ERBI score >30
(corresponding to good outcome) at discharge. Three clinical CMD patients died prior to dis-
charge from acute rehabilitation without recovering consciousness according to CRS-R
criteria.

Differences between the groups

We observed a clear difference in means (crude and adjusted) between the DOC and the clini-
cal CMD group for all response variables measured at discharge (all p-values < .001, Table 2).
At the same time, none of the adjusted differences between the clinical CMD and non-DOC
(control group) was statistically significant.
The analyses of the differences between discharge and admission response variables gave
similar results (not shown).
We did not observe any effect of etiology on the adjusted differences between groups.

Sensitivity and specificity of the consciousness recovery diagnostic

Considering clinical CMD as the positive issue between DOC and clinical CMD, the con-
sciousness recovery diagnostic based on functional CRS-R criteria has a sensitivity of 0.71
(0.62;0.79) and a specificity of 0.94 (0.75;0.99).

Discussion
The present study sought to investigate the functional and cognitive outcomes during early
intensive neurorehabilitation of a large sample of patients with severe brain injuries, compar-
ing the recovery patterns of individuals clinically identified as presenting with potential CMD,
to DOC and non-DOC patients. Overall, we demonstrated a strong improvement trajectory of
functional/cognitive recovery from admission to discharge for the clinical CMD group, which
significantly differed from the DOC group.
The reported findings supported our expectation regarding differential recovery patterns
of the clinical CMD, DOC and non-DOC groups. We observed poor functional and cogni-
tive outcomes for individuals with DOC, which was significantly different to that of the clini-
cal CMD group. This observation is consistent with other previous longitudinal studies in
DOC patients showing a time course of recovery extending over considerable periods of

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 Recovery in cognitive motor dissociation

Fig 1. Scores and categories on the outcome measurements and recovery of consciousness according to Coma
Recovery Scale-Revised criteria at discharge. Patients are categorized into three groups according to initial
neurobehavioral diagnosis at admission using the Coma Recovery Scale-Revised and the Motor Behavior Tool: clinical
Cognitive Motor Dissociation (CMD); Disorders of Consciousness (DOC); Non-DOC. (A) Score on the Glasgow
Outcome Scale (GOS) range from 1 to 5, with 5 indicating good recovery; Category on the Early Barthel Index (ERBI)
range from -325 to 100, with 100 indicating complete functional independence; Category on the Disability Rating Scale
(DRS) range from 0 to 29, with 0 indicating absence of disability; Category on the Rancho Los Amigos Levels of
Cognitive Functioning (LCF) range from 1 to 10, with 10 indicating modified independent; Category on the Functional
Ambulation Classification Scale (FAC) range from 0 to 5, with 5 indicating ambulator-independent; Score on the
modified Rankin Scale (mRS) range from 0 to 6, with 0 indicating no symptoms. Good outcomes were considered as
GOS > = 4, ERBI � -75, DRS< = 11, LCF � 6, FAC � 2 and mRS � 3. The red range corresponds to score/category
considered as poor. The blue range corresponds to score/category considered as good. (B) Recovery of Consciousness
according to CRS-R criteria per CMD and DOC groups. UWS = unresponsive wakefulness syndrome; MCS = minimally
conscious state; EMCS = emergence from minimally conscious state.
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time [14, 16, 25, 26], and clearly longer than the average time of rehabilitation in our unit. It
is noteworthy that there was no significant differences in outcomes comparing the clinical
CMD group with non-DOC individuals. Indeed, the data showed similar patterns of rapid
and good functional and cognitive evolution in both groups.

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 Recovery in cognitive motor dissociation

Table 2. Mean differences between the groups for the different response variables measured at the discharge.
Difference Crude estimate p-value Adjusted estimate p-value
GOS at discharge
CMD Non-DOC -0.22 (-0.63;0.18) .27 -0.27 (-0.62;0.08) .132
DOC Non-DOC -1.06 (-1.57;-0.54) < .001 -1.06 (-1.59;-0.53) < .001
DOC CMD -0.83 (-1.21;-0.45) < .001 -0.79 (-1.19;-0.39) < .001
ERBI at discharge
CMD Non-DOC -35.66 (-89.44;18.12) .192 -16.19 (-69.32;36.95) .548
DOC Non-DOC -239.1 (-307.78;-170.43) < .001 -220.82 (-294.66;-146.97) < .001
DOC CMD -203.44 (-254.73;-152.16) < .001 -204.63 (-256.46;-152.8) < .001
DRS at discharge
CMD Non-DOC 3.98 (0.78;7.17) .015 1.02 (-2.27;4.3) .543
DOC Non-DOC 16.08 (12;20.16) < .001 11.89 (7.2;16.58) < .001
DOC CMD 12.1 (9.05;15.14) < .001 10.88 (7.78;13.97) < .001
LCF at discharge
CMD Non-DOC -1.06 (-1.97;-0.15) .023 -0.28 (-1.17;0.62) .544
DOC Non-DOC -4.54 (-5.7;-3.38) < .001 -3.41 (-4.72;-2.1) < .001
DOC CMD -3.48 (-4.35;-2.61) < .001 -3.13 (-4;-2.26) < .001
FAC at discharge
CMD Non-DOC -0.35 (-1.02;0.31) .298 -0.57 (-1.15;0) .051
DOC Non-DOC -1.59 (-2.44;-0.74) < .001 -2.33 (-3.11;-1.56) < .001
DOC CMD -1.24 (-1.88;-0.61) < .001 -1.76 (-2.33;-1.19) < .001
mRS at discharge
CMD Non-DOC 0.24 (-0.26;0.74) .341 0.24 (-0.19;0.67) .276
DOC Non-DOC 1.31 (0.67;1.95) < .001 1.61 (1.02;2.21) < .001
DOC CMD 1.07 (0.59;1.55) < .001 1.38 (0.96;1.79) < .001

The adjusted differences are computed using linear regression. The adjustment variables are the values at admission (excepted for FAC), the age, sex and traumatic
status (TBI or non-TBI). Crude estimates of the differences (i.e. without any adjustment) are given for comparison. All differences are given with 95% confidence
intervals. CMD = cognitive motor dissociation; DOC = disorders of consciousness; GOS = Glasgow Outcome Scale; ERBI = Early Barthel Index; DRS = Disability
Rating Scale; LCF = Rancho Los Amigos Levels of Cognitive Functioning; FAC = Functional Ambulation Classification Scale; mRS = Modified Rankin Scale.

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Altogether, these observations suggest the high potential for recovery of CMD patients and
are aligned with clinical and paraclinical expectations that the presence of residual cognition/
covert awareness may lead to a more favorable outcome [10, 27–30]. Residual cognition indi-
cates preserved high-processing integration [27, 31] suggesting that CMD individuals may
present a higher level of connected brain networks than those with DOC. CMD paradoxically
resembles more a non-DOC condition after brain injury, suggesting that CMD patients may
be able to rely on more resources to mobilize during the recovery course. Motivational drive
could also be considered as explanation for the improved rate of rehabilitation [32, 33]. If the
defect is motor-related rather than consciousness-based, intentional behaviors could be elic-
ited from motivational loops, such as the mesocortical dopamine pathways [34]. The individu-
ally tailored goal interventions as our acute rehabilitation program offers may help promote
motivational stimulation hence modulate neural activity of the loop, resulting in an increase
in adaptive goal-oriented and functional behaviors sustaining recovery.
Consistent with our hypothesis, a majority of patients in the clinical CMD group achieved
significant gains in all measures applied, although some persistent functional/cognitive deficits
were still observed at discharge. Considering cut-offs determining good and poor score/cate-
gory for each applied scale; it is noteworthy that good ratings at discharge were observed on

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 Recovery in cognitive motor dissociation

average for the ERBI, LCF and DRS in the clinical CMD group. These scales were specifically
designed to assess patients throughout their recovery and inform on their personal autonomy
and reinsertion into the community [21, 22, 35]. Moreover, they explore in a more complex
and detailed manner the different neuropsychological, motivational and functional aspects
sustaining recovery, which may explain their higher sensitivity to assess subtle differences in
CMD patients. For example, the FAC extends walking ability assessment as it covers the whole
spectrum of possibilities, hence providing details on functional walking independence. Addi-
tionally, the DRS design allows recognition of mental representations of daily activities ignor-
ing motor disabilities to perform them; hence can ascertain patients presenting a dissociation
between their awareness of an activity and their ability to perform it. Indeed, it is not possible
to take-into-account the level of mental independence and how the patient would be able to
function in his environment using only the GOS and mRS scores to describe the CMD evolu-
tion pattern. A large majority of CMD patients were classified into the “severe to moderately-
severe disability” categories at discharge from the acute neurorehabilitation unit, mainly
because they still needed physical help and post-acute neurorehabilitation. Although the
GOS and mRS are widely used as outcome measures, some reservations were expressed con-
cerning their sensitivity and reliability [36–38].
The importance of using outcome measures providing a more complete and comprehensive
picture of recovery is in accordance with a growing number of studies that underline application
of the International Classification of Functions (ICF) framework [39] when targeting rehabilita-
tion goals for individual patients in terms of function, capabilities and participation [40–43].
Another relevant point concerns the sensitivity and specificity of evidence of recovery of
consciousness recovery according to CRS-R criteria of individuals presenting with clinical
CMD based on MBT. It proved to be more specific than sensitive with approximatively 30%
of clinical CMD patients not recovering consciousness if assessed only by the CRS-R, implying
that the recognition of overt consciousness recovery might be underestimated for a significant
number of conscious patients. Indeed, several clinical audits have exposed the particular diffi-
culty of accurately assessing low responsive patients and pointed out a persistent misdiagnosis
(30–40%) and outcome unpredictability when inappropriate scales are used [44, 45]. Behav-
ioral assessment can be limited by underlying deficits and concomitant factors (e.g., polyneur-
omyopathy, tracheostomy, fluctuation of vigilance, global aphasia) [46]. Most importantly,
severe damage to the motor system that affects motor planning and efferent motor pathways
may prevent partially or totally a patient from clinically displaying any voluntary responses,
thus invalidating the assessment.

Study limitations
The present study has several limitations. First, we categorized patients as presenting with
potential CMD solely based on clinical observations from the MBT rating. We did not per-
form active mental-imagery tasks according to the acknowledged operational definition of
CMD to confirm our clinical diagnosis [4]. Further studies should develop a synergistic
combination of clinical and paraclinical testing to provide exhaustive and objective mea-
sures of covert awareness/residual signs of cognition. Second, the differentiation of CMD
subtypes was not performed in this study. As previously proposed, several co-existing mech-
anisms may lead to a preserved cognitive capacity strongly dissociated from motor function
(i.e., preservation of cerebral functional integrity with specific damage to the corticothalamic
system, lack of executive motor functions following damage to the forebrain, motor efferent
loss following prominent damage to the brainstem, or in cases of critical illness polyneuro-
pathy) [47–50]. We should consider in future analyses, whether specific subtypes show

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 Recovery in cognitive motor dissociation

different recovery. Third, the retrospective part of the outcome measurements was assessed
with a non-standardized administration that could affect measurement error and therefore
reliability. Nonetheless, we expect potential effect to be minimized by the thorough review
of each patient’s clinical reports and video-recorded complete neurological examinations
at admission and discharge by a trained clinician. Additionally, we did not monitor medical
complications occurring during the patient’s stay, nor investigate their possible impact on
outcomes; however, we reported only three cases of death in this study. Similarly, we col-
lected the measurements at two time points, which did not allow us to determine the recov-
ery course during hospitalization. Last, the mono-centric nature of the present study and
the limited sample size of the group of DOC patients might limit its generalization. Hence,
multi-centric longitudinal studies of larger patient samples and with accurate monitoring
of medical complications and course of recovery might allow for a fine-grained analysis of
the overall recovery patterns of individuals with CMD compared to those with disorders of
consciousness.

Conclusion
Notwithstanding the above limitations, our data suggest that a large number of patients with
potential clinical CMD admitted to acute inpatient neurorehabilitation make rapid functional
progress and meaningful cognitive changes over a relatively short period in hospital. Our find-
ings support the concept that clinical CMD patients detected using the MBT constitute a sepa-
rate category of patients with different potential for improvement and functional outcomes
than patients suffering from DOC. This reinforces the need for them to be recognized as it
could have a direct impact on patient care, potentially leading to better therapeutic and re-
integrative interventions and influencing life-or-death decisions at an early stage.

Supporting information
S1 File.
(XLSX)

Acknowledgments
We thank Melanie Hirt for proofreading the manuscript.

Author Contributions
Conceptualization: Jane Jöhr.
Data curation: Jane Jöhr.
Formal analysis: Jérôme Pasquier.
Funding acquisition: Karin Diserens.
Investigation: Jane Jöhr, Floriana Halimi.
Supervision: Alessandro Pincherle, Nicholas Schiff, Karin Diserens.
Visualization: Jérôme Pasquier.
Writing – original draft: Jane Jöhr, Floriana Halimi, Jérôme Pasquier.
Writing – review & editing: Alessandro Pincherle, Nicholas Schiff, Karin Diserens.

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 Recovery in cognitive motor dissociation

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