498

CLINICAL NOTE

Neuropsychologic Assessment and Cognitive Rehabilitation in a
Patient With Locked-In Syndrome and Left Neglect
Luigi Trojano, MD, Pasquale Moretta, PsyD, Anna Estraneo, MD, Lucio Santoro, MD
ABSTRACT. Trojano L, Moretta P, Estraneo A, Santoro L.
Neuropsychologic assessment and cognitive rehabilitation in a
patient with locked-in syndrome and left neglect. Arch Phys
Med Rehabil 2010;91:498-502.
We describe a patient affected by severe incomplete
locked-in syndrome (LIS) and left neglect caused by a combination of vascular lesions. Our patient’s neglect prevented the
use of augmentative communication devices based on a computerized eye-tracker system. For this reason, we adapted a
visual scanning training for neglect rehabilitation. At the end of
the rehabilitative training, the patient had regained full exploration of the monitor and could use the eye-tracker system for
communicative purposes. This case report shows that specific
rehabilitative approaches can be devised in severely disabled
LIS patients with additional brain lesions and specific cognitive
defects.
Key Word: Rehabilitation.
© 2010 by the American Congress of Rehabilitation
Medicine
OCKED-IN SYNDROME IS characterized by quadripleL
gia and anarthria with preserved consciousness, cognitive
functions, and vertical eye movements. Patients affected by
1,2

this classic form of LIS most often show an ischemic lesion in
the ventral pons.3 Some patients may present other residual
movements, such as horizontal eye movements and small head
rotation; these cases are diagnosed as “incomplete” LIS and are
caused by lesions encroaching on the ventral pons as well.3 LIS
patients interact with the environment thanks to yes-no eye
code responses, but brain-computer interface devices can exploit patients’ eye movements for communicative purposes and
for interaction with the environment.4,5 However, additional
brain lesions may determine cognitive defects hindering the use
of technological systems.6-8
In the present article, we describe a patient affected by
severe incomplete LIS and left neglect caused by a combination of vascular lesions. Unilateral spatial neglect, frequently
associated with right brain damage, consists in the failure to
report, respond, or orient toward stimuli in the contralesional
side of space.9 Typically, patients with neglect show prolonged
observation times in the ipsilesional side during visual search,
reading, or free viewing tasks; in such patients, contralesional
saccades are fewer and slower to initiate with respect to ipsile-

From the Neuropsychology Lab, Department of Psychology, Second University of
Naples (Trojano); Salvatore Maugeri Foundation, IRCCS, Scientific Institute of
Telese Terme (BN) (Trojano, Moretta, Estraneo); Department of Neurological Sciences, Federico II University (Santoro), Naples, Italy.
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.
Reprint requests to Luigi Trojano, MD, Dept of Psychology, Second University of
Naples, Via Vivaldi 43, 81100 Caserta, Italy, e-mail: luigi.trojano@unina2.it.
0003-9993/10/9103-00376$36.00/0
doi:10.1016/j.apmr.2009.10.033

Arch Phys Med Rehabil Vol 91, March 2010

sional saccades.10,11 Accordingly, left neglect prevented efficient employment of technological aids in our patient. Faced
with this severe clinical picture, we developed a specific rehabilitation training aimed at allowing our patient to use an
eye-tracker system for communicative purposes. At the end of
the rehabilitation period, the patient had regained her ability to
explore the monitor and interact with the computerized system
to express her needs and feelings.
CASE REPORT
A 57-year-old right-handed woman developed multiple ischemic lesions secondary to endovascular embolization of a
ruptured aneurysm of the right middle cerebral artery. After
surgery, the patient presented prolonged unresponsiveness and
was transferred to an intensive care unit where a score of 8 on
the Glasgow Coma Scale12 was recorded. The patient remained
in a coma for about 20 days and eventually evolved to a
vegetative state.13 One month after surgery, brain magnetic
resonance imaging showed lesions in ventral pons and in deep
periventricular white matter of the right temporoparietal region
(fig 1).
Two months after onset, the patient was admitted in our
department where a comprehensive neurorehabilitation program was started. On admission, a minimally conscious state
was diagnosed14 because the patient showed inconsistent but
reproducible sustained horizontal and vertical eye movements
towards salient acoustic or visual stimuli (eg, visual pursuit of
her family members) without any other movement. At that
time, the patient was assigned a score of 2 on the Glasgow
Outcome Scale-Extended15 and a score of 3 on the Levels of
Cognitive Functioning Scale.16
In subsequent months, the patient’s responsiveness gradually
improved, and, at 6 months after onset, the patient gazed
towards people speaking to her and had learned to use an
eye-code communication system by keeping her eyes closed to
mean affirmative responses and looking up for negative responses. At that time, she had recovered spontaneous respiration through a tracheostomy tube and was fed by means of
enteral tube nutrition; she showed spared vertical and horizontal conjugated eye movements but showed lower cranial nerve
palsy, severe dysphagia, and anarthria. No voluntary head or
limb movement was possible, and there was presence of hyperreflexia and pyramidal signs; there was also sphincter incontinence. The patient could detect and localize somatosensory stimuli (touch) delivered to either side of her body. A
simplified confrontation procedure did not reveal clinically
evident visual field defects. The patient reacted to emotional
stimuli with bursts of laughing or crying and could answer
simple verbal and written questions via the eye-code system
although her responses were slow and laborious (Glasgow
Outcome Scale-Extended⫽3, Levels of Cognitive Functioning

List of Abbreviations
LIS

locked-in syndrome

NEGLECT AND LOCKED-IN SYNDROME, Trojano

499

Fig 1. T1 sagittal (A), T1 axial (B), and T2 coronal (C) magnetic resonance scans showing T1-hypointense and T2-hyperintense ischemic
lesions in the ventral pons (pointed to by a single arrow) and in deep periventricular white matter of the right temporoparietal region
(pointed to by a double arrow).

Scale⫽6). Repeated formal functional assessment by means of
the Coma Recovery Scale–Revised17 Italian version18 revealed
that the patient attended to examiner’s orders throughout the
evaluation (arousal scale: 3/3), comprehended auditorily and
visually presented sentences (communication scale: 2/2), consistently complied with auditorily perceived commands requiring eye responses (auditory function scale: 4/4), and could
visually recognize objects (visual function scale: 5/5) but presented only flexion withdrawal limb movements to painful
stimuli (motor function scale: 2/6) and oral reflex movements
on lip stimulation (oromotor/verbal function scale: 1/3). These
features clearly showed that our patient had recovered from a
minimally conscious state although she presented a very severe
motor impairment consistent with the diagnosis of incomplete
locked-in syndrome (3). However, during formal assessment
and in daily life, the patient tended to gaze preferentially
toward her right side and showed apparent difficulties and
delay in moving her eyes toward her left side, compatible with
the presence of left neglect in association with the incomplete
LIS. Such a combination of defects did not allow an extensive
assessment of cognitive functions with the procedures specifically devised for LIS patients.6,7 Within the limits imposed by
ocular fatigue on communicative eye movements, she appeared
to be oriented in time and space and correctly replied to simple
questions about word meaning and public events (semantic
memory) and about past and recent events of her personal life
(episodic memory); the attempts at assessing attention, reasoning, and executive functions with visuospatial material were
hampered by the apparent visual exploration bias.
Because our patient had regained consistent and reproducible responsiveness, showed rather selective cognitive impairments, and could communicate only by means of eye code
responses, we decided to use a computerized device based on
eye-tracker technology to exploit her functional interactive
skills. The patient gave her informed consent to the study; the
study was approved by the local ethics committee.
BASELINE ASSESSMENT OF
COMPUTER-INTERFACE USAGE
As a first step toward the use of augmentative communication devices, we assessed the patient’s abilities to interact with
a computerized eye-tracker system, and we used the same

apparatus to quantify her apparent rightward bias in eye movements.
Methods
Apparatus. Eye movements were recorded by a computerized infrared eye-tracker systema with 50-Hz sampling frequency. The system is based on a 17-in monitor around which
4 infrared illuminators and sensors are located. The system is
connected to a personal computer for task presentation and
recording and analysis of eye-movement patterns. The patient
sat at a 60-cm distance from the monitor, which covered a
visual angle of 28°.
Procedure: interaction with the eye-tracker system. Three
tasks were given to assess the patient’s ability to use the
electronic device. In the first (calibration) task, the patient was
asked to pursue a colored circle slowly moving on the monitor
and to fix it whenever it stopped and flashed (5 locations tested
per trial, 5 trials for session). In the second task, the patient was
required to look at 12 graphic buttons (arranged in a 3 ⫻ 4 grid)
representing physical needs (eg, drinking, eating); 10 buttons
were randomly assessed in each session, 5 per side. In the third
task, the patient was asked to search for and fixate the letters on
a simplified keyboard; in each session 10 letters were assessed
on the left side, 10 in the central position and 10 on the right
side. Instructions and stimuli were verbally presented. All 3
tasks were given in a fixed order in each session, and sessions
were repeated 3 times a few days apart.
Eye-movement analysis. Two tasks were used for obtaining a representative measure of the patient’s ability to move her
gaze in spontaneous eye behavior. In the first task, the patient
was asked to explore pictures of animals centered on 1 half (left
or right) of the monitor while scrambled pictures (matched with
stimuli for chromatic scale) appeared on the opposite half. Ten
stimuli were presented on the left and 10 on the right half of
the screen in a pseudorandom order; visual exploration time
was set at 10 seconds per stimulus. In the second task, the
patient was asked to look at her relatives’ faces presented on 1
half of the screen while unfamiliar faces were shown on the
opposite side. As described previously, 10 target stimuli were
shown on the left and 10 on the right half of the screen in a
pseudorandom order; each image was presented for 10 seconds. Among eye-movement parameters, we took into account
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NEGLECT AND LOCKED-IN SYNDROME, Trojano

Table 1: Patient’s Correct Responses on Computer Usage Tasks
Before and After the Rehabilitative Program

Visual pursuit
Left side
Central position
Right side
Looking at graphic buttons
Left side
Right side
Fixating letters
Left side
Central position
Right side

First
Baseline

Second
Baseline

End
Treatment

0/30
2/15
25/30

0/30
1/15
26/30

18/30*
15/15*
30/30

5/15
14/15

5/15
13/15

12/15*
15/15

3/30
24/30
29/30

8/30
25/30
28/30

26/30*
29/30
30/30

NOTE. No significant difference was observed in distribution of
correct responses at the first and the second baseline for all measurements.
*Significantly different from respective baseline measurements
(Fisher exact test ⱕ.05, 2-tailed).

the number of fixations and the total observation time that best
express exploratory behavior in prolonged tasks.11 Both tasks
for eye movements were performed on 3 separate sessions a
few days apart in different periods of the day.
To verify spontaneous evolution of the clinical picture over
time and to get a further baseline assessment, the patient was
evaluated again with the same procedure 1 month after the first
evaluation.
Results and Comment
Computer-usage tasks showed that the patient could comply
with task instructions and was potentially able to interact with
the infrared eye-tracker system but was affected by a strong
visual exploration bias toward the right side (table 1). A similar
pattern was observed in the 2 tasks for the quantitative assessment of eye movements in which the number of fixations and
the total observation time showed a significant asymmetry in
the 2 hemifields (table 2).
One month after the first baseline assessment, virtually the
same results were obtained, without significant differences of
eye-movement parameters between the 2 evaluations (see tables 1 and 2). Such a stable asymmetry of visual exploration
undermined the efficient use of augmentative communication software and induced us to devise a specific rehabilitative training.

REHABILITATIVE TRAINING
On the basis of well-established recommendations for applying visual-scanning strategies in rehabilitative treatment of
visuospatial neglect,19 we implemented a traditional visual
scanning training20 for administration via the computerized
eye-tracker system.
Procedure
Using the same apparatus as in the previous section, we
devised progressive visual-scanning exercises. Stimuli consisted of colored circles (diameter: 5cm; visual angle: 4.7°)
displayed on a contrasting background. In the simplest exercises (level 1), stimuli appeared in a linear sequence from the
right to the left and persisted on the screen for a long time (10
seconds); more complex exercises implied progressively
shorter presentation times (level 2), a higher number of stimuli
(level 3), and nonlinear presentation sequences (level 4). At the
most complex level of difficulty (level 5), the number of
stimuli, presentation time, and stimulus location varied from
trial to trial and were not predictable. In each exercise, the
patient was required to search and fixate to the targets, and, in
case of failure, she was verbally encouraged to complete the
task. Time spent over targets was recorded in each exercise,
and when the patient performed at least 90% correct on 3
exercises of a given level, she was presented with exercises of
the next level of complexity. The training started about 7
months after stroke, and lasted 4 weeks, with four 40-minute
sessions per week.
Results and Comment
The patient gradually recovered her visual exploration skills
during the training. In early sessions, she could fixate to targets
only for 53% of the time at the first level of complexity. By the
second week, she performed well on the first 2 levels and was
45% correct at the third level. At the end of the training, she
could fixate to targets 85% of the time at the fifth level, thus
showing a task-specific improvement.
END-TREATMENT ASSESSMENT
To verify possible generalization of the patient’s task-specific improvements and in order to start using augmentative
communication software, about 10 days after the end of the
training (and about 9 months after stroke), we reassessed the
patient on the same tasks as at the baseline.

Table 2: A Quantitative Assessment of Patient’s Eye Movements Before and After the Rehabilitative Program

Animal task
Fixation count: right side
Fixation count: left side
Observation length: right side
Observation length: left side
Face task
Fixation count: right side
Fixation count: left side
Observation length: right side
Observation length: left side

First Baseline

Second Baseline

End Treatment

17.3⫾3.26
4.7⫾2.52*
457.13⫾205.47
413.35⫾172.69*

17.9⫾3.31
4.8⫾2.43
455.51⫾234.33
415.92⫾189.16*

18.5⫾3.54
14.6⫾3.61†
466.23⫾290.79
467.34⫾293.83†

18.6⫾4.12
3.7⫾2.48*
526.47⫾318.42
342.01⫾143.44*

18.3⫾3.96
4.2⫾2.67*
518.78⫾334.81
352.32⫾154.03*

18.1⫾3.44
15.7⫾3.55†
500.80⫾359.48
401.01⫾232.01†

NOTE. Values are mean ⫾ SD unless otherwise indicated. No significant difference was observed between the first and the second baseline
for all measurements (paired t tests).
*Significantly different from the right side (paired t29 tests, Pⱕ.001 according to Bonferroni correction, 2-tailed).
†
Significantly different from the 2 respective baseline measurements (paired t29 tests, Pⱕ.001 according to Bonferroni correction, 2-tailed).

Arch Phys Med Rehabil Vol 91, March 2010

NEGLECT AND LOCKED-IN SYNDROME, Trojano

Results and Comment
The patient showed an obvious improvement of her ability to
scan the visual array of needs and letters although she occasionally failed in fixating the leftmost stimuli (see table 1). The
quantitative assessment of eye movements showed a significant
change of number of fixations and observation time on the left
side (see table 2).
DISCUSSION
LIS is a very disabling condition causing almost unbearable
burden for patients and their families, but it may be complicated by additional cognitive or neurologic defects in relation
to the extension, nature, and site of cerebral lesions.6-8 For
instance, in a small sample of 10 patients with chronic LIS, a
systematic neuropsychological assessment via a yes-no procedure revealed memory and attentional defects in 2 patients with
thalamic lesions associated with the pontine damage and executive defects and language comprehension impairments in 1
patient with additional frontal and temporal damage.6 The
patient described here showed an unfortunate combination of
brain lesions determining a severe incomplete LIS associated
with typical left neglect. This picture has never been reported
previously, but it represents the natural consequence of the
association of deep right temporoparietal damage21 with pontine lesions and could be recognized thanks to adequate assessment procedures.
In such cases special attention and further care and rehabilitative treatment are warranted. Actually, it has been underlined
that in LIS patients’ quality of life is entirely dependent on their
arduous communication with the environment. Any clinically
relevant cognitive deficit may reduce the efficiency of communication processes and the possibility of using the sophisticated
patient-computer interfaces permitting LIS patients to communicate and even to control their environment.22
To overcome additional limitations of the possibility to
interact with the environment, determined by neglect in our
patient, we devised a specific rehabilitative program tailored to
the patient’s clinical conditions. Manual or verbal responses
were impossible, so we had to limit the training program to a
visual scanning rehabilitative paradigm, specifically adapted
for the eye-tracker system. Although we cannot estimate the
role of spontaneous recovery in the evolution of the clinical
picture, the positive outcome in our patient would be in line
with controlled studies on neglect rehabilitation showing the
efficacy of visual scanning training.19 Recent studies warn that
visual scanning alone could have some limitations in neglect
rehabilitation, particularly as far as possible generalization is
concerned.23 However, in the present case, we obtained evidence suggesting that the training program improved the patient’s interaction with the eye-tracker system also on tasks
using different kinds of stimuli. In this sense, the improvement
of a visual scanning strategy was sufficiently generalized to
allow more efficient use of augmentative communication devices. From these findings, we cannot exclude that the patient
could still present defective explorative behavior on other kinds
of tasks, but this possibility could not be quantitatively verified
and was not particularly relevant for the patient’s clinical
conditions. Moreover, it is worth underlining that although the
time schedule of our study (2 baseline assessments 1 month
apart, end-treatment evaluation performed about 9 months after
stroke) minimized the possible weight of spontaneous recovery, the present results did not allow strong inferences about
the specific efficacy of our treatment because of the lack of
control conditions. However, our case report shows that reha-

501

bilitative approaches can be devised in severely disabled LIS
patients with additional brain lesions and cognitive defects.
In this perspective, it appears to be of paramount importance
that there is an accurate evaluation of cognitive abilities in LIS
patients, and, to this aim, specifically adapted testing procedures have been recently devised.6,24,25 In fact, specific cognitive defects have been observed even in LIS patients without
evidence of hemispheric lesions.6,24 For instance, in a recent
series of LIS patients with lesions centered on the brainstem,24
it has been shown that several cases may show defects in
relatively complex tasks involving complex sentence comprehension, mental calculation, and problem-solving abilities.
Therefore, it is evident that tailored rehabilitation programs
may be necessary to increase communication skills and to
improve the quality of life in LIS patients with or without
additional cortical lesions. We hope that the present case report
will stimulate new efforts in detecting neuropsychological impairments and in designing cognitive rehabilitation programs to
enable LIS patients to express their thoughts and feelings.21
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