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Assessment of visual fixation in vegetative and minimally conscious states

  • Haibo Di1, 2Email author,
  • Yunzhi Nie1,
  • Xiaohua Hu1, 3,
  • Yong Tong1, 4,
  • Lizette Heine2,
  • Sarah Wannez2,
  • Wangshan Huang1,
  • Dan Yu1, 3,
  • Minhui He1,
  • Aurore Thibaut2,
  • Caroline Schnakers2 and
  • Steven Laureys2
Contributed equally
BMC Neurology201414:147

DOI: 10.1186/1471-2377-14-147

Received: 17 January 2014

Accepted: 8 July 2014

Published: 16 July 2014

Abstract

Background

Visual fixation plays a key role in the differentiation between vegetative state/unresponsive wakefulness (VS/UWS) syndrome and minimally conscious state (MCS). However, the use of different stimuli changes the frequency of visual fixation occured in patients, thereby possibly affecting the accuracy of the diagnosis. In order to establish a standardized assessment of visual fixation in patients in disorders of consciousness (DOC), we compared the frequency of visual fixation elicited by mirror,a ball and a light.

Method

Visual fixation was assessed in eighty-one post-comatose patients diagnosed with a MCS or VS/UWS. Occurrence of fixation to different stimuli was analysis used Chi-square testing.

Result

40 (49%) out of the 81 patients showed fixation to visual stimuli. Among those, significantly more patients (39, 48%) had visual fixation elicited by mirror compared to a ball (23, 28%) and mirror compared to a light (20, 25%).

Conclusion

The use of a mirror during the assessment of visual fixation showed higher positive response rate, compared to other stimuli in eliciting a visual fixating response. Therefore, fixation elicited by a mirror can be a very sensitive and accurate test to differentiate the two disorders of consciousness.

Keywords

Disorders of consciousness Vegetative state Unresponsive wakefulness syndrome Minimally conscious state Visual fixation

Background

At present, there are many behavioral scales available for the evaluation of visual fixation in patients in post-comatose states. These disorders of consciousness (DOC) include VS (now also coined unresponsive wakefulness syndrome) [1], and MCS [2]. Indeed, the scales all use different stimuli to assess visual fixation: the Coma Recovery Scale-Revised (CRS-R) recommends using a brightly colored or illuminated object. The Sensory Modalities Assessment and Rehabilitation Technique (SMART) uses a photo of a baby. The Disorders of Consciousness Scale (DOCS) uses an object (e.g., ball). The Coma/Near Coma Scale employs flashes of light. The Wessex Head Injury Matrix (WHIM) uses a person, and the Western Neuro Sensory Stimulation Profile (WNSSP) only observes spontaneous eye contract (for references see review by Majerus and colleagues [3]).

The CRS-R is at present the most sensitive tool to differentiate between the different states of (un) consciousness [4]. However, visual behavior has been shown to still differ greatly with different stimuli [5]. Vanhaudenhuyse et al. used a mirror and other neutral stimuli to assess visual pursuit in patients with DOC, and showed that a mirror provokes visual pursuit more frequently in patients, due to the self-referential value [6]. Specifically, some patients showed visual pursuit when using a mirror, but not with other stimuli such as a colored ball or a bright light. To our knowledge, the increased effect of a mirror has not yet been investigated in visual fixation. Hence, in this study we choose the visual stimuli described in the CRS-R Administration and Scoring Guidelines: a yellow ball (as brightly colored object), a light (as illuminated object) and a mirror (as self-referential object) to induce visual fixation in patients with DOC. We will compare the ability of different stimuli in eliciting visual fixation in order to optimize the stimulation during the assessment of consciousness.

Method

Eighty-one patients recovering from coma were recruited from Wujing Hospital of Hangzhou City, Hangzhou, China, and were free of sedative drugs. Each patient was assessed in a sitting position. If patients exhibited sustained eyelid closure and/or stopped following commands for a period of at least one minute, a standardized arousal facilitation protocol (i.e., deep pressure stimulations from the facial muscles to the toes) was employed in order to prolong the time the patients maintained aroused, and this protocol was re-administered if patients showed sustained eye closure again or behavioral responsiveness ceased despite sustained eye opening [7]. Visual fixation was evaluated through the standardized methodology as described in the CRS-R [7]. In brief, a visual stimulus (i.e., a mirror (round, diameter = 15 cm), a ball (yellow, diameter = 6 cm) and a continuous burning light (power = 1.2w)) was presented by the experimenter in front of the patient’s face (15–20 cm) and then rapidly moved above and below the horizontal midline, as well as to the right and left of the vertical midline. Thus the stimulus moved once in each direction (4 trials). The order of presentation was randomized using a “random number” procedure in Excel. Visual fixation is defined as a movement of the eyes from the initial fixation point with a re-fixation on the new target location for more than 2 seconds. At least 2 episodes of fixation are required for the scoring of visual fixation. Differences between fixation as assessed by mirror, ball and light were measured using Chi-square test. Results were considered significant at p < 0.01. Eye movements were observed before administration of stimuli to avoid scoring of spontaneous movements. For example, for subjects with roving eye movements the stimuli were presented in a manner unrelated to pre-existing spontaneous eye movements. When any doubt existed, the movement was not scored. Patients’ visual reaction was visually judged by one experienced assessor who was blinded to diagnosis (e.g., did not do CRS-R assessment), and was unaware of the hypothesis of this study, and the same examiner conducted the trials in all patients. Clinical diagnosis was made according to the Aspen work group criteria for disorders of consciousness [2] and based on the CRS-R assessments [7] performed by two trained and experienced neuropsychologists. The study was approved by the Ethics Committee of Hangzhou Normal University and Wujing Hospital which complies with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Informed consents were obtained by the patient’s legal surrogates.

Result

Of the 81 patients (69 males; mean age 45 (SD17) years), 38 (47%) were diagnosed as in a VS/UWS and 43 (53%) in a MCS. Mean time between injury and assessment was 9 months (SD15). Etiology was traumatic in 59 (73%) and non-traumatic in 22 (27%) patients (Table 1). 40 (49%) out of the 81 patients showed visual fixation, which were all diagnosed as in a MCS. Of the patients who showed visual fixation, 39 (48%, 28 traumatic) showed fixation to a mirror, 23 (28%, 15 traumatic) showed fixation to a ball, and 20 (25%, 15 traumatic) showed fixation to light. Except one, no patient showed fixation to the ball or the light without the mirror. The global value of the observed Chi-2 statistic between the mirror, ball and light was 27.22, and p < 0.001. When doing the local comparisons between the three stimuli, the mirror elicited significantly more visual fixation compared to the two other stimuli (p < 0.001), while the difference between the frequency of visual fixation assessed by a ball and a light was not significant (Figure 1). The occurrence of visual fixation had no significant relationship with etiology or time since insult (p > 0.05). The overall behavioral responsiveness as assessed by the CRS-R total score tended to be higher when patients fixated on all three stimuli (n = 17) compared to no fixation (n = 41) (Table 1). In fact, patients showing a response to the mirror, the ball and the light had a mean CRS-R total score 9.6 whereas patients showing no fixation to any of the stimuli had a mean score 4.8, and patients having fixation to two (n = 8) or one (n = 15) stimuli showed intermediate mean CRS-R total scores of respectively 9.3 and 8.3. Correlation analysis showed that the rank correlation coefficient between the number of stimuli fixated by patients and the CRS-R total score was 0.743, p < 0.001. Multiple regression analysis did not show an effect of sex or age and the p values of the partial regression coefficient were 0.174 for sex and 0.553 for age.
Table 1

Clinical data of patients in VS/UWS and MCS

Patient

Gender

Aetiology

Time since injury**

CRS-R total score

Visual subscale score

Stimulation elicited positive visual fixation

MCS1

male

trauma

2

6

0

none

MCS2

male

trauma

6

6

1

none

MCS3

male

Non-trauma

12

8

1

none

MCS4*

male

trauma

3

5

3

mirror

MCS5*

male

trauma

4

5

3

mirror

MCS6*

female

trauma

1

6

3

mirror

MCS7*

male

Non-trauma

2

7

3

mirror

MCS8*

female

trauma

5

7

3

mirror

MCS9*

male

trauma

5

7

3

mirror

MCS10*

male

trauma

4

7

3

mirror

MCS11*

female

trauma

9

8

3

mirror

MCS12*

male

Non-trauma

119

8

3

mirror

MCS13*

male

trauma

33

9

3

mirror

MCS14*

male

trauma

3

9

3

mirror

MCS15*

male

trauma

7

10

4

mirror

MCS16*

male

trauma

4

13

3

mirror

MCS17*

male

trauma

7

16

4

mirror

MCS18

male

trauma

5

7

2

ball

MCS19

male

trauma

8

6

3

Mirror and ball

MCS20

male

trauma

9

7

3

Mirror and ball

MCS21

male

trauma

5

7

3

Mirror and ball

MCS22

male

trauma

27

8

3

Mirror and ball

MCS23

female

trauma

4

10

2

Mirror and ball

MCS24

male

Non-trauma

1

10

3

Mirror and light

MCS25

male

trauma

8

11

3

Mirror and light

MCS26

male

trauma

10

15

5

Mirror and light

MCS27

male

trauma

2

6

3

All three

MCS28

male

Non-trauma

2

6

4

All three

MCS29

male

trauma

3

7

3

All three

MCS30

female

trauma

37

8

3

All three

MCS31

male

Non-trauma

11

8

3

All three

MCS32

male

Non-trauma

2

8

2

All three

MCS33

male

trauma

12

8

3

All three

MCS34

female

Non-trauma

4

9

3

All three

MCS35

male

trauma

47

9

3

All three

MCS36

male

Non-trauma

31

9

3

All three

MCS37

female

trauma

12

10

3

All three

MCS38

female

Non-trauma

3

10

3

All three

MCS39

male

trauma

3

10

4

All three

MCS40

male

trauma

4

12

3

All three

MCS41

male

Non-trauma

12

13

4

All three

MCS42

male

trauma

6

15

4

All three

MCS43

male

Non-trauma

30

16

4

All three

VS1

male

trauma

5

1

0

none

VS2

female

Non-trauma

5

2

0

none

VS3

male

Non-trauma

11

2

0

none

VS4

male

trauma

3

2

0

none

VS5

male

trauma

9

2

0

none

VS6

male

trauma

1

3

0

none

VS7

male

Non-trauma

1

3

0

none

VS8

male

Non-trauma

5

3

0

none

VS9

female

trauma

1

3

0

none

VS10

male

trauma

6

3

0

none

VS11

male

trauma

7

3

1

none

VS12

male

trauma

3

4

1

none

VS13

male

trauma

8

4

0

none

VS14

male

trauma

4

4

1

none

VS15

male

trauma

8

4

0

none

VS16

male

trauma

6

4

1

none

VS17

male

trauma

3

4

1

none

VS18

male

Non-trauma

10

5

0

none

VS19

male

trauma

14

5

0

none

VS20

male

Non-trauma

3

5

0

none

VS21

male

trauma

5

5

0

none

VS22

male

trauma

9

5

0

none

VS23

male

trauma

8

5

1

none

VS24

male

trauma

4

6

0

none

VS25

male

trauma

3

6

0

none

VS26

male

Non-trauma

5

6

1

none

VS27

male

trauma

17

6

0

none

VS28

male

Non-trauma

5

6

1

none

VS29

male

Non-trauma

9

6

0

none

VS30

male

trauma

3

6

1

none

VS31

female

trauma

3

6

0

none

VS32

male

trauma

4

6

0

none

VS33

male

trauma

5

6

0

none

VS34

male

trauma

2

7

1

none

VS35

male

Non-trauma

2

7

0

none

VS36

male

trauma

12

7

1

none

VS37

female

trauma

5

7

1

none

VS38

male

trauma

5

7

1

none

*MCS patients who only showed visual fixation to a mirror but not to a ball and a light.

**Time since injury in months.

Figure 1

Visual fixation. Number of patients in VS/UWS and MCS showing fixation to visual stimuli (n = 40) as a function of the employed stimulus (mirror, ball and light).

Fourteen patients (MCS 4 to 17 labeled with “*” in Table 1) showed visual pursuit but no fixation when assessed with only a bright colored or illuminated object as stated in the CRS-R operation. However, they showed visual fixation when a mirror was presented.

Discussion

The aim of the present study was to determine whether the assessment of visual fixation in patients recovering from coma is influenced by the choice of visual stimuli. We used a mirror, a colored ball and a light to assess visual fixation and compared the occurrences elicited by different stimuli. Our results showed that indeed the frequency of visual fixation in patients with DOC is related to the visual stimulus used. MCS patients tended to fixate significantly more on their own reflection (48%) as compared to fixation on a brightly colored (28%) and illuminated object (25%). As mentioned by Vanhaudenhuyse et al. [6], auto referential stimuli capture our attention and give rise to a sense of self-awareness in everyday social interactions. This is reflected in the cocktail party phenomenon, which refers to the fact that one’s own name can easily catch his/her attention in a cacophony of conversations and background noise [8]. Similarly, one’s own name induced a larger response in patients with DOC as compared with neutral auditory stimuli [9]. Seeing one’s own face also has similarly strong attention grabbing properties [10]. Functional imaging has previously shown activation of anterior and posterior midline structures (i.e., mesiofrontal and precuneal cortices) during presentation of one’s own face in healthy volunteers [11]. Interestingly, these areas are amidst the most metabolically impaired in patients in a vegetative state [12], possibly explaining why they cannot visual follow or fixate.

The occurrence of visual fixation seems to be related to the patient’s overall behavioral profile. VS/UWS patients showed no visual fixation, the more stimuli the patient showed fixation to the higher the CRS-R score was (i.e., fixation to 0, 1, 2 and 3 stimuli, obtained a score of 4.8, 8.3, 9.3 and 9.6, respectively). Due to clinical limitations we could not use an eye-tracker, to more objectively measure fixation. However, our results overlap with a study that used an eye tracking machine to assess visual tracking behavior and was able to differentiate MCS from VS/UWS [13]. In our group, only three out of 43 patients in MCS failed to show visual fixation. Neurological assessment showed that one of these 3 patients failed to eye blink to threat, indicating impaired brainstem reflexes. The remaining two patients had intact brainstem reflexes and reproducible but inconsistent command following, which could be explained by a visual impairment [14].

Our results showed that except one, all of the patients who responded to the ball and light also responded to the mirror. The one patient that showed visual fixation to the ball but not to the mirror or light. In this case, presentation of the mirror was the last stimulus and hence the fluctuating levels of arousal, generally observed in MCS, might account for the fixation on a ball in the absence of fixation on the mirror. One could argue that the order of presentation could have impacted the level of response of our patients. However, the stimuli were presented in a randomized order and not in a fixed order; suggesting that the high rate of response observed using the mirror cannot be explained by the order of presentation.

According to current guidelines for behavioral assessment, visual fixation differentiates unresponsive from minimally responsive [2]. The assessment of visual fixation according to these guidelines (e.g., use an object), failed to show fixating behavior in many of our subjects, while higher cognitive functions existed. This is inconsistent with the structuring principle of CRS-R. However, this phenomenon disappears when a mirror is used for the assessment of visual fixation. Therefore, using a mirror for visual fixation is sensitive and accurate in the differentiation between MCS and VS/UWS. These results are in line with earlier work emphasizing the use of a mirror in the evaluation of visual following [6]. Thus, we advise to use a mirror for the assessment of visual fixation, especially when visual following is observed using other stimuli. The clinical implications of our findings are important. More than 35% of the MCS patients with visual fixation only fixate on a mirror (and not on other objects). Hence, these patients would be misdiagnosed as being unresponsive when other sensory modalities fail to elicit a behavioral response. Our findings emphasize the importance of using a mirror when evaluating visual fixation in post-comatose states.

Although the use of a mirror is a strong and sensitive stimulus to elicit visual responses due to its self-referential value, we have not tested all possible stimuli as advised in other existing scales. As the CRS-R is currently considered as the gold standard in the assessment of disorders of consciousness [4], we chose the visual stimuli described in the guidelines (i.e., a colored ball or a bright light). We here advise to use a mirror in the assessment of visual fixation; however we cannot make any conclusions about the sensitivity and accuracy of other stimuli, like those mentioned in other existing scales. Future research should therefore focus on including more visual stimuli. Besides, in our study, we did not have the opportunity to collect follow-up data. Nevertheless, this could be done in the future. Indeed, as considering visual fixation as a sign of consciousness has been previously debated [15], future studies should investigate if patients showing visual fixation (detected using a mirror) present a more frequently full recovery of consciousness as compared to patients who do not show such behavior.

One could argue that using an eye-recorder could standardize the way in which the data are collected. However, the use of such method is difficult in our population. Patients recovering from coma often have brainstem lesions or ocular trauma that may affect eye-movements and complicate the use of an automated recording (often validated in healthy volunteers).

Conclusions

This study emphasizes the use of a mirror during the assessment of visual fixation, as shown by the higher positive response rate of the mirror, compared to other stimuli in eliciting a visual fixating response, adding to previous studies the importance of using auto-referential stimuli in patients with disorders of consciousness (i.e., the use of a mirror in the assessment of visual tracking and one’s own name in the assessment of localization to sound [6, 9]).

Notes

Abbreviations

VS/UWS: 

Vegetative state/unresponsive wakefulness syndrome

MCS: 

Minimally conscious state

CRS-R: 

Coma Recovery Scale-Revised

DOC: 

Disorders of consciousness.

Declarations

Acknowledgments

This study was supported by the National Natural Science Foundation of China (KG08027,KG13007), the Science and Technology Department of Zhejiang Province (KZ09037), the Hangzhou Normal University (JTAS2011-01-016), the Belgian Funds for Scientific Research (FNRS), Fonds Léon Frédericq, and the University of Liège. The authors thank Cunlai Xu, Jian Gao, Kehong Liu, Kun Li,Yu Zhang, Hongyan Song and Yan Dong for their assistance in patients’ assessment, and Didier Ledoux for his statistical advices. LH and SW are doctoral researchers and SL is research director at FNRS.

Authors’ Affiliations

(1)
International Vegetative State and Consciousness Science Institute, Hangzhou Normal University
(2)
Cyclotron Research Centre and Neurology Department, Coma Science Group, University and University Hospital of Liege
(3)
Wujing Hospital of Hangzhou City
(4)
Huzhou Center Hospital

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  16. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/14/147/prepub

Copyright

© Di et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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