This is the first study to report on the evolution of QoL in a LIS population and is the largest and longest duration examination of a cohort of LIS patients ever conducted.
The LIS persons involved in this study already had chronic LIS statuses for long durations (the median LIS duration was 7 years in 2007). Several previous studies have reported the QoL of LIS persons in single assessments [14, 22, 23] through cross-sectional research studies that may not provide definite information about cause and effect relationships. Longitudinal design provides more valid information and more robust findings.
The first important finding is that the LIS patients exhibited a rather good QoL maintenance throughout the 6-year period; nearly ¾ of the patients reported a stable or improved QoL at 6 years. Regarding the few studies that have used the ACSA score to assess QoL, LIS patients have reported lower scores (after scoring harmonization) than subjects who have sustained whiplash injuries  and higher scores than patients with facial prostheses  and patients with new diagnoses of Alzheimer’s disease .
In the same period, the health/handicap (physical and psychological) statuses of some of the patients changed. We did not observed relationships between the objective parameters of the health/handicap statuses and level of QoL. Similarly, considering the 11 patients (of the total of 39) who objectively exhibited deteriorations in their health/handicap statuses between 2007, their QoL scores were not different from those of the other patients. It has been previously observed that patients’ subjective QoL is not related to physical impairments; this observation agrees with previous studies of different motor neuron disorders [4, 11, 15, 22, 27–32] and illustrates the “disability paradox” reported by Albrecht and Devlieger . These findings confirm that usual clinical assessments that are based on objective outcomes do not reflect all of the aspects that patients consider important in to live. This lack of association between objective health/handicap change and QoL could also be explained by the presence of the well-known ‘response shift phenomena’ . QoL is self-reported by the patient and might be influenced by this phenomena, which corresponds to the adaptation to the illness (i.e., adaptation to a bedridden state and restricted physical/social function in the specific case of LIS). The presence of a response shift may result in the over- or underestimation of the true changes and lead to challenges in interpreting QoL measures, especially in longitudinal studies . In this present case, the three classical components of the response shift may have been incriminated; i.e., reconceptualization defined by as a redefinition of QoL, reprioritization defined as a change in the importance attributed to the component domains that constitute QoL, and recalibration defined as a change in a patient’s internal measurement standard.
Although medical device use declined over time in terms of feeding tubes and tracheotomies, an important proportion of patients continued to depend on these devices throughout the study period. Indeed, in 2013, a high proportion of the patients (one-third) had gastrostomies and tracheotomies primarily due to incomplete swallow recovery, and 10 % had permanent urinary probes. In most studies, swallowing ability and improved continence have been found to reduce the need for medical devices [3, 4].
Another interesting finding concerns the role of communication. All of the LIS persons involved in this study could communicate; more than 50 % of the patients used electronic communication devices, and the other patients communicated only through a yes-no code. The proportion of patients who preferentially used a yes-no code to communicate tended to decrease over time, from 77 % in 2007 to and 62 % in 2013. This last restrictive mode of communication was the single parameter that was associated with a significantly lower QoL. Communication for LIS people implies the use of alternative communication, such as eye blinks or eye movements for a yes-no code or communication boards with letters or symbols that are indicated via eye movements, and both alternatives imply the avoidance of open-ended and the confirmation of answers with repeated questions when necessary. Communication is also very limited and requires the help of others. Electronic communication devices, including patient-computer interfaces such as infrared eye movement sensors and computer voice prosthetics, have a liberating effect on people with LIS and enable them to have real dialogues and use the internet instead of passively responding to the requests of others [36–38].
The autonomy afforded by an electric wheelchair is recognized as an important element for an LIS patient. In our study, nearly 60 % of the LIS patients stated that they were autonomous with a powered electric wheelchair and reported feelings of sufficient autonomy at home, and such feelings were associated with higher QoL scores, although this difference was not significant.
Another comment should be made concerning the life conditions of the patients. In 2013, 82 % (32/39) of the patients lived in their own homes. Among these patients, 81 % were already at home in 2007, but 19 % moved from an institutional setting to their personal home, which implies that both the health/handicap status and the family circle allowed for such a move. Surprisingly, the patients living in institutional settings reported systematically higher scores than those living at home (albeit this difference was non-significant), which could be explained by the soothing role of a medical environment. Marital status did not affect the QoL score, but single persons generally reported lower scores than the individuals who were part of a couple. Financial income was not related to overall well-being, which is probably reflective of the French health care system, specifically the universal health-care insurance and existence of resource allocations to help maintain very dependent persons at home via the financing of human and technical aid.
The mental/psychological conditions are important to consider. We did not observe a link between mood disorders and QoL levels, although a high proportion of our patients reported having mood disorders and/or feelings of depression. Previous studies that have assessed patients with severe diseases (e.g., amyotrophic lateral sclerosis) have reported contradictory relationships between depression and QoL . Nevertheless, more than a quarter of our cohort reporting having suicidal thoughts as previously described, and such thoughts unsurprisingly influence their QoL. Lastly, family members, careers and medical professionals frequently assume that LIS persons would choose to die, but this was not true. Our results indicate that the demand for euthanasia was almost non-existent in our group of patients, and a great number of the patients expressed a desire for resuscitation if necessary.
Strengths and limitations
The sample size was arguably too small. When we tried to identify linked factors using the multivariate approach, associations may have been missed due to low statistical power. Larger samples would allow for the confirmation of these findings despite the rarity of this condition. However, the present report is the only study that has followed patients for a rather long period.
The representativeness and the size of our sample should be discussed. Our patients appeared to be relatively similar to the populations of other studies in terms of age, gender, and LIS etiology [3, 4, 41]. As described in previous studies, [4, 5] the mortality rate was very low; two patients died in 6 years after initial medical stabilization (more than a year). According to Doble et al.,  the 10-year survival of LIS persons is 83 %, and the 20-year survival is 40 %. The limited data preclude an appreciation of the true prevalence/incidence of this syndrome, . While it can be assumed that a significant proportion of individuals with LIS are in contact with the French Association of Locked-In Syndrome, we can hypothesize that these individuals have a better social support compared to the individuals who are not in contact with patients’ associations. Future studies should better apprehend the exhaustiveness.
The proportion of patients lost to follow-up appears high and troublesome to the significance of findings. It could be hypothesized that the non-respondents included patients with more severe physical and/or mental and/or social conditions, more severe communication limitations, and more important cognitive impairment. This can lead to an overestimation of the QoL level. However, we can assume that the respondents did not differ from the non-respondents in terms of gender and age, which ensures the relative validity of our findings.
We were unable to confirm the impact of other potential QoL determinants. Cognitive impairment, social support and social bonding, and satisfaction with these supports were not collected in our study. Future studies should explore these parameters.
Finally, the communication limitations of LIS persons make patients’ assessments particularly difficult. As we did not collect the information whether the patient him/herself responded or if the caregiver filled out the questionnaire on behalf of the patient, we can provide an inaccurate estimation of the patient’s QoL. The QoL scale had to be selected based on the ease of use with this population and consisted mostly of the use of eye blinking and vertical eye movements to communicate. The use of the self-report Anamnestic Comparative Self-Assessment to determine the QoL level should be discussed. Indeed this questionnaire provides a single global measure restricting the QoL concept. Although we appreciate this tool for its capacity for self-administration and its short time of completion, we recognize that a more specific QoL questionnaire or a multidimensional questionnaire could provide a more satisfactory picture of the self-perceived lives of these patients.