In this cross-sectional study, 135 chronic TBI patients who were representative in most of the analyzed demographics and basic characteristics of the entire cohort of 439 adult, chronic TBI patients reported their health-related and disease-specific quality of life (HRQoL) up to 10 years after experiencing mild, moderate, or severe TBI. Approximately two thirds of the 135 patients reported good HRQoL. The initially classified TBI severity was only a slight contributor to—but not a strong predictor of—HRQoL among our chronic TBI patients. In contrast, none of the other parameters including TBI etiology, age at the time of TBI, age at the time of the survey, time elapsed since TBI, or sex distribution was correlated with HRQoL. One third of our patients reported unfavorable HRQoL with limited autonomy and cognition as decisive factors for unsatisfactory outcome—associated with an increased risk of anxiety and/or depressive disorders. Furthermore, the first year following TBI revealed unfavorable HRQoL with an increased risk of psychiatric sequelae, suggesting that early neuropsychiatric treatment is crucial to support patient’s adaption and resilience. The presented results are in line with the QOLIBRI validation study having analyzed 795 TBI patients (Supplementary Table S3) as well as with a Dutch study, which reported good HRQoL in 62% of patients having experienced diffuse axonal injury (DAI) [21, 38]. However, there are still controversial findings in the literature regarding age and sex differences that need further attention—most probably explainable due to the heterogeneity of TBI cohorts.
A representative TBI cohort
The response and participation rate were 37% (150 of 401 alive patients) and 90% (135 out of 150 participant of our survey cohort), respectively. These values are relatively high, given (1) the long-follow up period of up to 10 years after TBI, (2) the high age of participating patients, (3) the severity of TBI, and (4) the fact that a second contact by telephone was not permitted by German data protection laws. This response rate is consistent with a large German multicenter epidemiological survey of 4307 pediatric and adult TBI patients evaluated 1 year after TBI, which yielded a primary response rate of 40% .
Most demographic data and basic characteristics did not differ between the QOLIBRI cohort and the non-responders. However, patients of the QOLIBRI cohort gained better functional status at discharge from neurorehabilitation with a mean modified Rankin Scale of 2, indicating slight disability with good mobility and independence in activities of daily living though unable to carry out all previous activities, while the non-responders remained moderate disabled—indicating that a non-responder bias cannot fully be excluded, but most parameters were comparable to the entire cohort of 439 TBI patients, and thus the QOLIBRI cohort is most likely representative for this larger group of chronic TBI patients.
All participants underwent neurorehabilitation at Schoen Rehabilitation Center in Bad Aibling, Germany—one of the largest neurorehabilitation units in Europe—and were primarily referred by certified TBI centers within the Southern Upper-Bavaria Trauma Network, thereby providing the highest standard of medical care to patients in the acute phase of TBI. Despite the common lack of GCS documentation in 38% of medical records [25, 37], it is reasonable to assume that most patients experienced a severe brain injury, namely 36% due to the initially documented GCS and up to 34% due to secondary brain injury. Specifically, 27% of patients underwent decompressive craniectomy and 57% received either intracranial pressure (ICP) monitoring to detect and guide therapy of intracranial hypertension and brain edema or a permanent ventriculo-peritoneal shunt system, procedures indicating severe brain damage. Based on a close examination of the relative proportions of patients who underwent decompressive craniectomy and/or received ICP monitoring and/or a shunt device, 58 to 70% were either primarily or secondarily severe brain injured, thus our cohort is comparable to the QOLIBRI validation cohort . Other factors regarding our cohort, including TBI etiology and sex distribution, were consistent with the literature [23, 28, 39].
On average, our cohort was 20 years older than the cohort used to validate the QOLIBRI questionnaire, but this age difference did not change HRQoL and supports our finding that age is not a contributor to HRQoL in cTBI patients . In contrast, the Dutch study found younger age as an independent predictor of lower HRQoL after DAI, while others report older age as an independent risk factor for a decreased HRQoL or likewise no age effects [21, 40, 41]. In detail, Scholten et al. analyzed HRQoL using the SF-36 instrument at 6 and 12 months after predominantly mild and after moderate to severe TBI with a mean age of 44 years (range 27–57) compared to 53 (range 18–85) years at survey in our QOLIBRI cohort . This study emphasizes—well in line with our findings—that HRQoL increases over time until 12 months after TBI and this finding was most evident in the primarily mildly injured patients. Furthermore, severer injuries, less functional recovery, older age and female sex negatively correlated with better HRQoL but were potentially influenced by the 56 and 84% of patients lost to follow up at 6 and 12 months, respectively. Besides the initial TBI severity, i.e. patients of our QOLIBRI cohort reported better HRQoL after milder brain injuries—those findings are contradictory to the QOLIBRI cohort. Van Eijck and colleagues analyzed 86 chronic TBI patients aged 16–87 years on average up to 57 months (range 14–100 months post-TBI) after DAI due to a TBI with younger patients reporting less good HRQoL. This age-related finding which contrasts our current results, might be explained by the cognitive impairment after DAI . Nevertheless, the QOLIBRI validation cohort included 795 chronic TBI patients—aged 17 to 68 years—3 months and up to 18 years after TBI, thus highly comparable with our QOLIBRI cohort, with only very weak correlations (r ≤ 0.11) for age effects, education, time since injury, and severity of injury (GCS) with HRQoL . However, evidence of HRQoL in the elderly after TBI is scarce and might rather be associated with the preinjury and psychosocial capabilities than with the injury-related factors . Taking together, age might be relevant for HRQoL in a variety of subgroups including TBI injury patterns, timepoint of follow up and potentially sample sizes and certainly need further attention in future long-term HRQoL outcome studies.
Quality of life in the general German population
During the first year after TBI, HRQoL was reduced in our cohort indicating an increased risk of psychiatric sequelae and maladaptation to the post-TBI changes and this relevant finding is in line with the literature [24, 33, 40, 42]. Beyond one year post-TBI, HRQoL was even slightly better in our cohort than in the general German population and comparable to previous findings [22, 37, 43]. We suggest that future studies should investigate if good individual adaptation and resilience to the TBI-related changes are associated with better HRQoL outcome and the absence of psychiatric sequelae. Thus, these two factors—adaptation and resilience—should be prospectively focused and might be contributors to good HRQoL and long-term outcome after TBI.
Psychiatric sequelae after brain injury
Psychiatric disorders such as anxiety and depression are common in the general population with a 12-months prevalence of 18 and 9.5%, respectively . Following TBI, psychiatric sequelae are relevant and frequencies vary in the literature ranging from 18 to 83% due to methodological issues such as diagnostic criteria, injury severity and elapsed time since the brain impact . Especially, anxiety and affective disorders are most relevant after TBI with data ranges up to 70% for anxiety and between 25 and 77% for depressive disorders [9, 10, 46]. Approximately 40% of TBI patients even suffer from more than two psychiatric sequelae [10, 46].
In our chronic TBI cohort, one third of patients suffered from insufficient HRQoL associated with an increased risk of psychiatric sequelae, namely anxiety and/or depressive disorders. This finding is in line with results of a prospective study analyzing 817 TBI patients of which a total of 31% reported psychiatric disorders at 12 months after TBI . The latter finding suggests an increased risk for mental health changes such as depressive and/or anxiety disorders after TBI with the need for routine diagnostic of these posttraumatic sequelae that hamper patient’s quality of life. Furthermore, depressive symptoms might increase over time and psychiatric sequelae are a major reason for rehospitalization after TBI [22, 47]. Whether these psychiatric sequelae are associated with the functional decline described in one third of chronic TBI patients is still not elucidated. However, the link between the posttraumatic heterogeneous psychiatric sequelae and patient’s outcome becomes more and more obvious and need our attention throughout neurorehabilitation.
This study has several limitations that warrant discussion. First, the cross-sectional study design with the sample size of 135—albeit representative for the entire cohort of 439—chronic TBI patients allows descriptive conclusions. But, a recent systematic review and meta-analysis on post-TBI HRQoL revealed that the majority of the included 49 studies between 1991 to 2013 analyzed less than 100 post-TBI patients . Two further TBI studies analyzed HRQoL of 60 and 51 patients 10 years after TBI, respectively [22, 25]. Thus, the sample size of 135 chronic TBI patients in our study seems to be appropriate to highlight the need for psychiatric assessment on a regular base after TBI, especially when regarding the age range up to the 85-years-old, the long time period of up to 10 years after TBI as well as the given evidence, so far. Second, premorbid psychiatric sequelae, comorbidities, education, employment, living environment, injury patterns, and pharmacotherapy were not available. Third, neuroimaging data were not included to further characterize injury patterns as i) patients were referred from different trauma centers to neurorehabilitation, i.e. neuroimaging was per se less comparable or not available, ii) TBI patients—except for clinical deterioration or scheduling the bone flap replacement following decompressive craniectomy—do not get a routine neuroimaging while in neurorehabilitation, iii) state-of-the-art imaging for DAI (diffusion tensor imaging (DTI), tractography and susceptibility weighted imaging using a gradient recall echo (GRE-SWI)) was not available at the time when most of our patients were injured, i.e. more than 10 years ago, and iv) a multilevel diagnostic approach including neuroimaging and fluid biomarkers is recommended, but has not been implemented in the clinical routine, and thus were not available for our cohort . But, DAI does not seem to influence HRQoL up to 5 years after TBI, therefore the injury pattern itself might be a less relevant factor for long-term outcome . Fourth, functional status and comorbidities were not assessed in this survey-like cross-sectional study as written self-rating of functional status is most probably a less valid approach to get sustainable data. Fifth, caregiver’s quality of life and external assessments to elucidate a more objective perspective of the patients’ outcome was not done, but seem less relevant as indicated in the literature so far [50, 51]. Sixth, although a total score below 60 on the QOLIBRI questionnaire indicates an increased risk of psychiatric sequelae, a precise cut-off score has not been established; accordingly, our results on psychiatric disorders must be interpreted with care, but might help to implement cut-off scores and highlight the need for further evidence. Seventh, the initial GCS was not documented in 38% of cases in our cohort—a well-known finding in previous studies [25, 37]. Finally, the results’ generalizability might be limited due to the following issues: i) the age span of 18- to 85-year-olds, ii) the German population, iii) the heterogeneity of TBI in our cohort, and iv) treatment regimens including neurorehabilitation [21, 22]. Nevertheless, age does not seem to be relevant for long-term outcome regarding HRQoL as the presented results are comparable to the large QOLIBRI validation study, that included 20 years younger patients on average . Future long-term outcome studies with larger sample sizes should better stratify for TBI severity subgroups beyond GCS as targeted by the large TRACK-TBI and CENTER-TBI studies. The acute TBI treatment in certified hospitals of the Southern Upper-Bavaria Trauma Network and the subsequent neurorehabilitation in one neurorehabilitation center—using standardized rehabilitation protocols—most probably represent the highest standard of medical care, and therefore results are at least generalizable within industrialized countries.