This cross-sectional study describes the health-related quality of life following cranioplasty in a large cohort of patients using a battery of questionnaires. In our cohort, nearly 1 in 3 participants reported feeling extremely anxious or depressed, 1 in 6 reported feeling borderline anxious or depressed and 6 in 10 participants had a problem with mobility, self-care, pain or discomfort. Nearly 6 in 10 patients reported being conscious of their appearance or having negative feelings towards it.

Although cosmesis and appearance following cranioplasty has been explored by previous studies, all of them employed a study specific questionnaire. Appearance is expected to affect health-related quality of life especially in patients undergoing cranioplasty as the operation itself aims to repair a defect in the skull following a craniectomy. Previous studies that explored patient reported cosmetic results following cranioplasty reported satisfaction in appearance following cranioplasty in 60% to 90% of their cohort [12, 13]. The reported improvement is relative to baseline cosmetic appearance of a craniectomy defect and therefore precludes the impact of the cranioplasty on an individuals’ perception of appearance and how it may affect their social activities.

Results from the DAS-24 questionnaire demonstrated that the worst performing items were participants feeling irritable at home, adopting concealing gestures, distressed in supermarkets/department stores, feeling rejected, avoiding leaving the house, being in physical pain/discomfort and their appearance affecting their sex life. When these scores were categorised nearly 7 in 10 participants reported feeling conscious of their appearance at a given time-point. Poor scores in the above-mentioned domains would be expected to influence other aspects of participants’ lives including anxiety, depression, and general health. This is reflected by responses in the HADS depression domain where nearly one in three participants reported not looking forward to enjoying activities, losing interest in their appearance, feeling slowed down, not feeling cheerful, and not enjoying the activities they used to enjoy as much before. Additionally, results from SF-36 indicate impaired scores in domains of social functioning, emotional well-being, and role limitations due to emotional problems, all of which may be attributed to results from DAS-24 which revealed over 7 in 10 participants feeling conscious about their appearance. In addition, baseline reduction social functioning and emotional well-being would also be influenced by participants’ underlying pathology, of brain tumour, traumatic brain injury, and stroke.

Two of the five questionnaires administered directly explored anxiety or depression. HADS only consisted of two domains, anxiety, and depression, and explored these using multiple items. The median anxiety score is comparable to the median normative population scores from a UK cohort; however, the median depression score was twice the normative population value in this cohort [14]. Reasons for this increase in the depression score may be due to the underlying pathology, which includes TBI and underlying tumour which are known to have a negative impact on individuals’ mood [15,16,17]. Results from the DAS-24 revealed 7 in 10 participants were conscious of their physical appearance, which would be expected to have a negative impact on their emotional well-being. Additionally, participants responded during or right after the second COVID-19 lockdown was in place in the United Kingdom. Fancourt et al. described depression and anxiety symptoms in a cohort of 70,000 adults in the United Kingdom using the Generalised Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) and found the highest levels of depression and anxiety in the first COVID-19 lockdown however noticed a significant decline in scores across the second lockdown [18]. Longitudinal HRQoL results one-year post COVID-19 lockdown as described by Joensen et al. indicate that participants improved from their baseline scores however continue to have an impairment in HRQoL [19]. Results from these large-scale prospective studies indicate that the COVID-19 lockdown remained a confounding factor for our study when describing symptoms of anxiety and depression.

We found no difference in HRQoL as measured by HADS, SF-36, or DAS-24 when comparing indications for craniectomy in our cohort. Reasons for this may include a small sample size in each craniectomy indication cohort which may not achieve statistically significant differences, additionally, craniectomy indications represented in our cohort included TBI, tumour, infected bone flap, cerebral infarct, vascular, cystic lesions, or primary intracranial infection, all of which represent a high degree of morbidity for patients leading to a global decline in HRQoL, which is represented in the results of the overall cohort. Results from EQ-5D showed worse scores in domains of self-care and daily activity for patients who underwent a craniectomy due to cerebral infarct or other vascular pathology. Giese et al. previously compared HRQoL using EQ-5D across craniectomy indications and reported no significant difference between patients undergoing craniectomy for TBI. Infection, or intra-cerebral/subarachnoid haemorrhage, however found a worsened overall HRQoL for patients undergoing a craniectomy related to cerebral infarction/ischaemia. The results of our cohort are consistent with previously described HRQoL studies [20].

Previously, three studies employed the SF-36 to evaluate HRQoL following cranioplasty. One of these studies did not provide a breakdown of the domains and instead only provided a comparative overview comparing two materials [21]. Another study categorised their cohort into good and poor without providing scores for each domain, thus making comparisons to the normative population and other cranioplasty cohorts impossible [20]. The median score for the general health domain in our cohort was 50.0 which was significantly less when compared to a previous study, which reported a median general health score of 83.0 [22]. This large disparity could be attributed to the clinical profile of the participants: the study conducted by Worm et al. consisted of patients predominantly affected by TBI and among the 62 in the cohort, only 8 participants had other pathology. This contrasts with the Cranio-PRO cohort in which nearly one third of the cohort is affected by an underlying brain tumour which would lead to a decline in overall general health. The cohort mean VASc score was 70 which is similar to previous VASc scores of 63 and 60 reported in the literature [20, 23].

There are several limitations to the study. Although the focus of the study was to explore HRQoL following cranioplasty and this was conveyed via the PIS it is not possible to delineate which aspects of HRQoL are being affected by the cranioplasty itself, or by participants’ underlying pathology. Accordingly, we distributed a range of PROMs evaluating HRQoL, health status, anxiety and depression and self-reported problems with appearance. This was a cross-sectional study which precludes casual inference or temporal evaluation of HRQoL changes following cranioplasty, and as such longitudinal assessment of these patients is required. To address this gap, we will plan a longitudinal prospective study administering PROMs pre-operatively (baseline) and at post-operative clinic follow-up appointments. As this was a cross-sectional study with the aim of summarising multiple HRQoL domains using descriptive statistics for patients following a cranioplasty, sensitivity analyses were not performed. As the response rate was 30% no statistical tests were performed to account for missing data to avoid overstating descriptive results. Additionally, the first set of questionnaires were sent out during the second COVID-19 lockdown in the UK and hence some of the responses, related to overall emotional well-being and social activities may have been impacted by the pandemic as discussed above. The overall participation rate of our cohort was 30%. Reasons for a low response rate could include the clinical profile of the patients undergoing cranioplasty, with most patients having an existing pathology such as a brain tumour or traumatic brain injury, which could lead to impaired performance status and impaired cognitive ability [24]. Finally, several patients contacted resided in care homes which further expands on their functional status, with these patients not having capacity to consent. This might have led to our results not including those with most severe pathology.

As demonstrated by previous work, the cranioplasty operation has a major impact on patients’ long-term health-related quality of life. Clinicians could employ standardised PROM tools to better understand the patient perspective following the operation and explore factors that lead to an improvement or decline in HRQoL. Longitudinal HRQoL assessment of for patients starting prior to the cranioplasty can allow clinicians to identify deterioration in HRQoL and subsequently signpost patients to relevant well-being services.