Multiple frailty indices and markers of sarcopaenia and osteopaenia have been investigated in the context of various surgical and neurosurgical disciplines. In this study, we utilized risk scores for frailty, and markers of sarcopaenia and osteopaenia, and compared them against traditional prognostication tools for outcomes following aSAH. We found that TMT was the best performing marker; it unexpectedly outperformed traditional aSAH markers, such as WFNS grading and correlated well with various inpatient and long-term outcomes. Of the frailty markers, NSQIP Score performed the best, at levels comparable to traditional aSAH markers with clinical relevance, such as Modified Fisher scale.
In the context of newer scales and novel measures gaining traction in clinical practice, such as frailty, traditional markers used to prognosticate the outcomes of aSAH, age, WFNS grade and Fisher scale remain relevant. This demonstrates the disproportionate role that the patients’ age and presenting status play in the overall outcomes from this condition. Unexpectedly, MFI-11 and MFI-5 were not well able to predict the outcomes in aSAH. This was also reported in a previous study of aSAH [25]. There are a few potential reasons that this might be the case. The MFI-11 has an over-representation of cardiac (history of congestive heart failure, myocardial infarction, previous percutaneous procedures, or angina) and neurological related variables (impaired sensorium, transient ischaemic attack or cerebrovascular accident, neurological deficit after previous cerebrovascular accident). Although both systems are critical in the overall patient outcomes, MFI-11 does not cover other important domains of frailty such as nutritional status, mobility, strength, and mood [10]. MFI-5 [12], derived from MFI-11, purported to have the same predictive power, suffers from the same shortcomings. In addition, both scores did not represent other important physiological systems such as the renal and hepatic systems. The NSQIP score had a better performance than both MFIs (AUC 0.70 [0.54–0.86] vs. 0.58 [0.40–0.77] and 0.56 [0.37–0.74]) possibly due to its incorporation of other factors that were able to indicate the patient’s non-neurological clinical status. These included variables that correspond to the patient’s nutritional status (recent weight loss and body mass index), other important physiological systems (renal, hepatic, haematological, etc) and the acuteness of patient presentation (emergency case). The differences in performance between the NSQIP Score vs. MFI-11 and MFI-5 may well be attributable to the greater representation of systemic variables within the NSQIP Score, such as those correlated to susceptibility to infection (including systemic and wound infections, immunocompromised states such as disseminated cancer and steroid usage). Within the local context, frailty and mortality risks are known to be correlated with a high pathogenic load of latent infections [41].
Another reason that the MFI-11 and MFI-5 indices may fail to truly be indicative of the systemic load of comorbidities may be that these scores do not distinguish conditions by their severity. Patients with well-controlled hypertension, diabetes mellitus, congestive heart failure and chronic obstructive pulmonary disease were not distinguished in scoring from their poorly performing, chronically ill counterparts. Hence, MFI-11 and MFI-5 may not accurately reflect the supposed dynamic nature of frailty[42]. A further reason that frailty indices did not have the expected predictive value is the possibility that aSAH as an acute episode of brain injury overcomes the physiological reserves in a manner that having a frail or non-frail phenotype is inconsequential. This is likely true for patients who present with poor grade aSAH, where the major determinant for long-term good outcome remains the patients’ neurological status following response to resuscitation and amenability to interventions. This explains the findings of why frailty indices may correlate well with elective surgeries, which are clinical situations that do not stress the physiological reserves to the same extent as acutely ruptured intracranial aneurysms. Interestingly, other authors have demonstrated the relevance of frailty to higher frequency of presentation with poor grade aSAH [25]. In our study, grade of aSAH was indeed distinguished by frail vs. non-frail groupings. However, despite the differing presentations, as well as the increased burden of complications in the former group, there was a narrowing of the gap between them for longer-term outcomes. This, coupled with the relative importance of non-neurological factors in the NSQIP Score strongly suggest that, in our cohort, it may be possible to use such scoring towards implementing targeted interventions (such as to optimize nutrition and infection risks) to improve patient trajectories following aSAH.
Non-neurological factors such as nutritional status, may also explain why sarcopaenia, as measured here using TMT, demonstrated such a strong correlation with aSAH outcomes. The TMT marker supported the notion that non-frail patients were more likely to present with a favourable WFNS grade, less likely to experience delayed cerebral ischaemia and inpatient complications, were discharged at a better functional status and with faster recovery. Our results are consistent with published literature, in which sarcopaenia has been found to be reflective of clinical status and recovery in studies of patients undergoing rehabilitation [43, 44]. Deconditioning, which has been known to set in within the first day of admission [45] is demonstrative of the ability of sarcopaenia to reflect an acute to subacute context of frailty. In addition, our findings of sarcopaenia in this cohort are also consistent with local data demonstrating the correlation of measures of skeletal muscle mass with markers of subclinical vasculopathy, such as carotid intima-media thickness, albeit in an asymptomatic cohort [46]. Its capacity to encompass risk factors from multiple frailty domains, whilst also describing the dynamics of the physiological response to stressors, may therefore make sarcopaenia desirable as both a marker of muscle loss, as well as a surrogate for more global notions of an acutely “frail state”. Osteopenia, on the other hand, reacts much slower, possibly in the order of years. This is reflected in a study of the progression of osteopaenia in human immunodeficient virus infected patients using dual-energy X-ray absorptiometry [47]. Thus, it is not surprising that in acute non-traumatic brain injury, osteopaenia was not a good prognosticating factor for eventual clinical outcomes
There were two unexpected observations in our study amongst both groups with regards to the inpatient and long-term outcomes. Firstly, despite frail patients having up to four times the rate of complications compared to the non-frail patients, the length of stay in the NICU and the ward, and the proportion of patients discharged home or to a rehabilitation facility were similar. We attribute this to the prompt and aggressive subspecialist clinical management of aSAH complications such as delayed cerebral ischaemia, neurocardiac syndrome and infections. Secondly, although frail patients had a significantly larger proportion with unfavourable MRS on discharge, after a year of rehabilitation and community interventions, the gap between the frail and non-frail patients narrowed. Furthermore, the proportion of non-frail patients with favourable MRS did not change from discharge up to the 1-year follow up. This suggests that frailty alone should not be threshold at which the offer of clinical interventions should be decided. We hypothesise that the reason for this phenomenon was that both groups had a similar proportion of patients with the rehabilitation potential, as evidenced by the similar proportion of patients with favourable MRS at the 1-year interval. However, it may be that non-frail patients were more able to reach this potential in a shorter time duration due to their enhanced physiological reserves at presentation. Whilst it may not be possible to augment the reserves of frail patients, our results suggest that it may be possible to develop specific interventions to buffer them through an acute state of worsening frailty and sarcopaenia, in order to reach their potential for long-term good outcomes.
Our study limitations include to its retrospective nature and modest sample size. While we explored the possibility of using other notable frailty indices such as risk analysis index, hospital frailty risk score, and the FRAIL questionnaire, data gaps in important domains such as poor appetite, cognitive deterioration, a general feeling of fatigue, and walking distance, limited our efforts to do so successfully.Nevertheless, our study sheds light on use of the concept of frailty in the context of acute brain injury from aSAH. There is a need for the understanding of how best to apply both global surrogates and specific markers indicative of the state of acute to subacute frailty and to understand their relevance to specific surgical contexts [48–50].