Mismatch between midline shift and hematoma thickness as a prognostic factor of mortality in patients sustaining acute subdural hematoma

Background

Acute subdural hematoma (ASDH) is a traumatic lesion commonly found secondary to traumatic brain injury (TBI). The acceleration–deceleration resulting from trauma results in the rupture of the bridged veins, which causes the formation of hematoma.1–3 Damage to brain tissue cannot be attributed only to ASDH, as this hematoma is commonly associated with cerebral edema, brain concussions, and diffuse axonal lesions, which can worsen patient prognosis.4 5 Despite advances in prehospital and hospital support, this entity still has high mortality rates.6–8 The mortality rate in the literature ranges from 40% to 70%.6 9 10

Several factors are associated with the prognosis of these patients, such as the Glasgow Coma Scale (GCS) score at admission, age, pupillary response, and associated traumatic injuries.11 12 Radiological findings on CT, such as hematoma thickness (HT) and structures midline shift (MLS), have an important prognostic role and can be a determining factor for surgical management.13–17

MLS is caused by the hematoma itself and concomitant brain swelling.18 The effect of brain swelling can be shown on the initial head CT scan by the relationship of the MLS and the HT. Disproportionately increased MLS compared with HT would raise concerns of brain tissue injury and edema, and hence a higher intracranial pressure (ICP) and a worse prognosis could be anticipated. HT, MLS, ICP, and other factors including the severity of brain atrophy are interrelated.18–20

The concept of brain swelling is not new. However, complex scoring systems that assess radiological findings as prognostic factors for TBI include MLS and hematoma data in isolation and not associated, such as the Rotterdam21 and Helsinki22 scores.

The relationship between HT and MLS has been little studied in the literature.18 19 Zumkeller et al19 were the first to evaluate the difference between them as prognostic factors for survival in a cohort of patients. Recently, Bartels et al,9 in a retrospective cohort of 59 patients, determined that a difference between MLS and HT greater than 3 mm was associated with fatality. However, this parameter was not evaluated in a large sample and in low-income or middle-income countries (LMICs), a context of scarcity of resources that can benefit from simplified predictive models, thus requiring additional studies for external validation of its real predictive value. Thus, this study aimed to assess the prognostic value of the difference between MLS and HT for acute outcomes in patients with ASDH in an LMIC.

Methods

Outcome and variables of interest

Clinical variables

Epidemiological data such as sex and age were assessed. Trauma mechanisms were analyzed and classified as road traffic injury, fall, violence, and others. The GCS postresuscitation care for hospital admission and pupillary response were also included.

Radiological variables

The diagnosis of ASDH was made based on the admission CT evaluation performed using a multidetector 64-channel CT scanner (Philips Medical Systems World Headquarters, Best, The Netherlands) by a neurosurgeon and confirmed by an experienced radiologist. The Rotterdam and Helsinki scores were calculated according to the original article that describes them.21 22 These scores were chosen because they are complex models that include several radiological variables in their evaluation. Previous studies have already demonstrated that higher Helsinki and Rotterdam scores are associated with worse clinical outcomes in patients with TBI.8 16 18 The Marshall CT class was not evaluated because it was not originally constructed for outcome prediction and was developed in a patient population managed with protocols of care from the early 1980s, where aggressive surgical management for high ICP was not a common approach.24

MLS was assessed in the axial plane at the level of the interventricular foramen. This was measured as the longest perpendicular distance between the most displaced point of the pellucid septum and an imaginary sagittal line that associates the inner occipital protuberance and the frontal ridge.19 25 HT was assessed as the longest distance between the inner table and the cortex.6 Figure 1 shows an example of HT and MLS in a patient with ASDH. The HT was subtracted from the MLS to obtain the value described by Zumkeller et al19—the Zumkeller index (ZI=MLS−HT).

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Figure 1

The thickness of the acute subdural hematoma (red arrow) was measured on a CT scan as the largest distance between the cortex and the internal table: midline, orange line; midline shift, orange arrow. HT, hematoma thickness; MLS, midline shift.

To assess its relationship with the outcome, a categorical variable with three cut-off points was created, categorized as ZI, using the authors’ original work as a guide or key parameter.19 The first category included patients whose MLS was lower than HT. The second category included patients whose calculation was between 0.01 mm and 3 mm. The third category included patients who had a difference of MLS−HT greater than 3 mm. This categorization takes into account the principle that there is an underlying brain swelling when MLS is greater than HT.

Patients were followed up during their hospital stay. The predictive value of the ZI and other variables was assessed for the primary outcome of 14-day mortality, based on reports in the literature for assessing acute outcomes of TBI.26 27

Results

Survival analysis

The Kaplan-Meier survival analysis demonstrated a statistically significant difference in the survival function at the different levels of the ZI categorized for the 14-day follow-up (log-rank p=0.008) (figure 2). Cox regression analysis demonstrated that the third category of ZI was associated with 14-day survival (HR 2.924, 95% CI 1.388 to 6.160; p=0.005), as shown in table 2. This category proved to be an independent predictor of 14-day survival in adjusted Cox regression for surgical intervention, age, and GCS (online supplemental table 2).

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Figure 2

ROC curves for the multivariate model including age, Glasgow Coma Scale and categorical Zumkeller index (model 1), Helsinki CT score (model 2), Rotterdam CT score (model 3). AUC, area under the ROC curve; ROC, receiver operating characteristic.

Multivariable predictive models

Multivariate analysis was performed for all three models. Model 1 included age, GCS, and categorized ZI; model 2 included age, GCS, and Helsinki score; and model 3 included age, GCS, and Rotterdam score. All variables included were independent predictors of mortality. Models 1, 2, and 3 demonstrated an AUC equal to 0.747 (95% CI 0.654 to 0.826), 0.767 (95% CI 0.676 to 0.843), and 0.808 (95% CI 0.721 to 0.878), respectively, as shown in figure 3. The test by DeLong et al28 showed no significant differences between the AUC values (p>0.05). All models demonstrated adequate calibration using the Hosmer-Lemeshow test (p>0.05).

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Figure 3

Survival function for each category of Zumkeller index for 14-day mortality outcome.

Discussion

The present study stands out for presenting the prognostic value of a variable that is little reviewed in the literature, “Zumkeller index,” which was associated with acute outcomes and which may suggest the presence of cerebral edema or other associated injuries in patients with ASDH. The data presented corroborate the assumption by Zumkeller et al19 that an MLS that exceeds the thickness of the hematoma suggests the presence of associated cerebral edema and/or other parenchymal lesions, which contributes to worst clinical outcome.

In a review of approximately 3000 autopsy cases after TBI, Tandon29 concluded that ASDHs are rarely isolated lesions; in their study, 82% of the cases were associated with parenchymal lesions, which again demonstrates the importance of MLS evaluation. In our study, intraparenchymal lesions were found in 53.5% of patients, and a higher frequency of this finding was observed (90.9%) in patients who were classified as having a ZI >3. Several studies have associated the presence of ICH and its progression with poor prognosis.30–32 The study by Cepeda et al33 demonstrated that when studying the progression of ICH in patients with TBI, ASDH is associated more with this progression. In addition, it highlights the role of higher MLS values in the progression of ICH. In cases where the ZI was greater than 0, the role of MLS was notorious. Therefore, patients with these findings and associated ICH have a greater risk of lesion progression. Cepeda et al33 also demonstrated an unfavorable clinical outcome in 74% of patients with ICH progression, compared with 26% of those who did not. In addition, the number of patients undergoing decompressive craniectomy was significantly higher in patients with ICH progression (75% vs. 25%).

In our study, patients with ZI >3 had an increased frequency of IVH (45.5%) compared with 7.7% of patients with ZI between 0.001 and 3 and 21.1% of patients with negative ZI. According to the literature, the rate of occurrence of IVH in patients with moderate-to-severe TBI ranges between 7.1% and 22%.34–36 The presumed possible mechanisms of IVH are an extension of intracerebral hemorrhage into the ventricular system or rupture of the subependymal veins, which can be deformed by the negative pressure at the time of injury.37 Like ICH, several studies also associate IVH with a poor prognosis.21 The study by Laleva et al36 demonstrated that the main factor related to the onset of IVH is the presence of ICH on admission images. In our cohort, we observed high frequencies of the two lesions in patients with a ZI >3.

It was also observed that 100% of patients with a positive ZI had a traumatic subarachnoid hemorrhage (SAH). Diffuse bleeding resulting from rupture of the subarachnoid vessels in TBI is a predictor well described in the literature.38–40 Similar to what happens in the rupture of aneurysms, traumatic SAH induces vasospasm and cerebral ischemia, which can trigger inflammatory and neurotoxic processes and contribute to brain swelling, which contributes to worsening the outcome of patients.41 42

However, in cases of isolated ASDH, the ZI may play a role as a prognostic factor of mortality because, without a parenchymal lesion, the MLS exceeding the HT may be due to brain swelling and impairment of cerebrovascular reactivity.

The relationship between MLS and HT is promising in terms of prognosis and may help to estimate ICP. Recently, Liao et al20 constructed a model for ICP estimation based on a half-sphere finite-element model using only HT and MLS in ASDH. The ICP values obtained by the normogram created by the authors showed a high correlation with those measured, demonstrating an R² coefficient of 0.744. Using estimates like these and predictive models like ZI, neurosurgeons can do more with less. In patients with TBI with multiple traumas, estimating ICP and brain swelling also helps prioritize treatment of different regions of the body.

We highlight the high mortality rate of patients with an MLS >3 mm in relation to HT. In our series, there was 81.8% mortality within 14 days for these patients, an even higher rate than that found by Zumkeller et al.19 When the entire length of hospital stay was assessed, 10 of the 11 patients categorized as ZI >3 died. Bartels et al,9 when studying this difference in a small cohort of patients, found a mortality rate of 100% when ZI was greater than 3 mm, which indicates the accuracy of this indicator for use in clinical practice. The authors further suggested that in these patients, the trauma resulted in greater damage than that generated by the hematoma, in addition to having an influence on the anatomy and physiology of the brain, resulting in an acute onset of swelling. This assumption helps to justify the poorer clinical presentation at admission of patients with positive ZI, demonstrated by significantly lower GCS values in the second and third categories of the ZI, as well as the poor pupillary response of patients with ZI >3. It should also be noted that values greater than 3 mm, in addition to being associated with a worse outcome, also implied a reduction in the estimated survival time.

Additionally, our results highlight the potential role of ZI as a variable for modeling studies, since a comparison with more complex scores such as Rotterdam21 and Helsinki22 demonstrated acceptable AUC values. We hypothesize that the values close to the three multivariate models created to assess the prediction of acute ZI outcomes against these scores are because the brain injuries covered by the scores, such as IVH, ICH, and SAH, are related to the positive values of MLS–HT. It should be noted that the intention of our work is not to suggest the replacement of other existing tomography scores because they can be used in the context of other brain injuries and include variables that are associated with the prognosis of TBI; our objective was to present a complementary index to these scores which assesses something not directly included in them. The objective of our multivariate analysis, which compared the ZI with these scores, was to demonstrate that the ZI has a discriminative ability similar to these more complex models, demonstrating its clinical utility in the context of outcome prediction.

To date, only two studies have evaluated the ZI: Zumkeller et al,19 who described the index, and Bartels et al.9 Neither of these studies were conducted in LMICs, which have distinct epidemiological contexts from high-income countries. As we know, LMICs have the highest burden of neurotrauma; however, most of the scientific articles published in journals originate from high-income countries.43–45 Interestingly, in Brazil, many centers already use this “Zumkeller index,” not as a prognostic variable but to decide whether to perform a primary decompressive craniectomy in the setting of ASDH.46 As it is a post-hoc analysis of a prospective study, it is not possible to suggest the indication of decompressive craniectomies for patients with positive ZI. However, cerebral edema and/or associated injuries in this group of patients are notorious. We then suggest the proper management of intracranial hypertension and that future studies of primary decompressive craniectomy address this variable.

Finally, regarding the epidemiological data for ASDH, the literature demonstrates that high mortality rates are more often associated with advanced ages.6 47–49 Wilberger et al,50 in their study, demonstrated that the average age of non-survivors was 59 years, whereas that of survivors was 41 years, a finding similar to that seen in other studies.3 9 In our study, the average age of survivors was 44.4 years and that of non-survivors was 53.4 years. Ryan et al,51 in their study, described falls as the main injury mechanism (57%), followed by automobile crash (23%), which was very close to the study by Leitgeb et al,52 which also presented falls as the main mechanism (51.9%), followed by automobile crash (22.2%). In the present study, the percentages of ASDH resulting from automobile crash and falls were the same (43.9%). Several authors have already demonstrated epidemiological differences in different socioeconomic contexts.53 54 In LMICs, where traffic laws and enforcement are not as effective, automobile crash and trauma mechanisms related to aggression are predominant. Thus, we emphasize that the present study is the first to evaluate the MLS–HT relationship in an LMIC, which contributes to the process of external validation of its practical utility in different contexts.

Conclusion

The present study highlighted the potential usefulness of the difference between MLS and HT (the “Zumkeller index”) as a prognostic variable for patients with ASDH. A worse clinical presentation by GCS was demonstrated in patients with positive ZI, as well as a worse classification in the Rotterdam and Helsinki tomography scores. A higher frequency of other injuries associated with ASDH, such as SAH, IVH, and ICH, was found in patients with a ZI greater than 3. In addition, the present study demonstrated a lower survival rate in this group of patients. We advocate that such an index be used in future modeling studies or evaluate its potential in future studies of primary decompressive craniectomies.