Complications following cranioplasty: incidence and predictors in 348 cases

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OBJECT

The factors that contribute to periprocedural complications following cranioplasty, including patient-specific and surgery-specific factors, need to be thoroughly assessed. The aim of this study was to evaluate risk factors that predispose patients to an increased risk of cranioplasty complications and death.

METHODS

The authors conducted a retrospective review of all patients at their institution who underwent cranioplasty following craniectomy for stroke, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and trauma between January 2000 and December 2011. The following predictors were tested: age, sex, race, diabetic status, hypertensive status, tobacco use, reason for craniectomy, urgency status of the craniectomy, graft material, and location of cranioplasty. The cranioplasty complications included reoperation for hematoma, hydrocephalus postcranioplasty, postcranioplasty seizures, and cranioplasty graft infection. A multivariate logistic regression analysis was performed. Confidence intervals were calculated as the 95% CI.

RESULTS

Three hundred forty-eight patients were included in the study. The overall complication rate was 31.32% (109 of 348). The mortality rate was 3.16%. Predictors of overall complications in multivariate analysis were hypertension (OR 1.92, CI 1.22–3.02), increasing age (OR 1.02, CI 1.00–1.04), and hemorrhagic stroke (OR 3.84, CI 1.93–7.63). Predictors of mortality in multivariate analysis were diabetes mellitus (OR 7.56, CI 1.56–36.58), seizures (OR 7.25, CI 1.238–42.79), bifrontal cranioplasty (OR 5.40, CI 1.20–24.27), and repeated surgery for hematoma evacuation (OR 13.00, CI 1.51–112.02). Multivariate analysis was also applied to identify the variables that affect the development of seizures, the need for reoperation for hematoma evacuation, the development of hydrocephalus, and the development of infections.

CONCLUSIONS

The authors' goal was to provide the neurosurgeon with predictors of morbidity and mortality that could be incorporated in the clinical decision-making algorithm. Control of a patient's risk factors and early recognition of complications may help practitioners avoid the exhaustive list of complications.

ABBREVIATIONSAED = antiepileptic drug; DHC = decompressive hemicraniectomy; DM = diabetes mellitus; SAH = subarachnoid hemorrhage; TBI = traumatic brain injury.

Abstract

OBJECT

The factors that contribute to periprocedural complications following cranioplasty, including patient-specific and surgery-specific factors, need to be thoroughly assessed. The aim of this study was to evaluate risk factors that predispose patients to an increased risk of cranioplasty complications and death.

METHODS

The authors conducted a retrospective review of all patients at their institution who underwent cranioplasty following craniectomy for stroke, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and trauma between January 2000 and December 2011. The following predictors were tested: age, sex, race, diabetic status, hypertensive status, tobacco use, reason for craniectomy, urgency status of the craniectomy, graft material, and location of cranioplasty. The cranioplasty complications included reoperation for hematoma, hydrocephalus postcranioplasty, postcranioplasty seizures, and cranioplasty graft infection. A multivariate logistic regression analysis was performed. Confidence intervals were calculated as the 95% CI.

RESULTS

Three hundred forty-eight patients were included in the study. The overall complication rate was 31.32% (109 of 348). The mortality rate was 3.16%. Predictors of overall complications in multivariate analysis were hypertension (OR 1.92, CI 1.22–3.02), increasing age (OR 1.02, CI 1.00–1.04), and hemorrhagic stroke (OR 3.84, CI 1.93–7.63). Predictors of mortality in multivariate analysis were diabetes mellitus (OR 7.56, CI 1.56–36.58), seizures (OR 7.25, CI 1.238–42.79), bifrontal cranioplasty (OR 5.40, CI 1.20–24.27), and repeated surgery for hematoma evacuation (OR 13.00, CI 1.51–112.02). Multivariate analysis was also applied to identify the variables that affect the development of seizures, the need for reoperation for hematoma evacuation, the development of hydrocephalus, and the development of infections.

CONCLUSIONS

The authors' goal was to provide the neurosurgeon with predictors of morbidity and mortality that could be incorporated in the clinical decision-making algorithm. Control of a patient's risk factors and early recognition of complications may help practitioners avoid the exhaustive list of complications.

Cranioplasty is more than a cosmetic repair of cranial defects; it is part of the rehabilitation process following a patient's neurological injury. Recent studies have shown that cranioplasty may improve the patient's psychological status, social performance, and neurocognitive functioning.1,14,19,21 The factors that contribute to periprocedural complications, including patients' demographic information, comorbidities, surgical procedure, and underlying disease, need to be thoroughly evaluated. Previous studies that were intended to answer these questions were limited by their design or by their sample size. Our aim was to evaluate risk factors that predispose patients to an increased risk of cranioplasty complications. Recent evidence in the literature emphasizes patient-specific factors over surgery-specific factors as major predictors of cranioplasty complications.47,51 It is also becoming evident that surgical treatment for cranioplasty complications is associated with additional surgical procedures.17,46 In this study, we evaluated the association between patient-specific factors and complications following cranioplasty surgery. We also evaluated whether some complications increase the risk of developing others. Finally, we studied factors that are associated with patient death following cranioplasty.

Methods

Study Design

The Thomas Jefferson University Hospital Institutional Review Board approved the study protocol. We queried a prospectively maintained database of patients who had undergone cranioplasty at our institution between January 2000 and December 2011. The study included all patients who underwent a craniectomy for traumatic brain injury (TBI), subdural hematoma, hemorrhagic or ischemic stroke, epidural hematoma, and subarachnoid hemorrhage (SAH). The aim of the study was to identify the predictors of infections, seizures, hydrocephalus, and hematoma in the postoperative setting (in vascular patients specifically). We selected our patients to be comparable, as much as possible, in their baseline risks and pathological entity. Therefore, we excluded patients with craniotomy for seizure, infectious disease, and tumors.

Variables Studied

Patient demographic data including age and sex were collected, in addition to the following medical comorbidities: smoking history, hypertension, diabetes mellitus (DM), therapeutic indication for craniectomy (reason for craniectomy), urgency of the therapeutic craniectomy, and the cranioplasty graft material. Complications related to the cranioplasty were identified as postoperative hematoma requiring reoperation, infection of the cranioplasty graft, postcranioplasty hydrocephalus, postcranioplasty seizure, and death.

The variables were defined as follows. 1) Diabetes mellitus: any patient who has been diagnosed with DM Type 1 or Type 2. Patients were not stratified according to hemoglobin A1C level. 2) Hypertension: any patient who has been diagnosed with Stage 1 or more hypertension. Patients were not stratified to controlled versus uncontrolled hypertension. 3) Smoking: any patient who had smoked in the past, regardless of the number of packyears. A patient who stopped smoking after the craniectomy was still counted as a smoker. 4) Graft material: categorized as autologous or synthetic. 5) Urgency of craniotomy: categorized into urgent versus elective. 6) Location: convexity cranioplasty, bifrontal cranioplasty, suboccipital cranioplasty. 7) Postcranioplasty seizure: any patient who experienced a seizure after the cranioplasty operation. 8) Reoperation for hematoma: any intracranial hematoma that occurred after the cranioplasty and required an operation for evacuation. 9) Postcranioplasty hydrocephalus: a hydrocephalus that developed after the cranioplasty, documented by a CT scan. 10) Postcranioplasty infection: any case of graft infection that needed to be removed or any case in which infection was suspected and antibiotic therapy was administered for more than 2 weeks, regardless of culture results. 11) Race: Caucasian, African American, Asian, and Hispanic. 12) Reason for craniectomy: SAH, TBI, nontraumatic epidural hematoma, nontraumatic subdural hematoma, ischemic stroke, and hemorrhagic stroke.

Statistical Analysis

Data are presented as the mean and range for continuous variables, and as frequency for categorical variables. Analysis was performed using the unpaired t-test, chi-square, or Fisher exact tests as appropriate. Univariate analysis was used to test covariates predictive of cranioplasty complication. Interaction and confounding was assessed through stratification and relevant expansion covariates. Factors that were predictive in univariate analysis (p < 0.15)2 were entered into a multivariate logistic regression analysis. Probability values of ≤ 0.05 were considered statistically significant. Statistical analysis was performed with Stata version 10.0 software (StataCorp LP). Confidence intervals were calculated as the 95% CI.

Results

Baseline Characteristics

We enrolled 348 patients in our study. Patient demographic data and surgical indications are included in Table 1. The mean age (± SD) was 46.5 ± 12.7 years. The proportion of male patients in the study was 50.86%. The majority of the patients were Caucasians (72.99%), followed by African Americans (16.09%), Hispanics (6.90%), and Asians (4.02%). Diabetic patients constituted 14.94% (52 of 348) of the study population. The proportion of patients with hypertension was 54.31% (189 of 348), and the proportion of smokers was 47.13% (164 of 348). The majority of patients received autologous bone graft (67.24%). The most common indication for craniectomy was SAH (52.01%) followed by stroke (27.01%) and TBI (18.96%).

TABLE 1

Characteristics of 348 patients who underwent cranioplasty

VariableNo.
Sex
 Male177
 Female171
Mean age (yrs) ± SD46.5 ± 12.7
Race
 Caucasian254
 African American56
 Hispanic24
 Asian14
Smoking status164 smokers
Diabetic status52 patients w/ DM
Blood pressure189 patients w/ hypertension
Craniectomy indication
 SAH181
 TBI66
 Stroke94
 EDH/SDH7

EDH = epidural hematoma; SDH = subdural hematoma.

Predictors of Overall Complications

We studied the association between each of the following variables—age, sex, race, hypertension, DM, smoking status, reason for craniotomy, urgency status, and cranioplasty location—and the development of any complication postcranioplasty. The list of complications was as follows: reoperation for hematoma evacuation, postcranioplasty hydrocephalus, postcranioplasty seizures, and postcranioplasty infection.

The overall complication rate was 31.32% (109 of 348). The mortality rate was 3.16%. Table 2 lists the proportion of each complication encountered. Univariate predictors included in multivariate analysis were age, DM, hypertension, and hemorrhagic stroke. Univariate analysis applied for graft material type showed no difference between synthetic and autologous bone graft (OR 1.34; p = 0.20). In multivariate analysis, hypertension (OR 1.92, CI 1.22–3.02), increasing age (OR 1.02, CI 1.00–1.04), and hemorrhagic stroke (OR 3.84, CI 1.93–7.63) predicted complications (Table 3).

TABLE 2

Postcranioplasty complications and their proportions

Authors & YearNo. of PatientsMost Common IndicationComplications
OverallSeizuresSurgical Site HematomaHydrocephalusOverall InfectionSuperficial InfectionDeep InfectionDeath
Present study348SAH (52%)31.32%14.37%6.90%13.51%26.43%14.94%11.49%3.16%
Broughton et al., 201487TBI (46%)30.0%5.7%10.3%2.3%
Lee et al., 2013236TBI (60.17%)25.92%14.81%1.65%
Wachter et al., 2013136TBI (38.2%)30.1%6.6%
Gooch et al., 200962TBI (66%)33.8%11.3%
TABLE 3

Predictor of complications on multivariate analysis

PredictorsORp Value95% CI
Hypertension1.920.0051.22–3.02
Increasing age1.020.0291.00–1.04
Hemorrhagic stroke3.84<0.0011.93–7.63

Predictors of Postcranioplasty Hydrocephalus

Multivariate logistic regression analysis identified increasing age (OR 1.05, CI 1.011–1.08), therapeutic indication for SAH (OR 2.04, CI 1.16–3.58), and therapeutic indication for TBI (OR 2.12, CI 1.23–3.65) as significant predictors of postcranioplasty hydrocephalus development, whereas male sex was found to have a protective effect (OR 0.39, CI 0.19–0.80) (Table 4). Smoking was associated with postoperative hydrocephalus (OR 1.91, p = 0.001) in univariate analysis, but the association was no longer significant in multivariate analysis (OR 1.89, CI 0.94–3.80). The other variables (race, hypertension, DM, urgency status, graft material, cranioplasty location) did not affect the risk of hydrocephalus development in univariate analysis, and therefore were excluded from multivariate analysis.

TABLE 4

Multivariate analysis of hydrocephalus predictors

PredictorsORp Value95% CI
Male sex0.390.0100.19–0.80
Increasing age1.050.0041.011–1.08
Smoking1.890.0730.94–3.80
SAH2.040.0131.16–3.58
TBI2.120.0071.23–3.65

Predictors of Reoperation for Hematoma Evacuation

Multivariate logistic analysis (Table 5) identified male sex (OR 2.87, CI 1.13–7.25), African American race (OR 3.82, CI 1.50–9.72), and hypertension (OR 3.72, CI 2.93–5.30) as predictors of subsequent reoperation for hematoma evacuation. Right-sided hemicraniectomy was associated with a higher risk in univariate analysis, but the risk was no longer significant when multivariate analysis was applied (OR 4.32, CI 0.98–19.00). Urgency status, smoking, diabetic status, age, graft material, and reason for craniectomy were not associated with reoperation for hematoma evacuation in univariate analysis, and were therefore excluded from the multivariate analysis.

TABLE 5

Multivariate predictors of reoperation for hematoma

PredictorsORp Value95% CI
Male sex2.870.0261.13–7.25
African American race3.820.0051.50–9.72
Convexity hemicraniectomy4.320.0600.98–19.00
Hypertension3.72<0.0012.93–5.30

Predictors of Infection

All patients who underwent cranioplasty have received perioperative cefazolin. We also evaluated whether postcranioplasty hydrocephalus and reoperation for hematoma evacuation could affect the risk of infection, as long as these complications preceded the infection of the graft. Univariate analysis revealed that increasing age (OR 3.37, p = 0.05), DM (OR 1.84, p < 0.05), hemorrhagic stroke (OR 5.27, p < 0.05), postcranioplasty hydrocephalus (OR 1.91, p < 0.05), and reoperation for hematoma evacuation (OR 2.67, p = 0.051) were predictive of infection. Bilateral convexity cranioplasty showed a higher rate of infection when compared with suboccipital, bifrontal, and unilateral convexity cranioplasty (OR 12.01, p < 0.05) in univariate analysis. Sex, race, hypertension, smoking, graft material, and urgency status did not increase the risk of infection. In multivariate analysis (Table 6), bilateral convexity cranioplasty (OR 14.41, CI 1.52–36.66), postcranioplasty hydrocephalus (OR 1.90, CI 0.99–3.65; p = 0.05), and hemorrhagic stroke (OR 4.33, CI 1.66–11.34) remained associated with a higher risk of infection, whereas reoperation for hematoma evacuation showed a higher trend (OR 1.90, p = 0.054) but was not statistically significant (not shown).

TABLE 6

Multivariate predictors of infection

PredictorsORp Value95% CI
Bilat convexity cranioplasty14.410.0201.52–36.66
Hemorrhagic stroke4.330.0031.66–11.34
Hydrocephalus*1.900.0500.99–3.65
Older age (>65 yrs)0.270.0500.07–1.00

Hydrocephalus that appeared after cranioplasty.

Predictors of Seizure

We excluded from the analysis any patient who had experienced a seizure before the cranioplasty or any patients who were receiving antiepileptic drugs (AEDs). The large majority of patients who were temporarily receiving AEDs were no longer taking these drugs by the time of cranioplasty. Patients who were receiving long-term AEDs were excluded from the analysis, because they had experienced a seizure before cranioplasty or had a base-line disease (epilepsy) for which they were being treated with the drugs. Therefore, none of the patients analyzed in the seizure cohort was receiving AEDs at time of the cranioplasty surgery.

We also evaluated whether postcranioplasty infection, reoperation for hematoma, and postcranioplasty hydrocephalus affected the risk of seizures, provided they occurred before the seizure's onset. Univariate analysis revealed the following variables to be associated with a higher risk of postcranioplasty seizure: male sex (OR 2.37, p < 0.05), older age of > 60 years (OR 1.02, p < 0.05), bifrontal and convexity cranioplasty location when compared with suboccipital (OR 9.43, p < 0.05), decompressive hemicraniectomy (DHC) for trauma (OR 3.22, p < 0.05), cranioplasty site infection (OR 4.54, p < 0.05), and reoperation for hematoma evacuation (OR 3.40, p < 0.05). Smoking, hypertension, DM, race, and urgency status did reach statistical significance. There was no difference in seizure rate between patients who had a synthetic graft and those who had an autologous bone graft. In multivariate analysis (Table 7), male sex (OR 2.35, CI 1.14–4.85), increasing age (OR 1.04, CI 1.01–1.07), and cranioplasty graft infection (OR 4.12, CI 2.07–8.20) were associated with a higher risk of postcranioplasty seizure development. Trauma (OR 2.18, CI 0.93–5.09; p = 0.07) and cranioplasty location (OR 2.86, CI 0.93–8.81; p = 0.06) showed a trend of increased risk but did not achieve statistical significance.

TABLE 7

Multivariate analysis of seizure development

PredictorsORp Value95% CI
Male sex2.350.0201.14–4.85
Increasing age1.040.0051.01–1.07
Infection4.120.0002.07–8.20
Trauma2.180.0720.93–5.09
Bifrontal & convexity cranioplasty2.860.0670.93–8.81

Predictors of Mortality

We tested the following predictors: age, sex, race, diabetic status, hypertensive status, smoking, reason for craniectomy, urgency status of craniectomy, location of cranioplasty, graft material type, reoperation for hematoma evacuation, hydrocephalus postcranioplasty, graft infection, and seizure postcranioplasty. In multivariate analysis (Table 8), only DM (OR 7.56, CI 1.56–36.58), seizures (OR 7.25, CI 1.238–42.79), bifrontal cranioplasty (OR 5.40, CI 1.20–24.27), and repeated surgery for hematoma evacuation (OR 13.00, CI 1.51–112.02) predicted death.

TABLE 8

Multivariate analysis of predictors of mortality

PredictorsORp Value95% CI
DM7.560.0121.56–36.58
Bifrontal cranioplasty5.400.0281.20–24.27
Postcranioplasty seizures7.250.0291.238–42.79
Reop for hematoma evacuation13.000.0201.51–112.02

Discussion

Overview of Cranioplasty Complications

Cranioplasty is associated with a relatively high overall complication rate, estimated between 15% and 36.5%.8,10,13,17,27,30,35,39,41,47,49 Furthermore, 25%–76% of patients with postcranioplasty complications may need additional procedures to correct these complications.17,46 Therefore it is of paramount importance to understand, prevent, and treat the complications as they arise. The overall complication rate in our study was relatively high because the list of complications that we included was more exhaustive than in previous series. Another reason is that the definition of infected cranioplasty was not limited to cases that required reoperation. The complications in our study were as follows: postcranioplasty hydrocephalus, reoperation for hematoma evacuation, superficial and deep infection, new-onset seizure, and death. We did not include subgaleal fluid collection, bone desorption, and wound dehiscence that was not due to infection. The most common cause of craniectomy was SAH, followed by stroke, and then by TBI (the last being the most common cause of DHC in the literature).3,7,17,39,42,51 The aim of this study was to determine the most important predictors of complications and death.

Patient-specific and surgery-specific factors are historically reported to be the most important determinant of complications following cranioplasty. Recently, most studies have reported limited contributions of surgery-specific factors or implant material on the overall complication rate following cranioplasty. In addition, the data on time interval have been contradictory. Predictors of mortality have not been previously thoroughly examined. In our study, in addition to demographic data, we included in the analysis smoking status, hypertension, DM, the reason for cranioplasty, the urgency of the procedure, and graft type.

Demographic Information and Associated Comorbidities

We found that increased age and hypertension were associated with higher risk of complications. Smoking was associated with an increased risk of hydrocephalus development in univariate analysis, and showed a strong trend in multivariate analysis. A recent study by Wachter et al. identified smoking and older age (> 60 years) as factors associated with cranioplasty complications.46 These authors did not find sex to be a significant variable. We found that diabetic patients had a higher risk of death. Male patients had a higher rate of seizure, whereas females had a higher risk of hydrocephalus. Older age was also associated with seizure and hydrocephalus. Neurosurgeons should therefore recognize these factors (age, sex, DM, and smoking) as possible predictors of postoperative complications and take all necessary preventive measures.

Location of Cranioplasty

Patients with convexity cranioplasty had a higher risk of infections and postoperative hematoma requiring reoperation for evacuation when compared with bifrontal and suboccipital cranioplasties. We also found bifrontal cranioplasty to be associated with a higher risk of both seizure and death. Bifrontal defect was identified by Gooch et al.17 to be the only location significantly associated with cranioplasty complications. The authors postulated several reasons for this finding, such as a longer incision, a longer operative time, less soft-tissue coverage, and a possible violation of the frontal sinus. Indeed, frontal sinus breach has been reported to increase the risk of infection after cranioplasty.6,28

Timing, Infection, and Hydrocephalus

The timing of surgery is one of the most controversial topics in cranioplasty.4,11 Some studies have shown that patients who had early cranioplasties had better functional outcomes,3,5,46 whereas several others have shown that early cranioplasty (3–6 months) is associated with higher complication rates and worse outcomes,3,4,8–10,26,35,42 including hydrocephalus, increased intracranial pressure, and infection. Other studies have shown that late cranioplasty is associated with a higher risk of complications.17,38,42,48 Finally, recent studies, including a meta-analysis, have shown no difference in complication rates between early and late cranioplasties.5,24,39,51 We did not account for the timing of cranioplasty in our study because our patients underwent early operation unless there was a convincing need to delay it, such as the presence of wound dehiscence, hydrocephalus, or evidence of persistent brain swelling. We balanced the wait for maximal neurological improvement with early intervention to prevent hemodynamic changes in the CSF and cerebral blood flow that may occur if the flap was left out for a prolonged period of time.5 Still, the large majority of our patients have undergone early cranioplasty (within 3 months). We found no significant association of age, sex, DM, and mechanism of injury (SAH, trauma, ischemic stroke) with postcranioplasty infection, which is consistent with the published literature.22,29 Reoperation for hematoma showed no significant effect in our study, even though the need for multiple procedures has been shown to increase the risk of cranioplasty site infection.29,43,47 On the other hand, Cheng et al.'s work9 showed that the number of procedures does not affect the risk of graft infection following cranioplasty.

We found hemorrhagic stroke to be predictive of infection. One reason would be shared risk factors between stroke and infection, such as DM and smoking.15,45 Even though it has been proven that DM50 and smoking40 increase the risk of surgical infection, the association did not achieve statistical significance in our study. We believe that the lack of a significant effect of smoking and DM might be related to the fact that stratification did not account for present and past smokers, as well as controlled and uncontrolled DM. In many of our patients their DM was controlled, and many had quit smoking after experiencing a stroke or an SAH. Quitting smoking and controlling DM have been well known to decrease the patient's risk of developing postsurgery infection.16,32 Cranioplasty has been reported to contribute to the development of persistent hydrocephalus requiring permanent CSF flow diversion.48 We found that female sex, increasing age, and craniectomy for SAH increased the risk of postcranioplasty hydrocephalus.

Postcranioplasty Hemorrhage

Postcranioplasty hemorrhage includes epidural, subdural, and intraparenchymal hematomas that required reoperation.6,17,36 Postcranioplasty hemorrhage has been previously explained by many mechanisms, the most important of which is persistent bleeding by a scalp artery,36 along with a negative transluminal pressure caused by a subgaleal drain.37 Gooch and colleagues17 found that bifrontal cranial defect was associated with a need for reoperation, including infection and hematoma evacuation. The authors, however, only studied the complications that occurred within 30 days of surgery. In our study, convexity location showed a trend of higher risk of reoperation for hematoma evacuation when compared with suboccipital and bifrontal locations. Other significant risk factors in multivariate analysis were male sex and African American race. Although this finding may be due to the presence of hypertension, this factor was controlled for in multivariate analysis, which suggests that male sex and African American race are independent predictors of hemorrhage. The problem with subjecting a patient to another surgery is the increased risk of further complications8 and the increased length of hospital stay. Indeed, in our study, patients undergoing another operation for hematoma evacuation had a significantly higher mortality rate.

Postcranioplasty Seizures

Seizures that follow cranioplasty surgery might be the result of the underlying cause, the DHC surgery, or the cranioplasty operation itself. Surgery might produces free radicals, disturb the ionic balance, and manipulate the cerebral parenchyma, all of which have been postulated as mechanisms for postoperative seizure formation.25,48 In the literature, TBI, hemorrhagic stroke, and neurological deficits before cranioplasty increased the risk of seizures.25 In our study, we found that male sex, cranioplasty infection, and older age were significantly associated with seizures. Furthermore, seizure itself was significantly associated with death. On univariate analysis, reoperation for hematoma evacuation was a predictor of seizure (OR 3.40, p < 0.05), but the association was no longer significant on multivariate analysis. Male sex and older age have been described as independent factors for first adult seizure in the general population.18,20,23,31,44

Other Predictors

Graft material (synthetic vs autologous) failed to show any significant association with seizure, infection, death, or any other complication. The Glasgow Coma Scale, preoperative Barthel Index, and the Coma Remission Scale may predict the risk of cranioplasty complications.5,46 Even though the risk of infection with autologous graft can get relatively high (up to 33%),12,33,34,52 many studies, including ours, suggest no difference in the infection rate between synthetic and autologous grafts.9,47

Limitations and Strengths of the Study

The limitations of this study are the retrospective design; a possible selection bias; and the lack of stratification of diabetic, smoker, and hypertensive patients. The study also did not include any surgery-specific risk factor. We did not study the association between the timing of cranioplasty and outcomes, although this might affect the results. The strength of the study is the long-term follow-up and the large size of the cohort, allowing for a robust statistical analysis. Both the long follow-up and the large number of patients allowed the evaluation of rare complications.

Conclusions

Cranioplasty complications include infections, hydrocephalus, multiple operations, seizures, and even death. The independent predictors of mortality in the present series were DM, postcranioplasty seizure, reoperation for hematoma evacuation, and therapeutic indication for hemorrhagic stroke. Male sex could predispose a patient to seizures and additional operations. African American race also seemed to play a role in the development of hematoma requiring operation. Other important findings were the association of bilateral convexity cranioplasty with infections. Finally, old age was a predictor of postcranioplasty seizure. Our goal was to provide the neurosurgeon with predictors of morbidity and mortality that could be incorporated in the clinical decision-making algorithm. Control of the patient's risk factors and early recognition of complications may help avoid the exhaustive list of complications. Prospective multicenter trials are needed to settle the controversial question of risk factors.

Author Contributions

Conception and design: Tjoumakaris, Chalouhi, Starke, Clark, Jabbour, Rosenwasser. Acquisition of data: Zanaty, Clark, Bovenzi, Saigh, Schwartz, Kunkel, Efthimiadis-Budike, Dalyai. Analysis and interpretation of data: Zanaty, Chalouhi, Starke, Bovenzi, Saigh, Schwartz, Kunkel, Efthimiadis-Budike. Drafting the article: Tjoumakaris, Zanaty. Critically revising the article: Tjoumakaris, Chalouhi. Reviewed submitted version of manuscript: Zanaty, Chalouhi, Starke, Clark, Bovenzi, Saigh, Schwartz, Kunkel, Efthimiadis-Budike, Jabbour, Dalyai, Rosenwasser. Statistical analysis: Starke. Study supervision: Tjoumakaris, Jabbour.

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    Hauser WAAnnegers JFKurland LT: Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 34:4534681993

  • 19

    Honeybul SJanzen CKruger KHo KM: The impact of cranioplasty on neurological function. Br J Neurosurg 27:6366412013

  • 20

    Hopkins AGarman AClarke C: The first seizure in adult life. Value of clinical features, electroencephalography, and computerised tomographic scanning in prediction of seizure recurrence. Lancet 331:7217261988

  • 21

    Janzen CKruger KHoneybul S: Syndrome of the trephined following bifrontal decompressive craniectomy: implications for rehabilitation. Brain Inj 26:1011052012

  • 22

    Kim HSung SOKim SJKim SRPark ISJo KW: Analysis of the factors affecting graft infection after cranioplasty. Acta Neurochir (Wien) 155:217121762013

  • 23

    King MANewton MRJackson GDFitt GJMitchell LASilvapulle MJ: Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients. Lancet 352:100710111998

  • 24

    Lee CHChung YSLee SHYang HJSon YJ: Analysis of the factors influencing bone graft infection after cranioplasty. J Trauma Acute Care Surg 73:2552602012

  • 25

    Lee LKer JQuah BLChou NChoy DYeo TT: A retrospective analysis and review of an institution's experience with the complications of cranioplasty. Br J Neurosurg 27:6296352013

  • 26

    Liang WXiaofeng YWeiguo LGang SXuesheng ZFei C: Cranioplasty of large cranial defect at an early stage after decompressive craniectomy performed for severe head trauma. J Craniofac Surg 18:5265322007

  • 27

    Lu YHui GLiu FWang ZTang YGao S: Survival and regeneration of deep-freeze preserved autologous cranial bones after cranioplasty. Br J Neurosurg 26:2162212012

  • 28

    Marchac DGreensmith A: Long-term experience with methylmethacrylate cranioplasty in craniofacial surgery. J Plast Reconstr Aesthet Surg 61:7447532008

  • 29

    Matsuno ATanaka HIwamuro HTakanashi SMiyawaki SNakashima M: Analyses of the factors influencing bone graft infection after delayed cranioplasty. Acta Neurochir (Wien) 148:5355402006

  • 30

    Morina AKelmendi FMorina QDragusha SAhmeti FMorina D: Cranioplasty with subcutaneously preserved autologous bone grafts in abdominal wall—experience with 75 cases in a post-war country Kosova. Surgical Neurol Int 2:722011

  • 31

    Musicco MBeghi ESolari AViani F: Treatment of first tonic-clonic seizure does not improve the prognosis of epilepsy. Neurology 49:9919981997

  • 32

    Nagachinta TStephens MReitz BPolk BF: Risk factors for surgical-wound infection following cardiac surgery. J Infect Dis 156:9679731987

  • 33

    Odom GLWoodhall BWrenn FR: The use of refrigerated autogenous bone flaps for cranioplasty. J Neurosurg 9:6066101952

  • 34

    Osawa MHara HIchinose YKoyama TKobayashi SSugita Y: Cranioplasty with a frozen and autoclaved bone flap. Acta Neurochir (Wien) 102:38411990

  • 35

    Piedra MPThompson EMSelden NRRagel BTGuillaume DJ: Optimal timing of autologous cranioplasty after decompressive craniectomy in children. J Neurosurg Pediatr 10:2682722012

  • 36

    Rish BLDillon JDMeirowsky AMCaveness WFMohr JPKistler JP: Cranioplasty: a review of 1030 cases of penetrating head injury. Neurosurgery 4:3813851979

  • 37

    Roth JGaleano EMilla SHartmannsgruber MWWeiner HL: Multiple epidural hematomas and hemodynamic collapse caused by a subgaleal drain and suction-induced intracranial hypotension: case report. Neurosurgery 68:E271E2762011

  • 38

    Schuss PVatter HMarquardt GImöhl LUlrich CTSeifert V: Cranioplasty after decompressive craniectomy: the effect of timing on postoperative complications. J Neurotrauma 29:109010952012

  • 39

    Sobani ZAShamim MSZafar SNQadeer MBilal NMurtaza SG: Cranioplasty after decompressive craniectomy: an institutional audit and analysis of factors related to complications. Surg Neurol Int 2:1232011

  • 40

    Sorensen LTKarlsmark TGottrup F: Abstinence from smoking reduces incisional wound infection: a randomized controlled trial. Ann Surg 238:152003

  • 41

    Stephens FLMossop CMBell RSTigno T JrRosner MKKumar A: Cranioplasty complications following wartime decompressive craniectomy. Neurosurg Focus 28:5E32010

  • 42

    Thavarajah DDe Lacy PHussien ASugar A: The minimum time for cranioplasty insertion from craniectomy is six months to reduce risk of infection—a case series of 82 patients. Br J Neurosurg 26:78802012

  • 43

    Tokoro KChiba YTsubone K: Late infection after cranioplasty—review of 14 cases. Neurol Med Chir (Tokyo) 29:1962011989

  • 44

    van Donselaar CASchimsheimer RJGeerts ATDeclerck AC: Value of the electroencephalogram in adult patients with untreated idiopathic first seizures. Arch Neurol 49:2312371992

  • 45

    von Sarnowski BPutaala JGrittner UGaertner BSchminke UCurtze S: Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study. Stroke 44:1191252013

  • 46

    Wachter DReineke KBehm TRohde V: Cranioplasty after decompressive hemicraniectomy: underestimated surgery-associated complications?. Clin Neurol Neurosurg 115:129312972013

  • 47

    Walcott BPKwon CSSheth SAFehnel CRKoffie RMAsaad WF: Predictors of cranioplasty complications in stroke and trauma patients. J Neurosurg 118:7577622013

  • 48

    Waziri AFusco DMayer SAMcKhann GM IIConnolly ES Jr: Postoperative hydrocephalus in patients undergoing decompressive hemicraniectomy for ischemic or hemorrhagic stroke. Neurosurgery 61:4894942007

  • 49

    Wiggins AAusterberry RMorrison DHo KMHoneybul S: Cranioplasty with custom-made titanium plates—14 years experience. Neurosurgery 72:2482562013

  • 50

    Wukich DKLowery NJMcMillen RLFrykberg RG: Postoperative infection rates in foot and ankle surgery: a comparison of patients with and without diabetes mellitus. J Bone Joint Surg Am 92:2872952010

  • 51

    Yadla SCampbell PGChitale RMaltenfort MGJabbour PSharan AD: Effect of early surgery, material, and method of flap preservation on cranioplasty infections: a systematic review. Neurosurgery 68:112411302011

  • 52

    Yamada HSakai NTakada MAndo TKagawa Y: Cranioplasty utilizing a preserved autogenous bone flap coated with acrylic resin. Acta Neurochir (Wien) 52:2732801980

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Article Information

Correspondence Stavropoula I. Tjoumakaris, Department of Neurological Surgery, Division of Neurovascular Surgery and Endovascular Neurosurgery, Thomas Jefferson University Hospital, 901 Walnut St., 3rd Fl., Philadelphia, PA 19107. email: stavropoula.tjoumakaris@jefferson.edu.

INCLUDE WHEN CITING Published online March 13, 2015; DOI: 10.3171/2014.9.JNS14405.

DISCLOSURE Dr. Tjoumakaris is a consultant at Stryker.

© AANS, except where prohibited by US copyright law.

Headings

References

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Agner CDujovny MGaviria M: Neurocognitive assessment before and after cranioplasty. Acta Neurochir (Wien) 144:103310402002

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Archavlis ECarvi YNievas M: The impact of timing of cranioplasty in patients with large cranial defects after decompressive hemicraniectomy. Acta Neurochir (Wien) 154:105510622012

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Beauchamp KMKashuk JMoore EEBolles GRabb CSeinfeld J: Cranioplasty after postinjury decompressive craniectomy: is timing of the essence?. J Trauma 69:2702742010

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Bender AHeulin SRöhrer SMehrkens JHHeidecke VStraube A: Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Inj 27:107310792013

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Blum KSSchneider SJRosenthal AD: Methyl methacrylate cranioplasty in children: long-term results. Pediatr Neurosurg 26:33351997

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Broughton EPobereskin LWhitfield PC: Seven years of cranioplasty in a regional neurosurgical centre. Br J Neurosurg 28:34392014

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Chang VHartzfeld PLanglois MMahmood ASeyfried D: Outcomes of cranial repair after craniectomy. J Neurosurg 112:112011242010

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Cheng YKWeng HHYang JTLee MHWang TCChang CN: Factors affecting graft infection after cranioplasty. J Clin Neurosci 15:111511192008

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Chibbaro SDi Rocco FMirone GFricia MMakiese ODi Emidio P: Decompressive craniectomy and early cranioplasty for the management of severe head injury: a prospective multicenter study on 147 patients. World Neurosurg 75:5585622011

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Chun HJYi HJ: Efficacy and safety of early cranioplasty, at least within 1 month. J Craniofac Surg 22:2032072011

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Crotti FMMangiagalli EP: Cranial defects repair by replacing bone flaps. J Neurosurg Sci 23:2892941979

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De Bonis PFrassanito PMangiola ANucci CGAnile CPompucci A: Cranial repair: how complicated is filling a “hole”?. J Neurotrauma 29:107110762012

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Di Stefano CSturiale CTrentini PBonora RRossi DCervigni G: Unexpected neuropsychological improvement after cranioplasty: a case series study. Br J Neurosurg 26:8278312012

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Elkind MS: Epidemiology and risk factors. Continuum (Minneap Minn) 17:6 Secondary Stroke Prevention121312322011

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Furnary APGao GGrunkemeier GLWu YZerr KJBookin SO: Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:100710212003

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Gooch MRGin GEKenning TJGerman JW: Complications of cranioplasty following decompressive craniectomy: analysis of 62 cases. Neurosurg Focus 26:6E92009

18

Hauser WAAnnegers JFKurland LT: Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 34:4534681993

19

Honeybul SJanzen CKruger KHo KM: The impact of cranioplasty on neurological function. Br J Neurosurg 27:6366412013

20

Hopkins AGarman AClarke C: The first seizure in adult life. Value of clinical features, electroencephalography, and computerised tomographic scanning in prediction of seizure recurrence. Lancet 331:7217261988

21

Janzen CKruger KHoneybul S: Syndrome of the trephined following bifrontal decompressive craniectomy: implications for rehabilitation. Brain Inj 26:1011052012

22

Kim HSung SOKim SJKim SRPark ISJo KW: Analysis of the factors affecting graft infection after cranioplasty. Acta Neurochir (Wien) 155:217121762013

23

King MANewton MRJackson GDFitt GJMitchell LASilvapulle MJ: Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients. Lancet 352:100710111998

24

Lee CHChung YSLee SHYang HJSon YJ: Analysis of the factors influencing bone graft infection after cranioplasty. J Trauma Acute Care Surg 73:2552602012

25

Lee LKer JQuah BLChou NChoy DYeo TT: A retrospective analysis and review of an institution's experience with the complications of cranioplasty. Br J Neurosurg 27:6296352013

26

Liang WXiaofeng YWeiguo LGang SXuesheng ZFei C: Cranioplasty of large cranial defect at an early stage after decompressive craniectomy performed for severe head trauma. J Craniofac Surg 18:5265322007

27

Lu YHui GLiu FWang ZTang YGao S: Survival and regeneration of deep-freeze preserved autologous cranial bones after cranioplasty. Br J Neurosurg 26:2162212012

28

Marchac DGreensmith A: Long-term experience with methylmethacrylate cranioplasty in craniofacial surgery. J Plast Reconstr Aesthet Surg 61:7447532008

29

Matsuno ATanaka HIwamuro HTakanashi SMiyawaki SNakashima M: Analyses of the factors influencing bone graft infection after delayed cranioplasty. Acta Neurochir (Wien) 148:5355402006

30

Morina AKelmendi FMorina QDragusha SAhmeti FMorina D: Cranioplasty with subcutaneously preserved autologous bone grafts in abdominal wall—experience with 75 cases in a post-war country Kosova. Surgical Neurol Int 2:722011

31

Musicco MBeghi ESolari AViani F: Treatment of first tonic-clonic seizure does not improve the prognosis of epilepsy. Neurology 49:9919981997

32

Nagachinta TStephens MReitz BPolk BF: Risk factors for surgical-wound infection following cardiac surgery. J Infect Dis 156:9679731987

33

Odom GLWoodhall BWrenn FR: The use of refrigerated autogenous bone flaps for cranioplasty. J Neurosurg 9:6066101952

34

Osawa MHara HIchinose YKoyama TKobayashi SSugita Y: Cranioplasty with a frozen and autoclaved bone flap. Acta Neurochir (Wien) 102:38411990

35

Piedra MPThompson EMSelden NRRagel BTGuillaume DJ: Optimal timing of autologous cranioplasty after decompressive craniectomy in children. J Neurosurg Pediatr 10:2682722012

36

Rish BLDillon JDMeirowsky AMCaveness WFMohr JPKistler JP: Cranioplasty: a review of 1030 cases of penetrating head injury. Neurosurgery 4:3813851979

37

Roth JGaleano EMilla SHartmannsgruber MWWeiner HL: Multiple epidural hematomas and hemodynamic collapse caused by a subgaleal drain and suction-induced intracranial hypotension: case report. Neurosurgery 68:E271E2762011

38

Schuss PVatter HMarquardt GImöhl LUlrich CTSeifert V: Cranioplasty after decompressive craniectomy: the effect of timing on postoperative complications. J Neurotrauma 29:109010952012

39

Sobani ZAShamim MSZafar SNQadeer MBilal NMurtaza SG: Cranioplasty after decompressive craniectomy: an institutional audit and analysis of factors related to complications. Surg Neurol Int 2:1232011

40

Sorensen LTKarlsmark TGottrup F: Abstinence from smoking reduces incisional wound infection: a randomized controlled trial. Ann Surg 238:152003

41

Stephens FLMossop CMBell RSTigno T JrRosner MKKumar A: Cranioplasty complications following wartime decompressive craniectomy. Neurosurg Focus 28:5E32010

42

Thavarajah DDe Lacy PHussien ASugar A: The minimum time for cranioplasty insertion from craniectomy is six months to reduce risk of infection—a case series of 82 patients. Br J Neurosurg 26:78802012

43

Tokoro KChiba YTsubone K: Late infection after cranioplasty—review of 14 cases. Neurol Med Chir (Tokyo) 29:1962011989

44

van Donselaar CASchimsheimer RJGeerts ATDeclerck AC: Value of the electroencephalogram in adult patients with untreated idiopathic first seizures. Arch Neurol 49:2312371992

45

von Sarnowski BPutaala JGrittner UGaertner BSchminke UCurtze S: Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study. Stroke 44:1191252013

46

Wachter DReineke KBehm TRohde V: Cranioplasty after decompressive hemicraniectomy: underestimated surgery-associated complications?. Clin Neurol Neurosurg 115:129312972013

47

Walcott BPKwon CSSheth SAFehnel CRKoffie RMAsaad WF: Predictors of cranioplasty complications in stroke and trauma patients. J Neurosurg 118:7577622013

48

Waziri AFusco DMayer SAMcKhann GM IIConnolly ES Jr: Postoperative hydrocephalus in patients undergoing decompressive hemicraniectomy for ischemic or hemorrhagic stroke. Neurosurgery 61:4894942007

49

Wiggins AAusterberry RMorrison DHo KMHoneybul S: Cranioplasty with custom-made titanium plates—14 years experience. Neurosurgery 72:2482562013

50

Wukich DKLowery NJMcMillen RLFrykberg RG: Postoperative infection rates in foot and ankle surgery: a comparison of patients with and without diabetes mellitus. J Bone Joint Surg Am 92:2872952010

51

Yadla SCampbell PGChitale RMaltenfort MGJabbour PSharan AD: Effect of early surgery, material, and method of flap preservation on cranioplasty infections: a systematic review. Neurosurgery 68:112411302011

52

Yamada HSakai NTakada MAndo TKagawa Y: Cranioplasty utilizing a preserved autogenous bone flap coated with acrylic resin. Acta Neurochir (Wien) 52:2732801980

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