A Systematic Review and Meta-Analysis James G

Literature Review

Autologous Cranioplasty is Associated with Increased Reoperation Rate: A Systematic Review and Meta-Analysis James G. Malcolm1, Zayan Mahmooth1, Rima S. Rindler1, Jason W. Allen2, Jonathan A. Grossberg1, Gustavo Pradilla1, Faiz U. Ahmad1

Key words - OBJECTIVE: Consensus regarding selection of synthetic versus autologous - Complication flap reimplantation for cranioplasty after decompressive craniectomy has not - Cranioplasty - Infection been reached and the multiple factors considered for each patient make - Material comparative analysis challenging. This study examines the association between - Synthetic choice of material and related complications. - Reoperation - Resorption - METHODS: A systematic literature review and meta-analysis were performed using PubMed for articles reporting delayed cranioplasty after decompressive Abbreviations and Acronyms CI: Confidence interval craniectomy using a cohort design comparing autologous bone and synthetic OR: Odds ratio implants. Extracted data included implant material and incidence of infection, reoperations related to implant, wound complications, and resorption. From the Departments of 1Neurosurgery and 2Radiology, Emory University, Atlanta, Georgia, USA - RESULTS: One randomized controlled trial and 11 cohort studies were To whom correspondence should be addressed: included for a total of 1586 implants (950 bone, 636 synthetic). Autologous im- Faiz U. Ahmad, M.D. plants had significantly more reoperations than did synthetic implants (n [ 1586 [E-mail: [email protected]] implants; odds ratio [OR], 1.91; 95% confidence interval [CI], 1.40e2.61). Reop- Citation: World Neurosurg. (2018) 116:60-68. https://doi.org/10.1016/j.wneu.2018.05.009 erations were most often because of resorption (54%, n [ 159/295) followed by Journal homepage: www.WORLDNEUROSURGERY.org infection (41%, n [ 121/295). The pooled incidence of resorption in autologous Available online: www.sciencedirect.com implants was 20% (n [ 159/791). Among the other outcomes, there was no 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All significant difference for infections (n [ 1586; OR, 1.24; CI, 0.82e1.88) or wound rights reserved. complications (n [ 678; OR, 0.56; CI, 0.22e1.45). For the trauma subpopulation, there was no significant difference in infection rate with either material (n [ INTRODUCTION 197; OR, 1.89; CI; 0.59e6.09). Cranioplasty after decompressive craniec- - CONCLUSIONS: Autologous implants had significantly more reoperations tomy is a routine neurosurgical procedure to restore cosmesis, provide cerebral primarily because if the intrinsic risk of resorption (level of evidence 3b). protection, facilitate neurologic rehabilitation, and improve neurologic outcome.1 Cranioplasty, although considered the complications after cranioplasty using ((autologous OR bone OR allograft) AND routine by many, can be associated with either autologous bone or synthetic (synthetic OR bone-substitute OR poly- signiﬁcant morbidity.2-6 The choice of implants. methylmethacrylate OR PMMA OR tita- implant material has received nium OR acrylic OR hydroxyapatite))).” considerable attention as a potential The search was restricted to original 7-9 modiﬁable risk factor. This choice is METHODS clinical studies published between January typically at the discretion of the 2000 and April 2018. From preliminary operating surgeon or institution. In cases Search reading, studies preceding this period of fragmented or grossly infected bone, A systematic review of the literature tended to use nonstandard techniques or the use of synthetic implant seems adherent to PRISMA (Preferred Reporting materials no longer in common use, and obvious, but more often the choice is Items for Systematic Reviews and Meta- so the decision was made to exclude older one of cost or convenience. Analyses) guidelines was performed for studies. Thorough bibliographic searches The purpose of this study was to 1) published articles reporting on complica- of qualifying articles and relevant medical assess for reported associations between tions related to cranioplasty material.10 journals were also performed to identify implant material and subsequent compli- The PubMed/MEDLINE database was additional articles for inclusion. cations and 2) catalogue other risk factors searched for articles on cranioplasty for these complications. To answer these procedures that compared both bone Selection Criteria questions, a review of the literature and versus synthetic materials using the Articles reporting on complications after meta-analysis was performed to examine query: “cranioplasty AND (material OR cranioplasty using either autologous bone

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was used to quantify heterogeneity (0% ¼ no heterogeneity; 100% ¼ maximal heterogeneity).33 The c2 test was used to evaluate signiﬁcant differences between subgroups. P values < 0.05 were considered statistically signiﬁcant.

Assessment of Bias The study quality of individual articles was determined by using the Oxford Center for Evidence-Based Medicine guidelines.34 Risk of bias was assessed by the Newcastle-Ottawa Scale, which is a 3-category, 9-point scale assessing cohort selection, comparability, and outcome, with a higher score indicating higher quality.35

RESULTS Literature review results are shown in the Figure 1. PRISMA flow diagram. PRISMA flow diagram (Figure 1). The search identified 483 nonduplicate studies spanning January 1, 2000 to April 30, 2018. Five additional studies were or synthetic implant were included in the Data Extraction identified from bibliographies.31,36-39 analyses. With a large body of literature The following data were extracted from The final 12 included studies repre- mentioning material choice, only studies each article, if reported: number of sented 1586 cranioplasty procedures with a specifically designed to compare material patients, indication for initial craniectomy, clear preference toward use of a patient’s choice were included, (e.g., clinical trials number of autologous bone implants, own bone (950 bone, 636 synthetic). and cohort studies). Case series that number of synthetic implants, type of Table 1 lists individual study merely mention material choice were synthetic material, infection, reoperations, characteristics. Included were 1 excluded. Further, included studies must wound complications, clinically signifi- randomized controlled trial (Oxford have had at least 20 patients with at least 3 cant bone resorption (aseptic necrosis), Center for Evidence-Based Medicine evi- months follow-up. Technical notes, and any risk factors identified. If an dence level 1) and 11 cohort studies (level letters, and editorials were excluded. Re- implant included primarily bone but was 3b). Indications for initial craniectomy views were also excluded; however, refer- supplemented with allograft, it was included trauma (most common), enced articles were thoroughly screened considered an autograft.31 Nondestructive ischemic or hemorrhagic stroke, infection, for possible inclusion.2,7,11 Studies that processing of autologous bone was and tumors. Table 2 summarizes these involved animals, included noncalvarial or ignored (e.g., autoclave,31 fat characteristics across studies. maxillofacial procedures, or focused sonication32). A variety of synthetic implants were exclusively on the pediatric population used. Two of the most common were were excluded.12-14 Studies were excluded Statistical Analysis titanium and polymethylmethacrylate. if more than a quarter of patients under- Data were analyzed using Review Manager Various other combinations of pre- went nondecompressive single-stage cra- 5.3.5 (The Cochrane Collaboration). For fabricated or intraoperative molded im- niectomy (e.g., for resection of each complication, odds ratios (OR) and plants were made from polyethylene, meningioma).15,16 The search results were 95% confidence intervals (CI)s were polyetheretherketone, hydroxyapatite, and independently screened by 2 authors (J.M. calculated to estimate the odds of each various other acrylics and ceramics. and Z.M.); disagreements were resolved complication for autologous bone implant Autologous bone implants underwent a by consensus. The following studies were (i.e., OR <1 indicates bone is associated variety of handling protocols, most excluded: split calvarial or rib grafts,17-22 with decreased complication rate, whereas commonly soaking in betadine and frozen comparison only among different syn- synthetic material is associated with an storage; however, a few studies autoclaved thetic options,23-27 reporting data not increased rate). Odds ratios were pooled the bone before reimplantation. One study suitable for analysis,3,28 non-English lan- using the Mantel-Haenszel method with a used a method called Tutoplast processing guage,29 focused only on epidural fluid fixed-effects model, except where the c2 for autologous bone, which involves a collections,30 or a significant portion of test indicated significant heterogeneity combination of sonication to remove fat, patients with previous cranioplasty among studies, in which case a random- hydrogen peroxide to kill viruses, acetone procedures. effects model was used. The I2 metric to dry out prions, and gamma radiation.32

WORLD NEUROSURGERY 116: 60-68, AUGUST 2018 www.WORLDNEUROSURGERY.org 61 AE .MLOME L UOOOSCAIPAT SOITDWT NRAE EPRTO RATE REOPERATION INCREASED WITH ASSOCIATED CRANIOPLASTY AUTOLOGOUS AL. ET MALCOLM G. JAMES 62 www.SCIENCEDIRECT.com

Table 1. Characteristics of Included Studies Reporting Complications Related to Choice of Cranioplasty Material

Implants Complication

Level of Wound Bone Reference Design Evidence Quality Indication for Craniectomy Bone SyntheticSynthetic Material Infection Reoperations Complication Resorption

Kriegel et al., 200732 Cohort 3b 6 MCA infarct, SAH, infection, 18 30 PMMA Y Y Y Y trauma, ICH, tumor Cheng et al., 200840 Cohort 3b 5 Trauma, nontrauma 52 32 PMMA Y Y Lee et al., 200941 Cohort 3b 9 Trauma, infarction, ICH, SAH 91 40 PMMA Y Y Y Im et al., 201241 Cohort 3b 7 Trauma, vascular, tumor 83 48 PMMA, PE, YY Y Y bone cement Bobinski 201342 Cohort 3b 9 Trauma 30 19 PMMA Y Y Y Y OL NEUROSURGERY WORLD Lethaus et al., 201443 Cohort 3b 8 Trauma, CVA, tumor, infection, 16 17 Ti, PEEK Y Y Y hydrocephalus, epilepsy Iaccarino et al., Cohort 3b 7 Trauma, stroke, SAH, tumor, 31 65 PMMA, PEEK, HA Y Y Y 201544 infection Piitulainen et al., Cohort 3b 9 Trauma, tumor, infection, 20 80 PMMA, PE, HA, YY Y Y 201545 hemorrhagic, ischemic bioactive fiber- reinforced composite Schwarz et al., 20169 Cohort 3b 7 Trauma, infarction, extra-axial 503 128 PEEK, Ti, ceramic Y Y Y bleeding, SAH, ICH, tumor 8 , Honeybul et al., 2017 RCT 1 9 Trauma, ischemic, hemorrhagic, 32 32 Ti Y Y Y https://doi.org/10.1016/j.wneu.2018.05.009 tumor Kim et al., 201746 Cohort 3b 9 Trauma, ischemic, hemorrhagic, 30 97 PMMA Y Y Y Y tumor, infection Moles et al., 201847 Cohort 3b 9 Trauma, intracranial 44 48 HA Y Y Y Y hypertension, ischemic, SAH, infection, tumor Totals 950 636 12 12 7 10 1586

MCA, middle cerebral artery; SAH, subarachnoid hemorrhage; ICH, intracerebral hemorrhage; PMMA, polymethylmethacrylate; Y, yes; PE, porous polyethylene; CVA, cerebrovascular accident; Ti, titanium; PEEK, polyetheretherketone; HA, L ITERATURE hydroxyapatite; RCT, randomized controlled trial. R EVIEW LITERATURE REVIEW JAMES G. MALCOLM ET AL. AUTOLOGOUS CRANIOPLASTY ASSOCIATED WITH INCREASED REOPERATION RATE

Five of the studies8,32,40,42,46 included heterogeneity, so a fixed-effects model Table 2. Summary Characteristics of 2 only patients with trauma or reported data was used (I ¼ 3%; P ¼ 0.40). Included Studies separately for patients with trauma, which No study identified risk factors for n (%) allowed for a subgroup analysis shown in wound complications. Figure 3. The rate of infection was 6.6% Materials (n ¼ 13/197) and there was no difference Bone Resorption Bone 950 (60) in odds of infection for different Ten studies reported resorption rates materials (n ¼ 197; OR, 1.89; CI, 0.59e (Table 3). In general, a minimum of 6 Synthetic 636 (40) 6.09; P ¼ 0.28). No other subpopulation months of follow-up are necessary to Total 1586 (e.g., vascular) had enough data for appreciate resorption of autologous bone, Study design subgroup analysis. and most studies in this analysis consid- Only 1 study49 identified poor fi Randomized controlled trial 1 ered 1 year to be adequate. The de nition preoperative neurologic status as an of resorption varied among studies, but Cohort 11 independent risk factor for infection nearly all considered only clinically sig- Total 12 (Glasgow Outcome Scale score 2e3; nificant resorption that would necessitate hazard ratio, 5.2; CI, 1.1e25.2; P ¼ 0.04). Indication for craniectomy reoperation, such as palpable defects or implant loosening. The pooled rate of Trauma 656 (41) Reoperations resorption for autologous grafts was 20% ¼ Vascular 599 (38) All studies reported reoperation rates. (n 159/791). fi Tumor 61 (3.8) Among all reoperations (n ¼ 295), the most Two studies identi ed young age as a risk common cause was resorption (n ¼ 159/295, factor although they each considered it Infection 54 (3.4) e 54%) followed by infection (n ¼ 121/295, differently: OR, 0.97 (CI, 0.95 0.98) risk Nontrauma, unspecified 24 (1.5) 9 41%). Reoperations for hematoma evacua- reduction with each year of age, or < ¼ Unspecified 5 (0.3) alternatively age 20 years with P 0.033 tions or reoperation to treat the primary 32 disease process (e.g., aneurysm clipping) (no OR reported). Fragmented bone e were not considered related to cranioplasty graft into 2 pieces (OR, 3.71; CI, 1.89 The investigators compared this > material and thus not counted.32,41,43 7.29), fragmentation into 2 pieces (OR, processing protocol with acrylic e Figure 4 shows the meta-analysis for 22.01; CI, 9.43 51.61), or the presence of implants. One study used a subcutaneous a ventriculoperitoneal shunt at time of 47 odds of reoperation. The pooled rate of abdominal pocket. e reoperations was 23.2% (n ¼ 221/950) for cranioplasty (OR, 1.73; CI, 1.02 2.92) also The study quality averaged 7.8 of a 9 autologous bone and 11.6% (n ¼ 74/636) increased the risk of resorption. Tissue possible 9 points on the Newcastle-Ottawa processing may have been a factor. The Scale (range, 5e9; Table 1). Seven studies for synthetic implants (overall, 18.6%; ¼ highest rate of bone resorption (39% of had some level of cohort matching to n 295/1586). Across all studies, there fi patients with 6 months follow-up) was reduce the risk of selection bias (level was a signi cant increase in odds of ¼ observed in the 1 study using Tutoplast 3b).8,41-43,45-47 reoperation with bone (n 1586; OR, 1.91; CI, 1.40e2.61; P < 0.0001). There was no (Tutogen Medical GmbH, Neunkirchen am significant heterogeneity, so a fixed-effects Brand, Germany) processing of autogenous Infections 32 46 model was used (I2 ¼ 27%; P ¼ 0.18). bone. Similarly, another study that used All studies reported infection rates. fi No study identified specific risk factors signi cant processing (autoclaving, Infection was defined variably across for reoperation. hydrogen peroxide, and gas plasma) studies but in all cases required clinical reached 60% (n ¼ 18/30) resorption, symptoms such as persistent fever, men- although only 13% (n ¼ 4/30) were ingismus, positive systemic or wound Wound Complications significant enough to warrant reoperation. cultures, or purulent wound discharge. Seven studies reported wound complica- Although most studies classified infection tions. Examples of wound complications as requiring reoperation for debridement included aseptic wound dehiscence,32,41 DISCUSSION and washout, some included cases that dislodged implant,42 and unspecified This analysis shows that the use of autol- resolved with antibiotics alone.48 wound revision.49 ogous bone for cranioplasty is associated Figure 2 shows the meta-analysis for Figure 5 shows the meta-analysis for with significantly increased odds of reop- odds of developing infection. The pooled odds of developing wound complications. eration compared with synthetic grafts, rate of infection was 8.0% (n ¼ 76/950) for The pooled rate of wound complications likely because of infection or resorption. autologous bone and 7.1% (n ¼ 45/636) for was 1.3% (n ¼ 4/316) for autologous bone Although synthetic materials often require synthetic implants (overall, 7.6%; n ¼ 121/ and 2.8% (n ¼ 10/362) for synthetic increased upfront cost, the potential for 1586). There was a nonsignificant trend implants (overall 2.1%; n ¼ 14/678). additional cost of reoperation after autol- toward infection with bone (n ¼ 1586; OR, Although bone had fewer wound ogous implantation should be considered, 1.24; CI, 0.82e1.88; P ¼ 0.30). There was no complications, this did not reach signifi- especially in high-risk patients (i.e., poor significant heterogeneity, so a fixed-effects cance (n ¼ 678; OR, 0.56; CI, 0.22e1.45; neurologic status, fragmented bone graft, model was used (I2 ¼ 32%; P ¼ 0.14). P ¼ 0.23). There was no significant or a preexisting shunt). With more than a

WORLD NEUROSURGERY 116: 60-68, AUGUST 2018 www.WORLDNEUROSURGERY.org 63 LITERATURE REVIEW JAMES G. MALCOLM ET AL. AUTOLOGOUS CRANIOPLASTY ASSOCIATED WITH INCREASED REOPERATION RATE

Figure 2. Forest plot of studies reporting infection with autograft overall OR and 95% confidence intervals. The vertical solid line or allograft cranioplasty stratified by study design (cohort vs. indicates the line of no effect (OR, 1). Results indicate no overall series). The blue square markers indicate odds ratios (ORs) from difference in odds of infection with choice of material, but each study, with sizes reflecting the statistical weight of the higher-level cohort studies show a nonsignificant increase risk of study. The horizontal lines indicate 95% confidence intervals infections with bone. df, degree of freedom; M-H, (CIs). The diamond data markers represent the subtotal and Mantel-Haenszel. thousand procedures spanning a decade with an average reported incidence of synthetic material in this analysis (OR, of recent practice, this is the largest, most 7.6% regardless of material (n ¼ 121/1586). 1.24; CI, 0.82e1.88). This finding is rigorous study to date on the topic. This finding is consistent with the earlier consistent with previous reviews.7 Among Furthermore, it is the first study to review by Yadla et al.7 that also examined cited risk factors, there is a clear examine reoperations as a whole, which the relationship between material and consensus in the literature that poor affects patient outcomes and health care infections (8.6%, n ¼ 137/1582). Another preoperative neurologic status (variously costs regardless of indication. Despite it recent expanded review2 catalogued all defined) is a significant risk factor for being a widely discussed topic, only 1 reported cranioplasty complications and subsequent infection.31,36,51-54 small randomized controlled trial has reported a rate of 6.0% (n ¼ 565/9359). It In the trauma subpopulation, the inci- been reported, which showed no differ- is reasonable to quote an overall dence of infection after cranioplasty is ence against titanium.8,50 This study sug- expected infection rate between 5% and estimated at 7.4% (n ¼ 172/2318) gests that the choice of material may 10%, which is not trivial given the compared with 5.6% (n ¼ 393/7041) for reduce complications that would other- subsequent steps that are required to nontraumatic (e.g., ischemic stroke and wise set back overall recovery and address the infection (i.e., reoperation hemorrhagic stroke).2 The question then rehabilitation. for flap removal, long-term intravenous follows: should the original bone flap be antibiotics, and reoperation for skull discarded in patients with trauma? Infection reconstruction with synthetic material). According to our study, the answer is Infection was the most commonly re- Autologous bone did not seem to in- likely no, because there was no ported complication after cranioplasty, crease infection rates compared with difference in infections between bone

Figure 3. Forest plot of studies reporting infection in patients with either material. CI, conﬁdence interval; df, degree of with trauma. Results indicate no difference in odds of infection freedom; M-H, Mantel-Haenszel.

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Figure 4. Forest plot of studies reporting reoperations stratified confidence interval; df, degree of freedom; M-H, by study design. Among higher-quality cohort studies, there is a Mantel-Haenszel. significantly increased risk of reoperation with bone. CI, and synthetic implants (OR, 1.89; CI, that resulted in clinical infection, all grew 1.40e2.61) with little heterogeneity (I2 ¼ 0.59e6.09). This finding is, of course, in different species from those identified at 27%; P ¼ 0.18). Although in some cases, exclusion of any grossly contaminated time of craniectomy. These findings seem infection may be treated with antibiotics bone flap at the time of initial to indicate that the source of infection has alone, a return to the operating room first craniectomy. Given the heterogenous little to do with preimplantation steriliza- for explantation, and again later for nature of these data, prospective tion and handling. Rather, it may be that reimplantation, carries significant risk and controlled trials are needed to investigate aggressive processing and sterilization cost. When mentioned, all studies dis- this topic further. damage the bone and can lead to resorp- carded the previous autologous implant at Can infections be reduced with tion, as discussed later.32,46 reoperation and used a new synthetic improved handling or sterilization of the Antibiotic-impregnated synthetics, such implant, which further increases expense. implant? The answer seems to be no. One as acrylics and polymethylmethacrylate, Any cost analysis must take into consid- study swabbed all bone before storage; have shown promise.55 Two series have eration not just the initial implant and those with positive cultures were sterilized reported reduced infection rates using operative procedure but also some esti- by soaking in bacitracin before implanta- polymethylmethacrylate implants mate of these reoperations. tion, whereas those with negative cultures impregnated with vancomycin/ were reimplanted without additional pro- tobramycin56 and erythromycin/colistin.57 Wound Complications cessing.4 The investigators found no The pooled rate of wound complications difference among infection rates for Reoperations after cranioplasty was small, and similar in sterilized bone, nonsterilized bone, or Autologous bone implants showed a sig- both autologous and synthetic grafts (1.3% synthetic flaps. Furthermore, of the 3 nificant risk of reoperation secondary to autologous vs. 2.8% synthetic). The meta- positive-culture flaps requiring bacitracin infection or resorption (OR, 1.91; CI, analysis showed no significant difference

Figure 5. Forest plot of studies reporting wound complications of wound complications with either material. CI, conﬁdence stratiﬁed by study design. Results indicate no difference in odds interval; df, degree of freedom; M-H, Mantel-Haenszel.

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Table 3. Incidence of Resorption Reported in Each Study and Pooled Estimate

Reference Cases with Resorption Cases with Follow-Up Rate (%) Risk Factors

Kriegel et al., 200732 7 18 39 Young age Im et al., 201241 15 77* 19 Bobinski et al., 201342 63020 Lethaus et al., 201443 31619 Iaccarino et al., 201544 2316 Piitulainen et al., 201545 32015 Schwarz et al., 20169 108 503 21 Fragmented, young age, ventriculoperitoneal shunt Honeybul et al., 20178 731* 23 Kim et al., 201746 43013 Moles et al., 201847 435* 11 Total 159 791 20

*Number of patients in study with imaging and clinical follow-up appropriate to assess resorption.

in wound complications between use of prompt use of synthetic implants in the consider direct comparison of different autologous bone and synthetic implants. pediatric population when materials (e.g., titanium vs. Wound complications were relatively rare possible.9,32,52,58 Serial follow-up imaging polyetheretherketone vs. acrylic). In 1 occurrences and may require higher to screen for resorption is not recom- randomized controlled trial (n ¼ 52), numbers to better evaluate any difference mended; rather, patients should have titanium was associated with higher between groups. expectant follow-up and should be advised infection rates compared with to seek attention sooner if palpable defects hydroxyapatite, but both cohorts had Resorption are noted. Most cases can be managed similar reoperation rates.59 Third, there Resorption is an often underreported conservatively unless there is significant was a variety of definitions of infection complication, with little more than half bone loss or cosmetic defect. Significant (superficial vs. deep vs. global), the studies included in this analysis processing of bone grafts at the time of resorption (slight vs. significant), and providing data and follow-up. Resorption cranioplasty should be avoided, because it reoperation (explantation vs. typically takes up to a year to present with does not seem to improve infection rates supplementation). The nature of a symptomatic effects.9 Most patients do and may worsen resorption rates as a reoperation could not always be not undergo surveillance neuroimaging result of microstructural damage.22,32,46 discerned; future studies should specify unless there are specific concerns, so which reoperations involved complete resorption is usually discovered after a Limitations explantation (with delayed cranioplasty) patient develops a cosmetic defect. A Several factors potentially bias the findings rather than simple cosmetic recent systematic review estimated the in this study. First, all but 1 included study supplementation or debridement. Future prevalence of resorption to be about were retrospective observational cohorts, studies should also consider stratifying 16%,2 similar to our rate (20%). In and the 1 randomized controlled trial was major and minor complications. addition, the definition of significant relatively small (n ¼ 64).8 With a variety of Examples of major complications might resorption varies among studies, ranging reasons for decompression, the reason for include infection requiring explantation, from mild translucency on imaging that choosing a material is not controlled and resorption requiring replacement, or requires no intervention to complete full- there was a clear preference for reusing a supplementation for cosmetic defects. thickness erosion and cosmetic defects. patient’s own bone (950 bone vs. 636 Examples of minor complications might This spectrum has been divided into 2 synthetic). We recommend that future include superficial infection treated with types: thinning of the bone on imaging or studies stratify by primary disease (e.g., antibiotics, debridement, or simple by palpation (type I) versus complete lysis trauma, ischemic, hemorrhagic, or wound revision. Furthermore, some of the inner and outer tabula with loss of tumor). Second, complications for all patients may have been considered twice cerebral protection requiring revision (type synthetic material types were combined. in the same analyses. For example, II).9 In our review, nearly all studies It is likely that each material has patients who underwent reoperation with reported only resorption associated with different biomechanical properties that synthetic material after a failed cosmetic or palpable defects (type II). influence infection and wound healing. autologous cranioplasty were included in There is some evidence that younger age There are a multitude of synthetic both groups.15,40,43,60 The incidence of is a risk factor for resorption, which may options, but future studies should this situation is low enough that

66 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.05.009 LITERATURE REVIEW JAMES G. MALCOLM ET AL. AUTOLOGOUS CRANIOPLASTY ASSOCIATED WITH INCREASED REOPERATION RATE significant bias in this study is unlikely; material, and method of flap preservation on 22. Sahoo N, Roy ID, Desai AP, Gupta V. Comparative however, future studies should consider cranioplasty infections: a systematic review. evaluation of autogenous calvarial bone graft and Neurosurgery. 2011;68:1124-1130. alloplastic materials for secondary reconstruction keeping patients within their intent-to- of cranial defects. J Craniofac Surg. 2010;21:79-82. treat assignment to minimize bias. The 8. Honeybul S, Morrison DA, Ho KM, Lind CRP, comparative costs of these implants have Geelhoed E. A randomized controlled trial 23. Yang VXD, Pirouzmand F. A simple method for 20 comparing autologous cranioplasty with custom- controlled reduction duraplasty during cranio- not been fully examined. Autologous made titanium cranioplasty. J Neurosurg. 2017; plasty. Br J Neurosurg. 2016;30:269-271. bone requires long-term storage before 126:81-90. implantation, whereas synthetic grafts 24. Yang Ng Z, Ang WJJ, Nawaz I. Computer- 9. Schwarz F, Dünisch P, Walter J, Sakr Y, Kalff R, designed polyetheretherketone implants versus often come with a steep upfront cost. It is Ewald C. Cranioplasty after decompressive cra- titanium mesh (acrylic cement) in alloplastic unclear whether the risk of reoperation niectomy: is there a rationale for an initial artifi- cranioplasty: a retrospective single-surgeon, sin- that goes along with autologous grafts cial bone-substitute implant? A single-center gle-center study. J Craniofac Surg. 2014;25: fi experience after 631 procedures. J Neurosurg. 2016; e185-e189. justi es the regular use of synthetic 124:710-715. implants. 25. Thien A, King NKK, Ang BT, Wang E, Ng I. 10. 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