08 January 2025: Articles
Malignant Cerebral Edema After Cranioplasty: A Case Report and Literature Insights
Unusual clinical course, Unusual or unexpected effect of treatment, Clinical situation which can not be reproduced for ethical reasons
Melanie Mandell1EF*, Fabio Grassia2AB, Muhammad Riaz2AGDOI: 10.12659/AJCR.946230
Am J Case Rep 2025; 26:e946230
Abstract
BACKGROUND: Decompressive craniectomy is a common life-saving intervention in the setting of elevated intracranial pressure. Cranioplasty restores the calvarium and intracranial physiology once swelling recedes. Cranioplasty is often thought of as a low-risk intervention. However, numerous reports indicate that malignant cerebral edema (MCE) is an often-fatal complication of an otherwise uneventful cranioplasty. A careful review of the literature is needed to better understand this devastating condition.
CASE REPORT: A 41-year-old man presented after suffering a gunshot wound to the right frontal lobe. Upon initial evaluation, the patient had grossly visible brain matter, left-sided hemiparesis with a Glascow Coma Score (GCS) of 11, and vital signs concerning for elevated intracranial pressure. Computed tomography (CT) showed right-sided intraparenchymal and subarachnoid hemorrhage with a 5 mm leftward midline shift. The patient was taken to the operating room (OR) for right fronto-parietal craniectomy. Over the next 3 months, he recovered steadily and underwent PEEK cranioplasty on post-operative day 83. Pre-operative CT showed sunken skin flap syndrome with an 8-mm midline shift. Following an uneventful cranioplasty, he failed to regain consciousness. Examination revealed absent brainstem reflexes. CT showed global diffuse cerebral edema. The patient was declared brain dead.
CONCLUSIONS: Continued research is needed to better understand the pathophysiology of malignant cerebral edema so that future incidences may be prevented. A combination of negative-pressure suction drainage, sunken skin flap syndrome, and delayed time to cranioplasty likely play a significant role in the evolution of MCE. We urge neurosurgeons to consider the likelihood of MCE and adapt surgical planning accordingly.
Keywords: Brain Death, Craniocerebral Trauma, Neurosurgery
Introduction
Decompressive craniectomy (DC) is standard of care in patients with severe traumatic brain injury (TBI). Specifically, DC is indicated, although not always clinically appropriate, in the setting of acute subdural hematoma, parenchymal hemorrhage with mass effect, elevated intracranial pressure (ICP) refractory to medical management, and, less frequently, closed TBI with diffuse brain swelling [1]. After a period of decompression, patients undergo cranioplasty to restore the bony defect. Without replacement of the bone flap, there is risk of injury to underlying brain tissue and development of sinking skin flap syndrome (SSFS), also known as syndrome of the trephined or paradoxical herniation. This condition is characterized by sunken skin above the bone defect, with concomitant neurologic decline or plateau. Radiographically, SSFS typically presents with paradoxical midline shift or herniation [2]. Cranioplasty is indicated as the treatment for this condition, and restoration of the bony defect also restores the brain’s ability to regulate intracranial pressure [3].
When compared to a decompressive craniectomy, a procedure often performed in a high-acuity setting as a life-saving intervention, cranioplasty is often thought of as a benign operation with minimal risk to the patient. Complications such as local infection, epidural hematoma, and flap resorption are the most frequently documented [4]. Patient status also contributes to possible complications. The presence of SSFS or a VP shunt are both thought to increase the morbidity of the operation by increasing the incidence of intracranial fluid collections and infections [5,6]. Malignant cerebral edema, also termed pseudohypoxic brain swelling, is a devastating and often-fatal consequence of an otherwise uneventful cranioplasty. Cases of malignant cerebral edema are increasingly reported in the neurosurgical literature.
Case Report
We present the case of a 41-year-old man who suffered a gunshot wound (GSW) to the right frontal lobe. Initial evaluation in the ED showed hemorrhagic brain matter present at the superior frontal bone and an exit wound at the parietal bone, with a GCS of 11 (E3, V2, M6), and left-sided hemiparesis. He intermittently followed commands with his right upper extremity (RUE). Vital signs showed hypertension with bradycardia, consistent with elevated ICP. Following rapid-sequence intubation, a CT head scan demonstrated right-sided mixed intraparenchymal and subarachnoid hemorrhage with a leftward midline shift of 5 mm and pneumocephalus along the path of the penetrating GSW with retained ballistic fragments (Figure 1).
Given the severity of his injuries and concern for impending herniation, he was taken to the OR, where he underwent emergency right-sided frontoparietal decompressive craniectomy (DC), subdural hematoma evacuation, removal of necrotic and herniating brain matter, and external ventricular drain (EVD) placement (Figure 2). The dura was repaired with Integra DuraGen Dural Graft Matrix. Post-operatively, his hospital course was complicated by post-traumatic hydrocephalus 2 weeks after EVD removal (Figure 3A), which necessitated placement of a programmable Medtronic Strata ventriculoperitoneal (VP) shunt set to 1.5. Shunt placement was delayed 9 days after the initial development of hydrocephalus due to concern for meningitis in the setting of repeated fevers of unknown origin. After CSF cultures returned negative and the patient had completed a 2-week course of cefepime and vancomycin with resolution of fevers, the shunt was placed. A week after placement, the VP shunt was adjusted from 1.5 to 0.5 given persistent expanded ventricles on a CT head scan (Figure 3B). After 1 month, the shunt was programmed to 1.5 due to concern for possible over-shunting (Figure 3C). The patient remained hospitalized for the 3 months following the initial injury, where he gradually regained cognitive and motor abilities. By postoperative day (POD) 67, he had persistent LUE paralysis, LLE weakness, and required enteral nutrition due to severe oropharyngeal dysphagia. He followed commands and was able to converse spontaneously with the use of a tracheostomy due to vocal cord paralysis.
On POD 83, the patient had a GCS of 15 and returned to the OR for elective PEEK (polyetheretherketone) cranioplasty. Cranioplasty had been scheduled for POD 73 but was postponed due to a PEEK implant shipping delay. A pre-operative CT head scan showed radiographic evidence of sinking skin flap syndrome, with an 8-mm leftward midline shift (Figure 4). Continuous monitoring throughout the operation displayed a transient drop in blood pressure to 73/54 mmHg at the time of induction. In the middle of the case, there were brief episodes of bradycardia to the 40s. Otherwise, the operation was without incident, with no noted periods of hypercapnia or neurologic changes. The skin flap separated off the DuraGen with minimal manipulation and no adhesions. A subgaleal drain was placed prior to wound closure. At the time of extubation, the patient failed to regain consciousness. Neurologic examination revealed absent brainstem reflexes. An immediate postoperative CT scan demonstrated global diffuse cerebral edema and hypoperfusion (Figure 5). Three days later, he was declared brain dead. An autopsy performed ruled out other causes of death, including any cardiovascular events. On autopsy, the brain exhibited evidence of prolonged ventilatory support and hypoxic-ischemic changes.
Discussion
A careful review of the literature demonstrated many cases of MCE following an otherwise uneventful cranioplasty. MCE, also termed pseudohypoxic brain swelling, was first described in 2003 [7]. The condition is defined by early post-operative neurologic deterioration with concomitant bilateral imaging changes suggestive of edema, such as hypoattenuation. The authors who first reported MCE determined that anoxemic and ischemic hypoxia were unlikely to be the underlying causes [7].
This is consistent with symptom evolution despite adequate intra-operative mean arterial pressure, such as in the case presented here. This report and several others suggest that negative-pressure suction drainage plays an important role in the pathophysiology of MCE [7–15], likely due to interference with ICP auto-regulation. A study of pressure regulation in patients in the 12 hours before and 24 hours after cranioplasty showed significantly increased ICP once the calvarium was reconstructed [3]. This suggests that there is a period of acute pressure elevation following cranioplasty. The same study found significant differences in ICP between supine and seated positions in the week following cranioplasty [3], with participants experiencing an average pressure increase of 7.4±3.6 mmHg while supine. No significant change in pressure regulation was observed in the seated position. To date, there are no reports of cranioplasty performed in the seated position. This may be an important consideration given the increasing evidence that cranioplasty leads to transient ICP dysregulation, which is likely worsened by use of suction drainage. Additionally, it is thought that the presence of a VP shunt at the time of cranioplasty increases the risk of complications; specifically, the development of epidural and subdural fluid collections [5]. In the same study, ligation of the shunt prior to cranioplasty eliminated the risk of fluid collection. However, no data exist to suggest that the presence of a VP shunt at the time of cranioplasty increases the risk MCE. This gap in the literature is likely due to a limited number of cases where MCE develops and even fewer that occur with a VP shunt in place. It is reasonable to suggest that VP shunting increases the risk of MCE, especially given how many of the documented cases developed in the setting of negative-pressure suction drainage.
Negative-pressure suction drainage is standard of care following cranioplasty. If suction drainage and positioning alone caused MCE, it would be reasonable to expect a much higher incidence of the condition. Prior case reports have suggested that the presence of sunken skin flap syndrome elevates the risk of MCE [8,10,11,13,15–18]. The presence of a VP shunt is a known risk factor for development of SSFS [5]. As mentioned previously, SSFS increases the morbidity of cranioplasties, in part due to the intra-operative manipulation necessary to remove the skin flap from the underlying dura, resulting in trauma to the tissue [5]. The removal of the sunken skin flap and replacement of the bone fragment leave a larger potential space for post-operative fluid collections than would otherwise exist in a patient without SSFS. However, cranioplasty is often cited as the definitive management of SSFS [2,19]. Of the 22 cases we reviewed, 18 had SSFS prior to undergoing cranioplasty (Table 1). Some authors have postulated that delay of cranioplasty beyond 3 months after a decompressive craniectomy can contribute to evolution of SSFS and increase the risk of MCE [23,24]. While several reported cases of MCE delayed cranioplasty beyond this recommendation, 8 of 22 reviewed cases, including the case reported here, fell within the optimal timing interval. The combination of SSFS, a patent VP shunt, and the placement of a post-operative negative-pressure suction drain likely contributed to the intra-operative death of our patient.
Conclusions
Continued research is needed to better understand the pathophysiology of MCE so that future occurrences may be prevented. Based on the case reported in this paper and a review of the literature, a combination of negative-pressure suction drainage, an existing VP shunt, sunken skin flap syndrome, and delayed time to cranioplasty likely play a significant role in the evolution of MCE. Additionally, operative positioning may contribute to development of this condition. However, more investigation is needed to elucidate the exact effect of positioning on intracranial pressure in the OR. We urge neurosurgeons to consider the likelihood of MCE in their cranioplasty cases and to adapt surgical planning accordingly.
Figures
Figure 1.. Non-contrast CT head scan on initial presentation to the Emergency Department. Imaging shows right-sided mixed intraparenchymal and subarachnoid hemorrhage with a leftward midline shift of 5 mm and pneumocephalus along the path of the penetrating gunshot wound with retained ballistic fragments. Figure 2.. Non-contrast head CT scan following decompressive craniotomy. (A) Significant subdural hemorrhage noted at the falx cerebri. (B) Right frontal EVD and superior sagittal sinus thrombus. (C) Subdural hemorrhage present along the right tentorium. (D) Packing material present in the right middle cranial fossa. Figure 3.. Non-contrast CT head scan series illustrating VP shunt settings. (A) Initial development of post-traumatic hydrocephalus 2 weeks after EVD removal, demonstrated by rightward midline shift measuring up to 9 mm and an increase in ventricle size. (B) Persistent expanded ventricles 1 week after shunt placement. (C) Concern for over-shunting after 1 month, with decompression of the left ventricle and associated 5-mm leftward midline shift. Figure 4.. Non-contrast CT head scan prior to cranioplasty shows evidence of sunken skin flap with leftward midline shift measuring up to 8 mm. Figure 5.. Immediate post-operative imaging studies. (A) Non-contrast CT brain scan with new diffuse sulcal effacement, indistinct gray-white matter differentiation, and rightward midline shift measuring up to 6 mm. (B) CT brain scan with contrast perfusion demonstrating decreased blood flow and prolonged mean transit time.References:
1.. Kolias AG, Viaroli E, Rubiano AM, The current status of decompressive craniectomy in traumatic brain injury: Curr Trauma Rep, 2018; 4(4); 326-32
2.. Diaz-Segarra N, Jasey N, Improved rehabilitation efficiency after cranioplasty in patients with sunken skin flap syndrome: A case series: Brain Inj, 2024; 38(2); 61-67
3.. Lilja-Cyron A, Andresen M, Kelsen J, Intracranial pressure before and after cranioplasty: Insights into intracranial physiology: J Neurosurg, 2020; 133(5); 1548-58
4.. Zanaty M, Chalouhi N, Starke RM, Complications following cranioplasty: Incidence and predictors in 348 cases: J Neurosurg, 2015; 123(1); 182-88
5.. Hirschmann D, Kranawetter B, Kirchschlager C, Cranioplasty following ventriculoperitoneal shunting: Lessons learned: Acta Neurochir (Wien), 2021; 163(2); 441-46
6.. Mustroph CM, Malcolm JG, Rindler RS, Cranioplasty infection and resorption are associated with the presence of a ventriculoperitoneal shunt: A systematic review and meta-analysis: World Neurosurg, 2017; 103; 686-93
7.. Van Roost D, Thees C, Brenke C, Oppel F, Pseudohypoxic brain swelling: A newly defined complication after uneventful brain surgery, probably related to suction drainage: Neurosurgery, 2003; 53(6); 1315-26 discussion 1326–27
8.. Bui MH, Dong HV, Duong HD, Malignant cerebral edema after cranioplasty, a rare complication: Case series and literature review.: Ann Med Surg (Lond), 2023; 85(6); 3187-95
9.. Honeybul S, Damodaran O, Lind CR, Lee G, Malignant cerebral swelling following cranioplasty: J Clin Neurosci, 2016; 29; 3-6
10.. Klavansky D, Roa J, Liang J, Reversible malignant cerebral edema following cranioplasty: Crit Care Med, 2023; 51(1); 235-35
11.. Shen L, Zhou Y, Xu J, Su Z, Malignant cerebral swelling after cranioplasty: Case report and literature review: World Neurosurg, 2018; 110; 4-10
12.. Lee GS, Park SQ, Kim R, Cho SJ, Unexpected severe cerebral edema after cranioplasty: Case report and literature review: J Korean Neurosurg Soc, 2015; 58(1); 76-78
13.. Sviri GE, Massive cerebral swelling immediately after cranioplasty, a fatal and unpredictable complication: Report of 4 cases: J Neurosurg, 2015; 123(5); 1188-93
14.. Wang S, Luan Y, Peng T, Malignant cerebral edema after cranioplasty: A case report and literature review.: Brain Inj., 2023 [Online ahead of print]
15.. Woo PYM, Lo WHY, Wong HT, Chan KY, The “negative” impact of a subgaleal drain: Post-cranioplasty negative pressure subgaleal drain-induced ascending transtentorial herniation.: Asian J Neurosurg, 2019; 14(1); 256-61
16.. Bhatjiwale MM, Mariswamappa K, Chandrachari KP, Malignant bihemispheric cerebral edema after cranioplasty – an extension of the Monro-Kellie doctrine and predictive factors: Surg Neurol Int, 2023; 14; 271
17.. Cecchi PC, Rizzo P, Campello M, Schwarz A, Haemorrhagic infarction after autologous cranioplasty in a patient with sinking flap syndrome: Acta Neurochir (Wien), 2008; 150(4); 409-10 discussion 411
18.. Eom KS, Kim DW, Kang SD, Bilateral diffuse intracerebral hemorrhagic infarction after cranioplasty with autologous bone graft.: Clin Neurol Neurosurg, 2010; 112(4); 336-40
19.. Annan M, De Toffol B, Hommet C, Mondon K, Sinking skin flap syndrome (or syndrome of the trephined): A review: Br J Neurosurg, 2015; 29(3); 314-18
20.. Hassaneen W, Germanwala A, Tsimpas A, Malignant cerebral edema following cranioplasty: J Clin Neurosci, 2016; 25; 130-32
21.. Santana-Cabrera L, Perez-Ortiz C, Rodriguez-Escot C, Sanchez-Palacios M, Massive postoperative cerebral swelling following cranioplasty: Int J Crit Illn Inj Sci, 2012; 2(2); 107-8
22.. Wen G, Zeng P, Zhou J, Unexpected intracranial hemorrhage and death after cranioplasty in a patient with massive hemispheric infarction: J Craniofac Surg, 2019; 30(4); e378-e80
23.. Kim JH, Choo YH, Jeong H, Recent updates on controversies in decompressive craniectomy and cranioplasty: Physiological effect, indication, complication, and management: Korean J Neurotrauma, 2023; 19(2); 128-48
24.. De Cola MC, Corallo F, Pria D, Timing for cranioplasty to improve neurological outcome: A systematic review: Brain Behav, 2018; 8(11); e01106
Figures
In Press
Case report
Neonatal Familiar Cleidocranial Dysplasia: A Case ReportAm J Case Rep In Press; DOI: 10.12659/AJCR.946322
Case report
Acute Extensor Pollicis Longus Tendon Injury Associated with a Distal Radius Fracture: A Case ReportAm J Case Rep In Press; DOI: 10.12659/AJCR.946399
Case report
Severe Neonatal Asphyxia Associated with Ureaplasma urealyticum Infection: A Case ReportAm J Case Rep In Press; DOI: 10.12659/AJCR.946249
Case report
Impact of Lupus Anticoagulant on INR Using Recombinant Prothrombin Time ReagentAm J Case Rep In Press; DOI: 10.12659/AJCR.945579
Most Viewed Current Articles
21 Jun 2024 : Case report 82,657
Intracranial Parasitic Fetus in a Living Infant: A Case Study with Surgical Intervention and Prognosis Anal...DOI :10.12659/AJCR.944371
Am J Case Rep 2024; 25:e944371
07 Mar 2024 : Case report 49,061
Neurocysticercosis Presenting as Migraine in the United StatesDOI :10.12659/AJCR.943133
Am J Case Rep 2024; 25:e943133
20 Nov 2023 : Case report 23,527
Azithromycin Treatment for Acne Vulgaris: A Case Report on the Risk of Clostridioides difficile InfectionDOI :10.12659/AJCR.941424
Am J Case Rep 2023; 24:e941424
18 Feb 2024 : Case report 22,089
A Case of Thoracic Empyema Caused by Actinomyces naeslundiiDOI :10.12659/AJCR.943030
Am J Case Rep 2024; 25:e943030