Allergic Reaction to a Bovine-Derived Dural Graft without Eosinophilic Meningitis : A Case Report and Literature Review

Abstract

Bovine-derived dural substitutes are commonly used in cranial and spinal duraplasty. Although they are generally well tolerated, allergic reactions have been reported—almost all presented with eosinophilic meningitis. A 7-year-old girl with Li-Fraumeni syndrome and diffuse pediatric glioma underwent a third salvage resection in which a bovine collagen dural onlay was placed. Ten days post operatively, she developed fever, lethargy, and a subcutaneous scalp fluid collection. Cultures and imaging were negative for infection; cerebrospinal fluid (CSF) revealed pleocytosis (elevated white blood cells and protein) without eosinophilia. High-dose dexamethasone produced transient clinical and radiographic improvement, but fever and fluid re accumulated whenever steroids were tapered. Given the steroid dependence and persistently negative infectious work-up, the graft was explanted. Pathology demonstrated a foreign-body giant cell reaction without eosinophils, and the patient’s symptoms resolved permanently after removal. This report documents the first pediatric case of bovinederived dural graft hypersensitivity without eosinophilic meningitis. Clinicians should consider graft-related allergy in children who develop recurrent fluid collections and fevers after duraplasty—even when CSF eosinophils are absent and cultures remain negative and should recognize that definitive treatment may require graft removal rather than prolonged steroid therapy.

INTRODUCTION

Bovine-derived dural substitutes share the same type I collagen composition as native dura [1], enabling a watertight closure, cost-effectiveness, and ease of handling [2]. Despite these advantages, a rare but recognized complication is the development of an inflammatory or allergic reaction, supported by both in vivo research and sporadic human reports [2-7,13].

Previously, only five documented cases of allergic reactions to bovine dural grafts have been reported, each associated with aseptic eosinophilic meningitis [2,5-8,13]. Here, we present what appears to be the first report of a bovine dural graft-related allergy without eosinophilia in a pediatric patient with Li-Fraumeni syndrome and diffuse pediatric glioma.

CASE REPORT

A 7-year-old female with Li-Fraumeni syndrome and diffuse pediatric glioma (World Health Organization grade IV, isocitrate dehydrogenase [IDH] wild-type [wt], H3K27-wt, MYCN amplified) underwent a second tumor resection following an initial surgery performed overseas and then received chemoradiotherapy and radiation. Three months later, imaging showed rapid tumor regrowth, prompting a third salvage resection. Given multiple prior resections, her native bone and dura were deficient, and a bovine-derived dural graft (DuraMatrix Onlay; Stryker, Kalamazoo, MI, USA) was placed for dural closure.

Postoperative course (days 0–10)

On postoperative day 10, she returned with high fevers (39–40°C), lethargy, and a subcutaneous fluid collection. Lab tests including inflammatory markers were unremarkable, and blood and urine cultures were negative. Empirical antibiotics (ceftriaxone and vancomycin) were started due to her recent surgery and immunocompromised state. A gadolinium-enhanced magnetic resonance imaging demonstrated a small fluid collection superficial to the craniotomy with no abnormal enhancement. The surgical cavity showed mild postsurgical changes (Fig. 1).

Fig. 1.

Axial T1-weighted post-contrast magnetic resonance imaging demonstrating the evolution of the postoperative subgaleal fluid collection and associated changes. A : Postoperative day 10, showing an extracranial subgaleal fluid collection overlying the craniotomy site. B : During steroid therapy, demonstrating persistence and mild interval increase of the subgaleal fluid collection compared with panel A. C : Prior to definitive resolution, showing continued subgaleal fluid accumulation despite medical management, prompting surgical exploration and graft removal. D : Two months after surgical removal of the bovine dural graft, demonstrating resolution of the subgaleal fluid collection. The focal enhancing lesion represents postoperative change related to prior surgical intervention and tumor bed evolution, without evidence of recurrent fluid accumulation.

Because her incision remained intact without erythema or drainage, 40 mL of clear fluid was aspirated under sterile conditions and sent for cerebrospinal fluid (CSF) analysis (cell count, protein, glucose) and culture. The fluid revealed elevated white blood cell (WBC) and protein without eosinophils. Forty-eight-hour cultures were negative (but were collected after antibiotic initiation). The patient’s fever subsided spontaneously, and antibiotics were discontinued before discharge. Peripheral blood counts obtained during the symptomatic period and around the time of graft removal demonstrated no neutropenia. White blood cell counts were elevated, with neutrophils consistently comprising approximately 73–77% of the differential, resulting in an absolute neutrophil count well above normal thresholds (>10000/μL). Eosinophils were absent in peripheral blood and CSF throughout the clinical course.

Recurrent symptoms (days 11–21)

One week later, she returned with a fever (39°C), lethargy, and an enlarged fluid collection. A second aspiration again showed elevated WBC, elevated protein, and no eosinophils. Repeated blood, urine, and CSF cultures were negative. A multidisciplinary team debated whether the graft was infected or if this was a local allergic/inflammatory reaction. After 48 hours of negative cultures, antibiotics were stopped, and dexamethasone (2 mg every 6 hours) was initiated. Her fevers ceased, and the fluid diminished. She returned to the neurological baseline and was discharged on a slow steroid taper.

Persistent reliance on steroids (days 22–60)

At follow-up visits (2 weeks and 1-month post-discharge), the fluid collection remained absent, and she was clinically stable. However, each attempt to discontinue dexamethasone led to rapid reaccumulation of fluid and fever in the absence of infection. Because continued steroids posed serious risks in her immunocompromised state, surgical explantation of the graft was ultimately chosen.

Surgical explantation and outcome

Following the removal of the bovine dural graft, the native dura was reapproximated as much as possible. Given that the durotomy was supratentorial, no additional dural substitute was applied, as the risk of CSF leakage was considered low. Intraoperatively, a minimal amount of serous fluid was noted under the craniectomy site. The fluid and graft were sent for pathology and culture; neither revealed eosinophils. Pathological examination showed foreign body giant cells and foamy macrophages, consistent with a local inflammatory reaction. Postoperatively, her scalp swelling and pain resolved. Unfortunately, 3 weeks later, she experienced seizures suggestive of leptomeningeal spread and communicating hydrocephalus. A palliative shunt was placed, but she remained hospitalized for end-of-life pain management until she passed away one month later. Institutional Review Board approval was deemed unnecessary for a single-patient case report; consent was obtained from her mother.

DISCUSSION

Allergies to bovine-derived dural substitutes have traditionally been linked to eosinophilic meningitis, characterized by fever, lethargy, and elevated eosinophils in the CSF [2,5-7,13]. Our patient showed no eosinophilia despite recurrent fluid collections and fever, suggesting a variant hypersensitivity mechanism—possibly type IV, involving T-cell mediated cytokine release rather than an IgE-driven (type I) process. Her immunocompromised status may have further attenuated a typical eosinophilic response.

Steroid sensitivity and repeated negative cultures argue strongly against persistent bacterial infection. The presence of giant cells and foamy macrophages on pathology is consistent with local immune response, reinforcing the likelihood of an allergic or inflammatory graft reaction. In this scenario, explantation proved curative, aligning with other case reports that recommend graft removal if symptoms recur upon steroid taper.

Literature review

To contextualize this case, we summarized previously published cases of allergic reactions to bovine dural grafts in Table 1.

Table 1.

Summary of published cases of allergic reactions to bovine-derived dural grafts

Study	Patient age/sex	Indication for duraplasty	Clinical presentation	Eosinophilia	Management	Outcome
Foy et al. [4] (2008)	Pediatric/not stated	Lumbar duraplasty for myelomeningocele, tethered cord syndrome, post-op infection	Fever, allergic symptoms; later found eosinophilic meningitis	Yes (CSF)	Steroids initially; graft explanted	Resolved after graft removal
Ostendorf and Connolly [10] (2013)	Pediatric	Duraplasty for Chiari malformation	Fever, headache; CSF eosinophilia	Yes (CSF)	High-dose steroids only	Resolved (no graft removal)
Shah and Furman [11] (2015)	5-year-old/male	Duraplasty for Chiari malformation	Fever, lethargy, fluid collection; eosinophilic meningitis	Yes (CSF)	Steroids; graft explanted	Resolved post-explantation
Begley and Parkinson [1] (2022)	Adult	Dural reconstruction after tumor resection	Fever, meningeal signs; eosinophilia	Yes (CSF)	Steroids + antibiotics (no explant)	Resolved medical management
Lee et al. [7] (2017)	33-year-old/male	Duraplasty for Arnold-Chiari Malformation	Fever, headache, eosinophilic meningitis	Yes (CSF)	Steroids + antibiotics (no explant)	Resolved medical management
Present case	7-year-old/female	Re-resection for diffuse pediatric glioma (Li-Fraumeni)	Fever, lethargy, fluid collections; no eosinophils	No	Steroids temporarily; graft explant	Resolved after graft removal; final decline due to oncologic progression

References correspond to those cited in the manuscript. CSF : cerebrospinal fluid, PICA : posterior inferior cerebellar artery, sx : symptoms

As illustrated in Table 1, all previously reported cases displayed eosinophilia in either the peripheral blood or CSF, confirming an IgE- or eosinophil-driven reaction. In contrast, our patient lacked eosinophils entirely, suggesting a possible cell-mediated immune response. Management typically involves steroids with or without graft explantation. Graft removal is often reserved for recurrent or refractory presentations, in line with our experience.

The key finding in our case was that a presumed inflammatory/allergic reaction to the bovine dural graft occurred in the absence of eosinophilia—an atypical presentation compared to the previously reported cases. Her clinical course indicated minimal response to antibiotics, negative cultures, and robust responsiveness to steroids. Ultimately, graft removal was required to permanently resolve her graft-related symptoms.

Future directions

An important challenge in managing suspected bovine dural graft hypersensitivity is deciding whether to pursue long-term steroid therapy or to explant the graft. Some patients respond well to a short course of steroids, with no recurrence after tapering, while others experience repeated fluid collections or fevers and eventually require graft removal. This variability may reflect individual immune profiles, underlying comorbidities, or specific graft properties [2]. Further research into biomarkers that predict responsiveness to steroids, such as cytokine panels, immune cell profiling, or genetic predispositions, could help guide clinicians in tailoring therapy.

Additionally, no standardized preoperative allergy testing for bovine collagen currently exists. Conventional IgE-based skin prick tests may fail to detect a type IV (cell-mediated) reaction and anecdotal patch testing has uncertain predictive value [9]. Future development of in vitro assays (e.g., T-lymphocyte reactivity tests) or improved patch-testing protocols could clarify a patient’s hypersensitivity risk before graft placement. Such tools might be especially relevant for high-risk populations, such as those with immunodeficiency or complex genetic syndromes [10].

It is also possible that some presentations categorized as allergic could be indolent infections, for instance, atypical viral processes that do not elevate standard infectious markers [11,14]. This confounder warrants cautious interpretation of negative cultures, particularly if fluid samples are collected after antibiotic administration. Another open question is the degree to which tumor-related inflammation, or the broader tumor microenvironment, might predispose to inflammatory graft reactions. Patients with malignant disease could have altered immune responses that either mask typical eosinophilic markers or trigger alternative pathways of graft rejection [12]. These considerations highlight the need for prospective studies and long-term registries that collect comprehensive immunologic and microbiologic data from patients undergoing dural grafting. By better delineating risk factors, we may ultimately develop both improved diagnostic tests and more personalized management algorithms for graft-related hypersensitivity.

CONCLUSION

Our case illustrates an uncommon presentation of bovine dural graft-related allergy or inflammation without eosinophilia. Neurosurgeons should remain alert to graft hypersensitivity when repeated negative cultures coincide with fluid collections responsive only to steroids. Although steroids alone can sometimes suffice, persistent or recurrent symptoms may necessitate explantation—particularly in immunocompromised patients. Further research is needed to delineate risk factors, the role of potential preoperative testing, and the pathophysiology underlying atypical (non-eosinophilic) allergic responses to bovine dural grafts.