Letter: Use of Antibacterial Envelopes in Neuromodulation Surgeries With Implantable Device Insertion: A Systematic Review and Meta-Analysis

To the Editor: We read with great interest the article by Oliveira et al,1 entitled “Use of Antibacterial Envelopes in Neuromodulation Surgeries With Implantable Device Insertion: A Systematic Review and Meta-Analysis.” This study, which included 4 clinical controlled trials involving 1242 patients, evaluated the role of antibacterial envelopes in reducing infection rates associated with neuromodulation implants. Analysis demonstrated a 77% reduction in infection risk among patients using antibacterial envelopes compared with the control group (RR = 0.23, 95% CI: 0.12-0.45), a compelling result. Given that infection after neuromodulation device implantation can lead to catastrophic outcomes—including mandatory device removal and surgical failure—mitigating infection risk is pivotal for enhancing procedural safety. We wish to address 2 critical considerations arising from this study: First, the study's follow-up duration of “at least 3 months” may be insufficient to evaluate the long-term safety of neuromodulation devices. As neuromodulation devices are intended for lifelong implantation, the timing of postsurgical infections varies significantly: some occur during the perioperative period,2 others emerge 3–6 months postimplantation,3 and delayed infections may even manifest 2 years or later after surgery.4 Similar patterns are observed in cardiac pacemaker implantation; for example, Lekkerkerker et al5 reported that 24% of pacemaker-related infections occur beyond 24 months postimplantation, with such late-onset infections showing significantly lower bacterial culture positivity rates than those within 24 months. This underscores the need for long-term follow-up to detect infection signs. In our own practice, we have encountered a deep brain stimulation patient who developed purulent wound exudate 2 years postsurgery. Despite initial improvement after prolonged antibiotic therapy and local wound care, the exudate recurred, ultimately necessitating device removal. Intraoperative observation revealed extensive pus accumulation around the implant, with inflammation confined to the perigraft tissue without spreading to other central nervous system regions, indicating that infections can be insidious. Thus, a 3- to 6-month observation window may fail to capture late-onset infections, limiting the ability to assess the long-term antibacterial efficacy of these envelopes. Notably, multiple studies on postimplantation infections in neuromodulation have adopted follow-up periods exceeding 12 months,6,7 further supporting the necessity of long-term observation to clarify late infection risks. Second, noninfectious risks associated with antibacterial envelopes warrant attention. These envelopes typically consist of metal/metal ion-releasing, antibiotic-releasing, polymer, or organic materials.8 Take metal ion-releasing envelopes as an example: Sustained release of metal ions may activate host immune cells, increasing local inflammatory cytokine secretion, which in turn triggers aggregation of foreign body giant cells and fibrous tissue hyperplasia.9 In neuromodulation device implantation, continuous release of antibacterial envelopes within brain tissue can induce excessive perielectrode fibrosis, elevating stimulation thresholds, attenuating therapeutic efficacy,10 and increasing the risk of chronic immunogenic inflammation. In addition, although local drug release doses are low, long-term implantation may lead to trace metal ion accumulation. For instance, case reports describe irreversible argyria in patients with metal ion-coated implants 2 to 5 years postsurgery, with dermal silver particle deposition confirmed by tissue biopsy.11 These findings suggest that clinical application of antibacterial envelopes requires precise balancing of infection control benefits against biocompatibility risks. Given the delayed and insidious nature of related complications, safety assessments of antibacterial envelope-coated neuromodulation implants must consider both infection prevention benefits and biocompatibility risks, with particular focus on long-term potential risks of envelope material infiltration into tissues. Overall, this study, as an early and significant exploration in this field, establishes a preliminary evidence-based foundation for infection prevention in neuromodulation surgeries. We look forward to the authors' responses to the issues raised, which may further advance our understanding of the safety of antibacterial envelope-coated neuromodulation implants.