Lesion-like effect of gliosis secondary to deep brain stimulation electrode infection: illustrative case

Abstract

BACKGROUND

Deep brain stimulation (DBS) is commonly used to treat Parkinson's disease (PD) and other movement disorders when other treatments fail. Although DBS can significantly improve motor symptoms, it carries risks such as infections, which can require multiple surgeries and prolonged antibiotic therapy. Research on the long-term neurological effects of DBS-related infections is limited.

OBSERVATIONS

A 58-year-old man with a 13-year history of PD, refractory to optimized clinical management, underwent subthalamic nucleus (STN) DBS after previous contralateral lesioning of the posterior subthalamic area. Postoperatively, the DBS lead migrated upward and was repositioned, but he developed perielectrode cerebritis 5 days later. The DBS system was completely removed, and he underwent a 28-day course of intravenous antibiotics. Initially, his motor symptoms remained unchanged, but 4 months later, he experienced a significant and sustained motor symptom improvement that continued until the last follow-up assessment (40 months). Magnetic resonance imaging performed 2 years after the explantation showed gliosis and hemosiderin deposition in the STN, suggesting that the infection-induced gliosis had a lesion-like effect, leading to the observed clinical improvement.

LESSONS

This case suggests that infection-induced gliosis from DBS complications can unexpectedly result in long-term motor symptom improvements, potentially influencing future management strategies for similar cases.

https://thejns.org/doi/10.3171/CASE24502

Deep brain stimulation (DBS) has become a widely accepted technique for treating motor symptoms in Parkinson’s disease (PD) and other movement disorders that become refractory to the best conservative management. DBS can provide significant and lasting improvement in motor symptoms, greatly enhancing the quality of life and independence for patients with PD over short-, medium-, and long-term periods.^1–3

Given its importance and prevalence, complications of DBS must be carefully identified, studied, and managed effectively. Surgical site infections, which are the most common adverse events following this procedure, can affect any component of the DBS system, including the implantable pulse generator, the extension cables, or the brain leads. The significance of these infections lies in several factors: the potential for serious complications such as meningoencephalitis or brain abscess, the frequent need for two additional surgeries (first, removal of the hardware and an extended course of parenteral antibiotic therapy, followed several months later by reimplantation of the system if the patient remains a surgical candidate), and the high cost of the DBS system.^{4, 5}

Despite extensive research into the risk factors and clinical management of DBS-related infections, there is limited documentation on the potential long-term neurological effects when the brain is affected.^{1, 4} In this report, we present the case of a DBS-related infection that required complete removal of the system and an extended course of parenteral antibiotic therapy. Remarkably, the patient experienced a significant improvement in parkinsonian motor symptoms months after treatment, without requiring additional surgery.

Illustrative Case

A 58-year-old male, diagnosed with PD 13 years earlier, presented with bilateral tremor, rigidity, and bradykinesia, along with levodopa-induced dyskinesia, which had developed 8 years earlier but became severe only in the last 2 years. Despite receiving optimized treatment at the outpatient clinic with the movement disorders team, including levodopa 250 mg plus entacapone 200 mg six times daily and amantadine 100 mg three times daily, the patient continued to experience significant motor symptoms. These symptoms severely compromised his daily activities and quality of life, leading to a referral to the Stereotactic and Functional Neurosurgery Service. According to the surgical protocol at our institution, the patient was scheduled for a right-sided lesioning and left-sided DBS (dominant hemisphere).

The patient underwent right-sided posterior subthalamic area radiofrequency lesioning (Fig. 1A), which provided substantial symptom relief in the left hemibody without intra- or postoperative complications. The patient continued with the preoperative medications and maintained regular outpatient follow-up.

FIG. 1.

Postoperative axial and coronal T2-weighted/short tau inversion recovery MRI showing a right-sided posterior subthalamic area (PSA) radiofrequency lesion (A), the DBS lead in the left STN (B), and a focal hyperintense area with a hypointense halo immediately distal to the tip of the electrode, suggestive of cerebritis, along with a diffuse hyperintense signal surrounding the lead implanted in the left STN that likely indicates either inflammation (cerebritis) or edema (C). Note that the previous PSA lesion (A) is no longer observed in the images obtained 2 years after the lesioning procedure (B and C).

Approximately 2 years later, due to ongoing right hemibody symptoms, the patient underwent left subthalamic nucleus (STN) DBS system implantation (Fig. 1B). Stimulation began on the 7th postoperative day. Contrary to the intraoperative findings, the initial improvement in motor symptoms was unsatisfactory. A head magnetic resonance imaging (MRI) scan revealed upward migration of the electrode. Sixteen days after the initial implantation, the patient underwent surgery for electrode repositioning, which resulted in improved control of motor symptoms.

On the 5th postoperative day following electrode repositioning, the patient developed severe headache, fever, malaise, and erythema at the site of the left frontal surgical wound. Blood and cerebrospinal fluid laboratory tests revealed leukocytosis, neutrophilia with a left shift, elevated C-reactive protein levels, and meningoencephalitis. Head MRI confirmed adequate electrode placement but showed a perielectrode infection (Fig. 1C), prompting early explantation of the DBS system on the 7th postoperative day, when the presence of subgaleal pus was noticed. Cultures of the cerebrospinal fluid, wound pus, and DBS lead and extension showed no bacterial growth. Initially, parkinsonian symptoms on the right hemibody remained unchanged, with no observable insertional effects. The patient was treated with intravenous antimicrobial therapy with meropenem and vancomycin for 28 days and was subsequently discharged, pending future surgical scheduling as needed. However, at the 4-month outpatient follow-up, a marked improvement in all parkinsonian motor symptoms was reported and observed on the right hemibody. Head MRI 2 years after explantation showed changes consistent with postinfectious reactive gliosis and hemosiderin deposition probably secondary to the previous electrode infection in the topography of the left STN (Fig. 2). Now, 40 months after explantation of the infected DBS system, the patient remains under outpatient care with well-controlled right hemibody motor symptoms and no recurrences, maintaining clinical management with the same medications.

FIG. 2.

Axial T2 fluid-attenuated inversion recovery (A) and gradient-echo (B) MRI 2 years after explantation of the DBS system, revealing a focal hyperintense area consistent with postinfectious gliosis (A) and likely hemosiderin deposition (B) in the topography of the left STN. Notably, an axial computed tomography image at the same level did not show calcification.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Stereotactic ablative surgeries for PD and other movement disorders began in the 1940s. However, with the clinical introduction of levodopa therapy in the late 1960s, there was a sharp decline in the number of these procedures worldwide. In the 1990s, following the introduction of DBS for treating movement disorders and the increased recognition of levodopa-induced motor complications, surgical treatment for these conditions regained interest and therapeutic significance. Today, DBS is recognized for its safety and short-, medium-, and long-term efficacy in controlling cardinal motor symptoms of PD while also effectively managing levodopa-induced motor fluctuations and dyskinesias.^{4, 6}

Infection remains a significant complication of DBS, with reported rates ranging from 1.2% to 15.2%. Key risk factors include prolonged surgery, a short period of prophylactic antibiotic therapy, intensive care unit postoperative management, a history of previous DBS system infection, and patient-related factors such as obesity, diabetes, and smoking.^{5, 7} In cases of DBS infection, prolonged antibiotic therapy is usually the first treatment choice; however, in many situations, complete removal of the system may be necessary, especially if the infection involves the brain electrode and leads to cerebritis. In such cases, disease treatment is compromised, as it leads to the reemergence of motor symptoms.^{4, 5, 7}

Observations

Our patient experienced spontaneous improvement in motor symptoms 4 months after the removal of the brain electrode, without any changes in medication or additional surgeries. Follow-up head MRI performed 2 years after the electrode infection and explantation revealed changes consistent with postinfectious reactive gliosis and hemosiderin deposition in the left STN. We hypothesize that the gliosis produced a lesion-like effect at the surgical target, determining the patient’s clinical improvement without the need for further surgery or adjustments in medications. This hypothesis is supported by findings from Vilela-Filho et al., who observed that gliosis significantly reduced the tremor in four of five rats following sham lesioning of the posterior striatum in an animal model of essential tremor induced by harmaline.^{8, 9} Importantly, as the improvement occurred only months after resolution of the cerebritis, it suggests that the acute infection was not the cause of the improvement.

Lessons

A literature review revealed no previous cases where DBS electrode-related infection led to gliotic changes affecting the course of PD. The gliosis produced a beneficial, lesion-like, long-term effect (ongoing for 40 months) in the DBS target area (STN), resulting in a significant improvement in motor symptoms.

Clinically, this case expands our understanding of the potential long-term neurological effects of postoperative infections in DBS, an area often overlooked in studies that focus on immediate complications and management. It underscores the importance of considering both the immediate- and long-term impacts of such infections.

Additionally, the observed improvement without DBS reimplantation or medication adjustments suggests that lasting benefits can occur even after removing the DBS system, potentially influencing future clinical management and therapeutic strategies for similar complications. Considering our findings, it would probably be wise to postpone a new lead implantation for at least a few months (4–6 months) to determine if it is really necessary, as the patient may present delayed improvement after a lead infection or cerebritis due to a lesion-like effect induced by postinfectious reactive gliosis.

The main limitation of this study lies in the inability to confirm the diagnosis of gliosis through an anatomopathological examination. This is significant given our primary hypothesis that gliosis was the underlying cause of the observed clinical improvement, even though the MRI findings were highly suggestive of this diagnosis.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Vilela-Filho. Acquisition of data: Oliveira-Alves, Alvim-Alves, Silva. Analysis and interpretation of data: all authors. Drafting the article: Vilela-Filho, Oliveira-Alves, Alvim-Alves. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Vilela-Filho. Study supervision: Vilela-Filho.

Correspondence

Osvaldo Vilela-Filho: Medical School, Federal University of Goiás, Goiânia, Goiás, Brazil. ovilelafilho@clanfer.com.