Symptomatic, non-infectious, non-hemorrhagic edema after subthalamic nucleus deep brain stimulation surgery for Parkinson's disease

doi:10.1016/j.jns.2017.10.003

Journal of the Neurological Sciences

Volume 383, 15 December 2017, Pages 42-46

https://doi.org/10.1016/j.jns.2017.10.003 Get rights and content

Highlights

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Delayed symptomatic brain edema occurs in approximately 3% of implanted DBS leads
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Delayed symptomatic brain edema is more common in lead re-implantations (9%) compared to new lead implantations (2%)
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In re-implantations, brain edema is more common when the same trajectory is used (18%) compared to a new trajectory (0%)
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Delayed symptomatic brain edema generally occurs 2–8 days after implantation, although immediate post-op CT is normal
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Seizures are a common presenting feature of delayed symptomatic brain edema

Abstract

Object

We review our experience with Parkinson's disease (PD) patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) and then developed noninfectious, non-hemorrhagic, delayed, symptomatic brain edema associated with a DBS lead.

Methods

All PD patients who underwent STN DBS lead implantation from 2007 to 2015 were included. The same neurosurgeon performed all surgeries, typically in staged fashion, utilizing single pass microelectrode recordings (MER) within a stereotactic frame. A brain CT was obtained in recovery and subsequently if indicated.

Results

There were 189 patients who underwent 363 STN lead implantations among which 35 (9.6%) represent re-implantations of removed leads in 28 (14.8%) patients. Among the 363 STN leads implanted, there were 12 (3.3%) cases of delayed symptomatic edema associated with a DBS lead involving 10 (5.3%) of the patients studied. Of the 328 leads representing first-time operations, there were 9 (2.1%) cases of delayed symptomatic edema in 7 (3.7%) patients, one of whom (14.3%) presented with seizures. For lead re-implantations, there were 3 (8.6%) cases of the brain edema in 3 (10.7%) patients; all presenting with seizures. For the 35 re-implantations, the trajectory to target was the same or very similar via the same burr hole as prior surgery in 17 (48.6%); 3 (17.6%) of whom developed edema. There was no case of brain edema in the 18 re-operated cases using a different burr opening. Edema patients were treated with a course of anticonvulsant medication and dexamethasone. Lead-associated edema resolved over generally a 4 to 6-week course.

Conclusions

Noninfectious, non-hemorrhagic, delayed, symptomatic brain edema occurs in approximately 3% of implanted leads and is more common in re-implantations (9%) compared to new implantations (2%). In re-implantations, the edema is more common when the same trajectory is used (18%) compared to a new trajectory (0%). The edema generally occurs 3 to 8 days after implantation, although immediate post-op CT is normal and seizures are a common presenting feature.

Introduction

Many studies have documented complications associated with deep brain stimulation (DBS) surgery including infection, bleeding, neurologic deficits, and cognitive or emotional changes [1]. A complication periodically encountered, delayed symptomatic brain edema, has been recognized in the recent DBS literature [2], [3], [4], [5], [6], [7], [8]. This edema is associated with a DBS lead in the absence of hemorrhage or infection in patients who initially did very well and had unremarkable brain imaging immediately following lead implantation. In the present report, we review our experience over an 8-year period in patients with Parkinson's disease (PD) who underwent subthalamic nucleus (STN) DBS and developed delayed symptomatic, noninfectious, non-hemorrhagic brain edema associated with a DBS lead.

Section snippets

Methods

All PD patients who underwent STN DBS lead (Medtronic Inc., Minneapolis, MN) implantation from January 2007 through December 2015 at the University of Kansas Medical Center (KUMC) were included in this study. Patients were evaluated prior to surgery by the same neurologist (RP). The inclusion criteria for surgery included the diagnosis of PD as defined by the United Kingdom Parkinson's Disease Society Brain Bank criteria, responsiveness to levodopa, and medication-resistant motor fluctuations,

Results

Over the time period studied, 189 patients underwent 363 STN lead implantations. There were 137 males (72.5%) and 52 females (27.5%) with an average age of 63.5 years, ranging from 26 to 84 years of age at the time of the initial STN DBS surgery. The average disease duration at the time of initial surgery was 10.7 years, ranging from 0.5 to 38 years. Among the 363 STN leads implanted, 35 (9.6%) represent re-implantations of removed leads in 28 (14.8%) of the 189 STN patients, resulting in bilateral

Discussion

The development of delayed, symptomatic, non-hemorrhagic noninfectious edema following DBS lead placement occurred in 3.3% of the reported lead placements, representing 5.3% of PD patients operated at our medical center from 2007 to 2015. After the initial lead placements, this edema developed in 2.7% of the leads, representing 3.7% of patients operated. In contrast, for those that required re-operations due to prior lead removal, this edema occurred in 8.6% of the leads, representing 10.7% of

Financial support

This study was funded by the Helen Gold Fund for Parkinson's Disease Research donated to the KUMC PD Center.

Disclosures

Dr. Nazzaro has no disclosures. Dr. Pahwa and Dr. Lyons have served as consultants for St. Jude Medical. Dr. Pahwa has received research support to his university from St. Jude Medical and Boston Scientific.

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Cited by (24)

Decreased brain volume may be associated with the occurrence of peri-lead edema in Parkinson's disease patients with deep brain stimulation
2024, Parkinsonism and Related Disorders
Peri-lead edema (PLE) is a poorly understood complication of deep brain stimulation (DBS), which has been described in patients presenting occasionally with profound and often delayed symptoms with an incidence ranging from 0.4% up to even 100%. Therefore, our study aims to investigate the association of brain and brain compartment volumes on magnetic resonance imaging (MRI) with the occurrence of PLE in Parkinson's disease (PD) patients after DBS implantation in subthalamic nuclei (STN).
This retrospective study included 125 consecutive PD patients who underwent STN DBS at the Department of Neurosurgery, Dubrava University Hospital from 2010 to 2022. Qualitative analysis was done on postoperative MRI T2-weighted sequence by two independent observers, marking PLE on midbrain, thalamus, and subcortical levels as mild, moderate, or severe. Quantitative volumetric analysis of brain and brain compartment volumes was conducted using an automated CIVET processing pipeline on preoperative MRI T1 MPRAGE sequences. In addition, observed PLE on individual hemispheres was delineated manually and measured using Analyze 14.0 software.
In our cohort, PLE was observed in 32.17%, mostly bilaterally. Mild PLE was observed in the majority of patients, regardless of the level observed. Age, sex, diabetes, hypertension, vascular disease, and the use of anticoagulant/antiplatelet therapy showed no significant association with the occurrence of PLE. Total grey matter volume showed a significant association with the PLE occurrence (r = −0.22, p = 0.04), as well as cortex volume (r = −0.32, p = 0.0005). Cortical volumes of hemispheres, overall hemisphere volumes, as well as hemisphere/total intracranial volume ratio showed significant association with the PLE occurrence. Furthermore, the volume of the cortex and total grey volume represent moderate indicators, while hemisphere volumes, cortical volumes of hemispheres, and hemisphere/total intracranial volume ratio represent mild to moderate indicators of possible PLE occurrence.
The results of our study suggest that the morphometric MRI measurements, as a useful tool, can provide relevant information about the structural status of the brain in patients with PD and represent moderate indicators of possible PLE occurrence. Identifying patients with greater brain atrophy, especially regarding grey matter before DBS implantation, will allow us to estimate the possible postoperative symptoms and intervene in a timely manner. Further studies are needed to confirm our findings and to investigate other potential predictors and risk factors of PLE occurrence.
Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: Case series and review of the literature
2023, Clinical Neurology and Neurosurgery
Idiopathic peri-lead edema (IPLE) is being increasingly described as a potential complication occurring after DBS surgery. Its incidence and relationship to post-operative symptoms, though, are still poorly defined and its understanding and management yet limited.
We reviewed delayed (≥ 72 h) post-operative CT imaging of patients who underwent DBS surgery at our Institution. A comparison of clinical and laboratory findings was carried out between patients with IPLE and controls.
61 patients, accounting for 115 electrodes, were included. Incidence of IPLE was 37.7 % per patient and 29.5 % per electrode. Patients with IPLE were significantly older than controls (52.82 ± 15.65 years vs 44.73 ± 18.82 years, p = 0.04). There was no difference in incidence of new-onset neurological symptoms between patients with IPLE and controls. Longer operative time (180.65 ± 34.30 min vs 158.34 ± 49.28 min, p = 0.06) and a greater number of MERs per electrode were associated with IPLE (3.37 ± 1.21 vs 3.00 ± 1.63, p = 0.089), though these comparisons did not meet the statistical significance. None of the patients with IPLE underwent hardware removal, with IPLE vanishing spontaneously over months.
IPLE is an underestimated, benign event that may occur after DBS surgery. Age, longer operative time and MER use may represent risk factors for IPLE formation, but further studies are needed. The presence of post-operative neurological symptoms and fever was not associated with IPLE presence, highlighting its benign nature and suggesting that empiric treatment may not be always justified.
Relationship of brain edema after deep brain stimulation surgery with motor and cognitive function
2022, Heliyon
Some patients with Parkinson's disease (PD) develop peri-lead brain edema after deep brain stimulation (DBS) surgery. The influence of edema on neurological function is not well characterized. We investigated the relationship of brain edema after DBS surgery with motor and cognitive function.
Thirteen patients with PD (6 males and 7 females; mean age: 61.2 years) who underwent bilateral subthalamic nucleus (STN) DBS surgery were included. All patients underwent magnetic resonance imaging (MRI) examination on day 6 post-DBS surgery. The volume of edema was measured either in the frontal white matter or STN on fluid attenuated inversion recovery (FLAIR) images. We examined the relationship between these volumes and changes in cognitive and motor function.
Patients were divided into those with frontal subcortical edema (FE) ≥3,000 mm³ (FE + group; n = 7) and <3,000 mm³ (FE–group; n = 6). In the FE + group, the postoperative Mini-Mental State Examination score worsened by 2.4 points after one week compared with that immediately before surgery, while that in the FE-group worsened only by 0.2 points (p = 0.038). On comparing patients with peri-STN edema (SE) ≥1,000 mm³ (SE + group; n = 3) and those with SE < 1,000 mm³ (SE-group; n = 10) showed that frequency of DBS tuning in the early postoperative period of the SE + group was lesser than that in the SE-group.
Development of FE after DBS surgery was related to transient cognitive decline. On the other hand, SE seemed associated with altered motor function and reduces the requirement for tuning in the initial period after DBS implantation.
Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology. Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy
2021, Progress in Brain Research
Citation Excerpt :
Breakdown of the BBB and reduction in the CBF lead to disturbances in fluid microenvironment of the brain in PD (Niu et al., 2020; Sharma et al., 2020). These pathophysiological events lead to brain edema and volume swelling in pre-clinical (Niu et al., 2020; Ozkizilcik et al., 2018a, 2019; Sharma et al., 2020) and in clinical cases of PD (Borellini et al., 2019; Nazzaro et al., 2017; Trezza et al., 2018). We measured brain edema and volume swelling during the course of MPTP administration in the mouse model of PD.
Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO₂ nanowired BF 2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25 μL) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier.
Idiopathic delayed-onset edema associated with deep brain stimulation
2021, Neurologia
Does post-operative symptomatic lead edema associated with subthalamic DBS implantation impact long-term clinical outcomes?
2020, Journal of the Neurological Sciences
Citation Excerpt :
The long-term impact of symptomatic lead edema is not clear and understanding its effect on clinical outcomes may help clinicians to counsel patients and establish management protocols. We previously reported our experience with the development of delayed non-infectious, symptomatic edema around DBS leads implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). [3] In that study we found that symptomatic lead edema can occur in approximately 3.3% of implanted leads in PD patients and is more common after re-implantation.
Post-operative, non-hemorrhagic, non-infectious symptomatic delayed edema around the DBS lead is an uncommon complication of DBS surgery. We investigated whether this complication impacts clinical outcomes or has long-term sequelae.
All Parkinson's disease (PD) patients with subthalamic nucleus (STN) DBS implantation who developed delayed symptomatic lead edema were identified. UPDRS part III motor, Parkinson's Disease Questionnaire (PDQ-39) total and MoCA scores were analyzed to assess motor outcome, quality of life and cognitive status at 1 year.
A total of 260 patients underwent 482 STN lead placements. Of these, 16 patients (20 leads, 4.1% of total 482 leads) developed this delayed complication. None of the patients had edema on immediate post-operative scan. Patients presented with varied symptoms including speech difficulty (n = 8), mild confusion (n = 6), headaches (n = 4), gait difficulty (n = 4) and seizures (n = 3). The mean duration for the diagnosis was 5.8 days after lead implantation and the mean duration for which follow-up CT scans reported complete/near complete resolution or improvement of edema was 4.7 weeks (range 2–10 weeks). At 1-year post-DBS, UPDRS motor scores improved significantly (42.5%, p < .001); quality of life improved, but the change was not statistically significant (21.3%, p = .197). There was no decline in cognitive function at 1 year (26.6 vs 26.4, p = .567). No long-term complication related to lead edema occurred in these patients.
Symptomatic lead edema after DBS surgery is an uncommon complication which typically resolves over time. In our series, there were no long-term sequelae of this complication and clinical outcomes were comparable to that reported in the literature.

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^☆: Portions of this work were presented at the Annual Meeting of the American Association of Neurological Surgeons, Los Angeles, CA, April, 2017.

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Symptomatic, non-infectious, non-hemorrhagic edema after subthalamic nucleus deep brain stimulation surgery for Parkinson's disease☆

Highlights

Abstract

Object

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Financial support

Disclosures

J. Clin. Neurosci.

Brain Stimul.

Neuromodulation

Parkinsonism Relat. Disord.

Deep brain stimulation for Parkinson's disease: current status and future outlook

Neurodegener. Dis. Manag.

Abnormal T2-weighted MRI signal surrounding leads in a subset of deep brain stimulation patients

Stereotact. Funct. Neurosurg.

Acute brain reaction to DBS electrodes after deep brain stimulation: chronological observation

Acta Neurochir.