Original Article
Peri-Lead Edema After Deep Brain Stimulation Surgery: A Poorly Understood but
Frequent Complication
Alexander C. Whiting, Joshua S. Catapano, Corey T. Walker, Jakub Godzik, Margaret Lambert, Francisco A. Ponce
- OBJECTIVE: Postoperative peri-lead edema (PLE) is a
poorly understood complication of deep brain stimulation
(DBS), which has been described sporadically in patients
presenting with profound and often delayed symptoms. We
performed a prospective evaluation of patients undergoing
DBS to determine the frequency of and identify risk factors
for PLE.
- METHODS: Patients underwent DBS electrode place-
ment by a single physician. Postoperative magnetic reso-
nance imaging (MRI) was performed approximately 6
weeks after the operation in asymptomatic subjects and
analyzed for presence of PLE. All symptomatic subjects
underwent MRI at the time of presentation. Data regarding
index disease, preoperative medical issues, operative
technique, and intraoperative variables were collected and
statistically analyzed.
- RESULTS: A total of 191 leads were placed in 102 sub-
jects; 15 patients (14.7%) demonstrated PLE. Seven patients
(6.9%) presented with symptoms related to PLE, most often
altered mental status or neurologic deficit. Many of the
MRI findings were profound, with PLE sometimes several
centimeters in diameter. No statistically significant differ-
ence was found between PLE-positive and normal subjects
when analyzing multiple variables, including presence of
vascular disease, hypertension, anticoagulant/antiplatelet
use, electrode target, index disease, unilateral versus
bilateral lead placement, number of brain penetrations, and
presence or absence of microelectrode recording.
- CONCLUSIONS: Patients with postoperative PLE can
present with severe symptoms or can be asymptomatic and
go undiagnosed. Because of the delayed-onset potential,
Key words
- Complications
- Deep brain stimulation
- Functional neurosurgery
- Peri-lead edema
Abbreviations and Acronyms
CT: Computed tomography
DBS: Deep brain stimulation
MRI: Magnetic resonance imaging
PLE: Peri-lead edema
WORLD NEUROSURGERY -: e1-e6, - 2019
PLE may be more common than previously reported. No
clear risk factors have been identified; therefore, further
studies and increased clinical vigilance are paramount for
improving comprehension and possible prevention of PLE.
INTRODUCTION
D eep brain stimulation (DBS) has become a frequently
performed neurosurgical intervention for a wide variety
of diseases. Although it is often used for its combination
of successful outcomes and low frequency of major complications,
patients undergoing DBS may experience a range of complica-
tions, many of which are still being elucidated. More serious, rare
complications include intracerebral hemorrhage, ischemic stroke,
venous infarction, and air embolism. Various studies have found a
permanent morbidity rate ranging from 0.4% to 1.0% and a
mortality rate of 0% to 0.4%.1-5 Although superficial infectious
complications have been found to range from 3.0% to 15.2%,6-10
intracranial postoperative infections are exceedingly rare.3,6
Recently, a novel complication, peri-lead edema (PLE) found on
T2-weighted magnetic resonance imaging (MRI), has been
described (Figure 1).11-13 Ryu et al.11 first described this finding in
several patients who underwent MRI before the second stage of
their DBS surgery, all of whom were asymptomatic. Another
study found an incidence of 6.3% (15/229 implants) among 133
patients who had undergone DBS electrode implantation with
MRI performed within 14 days after surgery,12 with 4 of 15
patients symptomatic at the time of the finding. Here, we report
an unexpectedly high incidence of PLE among DBS patients and
present a comprehensive analysis of perioperative and clinical
variables for these patients.
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and
Medical Center, Phoenix, Arizona, USA
To whom correspondence should be addressed: Francisco A. Ponce, M.D.
[E-mail: Neuropub@barrowneuro.org]
Citation: World Neurosurg. (2019).
https://doi.org/10.1016/j.wneu.2018.12.092
Journal homepage: www.journals.elsevier.com/world-neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery e1

ALEXANDER C. WHITING ET AL.
Figure 1. T2-weighted magnetic resonance imaging showing mild peri-lead edema (A) and moderate-to-severe
peri-lead edema (B) in 2 patients. (Used with permission from Barrow Neurological Institute, Phoenix, Arizona.)
METHODS
Subjects and Surgical Technique
This study was conducted with approval from St. Joseph’s Hospital
and Medical Center Institutional Review Board for Human
Research (Phoenix, Arizona, USA). Study participants provided
informed consent. Patients scheduled to undergo stereotactic DBS
electrode placement with either 1 or 2 leads between September
2012 and October 2014 by a single surgeon were eligible for
prospective enrollment.
The DBS procedure included stereotactic planning of electrode
placement performed via a merged preoperative MRI and intra-
operative frame-based computed tomography (CT). Unilateral or
bilateral electrode leads were then placed stereotactically with
patients either awake with twilight anesthesia or asleep with
general anesthesia, depending on patient preference at the time of
consent.
Data Collection
A retrospective chart review was conducted for all subjects
included in the study to collect radiographic and perioperative
data. Subject characteristics documented included age, sex,
presence of antiplatelet or anticoagulant use preoperatively or
postoperatively, and presence of hypertension. Subjects with
known vascular disease were documented, with vascular disease
defined as the presence of one or more of the following: carotid
artery stenosis requiring intervention, known hypercoagulable
state, previous deep vein thrombosis or pulmonary embolism,
coronary heart disease manifested by myocardial infarction or
e2 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.092
ORIGINAL ARTICLE
PERI-LEAD EDEMA AFTER DBS
heart failure, cerebrovascular disease manifested by prior stroke or
transient ischemic attack, peripheral artery disease manifested by
intermittent claudication, or known thoracic or abdominal aortic
aneurysm. Preexisting hypertension or the use of anticoagulants or
antiplatelets was also recorded. Prospectively collected surgical
information included disease indication for surgery, surgical
target of lead placement, awake or asleep placement of electrode
leads, microelectrode recording, and number of brain penetra-
tions required for accurate and final lead placement. Brain pene-
trations were defined as any separate trajectory causing a
penetration of the brain by a microelectrode for recording
purposes or by an electrode for presumptive final placement.
Imaging
Postoperative T1- and T2-weighted brain MRI was performed
prospectively in an outpatient setting in all willing and capable
subjects at approximately 2 months after surgery.14 Additionally,
any patients who presented to the hospital or the outpatient
clinic with postoperative neurologic symptoms underwent brain
MRI. All MRIs were subsequently reviewed by a radiologist and
neurosurgeon for T2-weighted hyperintensity along the lead
tracts. Any T2 signal greater than twice the diameter of the leads
was considered to be positive for PLE.12
Statistical Analysis
Subjects with PLE were compared with subjects with normal MRI
findings using a 2-tailed Fisher exact test, with statistical signifi-
cance set at P < 0.05.
 ORIGINAL ARTICLE
ALEXANDER C. WHITING ET AL. PERI-LEAD EDEMA AFTER DBS

DBS during this time frame participated in the study. Among the
Table 1. Patient Demographic Characteristics (N ¼ 102) study population, 22.5% (23/102) underwent awake DBS, whereas
Characteristic Number of Patients (%) 77.5% (79/102) underwent asleep DBS. Microelectrode recording
and intraoperative CT were used to verify correct placement in
Sex 15 subjects, whereas accurate anatomic placement on
Male 60 (58.8) intraoperative postplacement CT alone was used for verification
in 87 subjects.
Female 42 (41.2)
Postoperative MRIs were performed between September 2012
DBS procedure and October 2014. Of the 102 subjects, 15 subjects (14.7%)
Awake 23 (22.5) demonstrated PLE that met the predefined criteria (Table 2). For
subjects found to demonstrate PLE, the time between surgery
Asleep 79 (77.5)
and the subsequent MRI was a mean of 59.1 days and a median
Lead target of 50 days. Of the 15 subjects with PLE, 7 (46.7%) were
GPi 61 (59.8) symptomatic on discovery of the MRI finding. Symptomatic
clinical findings included seizures, confusion, and transient
VIM 21 (20.6)
speech or motor neurologic deficit (Table 3). All clinical
STN 20 (19.6) manifestations of PLE resolved over time. Of the 15 subjects
Disease with PLE, the mean time between DBS and MRI was 48.9 days
(median, 19 days) for the 7 symptomatic patients versus 68.1
PD 78 (76.5)
days (median, 54.5 days) for the 8 asymptomatic patients. Three
ET 22 (21.6) of the 15 subjects (20.0%) with PLE had microelectrode
Dystonia 2 (2.0) recordings performed during surgery.
The 15 subjects found to have PLE and the 87 subjects found to
DBS, deep brain stimulation; GPi, globus pallidus interna; VIM, ventral intermediate
have normal MRI findings were then stratified based on sex,
nucleus; STN, subthalamic nucleus; PD, Parkinson disease; ET, essential tremor.
presence of vascular disease, presence of hypertension, anticoag-
ulant or antiplatelet use, use of awake or asleep DBS, indication
RESULTS for surgery, DBS target, presence or absence of more than 1 brain
The 102 subjects enrolled in the study who underwent DBS had a penetration per lead, and presence or absence of microelectrode
total of 191 leads placed (Table 1). Not all patients who underwent recording. When comparing subjects with PLE and subjects with

Table 2. Demographic, Surgical, and Presentation Data for All Patients Found to Have Peri-Lead Edema
Patient
Identification
Number Age (Years) Sex Procedure Location Disease MER Leads Total Brain Penetrations Laterality of PLE Presentation

1 46 M Awake GPi PD Yes 2 6 (3 on right, 3 on left) Right Asymptomatic

2 55 F Awake VIM ET No 1 1 Left Asymptomatic
3 70 F Awake GPi PD Yes 1 2 Right Symptomatic
4 71 F Asleep GPi PD No 1 1 Left Asymptomatic
5 49 F Asleep STN PD No 2 2 Bilateral Asymptomatic
6 67 M Asleep GPi PD No 2 3 (2 on right, 1 on left) Left Asymptomatic
7 51 M Awake GPi PD Yes 2 3 (1 on right, 2 on left) Bilateral Asymptomatic
8 65 F Asleep VIM ET No 2 2 Left Asymptomatic
9 51 F Asleep GPi PD No 2 2 Left Symptomatic
10 57 M Asleep GPi PD No 2 2 Left Symptomatic
11 64 M Asleep STN PD No 2 2 Right Symptomatic
12 66 M Asleep GPi PD No 2 2 Left Asymptomatic
13 55 M Asleep GPi PD No 1 1 Right Symptomatic
14 68 M Asleep VIM ET No 2 2 Right Symptomatic
15 70 F Asleep VIM ET No 2 2 Left Symptomatic

MER, microelectrode recording; PLE, peri-lead edema; M, male; GPi, globus pallidus interna; PD, Parkinson disease; F, female; VIM, ventral intermediate nucleus; ET, essential tremor; STN,
subthalamic nucleus.

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 ORIGINAL ARTICLE
ALEXANDER C. WHITING ET AL. PERI-LEAD EDEMA AFTER DBS

Table 3. Demographics and Presentation of Symptomatic Table 4. Subjects with Peri-Lead Edema on Magnetic
Patients with Peri-Lead Edema Resonance Imaging Versus Subjects with Normal Magnetic
Resonance Imaging
Subject Identification Age Symptomatic
Number (Years) Sex Presentation P
Variable PLE (n [ 15) Normal (n [ 87) Value
3 70 F Seizure
9 51 F Gait disturbance Mean age (years) 60.3 64.1 0.18

10 57 M Transient aphasia, Mean time from DBS to MRI (days) 59.1 72.0 0.36
confusion Sex 0.78
11 64 M Seizure Male 8 (53.3) 52 (59.8)
13 55 M Seizure Female 7 (46.7) 35 (40.2)
14 68 M Transient hemiparesis Vascular disease 0.12
15 70 F Transient aphasia Yes 0 (0.0) 16 (18.4)
F, female; M, male. No 15 (100.0) 71 (81.6)
Hypertension 0.54
normal MRI findings, no significant differences were found for Yes 3 (20.0) 27 (31.0)
these variables (Table 4). Of note, 26.7% of subjects (4/15) with No 12 (80.0) 60 (69.0)
PLE underwent more than 1 brain penetration per lead
Anticoagulant/antiplatelet use 0.29
compared with 18.4% of subjects (16/87) with normal MRI
findings (P ¼ 0.49). Additionally, 20.0% of subjects (3/15) with Yes 1 (6.7) 18 (20.7)
PLE underwent microelectrode recording compared with 14.9% No 14 (93.3) 69 (79.3)
of subjects (13/87) with normal MRI findings (P ¼ 0.70).
DBS procedure type 0.74
Awake 4 (26.7) 19 (21.8)
DISCUSSION
Because DBS has become a widely practiced neurosurgical treat- Asleep 11 (73.3) 68 (78.2)
ment modality, our understanding of its complications has Lead target 0.72
improved. Complications with more obvious presentations, such GPi 9 (60.0) 52 (59.8)
as infection and hemorrhage, have been widely published and are
VIM 4 (26.7) 17 (19.5)
better understood,6-10 but reports of PLE have been limited to only
a few publications, most of which are case reports or case se- STN 2 (13.3) 18 (20.7)
ries.11,13,15-18 PLE is poorly understood and only marginally Indication 0.74
reported in the literature. It is frequently reported as a potential
PD 11 (73.3) 67 (77.0)
infection by radiologists; however, it appears to be a fundamen-
tally noninfectious process. Additionally, PLE is sometimes ET 4 (26.7) 18 (20.7)
described as an artifact, but it often extends well beyond the 2e4 Dystonia 0 (0.0) 2 (2.3)
mm considered to be actual MRI image distortion based on prior
Number of leads 0.10
studies.19 At our institution, PLE has also been postulated to be
venous congestion from the electrode penetration, but this Unilateral 4 (26.7) 9 (10.3)
appears to be untrue because the PLE often follows the length Bilateral 11 (73.3) 78 (89.7)
of the electrode circumferentially in a radial distribution
>1 brain penetration per lead 0.49
(Figure 2). The goal of this study was to better elucidate the
prevalence of this unusual and poorly understood complication Yes 4 (26.7) 16 (18.4)
and to determine any preoperative or perioperative variables that No 11 (73.3) 71 (81.6)
may contribute to its development. In our study, 15 subjects
Microelectrode recording 0.70
were determined to demonstrate PLE after DBS, which equals
the largest series of subjects in the literature. These patients Yes 3 (20.0) 13 (14.9)
with PLE were then compared with 87 subjects who had No 12 (80.0) 74 (85.1)
prospective MRIs and normal findings after similar DBS
Data are number of patients (%) or as otherwise indicated.
procedures.
PLE, peri-lead edema; DBS, deep brain stimulation; MRI, magnetic resonance imaging;
DBS is often performed with microelectrode recordings,
GPi, globus pallidus interna; VIM, ventral intermediate nucleus; STN, subthalamic
which may increase the number of potentially traumatic trajec- nucleus; PD, Parkinson disease; ET, essential tremor.
tories through the brain. Additionally, DBS performed using

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ALEXANDER C. WHITING ET AL.
Figure 2. T2-weighted magnetic resonance imaging demonstrating radial
peri-lead edema. (Used with permission from Barrow Neurological
Institute, Phoenix, Arizona.)
intraoperative CT can reveal imprecise electrode placement,
which requires a new trajectory and replacement of the final
electrode lead. Both result in an increase in the number of
potentially traumatic trajectories as electrodes are advanced
through the brain, possibly increasing the risk for PLE. However,
the results of this study demonstrated no significant difference
in the number of brain penetrations between subjects who
demonstrated PLE and those with normal MRI findings. This
augments other reports of PLE, which also found no relationship
between the number of brain penetrations and the likelihood of
developing PLE.12,15 Moreover, when examining preoperative
risk factors, such as presence of vascular disease, hypertension,
or anticoagulant use, no statistically significant difference was
found between subjects who developed PLE and subjects who
did not. The sample size of this study was relatively small,
particularly for a rare phenomenon, but the results may still
speak to the underlying etiology of this unusual complication in
that it does not appear to be related to preoperative cardiovas-
cular or vascular issues.
Additionally, in the prior reports of PLE, the index MRI tended
to be performed over a much shorter time period than was the
case in our study.11-13 In the study by Englot et al.,12 the MRIs
demonstrating PLE were performed between 2 and 13 days after
the operation. In the study by Fenoy et al.,13 the MRIs
demonstrating PLE were performed between 1 and 14 days after
the operation. Conversely, in our study, the MRI was performed
at a much later time for both the normal subjects and the
subjects with PLE. The mean time from the DBS electrode
WORLD NEUROSURGERY -: e1-e6, - 2019
ORIGINAL ARTICLE
PERI-LEAD EDEMA AFTER DBS
placement to MRI was 59.1 days for subjects demonstrating PLE
and 72.0 days for subjects with normal MRI findings. Among
those with PLE, symptomatic patients had an MRI at a mean of
48.9 days (median, 19 days) after surgery, whereas patients who
were asymptomatic had an MRI at a mean of 68.1 days after
surgery (median, 54.5 days). Our finding of PLE at a mean of
48.9 days after DBS in symptomatic patients and 54.5 days after
DBS in asymptomatic patients establishes that this complication
is not solely relegated to the first 2 postoperative weeks but can
be found several weeks after surgery. This again highlights the
possibility that PLE is not necessarily related to the initial
trauma of placing the electrodes. It is also possible that, by
acquiring the MRI several weeks after surgery, we may have
underreported the number of subjects who developed
asymptomatic PLE immediately after surgery that self-resolved
before the scheduled follow-up MRI.
Several studies have demonstrated the presence of transient
confusion after DBS surgery, with one study estimating the prev-
alence to be greater than 15% after subthalamus DBS surgery.20
Another review placed the rate of mental status and behavior
changes after DBS surgery at 18.4% for subthalamus and 9.3%
for globus pallidus interna stimulation.21 Because postoperative
MRIs are not routinely ordered for DBS patients, it is possible
that a segment of patients who develop these symptoms may
actually have unreported PLE. Furthermore, CT is often used
instead of MRI for postoperative imaging, which is less sensitive
for identifying edema and demonstrates more extensive scatter
around the leads.
It is not yet understood what causes the unusual finding of PLE
or what the appropriate management should be. PLE does not
appear to be infectious in nature and has been postulated to be an
inappropriate immune reaction to the DBS electrode.15 Because
patients can often develop unilateral PLE with bilateral electrode
lead placement, this theory does not fully explain this
complication. In this study, 11 of the subjects who demonstrated
PLE underwent simultaneous bilateral lead placement, but only
2 of these subjects demonstrated bilateral PLE. It is possible
that some other intraoperative component could be inducing an
immune reaction, which would better explain why so many
patients with bilateral electrodes demonstrate PLE only
unilaterally. At our institution, we had previously placed fibrin
glue after making our durotomy to form an airtight seal along
the dura before electrode placement. It is possible that this
fibrin glue, or some other intraoperative element, could have
been pulled along the electrode path, causing a delayed
reaction. Moreover, autopsy studies examining peri-electrode
microscopic pathology have discovered no signs of overt
neuronal death along the length of the electrode,22 and they have
demonstrated only mild reactive changes confined to the
immediate vicinity of the electrode tracts.22-24
The prognosis of patients with symptoms related to PLE appears
to be good. Steroids and patience have become the mainstays of PLE
treatment, with self-resolution reported in almost all cases of
symptoms; however, no specific studies have looked at comparing
treatment modalities. Patients who develop symptoms can be
reassured that any deficit is expected to resolve with time.
This study was limited by the retrospective nature of the
preoperative data review and the relatively small sample size
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 ORIGINAL ARTICLE
ALEXANDER C. WHITING ET AL. PERI-LEAD EDEMA AFTER DBS

compared with the presumed incidence of PLE. The subjects were
heterogeneous in their type of procedure (awake vs. asleep), target
location, and disease entity, and although this study did not show
a statistically significant difference between patients with PLE and
normal subjects in any of these variables, the sample sizes of each
group were possibly too small to adequately detect a difference.
Additionally, as mentioned previously, the MRIs were ordered
several weeks after the surgery was performed; therefore, our re-
sults may have underreported the number of subjects who
demonstrated PLE early after surgery.
CONCLUSIONS
This study describes 15 subjects who demonstrated PLE, 7 of
whom presented symptomatically. Medical teams caring for
postoperative DBS patients should maintain a high index of
suspicion for this complication in any patients demonstrating
altered mental status or neurologic deficits after surgery. As this
study demonstrates, this complication can be found several weeks
after surgery and may be more common than expected. Patients
can be reassured that any deficits resulting from PLE are expected
to be transient. More research is necessary to elucidate the exact
mechanism, risk factors, and most effective treatment paradigms
for this unusual complication.
ACKNOWLEDGMENTS
The authors thank the staff of Neuroscience Publications at
Barrow Neurological Institute for assistance with manuscript
preparation.

10. Umemura A, Jaggi JL, Hurtig HI, et al. Deep brain 19. Uitti RJ, Tsuboi Y, Pooley RA, et al. Magnetic
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Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 19 September 2018; accepted 13 December 2018
Citation: World Neurosurg. (2019).
https://doi.org/10.1016/j.wneu.2018.12.092
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All
rights reserved.

e6 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.092