COMPLICATION Acute Ischemic Stroke During Deep Brain Stimulation Surgery of Globus Pallidus Internus: Report of 5 Cases BACKGROUND: Cerebrovascular accident (CVA) is a potentially devastating complication of deep brain stimulation (DBS) surgery. Although there are substantial data reporting the incidence and cause of hemorrhagic CVA, reports of acute ischemic infarctions during DBS implantation surgery are rare. OBJECTIVE: To present a series of 5 patients who experienced clinically significant ischemic CVA during microelectrode-guided globus pallidus internus (GPi) DBS, and evaluate the potential risk factors and mechanisms. METHODS: A retrospective analysis of GPi DBS surgeries performed between June 2010 and February 2015 at UCLA Medical Center and June 2010 and February 2014 at CedarsSinai Medical Centers was performed to identify stroke risk factors. Statistical analysis was performed, comparing the stroke group with all patients undergoing GPi DBS. RESULTS: All 5 patients developed acute onset of lethargy, dysarthria, and contralateral facial and/or hemibody weakness intraoperatively. Computed tomographic scans in all cases were negative for hemorrhage. Magnetic resonance images obtained in 3 patients revealed infarction in the posterior limb of the internal capsule. During the time period analyzed, a total of 234 GPi leads were placed in 129 patients, yielding a 2.14% rate of ischemic stroke per lead. No statistically significant risk factors were identified in the stroke group. Given the variability of symptom onset during surgery, the mechanism is not clear, but it could be related to compression, compromise, or vasospasm of lenticulostriate arteries and/or anterior choroidal branches near the GPi target. CONCLUSION: Ischemic stroke in GPi DBS is a significant complication for clinicians to be aware of and discuss with their patients preoperatively. Angela E. Downes, MD* Patrick Pezeshkian, MD‡ Eric Behnke, BS‡ Yvette Bordelon, MD, PhD§ Michele Tagliati, MD¶ Adam Mamelak, MDk Nader Pouratian, MD, PhD‡ *Department of Neurosurgery, University of South Florida Morsani College of Medicine, Tampa, Florida; Departments of ‡Neurosurgery, and §Neurology, University of California, Los Angeles, Los Angeles, California; Departments of ¶Neurology, and kNeurosurgery, Cedars Sinai Medical Center, Los Angeles, California Correspondence: Angela E. Downes, MD, Department of Neurosurgery, University of Colorado, 12631 E. 17th Avenue, C307, Aurora, CO 80045. E-mail: angela.downes@ucdenver.edu Received, September 23, 2015. Accepted, June 5, 2016. Published Online, July 25, 2016. KEY WORDS: Complications, Deep brain stimulation, Globus pallidus internus, Ischemia, Stroke Operative Neurosurgery 12:383–390, 2016 Copyright © 2016 by the Congress of Neurological Surgeons. T he efficacy of globus pallidus internus (GPi) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD) and dystonia is well documented.1-4 The Veterans Affairs cooperative trial and several other trials have concluded that GPi and subthalamic nucleus (STN) DBS are equally effective for the management of the motor symptoms of PD.2 Because STN DBS is possibly associated with greater rates ABBREVIATIONS: DBS, deep brain stimulation; GPi, globus pallidus internus; MER, microelectrode recording; PD, Parkinson disease; PLIC, posterior limb of the internal capsule; STN, subthalamic nucleus OPERATIVE NEUROSURGERY DOI: 10.1227/NEU.0000000000001359 of neurocognitive decline and falls,1,2 GPi DBS has regained relative interest. Arguably, the most dangerous and clinically significant complication of DBS is intracerebral hemorrhage. In a large series of 567 electrode placements, Sansur et al5 reported a 1.2% risk of symptomatic hemorrhage and a 0.7% risk of hemorrhage resulting in permanent neurological deficit. The authors did not find a statistically significant difference in hemorrhage rates between STN, GPi, and thalamic targets. Although studies have extensively analyzed hemorrhagic complications,5-8 few reports describe, detail, or quantify subcortical ischemic adverse events related to DBS implantation. Although it is mentioned in some complication analyses,9 only 2 reports in literature VOLUME 12 | NUMBER 4 | DECEMBER 2016 | 383 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. DOWNES ET AL specifically describe nonhemorrhagic infarctions occurring during DBS surgery.10,11 Herein, we report 5 cases of clinically significant ischemic events occurring during stereotactic GPi DBS procedures. We quantify the incidence of this complication across 2 centers and describe the clinical presentation of each patient, their neurological outcomes, and neuroradiological findings. METHODS A retrospective analysis of GPi DBS surgeries performed between June 2010 and February 2015 at UCLA Medical Center and June 2010 and February 2014 at Cedars-Sinai Medical Centers was performed. Cases in which ischemic events occurred (based on acute clinical deficit without gross radiographic evidence of hemorrhage) were reviewed in detail. Clinical history, presentation, surgical indications, neurological outcomes, and neuroradiological outcomes were reviewed. Potential risk factors were evaluated, including age, sex, diagnosis, smoking history, history of cardiovascular and cerebrovascular disease (including history of hypertension, stroke, and myocardial infarction), use of microelectrode recording (MER), and intraoperative blood pressure. Surgical Procedure All patients underwent frame-based stereotactic GPi DBS implantation with similar pre- and intraoperative steps. Before surgery, 3-T stereotactic magnetic resonance (MR) imaging of the brain with contrast was performed. On the morning of surgery, a stereotactic frame (Leksell [Elekta, Stockholm, Sweden] at UCLA, CRW [Integra, Plainsboro, New Jersey] at Cedars-Sinai) was placed under brief propofol sedation and local anesthesia, after which a computed tomography (CT) scan of the head with a localizer was obtained. CT and MRI data were registered using a commercial software (BrainLab [Munich, Germany] at UCLA, Framelink [Medtronic, Dublin, Ireland] at Cedars-Sinai), and the GPi was targeted using a burr hole approximately at the coronal suture and 0 to 10 degrees lateral in the coronal plane, as indicated by a trajectory that avoided the ventricle. Target coordinates are detailed below for each case. Skin incision and burr holes were made with propofol-induced light sedation. After reexamining the patient and confirming normal blood pressure as measured by cuff (systolic less than 160 mm Hg), MER was performed using single-use microelectrodes with the Alpha Omega recording system (Alpha Omega, Nazareth, Israel) and microdrive with a single pass in each case. After MER targeting, the DBS electrode (Medtronic model number 3387) was implanted and intraoperative macrostimulation testing performed. RESULTS A total of 234 GPi leads were stereotactically implanted in 129 patients, including first implants and revisions (Table 1). Diagnoses include PD (n = 112, 86.8%), dystonia (n = 16, 12.4%), and Tourette disease (n = 1, 0.78%). The mean age at the time of surgery was 60.3 6 14.3 years, and 59.7% were male. Microelectrode recordings were used in 126 cases (97.7%). Incidence of Ischemic Stroke Ischemic strokes occurred during implantation of 5 of 234 leads, resulting in a 2.14% rate of ischemic stroke per lead 384 | VOLUME 12 | NUMBER 4 | DECEMBER 2016 implanted. Details of each case are presented below. Of the patients who had a stroke, 4 (80%) had a diagnosis of PD and 1 (20%) was diagnosed with dystonia, in comparison with 86.8% and 12.4%, respectively, for the overall population. In the cohort of patients who did not have a stroke, there was 1 hemorrhage noted on postoperative scans in a patient who also experienced a neurological deficit (0.78% symptomatic hemorrhage rate), with symptoms that resolved within 3 months of implantation. Risk Factors Potential risk factors in patients with ischemic stroke were compared with the rest of the cohort of patients who received implants in the GPi (Table 1). No significant age difference was observed: 54.2 6 4.2 years for ischemic cerebrovascular accident vs 60.3 6 14.3 years for all others (P = .08, t test with unequal variance). Eighty percent of affected patients were female, and only 1 (20%) had known stroke risk factors, including hypertension and obesity (Table 2). None of the patients who had an ischemic complication were past or current smokers. Microelectrode recording was used in all cases in which stroke occurred. Blood loss was minimal in each case. Imaging CT scan was performed immediately postoperatively in all 5 patients. MRIs were obtained in 3 of the 5 patients. There was no evidence of blood on either CT or MRI in any patient. The ischemic zones as seen on MRI are outlined in Table 2. Case Report 1 A 64-year-old woman underwent bilateral GPi DBS for a 6year history of PD presenting with left-handed tremor, bradykinesia, rigidity, and on-time dyskinesias. Vascular risk factors included obesity and hypertension, for which she was taking atenolol, Lisinopril, and terazosin. GPi was targeted at X = 19.0 mm, Y = 2.0 mm, and Z = 25.0 mm (AC-PC length = 25.9 mm). At surgery, left-hemisphere MER was uneventful, with excellent recordings confirming the GPi target. Upon implantation of the DBS lead, but before stimulation, the patient developed acute-onset dysarthria and weakness of the right face, arm, and leg (4/5). Stimulation testing demonstrated excellent clinical response. The right-side DBS lead was rapidly implanted without MER. Immediate postoperative head CT did not reveal intracerebral hemorrhage (although a small hemorrhage obscured by the DBS lead cannot be definitively excluded), but on retrospective review revealed an area of infarction of the left posterior limb of the internal capsule (PLIC), posterior and medial to the DBS lead tip. At 3-month follow-up, a brain MRI revealed hyperintensity in the left PLIC, consistent with chronic infarct. Wallerian degeneration was also seen in the left corticospinal tract in the brainstem (Figure 1). At 6-month follow-up, the patient had persistent slight right facial droop and pronator drift with 41 strength in the www.operativeneurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. ACUTE ISCHEMIC STROKE IN GPI DBS TABLE 1. Characteristics of All Patients Undergoing GPi DBS From June 2010 to February 2015 at Both Institutions in This Seriesa Patients With Ischemic Stroke During GPi DBS Surgery All GPi DBS Patients Without Ischemic Stroke 5 5 54.2 6 4.2 20 129 234 60.3 6 14.3 59.7 80 20 0 86.8 12.4 0.78 No. patients No. electrodes Mean age Male, % Diagnosis, % Parkinson disease Dystonia Tourette a P N/A N/A ..08 (t test) ..05 (Fisher exact test) ..05 (2-way ANOVA) ANOVA, analysis of variance; DBS, deep brain stimulation; GPi, globus pallidus internus. right upper extremity. PD motor symptoms are well controlled with bilateral GPi stimulation. Case Report 2 A 54-year-old woman presented with a 30-year history of PD with features of right-sided greater than left-sided rigidity, bradykinesia, and on-time dyskinesia. At baseline, her examination was significant for dysarthric speech secondary to a history of tonsillar carcinoma treated with radiation to the pharynx and chemotherapy 5 years earlier. She did not have a history of tobacco use, hypertension, stroke, or myocardial infarction. GPi was targeted at X = 20.0 mm, Y = 2.6 mm, and Z = 23.4 mm (AC-PC length = 28.2 mm). At surgery, MER and lead placement in the left hemisphere proceeded uneventfully, as well as the initial MER and subsequent implant of the right-sided GPi lead. Upon initiation of macrostimulation testing of the right-side lead, the patient became acutely somnolent and developed a subtle left-sided facial droop, left arm weakness (4/5), and worsened dysarthria. She remained arousable to voice and followed commands. Head CT performed postoperatively did not demonstrate hemorrhage but revealed a right PLIC hypodensity, again posterior and medial to the DBS lead tip. At 6-month follow-up, left arm weakness had resolved, but her mild left facial weakness and dysarthria were still present, associated with dysphagia and sialorrhea from the left mouth. These symptoms have been evaluated and managed on an outpatient basis with speech and occupational therapy. PD motor symptoms are well controlled with bilateral GPi stimulation. Case Report 3 A 52-year-old man with a 12-year history of PD underwent DBS for motor fluctuations with disabling on-time dyskinesias. He did not have a history of tobacco use, hypertension, stroke, or myocardial infarction. GPi was targeted at X = 20.0 mm, Y = 2.0 mm, and Z = 23.0 mm (AC-PC length = 27.2 mm). At surgery, left-sided MER and lead placement proceeded uneventfully. During right-sided MER, approximately 6 mm from target, the patient became somnolent, had decreased spontaneous speech, dysarthria, and slight left facial droop, in the absence of limb weakness, while rigidity and tremor in the left upper and lower extremities completely resolved. Electrical silence on the MER was observed. The lead was implanted, stimulation TABLE 2. Characteristics of Patients Experiencing Ischemic Stroke During GPi DBS Implantationa a Patient Age Vascular Risk Factors Diagnosis Onset Time of Ischemic Symptoms Symptoms of Ischemia Location of Ischemia 1 64 Obesity, HTN PD Macroelectrode insertion (no stimulation) Dysarthria, weakness of right face, arm, leg Left PLIC and lateral putamen 2 54 None PD 52 None PD 4 51 None PD MER 5 52 None Dystonia MER Somnolence, dysarthria, weakness of left face and arm Somnolence, dysarthria, left face weakness, resolution of tremor Left gaze preference, dysarthria, right arm and leg weakness Somnolence, resolution of right-sided dyskinesias Right PLIC 3 Macroelectrode stimulation MER Right PLIC Left GPi and PLIC Left GPi and PLIC GPi, globus pallidus internus; HTN, hypertension; MER, microelectrode recording; PD, Parkinson disease; PLIC, posterior limb of internal capsule. OPERATIVE NEUROSURGERY VOLUME 12 | NUMBER 4 | DECEMBER 2016 | 385 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. DOWNES ET AL FIGURE 1. Case 1. A, axial FLAIR MRI obtained 3 months poststroke showing low-intensity signal medial and posterior to left electrode representing chronic infarct in PLIC. B, axial T2-weighted MRI showing hyperintense area of encephalomalacia in this region. C, axial T2-weighted MRI depicting Wallerian degeneration down to the left cerebral peduncle. FLAIR, fluidattenuated inversion recovery; MRI, magnetic resonance imaging; PLIC, posterior limb of the internal capsule. testing was performed to ensure appropriate side-effect thresholds, and the lead was secured at the radiographic target. Postoperative head CT was negative for hemorrhage but revealed a right PLIC hypodensity, posterior and medial to the DBS lead tip. At 6-month follow-up, left facial weakness and dysarthria had resolved. PD symptoms were very well controlled with DBS and medications. In particular, the left arm continued to be free of tremor and rigidity with minimal stimulation amplitude (1.5 V). Case Report 4 A 51-year-old woman presented with a 10-year PD history characterized by progressive bradykinesia, rigidity, and tremor that eventually required bilateral GPi DBS implantation. GPi was targeted at X = 20.0 mm, Y = 2.0 mm, and Z = 24.0 mm (ACPC length = 25.0 mm). At surgery, left-sided MER of GPi was recorded from 7 mm above target to 1.5 mm below target. During MER and just after entering GPi, the patient developed left gaze preference and right-sided weakness (2/5) but remained alert and able to follow commands. Within 5 minutes, the gaze preference resolved and hemiparesis improved to 4/5. Given quick symptom resolution, a seizure was suspected and surgery proceeded. The original lead was removed and a second trajectory was performed 2 mm lateral to the initial trajectory, with macrostimulation confirmation of excellent therapeutic thresholds. The right GPi DBS was deferred because of a persistent, mild right hemiparesis and dysarthria. Postoperative CT showed no evidence of hemorrhage. A brain MRI obtained on the same day demonstrated restricted diffusion in the left globus pallidus and PLIC just posterior and medial to the electrode (Figure 2). Three months after surgery, she had marked improvement in right-sided rigidity and tremor with some persistent dysarthria and mild right hemiparesis. 386 | VOLUME 12 | NUMBER 4 | DECEMBER 2016 Case Report 5 A 52-year-old woman with a 13-year history of tardive dystonia secondary to neuroleptic use presented for revision of bilateral GPi DBS. After undergoing initial DBS surgery without resolution of symptoms 2 years earlier, it was recommended that she undergo revision of the GPi electrodes. Left GPi was targeted at X = 23.9 mm, Y = 2.3 mm, and Z = 24.8 mm (AC-PC length = 23.1 mm). Beginning with the left hemisphere, MERs were performed but were poor quality without any clear localization, presumably because of the gliosis created by the previous macroelectrode placement. During MER, the patient became somnolent and developed dysarthria and mild right-sided hemiparesis (4/5) along with complete resolution of her right-sided dystonic movements. The DBS electrode was then inserted to target, which was 1 mm medial to the previously placed electrode. Because of her somnolence and concern for possible hemorrhage, the rightside implantation was deferred. A postoperative CT scan demonstrated no evidence of intracerebral hemorrhage. A brain MRI performed on the same day revealed restricted diffusion in the distribution of the globus pallidus and PLIC (Figure 3), again posterior and medial to the DBS lead tip. Three months postoperatively, the hemiparesis had resolved, but her speech remained slightly dysarthric. Dystonic symptoms were initially improved on the right side but subsequently returned. DISCUSSION The most commonly discussed complications of DBS surgery are intracerebral hemorrhage and infection. Symptomatic hemorrhage has a reported incidence of 1.2%, with a 0.7% risk of causing permanent neurological deficit, without a statistical difference between targets.5 Acute ischemic stroke is a rare complication of DBS surgery. Although it is mentioned in some complication www.operativeneurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. ACUTE ISCHEMIC STROKE IN GPI DBS FIGURE 2. Case 4. A, axial DW MRI obtained within 1 hour postoperatively demonstrating acute infarct medial and posterior to the left electrode, corresponding to B, axial ADC map. C, axial T2-weighted MRI showing increased signal of acute stroke in left PLIC. DW, diffusion-weighted; MRI, magnetic resonance imaging; PLIC, posterior limb of the internal capsule. analyses,9 only 2 reports in literature describe nonhemorrhagic infarctions occurring acutely during DBS surgery.10,11 Several studies have focused on the incidence and risk factors associated with hemorrhage both before and during surgery,5-9,12 but little is known about the causes of nonhemorrhagic stroke as a complication of DBS. A recent meta-analysis reported a 2.0% incidence of nonhemorrhagic stroke with GPi DBS and 0.2% in STN DBS. Unfortunately, only 1 of the 18 articles referenced in this meta-analysis actually described an intraoperative stroke in detail.13 The authors reported a 42-year-old male patient who experienced hemiparesis and aphasia during the simultaneous advancement of 5 parallel microelectrodes targeting GPi.13 In our series, the incidence of ischemic stroke during GPi DBS was 2.14% per lead. Only 1 patient had known stroke risk factors—hypertension and obesity—for which she was receiving treatment. None of the patients were past or current smokers (Table 2). MER was used in all cases in which strokes occurred, but only 3 patients experienced symptom onset during MER, suggesting the observed strokes were unlikely to be causally related to the duration of mapping. Interestingly, we observed electrical silence during the MER of patient 3. In patient 4, a second MER tract was performed, for which recordings were less optimal than the first. In patient 1, symptoms were not noted until the DBS lead was implanted but before the initiation of macrostimulation. Finally, in patient 2, symptom onset was during macrostimulation. Although our patients developed symptoms at various times during the case, including both MER and macroelectrode placement, the first clear indication in each instance of a problem was clinical deterioration. Only 3 publications detail intraoperative ischemic events during DBS surgery, across all targets.10,11,14 Three ischemic strokes were reported in association with STN DBS surgery. FIGURE 3. Case 5. A, axial DW MRI obtained within 1 hour postoperatively depicting acute infarct medial and posterior to the left DBS electrode. B, axial ADC map with corresponding hypointensity. C, axial T2-weighted MRI again showing hyperintense signal in globus pallidus and PLIC. DBS, deep brain stimulation; DW, diffusion-weighted; MRI, magnetic resonance imaging; PLIC, posterior limb of the internal capsule. OPERATIVE NEUROSURGERY VOLUME 12 | NUMBER 4 | DECEMBER 2016 | 387 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. DOWNES ET AL Larson et al14 described an ischemic event after unilateral STN DBS: when the generator was activated, the patient experienced marked decrease in premorbid bilateral tinnitus. A focal area of ischemia of the anterior body of the caudate was seen on postoperative MRI. The lead was adjacent to but not within the lesion, which raises questions about the extent of electrically induced vasoconstrictive effects. Novak et al11 reported 2 cases of ischemic stroke associated with STN DBS. In the first case, the 56-year-old patient with vascular risk factors, including prior ischemia, obesity, and mitral valve disease, developed slurred speech and contralateral motor weakness during the final of 5 MER passes through the STN. There was a 10-second period of electrical silence on the MER, which was present simultaneously with the patient’s clinical deterioration. The authors theorized that the high voltage used during microstimulation induced small vessel vasospasm and caused ischemia, represented as electrical silence. The second was less specific, with confusion and short-term memory loss occurring in a 67-year-old patient approximately 3 to 6 days after surgery. Seven MER tracks were made to target the STN in this patient, and after the third pass, the electrical recordings were unusually quiet throughout the STN area. The patient had no neurological deficits during surgery. Similar to the pallidotomy patients who experienced delayed ischemia, this patient had several vascular risk factors, including hypercholesterolemia, obesity, and previous ischemia. The authors hypothesize that the delayed ischemia in the periventricular and subcortical white matter in both cases is related to vasoconstriction. Electrical stimulation, edema surrounding the leads, or simply mechanical disruption of small vessels may cause irritation and thus vasospasm of the perforating arteries, resulting in a lacunar infarct. To our knowledge, only 1 ischemic stroke of the posterior limb of the internal capsule during GPi DBS has been reported, which was in a 34-year-old patient with cervical dystonia.10 The patient was otherwise healthy and had no stroke risk factors. Right-sided microelectrode stimulation was performed up to an amplitude of 8 mA to elicit side effects of parasthesias before lead insertion. Blood pressure was elevated at 153/98 during the neurological examination at this time. The DBS lead was then implanted and secured, and the contralateral DBS implantation was begun. It was not until the left-side procedure was started that the patient was found to have slurred speech and left facial weakness. MRI revealed ischemia in the right posterior limb of the internal capsule. The authors suggest small-vessel vasospasm secondary to high-amplitude stimulation as a possible etiology. Alternatively, one might consider that ischemia was due to physical compression or interruption of an anterior choroidal branch or a lenticulostriate artery, because there was a several-minute delay before symptom onset. Interestingly, ischemia occurring near a radiofrequency pallidotomy lesion has been reported to occur both in a delayed15 and acute fashion.16 Lim et al15 described 3 of 50 patients who experienced a delayed stroke in the posterior internal capsule. The proximity to the lesion suggests that local changes such as breakdown of the blood-brain barrier contribute to increased susceptibility of the region to ischemia. The authors suggest that 388 | VOLUME 12 | NUMBER 4 | DECEMBER 2016 the higher vascularity in the gray matter is protective against ischemia, and thus the white matter tracts of the internal capsule are more vulnerable. The temporal delay of the onset of ischemia, which ranged from 10 to 117 days, could be related to the statistically significant vascular risk factors that existed in all affected patients. Christoforidis et al16 described 1 case of ischemic stroke occurring during radiofrequency pallidotomy in a 54-year-old man with PD. The patient underwent intraoperative MER and stimulation uneventfully. As the thermocoagulation lesion was created, the patient experienced right facial droop and right pronator drift, and the procedure was aborted. MRI revealed ischemia in the left posterior limb of the internal capsule and the radiofrequency lesion in the GPi. Considering the area of ischemia was not in the immediate vicinity of the lesion, the authors’ proposed etiology was electrical stimulus causing thrombosis or vasospasm of a lenticulostriate artery that supplied the area of infarction. Risk factors for stroke were not mentioned. Because the clinical manifestation of ischemic damage occurred at very diverse stages of DBS implantation (during MER, after DBS lead implant before stimulation, and after macrostimulation) both in this series and as reported in the literature, it is challenging to pinpoint a single causative factor for ischemic events during GPi DBS implantation. On retrospective review, none of the patients had unusual anatomy in the region of the GPi, such as enlarged Virchow-Robin spaces or tortuous vessels. Possible etiologies include physical disruption or compression of the anterior choroidal or lenticulostriate branches, trauma-induced vasospasm, or electrically induced atraumatic vasoconstriction. Interestingly, the location of ischemia was consistently posterior and medial to the final DBS lead position (and stereotactic trajectory), supporting a likely vascular etiology (Figure 4). With respect to trajectory, it is possible that the location of the burr hole near the coronal suture could result in a more posterior entry to GPi, possibly predisposing to an encounter with the anterior choroidal artery or lenticulostriate arteries. Of note, we cannot definitively exclude small hemorrhages associated with these ischemic events, because the artifact from the DBS lead obscures clear visualization. Nonthermal vasoconstriction and thrombosis of femoral and mesenteric arteries and veins using short electric pulses has been proposed as a novel treatment of traumatic noncompressible hemorrhages.17 In vivo animal studies have demonstrated that electrically induced vasoconstriction occurs as a function of the electrical stimulus amplitude and duration, as well as the pulse width. For example, hemorrhage from a complete transection of the femoral artery was controlled by applying 100 microsecond pulses of 150 V at a pulse width of 10 Hz for 30 seconds, which resulted in 75% constriction of the artery. Possible mechanisms for this profound effect are numerous: stimulation of sympathetic innervation and direct contact stimulating smooth muscle contraction, but not due to thermal mechanisms.17 The authors also suggest that electrically induced vasoconstriction is even more powerful than any reported pharmacological effects. Although vasoconstriction via this mechanism is plausible for the cases occurring during macroelectrode stimulation testing, 2 of our cases www.operativeneurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. ACUTE ISCHEMIC STROKE IN GPI DBS a definitive cause is not known, and given the variability in the temporal onset of neurological symptoms and the location of ischemic lesions, it may be difficult to avoid such an undesirable event in the future. Nonetheless, this is an important adverse event for clinicians to be aware of and to discuss with their patients before GPi DBS surgery. Disclosures Nader Pouratian has fellowship support from Medtronic. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES FIGURE 4. Axial T2 MRI depicting the typical location of the GPi target, the area of infarct, and relative color-coded vascular territories of lenticulostriate and anterior choroidal arteries. GPi, globus pallidus internus; MRI, magnetic resonance imaging. and 2 cases described by Novak et al occurred during MERs. The alternative explanation of compromise of branches of the anterior choroidal artery due to adjacent tissue trauma from the stereotactic procedure must therefore be considered the leading potential etiology in this intraoperative series of acute ischemia. In our series, all patients had CT- or MRI-verified evidence of injury to the posterior limb of the internal capsule. This region is fed by the anterior choroidal artery, and a trajectory through the GPi could certainly lead to compression or spasm of this vessel or a branch, leading to the observed outcomes. The absence of any evidence of subarachnoid or intraparenchymal blood would argue against direct puncture of the vessel, but compression due to microor macroelectrodes is a reasonable hypothesis as well. Given that these strokes were therapeutic in these patients, this pathoetiology would be concordant with the therapeutic effects of anterior choroidal ligation originally described by Irving Cooper.18 CONCLUSION Although ischemic stroke during GPi DBS implantation has not been extensively described in the literature, we provide a detailed account of this adverse event in 5 patients. Unfortunately, no unifying or modifiable risk factor could be identified. Considering that OPERATIVE NEUROSURGERY 1. Okun MS, Fernandez HH, Wu SS, et al. Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol. 2009;65(5):586-595. 2. Weaver FM, Follett KA, Stern M, et al. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes. Neurology. 2012;79(1):55-65. 3. Follett KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. New Engl J Med. 2010;362(22):2077-2091. 4. Odekerken V, van Laar T, Staal MJ, Mosch A. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 2013;12:37-44. 5. Sansur CA, Frysinger RC, Pouratian N, et al. Incidence of symptomatic hemorrhage after stereotactic electrode placement. J Neurosurg. 2007;107(5):998-1003. 6. Ben-Haim S, Asaad WF, Gale JT, Eskandar EN. Risk factors for hemorrhage during microelectrode-guided deep brain stimulation and the introduction of an improved microelectrode design. Neurosurgery. 2009;64(4):754-762; discussion 762-763. 7. Elias WJ, Sansur CA, Frysinger RC. Sulcal and ventricular trajectories in stereotactic surgery. J Neurosurg. 2009;110(2):201-207. 8. Zrinzo L, Foltynie T, Limousin P, Hariz MI. Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg. 2012;116(1):84-94. 9. Videnovic A, Metman LV. Deep brain stimulation for Parkinson’s disease: prevalence of adverse events and need for standardized reporting. Movement Disord. 2008;23(3):343-349. 10. Kang DW, Kim HY, Chang JW. Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. Stereotact Funct Neurosurg. 2011;89(4): 201-204. 11. Novak KE, Nenonene EK, Bernstein LP, et al. Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson’s disease. Mov Disord. 2006;21(9):1477-1483. 12. Binder DK, Rau GM, Starr PA. Risk factors for hemorrhage during microelectrode-guided deep brain stimulator implantation for movement disorders. Neurosurgery. 2005;56(4):722-732; discussion 722-732. 13. Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol. 2005;62(4):554-560. 14. Larson PS, Cheung SW. A stroke of silence: tinnitus suppression following placement of a deep brain stimulation electrode with infarction in area LC. J Neurosurg. 2013;118(1):192-194. 15. Lim JY, de Salles AA, Bronstein J, Masterman DL, Saver JL. Delayed internal capsule infarctions following radiofrequency pallidotomy. J Neurosurg. 1997;87 (6):955-960. 16. Christoforidis GA, Spickler EM, Papaioannou G, Junn F. Lacunar infarct during pallidotomy: case report. Neuroradiology. 2001;43(4):321-324. 17. Mandel Y, Manivanh R, Dalal R, et al. Vasoconstriction by electrical stimulation: new approach to control of non-compressible hemorrhage. Sci Rep. 2013;3:2111. 18. Cooper IS. Ligation of the anterior choroidal artery for involuntary movements; parkinsonism. Psychiatr Q. 1953;27(2):317–319. Acknowledgments MRI anatomic illustration was created by Zach Folzenlogen, MD, of University of Colorado, Department of Neurosurgery. VOLUME 12 | NUMBER 4 | DECEMBER 2016 | 389 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. DOWNES ET AL COMMENT T he authors have described 5 cases of ischemic stroke in 129 patients who underwent (mostly) bilateral globus pallidus internus deep brain stimulation (GPi DBS) implantation over a 4-year period at an experienced medical center. Their examination of the circumstances in each case is reasonable and does suggest that, more likely than not, they were, in fact, seeing the complication of an ischemic infarction in these cases rather than other potential explanations for the outcomes (hemorrhage, circuitry disruption, medication alterations, poor electrode placement). This complication, I suspect, will be viewed as surprising to many in the field, perhaps mostly because there were 5 and not just 1 or 2. I think the most likely explanation is at the “systems” level, in that the general trajectory this center takes for GPi is slightly posterior to what many of us use. Their burr hole position alone suggests this, as 390 | VOLUME 12 | NUMBER 4 | DECEMBER 2016 they describe it at the coronal suture rather than just anterior to it. While no one can be sure of this conclusion (authors, reviewers, or readers), their rate of over 2% is higher than other reports of ischemic stroke or even the more common hemorrhage rates that have been found (well documented now to be about 1.8%), suggesting they have a nuance in their technique that makes the possibility of injury to a lenticulo-striate or anterior choroidal artery slightly more probable. In any case, they should be lauded for bringing these cases to the fore and assessing them in a transparent way, because we all can try to learn from them. DBS is often a highly beneficial treatment, but it has risks, and our understanding of complication avoidance starts with the acknowledgement of the complication itself, as these authors have done. Jeff Arle Boston, Massachusetts www.operativeneurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.