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Peter M. Intemann, Donna Masterman, Indu Subramanian, Antonio DeSalles, Eric Behnke, Robert Frysinger and Jeff M. Bronstein

Object. Several investigators have described the motor benefits derived from performing unilateral stereotactic pallidotomy for the treatment of Parkinson disease (PD), but little is known about the efficacy and complication rates of bilateral procedures. The goal of this study was to assess both these factors in 12 patients.

Methods. Eleven patients with medically intractable PD underwent staged bilateral pallidotomy and one patient underwent a simultaneous bilateral procedure. Unilateral pallidotomy resulted in an improvement in the patients' Unified Parkinson Disease Rating Scale (UPDRS) total scores and motor subscores, Hoehn and Yahr stages, and Schwab and England Activities of Daily Living scores. There were no complications. The second procedures were performed 5 to 25 months after the first, and nearly complete 3-month follow-up data are available for eight of these patients. Staged bilateral pallidotomy did result in further improvements in some symptoms, but the patients proved to be less responsive to levodopa. In contrast to outcomes of the initial unilateral pallidotomy, there were significant complications. One patient suffered an acute stroke, two patients suffered delayed infarctions of the internal capsule, four patients had mild-to-moderate worsening of speech and increased drooling, and one patient complained of worsening memory.

Conclusions. Bilateral pallidotomy results in modest benefits but is associated with an increased risk of complications.

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W. Jeffrey Elias, Kai-Ming Fu and Robert C. Frysinger

Object

The success of stereotactic surgery depends upon accuracy. Tissue deformation, or brain shift, can result in clinically significant errors. The authors measured cortical and subcortical brain shift during stereotactic surgery and assessed several variables that may affect it.

Methods

Preoperative and postoperative magnetic resonance imaging volumes were fused and 3D vectors of deviation were calculated for the anterior commissure (AC), posterior commissure (PC), and frontal cortex. Potential preoperative (age, diagnosis, and ventricular volume), intraoperative (stereotactic target, penetration of ventricles, and duration of surgery), and postoperative (volume of pneumocephalus) variables were analyzed and correlated with cortical (frontal cortex) and subcortical (AC, PC) deviations.

Results

Of 66 cases, nine showed a shift of the AC by more than 1.5 mm, and five by more than 2.0 mm. The largest AC shift was 5.67 mm. Deviation in the x, y, and z dimensions for each case was determined, and most of the cortical and subcortical shift occurred in the posterior direction. The mean 3D vector deviations for frontal cortex, AC, and PC were 3.5 ± 2.0, 1.0 ± 0.8, and 0.7 ± 0.5 mm, respectively. The mean change in AC–PC length was −0.2 ± −0.9 mm (range −4.28 to 1.66 mm). The volume of postoperative pneumocephalus, assumed to represent cerebrospinal fluid (CSF) loss, was significantly correlated with shift of the frontal cortex (r = 0.640, 64 degrees of freedom, p < 0.001) and even more strongly with shift of the AC (r = 0.754, p < 0.001). No other factors were significantly correlated with AC shift. Interestingly, penetration of the ventricles during electrode insertion, whether unilateral or bilateral, did not affect volume of pneumocephalus.

Conclusions

Cortical and subcortical brain shift occurs during stereotactic surgery as a direct function of the volume of pneumocephalus, which probably reflects the volume of CSF that is lost. Clinically significant shifts appear to be uncommon, but stereotactic surgeons should be vigilant in preventing CSF loss.

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Charles A. Sansur, Robert C. Frysinger, Nader Pouratian, Kai-Ming Fu, Markus Bittl, Rod J. Oskouian, Edward R. Laws and W. Jeffrey Elias

Object

Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition.

Methods

Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits.

Results

The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home.

Conclusions

The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.

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W. Jeff Elias, Charles A. Sansur and Robert C. Frysinger

Object

The authors analyzed deep brain stimulation electrode trajectories on MR images to identify risks of cerebrovascular complications associated with the number of electrode insertions, traversal of a sulcus, and penetration of the ventricle.

Methods

Pre- and postoperative MR volumes were fused to determine the proximity of electrodes to a sulcus or ventricle and whether there were cortical, subcortical, or intraventricular complications. Complications were further classified as hemorrhagic or nonhemorrhagic and symptomatic or asymptomatic. The authors examined 258 electrode implantation for deep brain stimulation. There were 4 symptomatic events (1.6% incidence): 3 hemorrhagic and 1 nonhemorrhagic, all within the cortex. Asymptomatic events included cortical hemorrhage in 1 patient, nonhemorrhagic cortical changes in 6, pallidal hemorrhage in 1, thalamic infarction in 1, and intraventricular hemorrhage (IVH) in 5 patients.

Results

Proximity to a sulcus was a significant risk factor for hemorrhagic and nonhemorrhagic cortical complications (p = 0.001). There was a complication rate of 10.1% within the trajectories penetrating or adjacent to a sulcus, and a 0.7% rate with trajectories clearly positioned within the gyrus. Asymptomatic IVH was observed in 5% of ventricular penetrations. A history of hypertension was a risk factor for cortical hemorrhage (p = 0.019), but not for cortical ischemic/edematous events (p = 0.605). The number of electrode penetrations did not differ between patients with and without complications (p = 0.868), and the sequence of electrode insertions was not a risk factor in bilateral surgeries.

Conclusions

Symptomatic cortical complications occur when electrodes traverse close to a sulcus. Asymptomatic IVH occurs infrequently with ventricular penetration. Despite intraoperative efforts to avoid cortical sulci, a higher than expected incidence of electrode proximity to the sulci was identified on careful postoperative trajectory analysis. This finding emphasizes the importance of assiduously planning trajectories and reviewing cases with thorough MR analysis.

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Nader Pouratian, Davis L. Reames, Robert Frysinger and W. Jeff Elias

Object

The aim of this study was to assess risk factors for postoperative seizures after deep brain stimulation (DBS) lead implantation surgery and the impact of such seizures on length of stay and discharge disposition.

Methods

The authors reviewed a consecutive series of 161 cases involving patients who underwent implantation of 288 electrodes for treatment of movement disorders at a single institution to determine the absolute risk of postoperative seizures, to describe the timing and type of seizures, to identify statistically significant risk factors for seizures, and to determine whether there are possible indications for seizure prophylaxis after DBS lead implantation. The electronic medical records were reviewed to identify demographic details, medical history, operative course, and postoperative outcomes and complications. To evaluate significant associations between potential risk factors and postoperative seizures, both univariate and multivariate analyses were performed.

Results

Seven (4.3%) of 161 patients experienced postoperative seizures, all of which were documented to have been generalized tonic-clonic seizures. In 5 (71%) of 7 cases, patients only experienced a single seizure. Similarly, in 5 of 7 cases, patients experienced seizures within 24 hours of surgery. In 6 (86%) of the 7 cases, seizures occurred within 48 hours of surgery. Univariate analysis identified 3 significant associations (or risk factors) for postoperative seizures: abnormal findings on postoperative imaging (hemorrhage, edema, and or ischemia; p < 0.001), age greater than 60 years (p = 0.021), and transventricular electrode trajectories (p = 0.023). The only significant factor identified on multivariate analysis was abnormal findings on postoperative imaging (p < 0.0001, OR 50.4, 95% CI 5.7–444.3). Patients who experienced postoperative seizures had a significantly longer length of stay than those who were seizure free (mean ± SD 5.29 ± 3.77 days vs 2.38 ± 2.38 days; p = 0.002, Student 2-tailed t-test). Likewise, final discharge to home was significantly less likely in patients who experienced seizures after implantation (43%) compared with those patients who did not (92%; p = 0.00194, Fisher exact test).

Conclusions

These results affirm that seizures are an uncommon complication of DBS surgery and generally occur within 48 hours of surgery. The results also indicate that hemorrhage, edema, or ischemia on postoperative images (“abnormal” imaging findings) increases the relative risk of postoperative seizures by 30- to 50-fold, providing statistical credence to the long-held assumption that seizures are associated with intracranial vascular events. Even in the setting of a postimplantation imaging abnormality, long-term anticonvulsant therapy will not likely be required because none of our patients developed chronic epilepsy.

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W. Jeff Elias, Mohamad Khaled, Justin D. Hilliard, Jean-Francois Aubry, Robert C. Frysinger, Jason P. Sheehan, Max Wintermark and Maria Beatriz Lopes

Object

The purpose of this study was to use MRI and histology to compare stereotactic lesioning modalities in a large brain model of thalamotomy.

Methods

A unilateral thalamotomy was performed in piglets utilizing one of 3 stereotactic lesioning modalities: focused ultrasound (FUS), radiofrequency, and radiosurgery. Standard clinical lesioning parameters were used for each treatment; and clinical, MRI, and histological assessments were made at early (< 72 hours), subacute (1 week), and later (1–3 months) time intervals.

Results

Histological and MRI assessment showed similar development for FUS and radiofrequency lesions. T2-weighted MRI revealed 3 concentric lesional zones at 48 hours with resolution of perilesional edema by 1 week. Acute ischemic infarction with macrophage infiltration was most prominent at 72 hours, with subsequent resolution of the inflammatory reaction and coalescence of the necrotic zone. There was no apparent difference in ischemic penumbra or “sharpness” between FUS or radiofrequency lesions. The radiosurgery lesions presented differently, with latent effects, less circumscribed lesions at 3 months, and apparent histological changes seen in white matter beyond the thalamic target. Additionally, thermal and radiation lesioning gradients were compared with modeling by dose to examine the theoretical penumbra.

Conclusions

In swine thalamus, FUS and radiosurgery lesions evolve similarly as determined by MRI, histological examination, and theoretical modeling. Radiosurgery produces lesions with more delayed effects and seemed to result in changes in the white matter beyond the thalamic target.

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Nicholas Said, W. Jeff Elias, Prashant Raghavan, Alan Cupino, Nicholas Tustison, Robert Frysinger, James Patrie, Wenjun Xin and Max Wintermark

Object

The purpose of this study was to investigate whether diffusion tensor imaging (DTI) of the corticospinal tract (CST) is a reliable surrogate for intraoperative macrostimulation through the deep brain stimulation (DBS) leads. The authors hypothesized that the distance on MRI from the DBS lead to the CST as determined by DTI would correlate with intraoperative motor thresholds from macrostimulations through the same DBS lead.

Methods

The authors retrospectively reviewed pre- and postoperative MRI studies and intraoperative macrostimulation recordings in 17 patients with Parkinson disease (PD) treated by DBS stimulation. Preoperative DTI tractography of the CST was coregistered with postoperative MRI studies showing the position of the DBS leads. The shortest distance and the angle from each contact of each DBS lead to the CST was automatically calculated using software-based analysis. The distance measurements calculated for each contact were evaluated with respect to the intraoperative voltage thresholds that elicited a motor response at each contact.

Results

There was a nonsignificant trend for voltage thresholds to increase when the distances between the DBS leads and the CST increased. There was a significant correlation between the angle and the voltage, but the correlation was weak (coefficient of correlation [R] = 0.36).

Conclusions

Caution needs to be exercised when using DTI tractography information to guide DBS lead placement in patients with PD. Further studies are needed to compare DTI tractography measurements with other approaches such as microelectrode recordings and conventional intraoperative MRI–guided placement of DBS leads.