Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Preoperative Decision-Making in Microvascular Decompression for Trigeminal Neuralgia: A Survey of Practicing Neurosurgeons.

OBJECTIVE: Microvascular decompression (MVD) for trigeminal neuralgia (TN) results in durable pain freedom in a large percentage of appropriately selected patients. The decision to perform MVD is based on a combination of clinical symptomatic presentation and imaging findings demonstrating neurovascular compression (NVC) with surgeons weighting these variables differently. This study sought to determine the relative importance of clinical symptomatic presentation and imaging findings of NVC in decision-making to pursue MVD for TN among North American board-certified neurosurgeons. METHODS: An online survey detailing the decision-making process involved in the workup and treatment of TN with MVD was distributed to all American Association of Neurological Surgeons registered board-certified neurosurgeons in North America. RESULTS: From 3010 functional email addresses, there were 309 responses to the survey (10% response rate). The majority of respondents (76%) reported only operating on patients with classic type 1 TN (T1TN) while only 32% chose to operate on patients with imaging findings of vascular compression in the absence of T1TN symptoms. In contrast to low-volume surgeons, high-volume surgeons weighed imaging evidence of vascular compression more heavily into the decision-making process to operate. CONCLUSIONS: The majority of responding neurosurgeons weigh symptomatic presentation more heavily than imaging evidence of NVC when deciding on whom to perform MVD. High-volume surgeons tend to be more attentive to NVC in their decision-making to perform MVD when compared with low-volume surgeons.

Subcortical short-term plasticity elicited by deep brain stimulation.

OBJECTIVE: To investigate local short-term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders. METHODS: During DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short-term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models. RESULTS: DBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 ± 0.10 msec peak latency, mean ± SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P < 0.001) and display absolute and relative refractory periods (0.56 ± 0.08 and 2.94 ± 1.05 msec, respectively). We also identified later oscillatory activity in the subthalamic-pallidal circuit (4.50 ± 1.11 msec peak latency) that displays paired pulse facilitation (present in 5/8 subthalamic, 4/5 pallidal, and 0/6 thalamic trajectories, P = 0.018, Fisher's exact test), and correlates with resting beta frequency power (P < 0.001), therapeutic DBS frequencies, and stimulation sites chosen later for therapy in the ambulatory setting (P = 0.031). INTERPRETATION: Paired DBS pulses synchronize local circuit electrophysiology and elicit short-term neuroplasticity in the subthalamic-pallidal circuit. Collectively, these responses likely represent the earliest detectable interaction between the DBS pulse and local neuronal tissue in humans. Evoked subcortical field potentials could serve as a predictive biomarker to guide the implementation of next-generation directional and adaptive stimulation devices.

The Use of MRI in Preoperative Decision-Making for Trigeminal Neuralgia: A Single-Center Study.

OBJECTIVE: Few studies have examined associations between vascular compression and postoperative pain relief in patients undergoing microvascular decompression (MVD) for treatment of medically refractory type 1 trigeminal neuralgia (TN). The authors sought to examine for associations between vascular compression and postoperative pain relief to determine the utility of preoperative magnetic resonance imaging (MRI) in surgical decision-making for TN. METHODS: The charts of 59 patients who underwent 60 MVDs for TN between 2007 and 2017 at a single academic institution were reviewed. Patient demographics, the presence of compressing vessel on preoperative MRI and intraoperatively, complications, follow-up time, performance of a partial sensory rhizotomy, and pain resolution at most recent follow-up were recorded. Sensitivity and specificity of MRI for detecting vascular compression were calculated and associations between preoperative and intraoperative evidence of vascular compression with postoperative pain relief were examined. RESULTS: Sensitivity and specificity of preoperative MRI determined through blinded reads by the senior author were 65.3% (95% confidence interval, 13.5-32.0) and 90.9% (95% confidence interval, 86.1-100.0), respectively. Overall, 76.3% of patients were pain free at most recent follow-up. Preoperative MRI and intraoperative evidence of vascular compression were not associated with postoperative pain relief at most recent follow-up (P = 0.47 and 0.43, respectively). CONCLUSIONS: The findings of lower sensitivity and poor interrater reliability of MRI, as well as a lack of association between compressive vessel and postoperative pain relief reported in this study, suggest the decision to pursue MVD for TN should be based more heavily on classic symptomatic presentation over preoperative evidence of vascular compression.

Incidence and risk factors for seizures associated with deep brain stimulation surgery.

OBJECTIVE: The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. METHODS: The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. RESULTS: A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson's disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation-related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02-1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. CONCLUSIONS: Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

Latency of subthalamic nucleus deep brain stimulation-evoked cortical activity as a potential biomarker for postoperative motor side effects.

OBJECTIVE: Here, we investigate whether cortical activation predicts motor side effects of deep brain stimulation (DBS) and whether these potential biomarkers have utility under general anesthesia. METHODS: We recorded scalp potentials elicited by DBS during surgery (n = 11), both awake and under general anesthesia, and in an independent ambulatory cohort (n = 8). Across a range of stimulus configurations, we measured the amplitude and timing of short- and long-latency response components and linked them to motor side effects. RESULTS: Regardless of anesthesia state, in both cohorts, DBS settings with capsular side effects elicited early responses with peak latencies clustering at <1 ms. This early response was preserved under anesthesia in all participants (11/11). In contrast, the long-latency components were suppressed completely in 6/11 participants. Finally, the latency of the earliest response could predict the presence of postoperative motor side effects both awake and under general anesthesia (84.8% and 75.8% accuracy, awake and under anesthesia, respectively). CONCLUSION: DBS elicits short-latency cortical activation, both awake and under general anesthesia, which appears to reveal interactions between the stimulus and the corticospinal tract. SIGNIFICANCE: Short-latency evoked cortical activity can potentially be used to aid both DBS lead placement and post-operative programming.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

INTRODUCTION: Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. METHODS: We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). RESULTS: Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. CONCLUSION: Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Walking Speed Reliably Measures Clinically Significant Changes in Gait by Directional Deep Brain Stimulation.

Introduction: Although deep brain stimulation (DBS) often improves levodopa-responsive gait symptoms, robust therapies for gait dysfunction from Parkinson's disease (PD) remain a major unmet need. Walking speed could represent a simple, integrated tool to assess DBS efficacy but is often not examined systematically or quantitatively during DBS programming. Here we investigate the reliability and functional significance of changes in gait by directional DBS in the subthalamic nucleus. Methods: Nineteen patients underwent unilateral subthalamic nucleus DBS surgery with an eight-contact directional lead (1-3-3-1 configuration) in the most severely affected hemisphere. They arrived off dopaminergic medications >12 h preoperatively and for device activation 1 month after surgery. We measured a comfortable walking speed using an instrumented walkway with DBS off and at each of 10 stimulation configurations (six directional contacts, two virtual rings, and two circular rings) at the midpoint of the therapeutic window. Repeated measures of ANOVA contrasted preoperative vs. maximum and minimum walking speeds across DBS configurations during device activation. Intraclass correlation coefficients examined walking speed reliability across the four trials within each DBS configuration. We also investigated whether changes in walking speed related to modification of step length vs. cadence with a one-sample t-test. Results: Mean comfortable walking speed improved significantly with DBS on vs. both DBS off and minimum speeds with DBS on (p < 0.001, respectively). Pairwise comparisons showed no significant difference between DBS off and minimum comfortable walking speed with DBS on (p = 1.000). Intraclass correlations were ≥0.949 within each condition. Changes in comfortable walk speed were conferred primarily by changes in step length (p < 0.004). Conclusion: Acute assessment of walking speed is a reliable, clinically meaningful measure of gait function during DBS activation. Directional and circular unilateral subthalamic DBS in appropriate configurations elicit acute and clinically significant improvements in gait dysfunction related to PD. Next-generation directional DBS technologies have significant potential to enhance gait by individually tailoring stimulation parameters to optimize efficacy.

Burosumab in tumor-induced osteomalacia: A case report.

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8mg/dL (reference range: 2.4-5.0mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia.

Patient Satisfaction in Surgery for Parkinson's Disease: A Systematic Review of the Literature.

The objective of the study was to establish how patient satisfaction with surgical treatment of Parkinson's disease (PD) has been previously measured, determine whether an ideal patient satisfaction instrument exists, and to define the dimensions of care that determine patient satisfaction with the surgical treatment of PD. A systematic search of four online databases, unpublished sources, and citations was undertaken to identify 15 studies reporting patient satisfaction with the surgical treatment of PD. Manuscripts were reviewed and instruments were categorized by content and method axes. One study was found to utilize two distinct patient satisfaction instruments, which brought the total number of satisfaction instruments assessed to 16. Major factors influencing patient satisfaction were identified and served as a structure to define the dimensions of patient satisfaction in the surgical treatment of PD. Studies used predominantly multidimensional (10/16), rather than global (6/16) satisfaction instruments. Generic (12/16) rather than disease-specific (4/16) instruments were utilized more frequently. Every study reported on satisfaction with outcome and four studies reported on satisfaction with outcome and care. Six dimensions of patient status, outcome and care experience affecting patient satisfaction were identified: motor function, patient-specific health characteristics, programming/long-term care, surgical considerations, device/hardware, and functional independence.  At present, no patient satisfaction instrument exists that is disease-specific and covers all dimensions of patient satisfaction in surgery for PD. For quality improvement, such a disease-specific, comprehensive patient satisfaction instrument should be designed, and, if demonstrated to be reliable and valid, widely implemented.

Reoperation for device infection and erosion following deep brain stimulation implantable pulse generator placement.

OBJECTIVE: Infection and erosion following implantable pulse generator (IPG) placement are associated with morbidity and cost for patients with deep brain stimulation (DBS) systems. Here, the authors provide a detailed characterization of infection and erosion events in a large cohort that underwent DBS surgery for movement disorders. METHODS: The authors retrospectively reviewed consecutive IPG placements and replacements in patients who had undergone DBS surgery for movement disorders at the University of Alabama at Birmingham between 2013 and 2016. IPG procedures occurring before 2013 in these patients were also captured. Descriptive statistics, survival analyses, and logistic regression were performed using generalized linear mixed effects models to examine risk factors for the primary outcomes of interest: infection within 1 year or erosion within 2 years of IPG placement. RESULTS: In the study period, 384 patients underwent a total of 995 IPG procedures (46.4% were initial placements) and had a median follow-up of 2.9 years. Reoperation for infection occurred after 27 procedures (2.7%) in 21 patients (5.5%). No difference in the infection rate was observed for initial placement versus replacement (p = 0.838). Reoperation for erosion occurred after 16 procedures (1.6%) in 15 patients (3.9%). Median time to reoperation for infection and erosion was 51 days (IQR 24-129 days) and 149 days (IQR 112-285 days), respectively. Four patients with infection (19.0%) developed a second infection requiring a same-side reoperation, two of whom developed a third infection. Intraoperative vancomycin powder was used in 158 cases (15.9%) and did not decrease the infection risk (infected: 3.2% with vancomycin vs 2.6% without, p = 0.922, log-rank test). On logistic regression, a previous infection increased the risk for infection (OR 35.0, 95% CI 7.9-156.2, p < 0.0001) and a lower patient BMI was a risk factor for erosion (BMI ≤ 24 kg/m2: OR 3.1, 95% CI 1.1-8.6, p = 0.03). CONCLUSIONS: IPG-related infection and erosion following DBS surgery are uncommon but clinically significant events. Their respective timelines and risk factors suggest different etiologies and thus different potential corrective procedures.

Cortical Activation Elicited by Subthalamic Deep Brain Stimulation Predicts Postoperative Motor Side Effects.

OBJECTIVE: Although deep brain stimulation (DBS) is an effective treatment for movement disorders, improvement varies substantially in individuals, across clinical trials, and over time. Noninvasive biomarkers that predict the individual response to DBS could be used to optimize outcomes and drive technological innovation in neuromodulation. We sought to evaluate whether noninvasive event related potentials elicited by subthalamic DBS during surgical targeting predict the tolerability of a given stimulation site in patients with advanced Parkinson's disease. METHODS: Using electroencephalography, we measured event related potentials elicited by 20 Hz DBS over a range of stimulus intensities across the spatial extent of the implanted electrode array in 11 patients. We correlated event related potential timing and morphology with the stimulus amplitude thresholds for motor side effects during postoperative programming at ≥130 Hz. RESULTS: During surgical targeting, DBS at 20 Hz elicits large amplitude, high frequency activity (evoked HFA) with mean onset latency of 9.0 ± 0.3 msec and a mean frequency of 175.8 ± 7.8 Hz. The lowest DBS amplitude that elicits the HFA predicts thresholds for motor side effects during postoperative stimulation at ≥130 Hz (p < 0.001, ANOVA). CONCLUSION: Event related potentials elicited by DBS can predict clinically relevant corticospinal activation by stimulation after surgery. Noninvasive scalp physiology requires no patient interaction and could serve as a biomarker to guide targeting, postoperative programming, and emerging technologies such as directional and closed-loop stimulation.

Awake Testing during Deep Brain Stimulation Surgery Predicts Postoperative Stimulation Side Effect Thresholds.

Despite substantial experience with deep brain stimulation for movement disorders and recent interest in electrode targeting under general anesthesia, little is known about whether awake macrostimulation during electrode targeting predicts postoperative side effects from stimulation. We hypothesized that intraoperative awake macrostimulation with the newly implanted DBS lead predicts dose-limiting side effects during device activation in clinic. We reviewed 384 electrode implants for movement disorders, characterized the presence or absence of stimulus amplitude thresholds for dose-limiting DBS side effects during surgery, and measured their predictive value for side effects during device activation in clinic with odds ratios ±95% confidence intervals. We also estimated associations between voltage thresholds for side effects within participants. Intraoperative clinical response to macrostimulation led to adjustments in DBS electrode position during surgery in 37.5% of cases (31.0% adjustment of lead depth, 18.2% new trajectory, or 11.7% both). Within and across targets and disease states, dose-limiting stimulation side effects from the final electrode position in surgery predict postoperative side effects, and side effect thresholds in clinic occur at lower stimulus amplitudes versus those encountered in surgery. In conclusion, awake clinical testing during DBS targeting impacts surgical decision-making and predicts dose-limiting side effects during subsequent device activation.

Benefits and risks of unilateral and bilateral ventral intermediate nucleus deep brain stimulation for axial essential tremor symptoms.

INTRODUCTION: Many experts assume bilateral deep brain stimulation (DBS) is necessary to improve axial tremor in essential tremor (ET). In the largest clinical trial of DBS for ET to date evaluating a non-directional, constant current device, we studied the effects of unilateral and staged bilateral DBS on axial tremor. METHODS: We included all participants from the original trial with unilateral ventral intermediate nucleus (VIM) DBS and 90-day follow up at minimum. Primary outcomes were changes in pooled axial subscores in the Clinical Rating Scale for Tremor (CRST) at 90 and 180 days after activation of unilateral VIM DBS compared to pre-operative baseline (n=119). Additionally, we performed within-subject analyses for unilateral versus bilateral DBS at 180 days in the cohort who underwent staged surgery to bilateral DBS (n=39). RESULTS: Unilateral VIM DBS improved midline tremor by 58% at 90 days (median[IQR]) (3[3] to 1[2], p<0.001) and 65% at 180 days (3[3] to 1[2], p<0.001) versus pre-op baseline. In the staged to bilateral DBS cohort, midline tremor scores further improved after bilateral DBS at 180 days by 63% versus unilateral DBS (3[3] to 1[3], p=0.007). There were, however, 35 additional DBS and surgery-related adverse events, 14 related to incoordination, gait impairment, or speech impairment, versus 6 after unilateral DBS. CONCLUSION: Unilateral VIM DBS for ET significantly improved associated axial tremor. Staged bilateral DBS was associated with additional axial tremor improvement but also additional adverse events. Unilateral VIM DBS may be sufficient to achieve a goal of contralateral limb and axial tremor attenuation.

The virtual cone: A novel technique to generate spherical dose distributions using a multileaf collimator and standardized control-point sequence for small target radiation surgery.

PURPOSE: The study aimed to develop and demonstrate a standardized linear accelerator multileaf collimator-based method of delivering small, spherical dose distributions suitable for radiosurgical treatment of small targets such as the trigeminal nerve. METHODS AND MATERIALS: The virtual cone is composed of a multileaf collimator-defined field with the central 2 leaves set to a small gap. For 5 table positions, clockwise and counter-clockwise arcs were used with collimator angles of 45 and 135 degrees, respectively. The dose per degree was proportional to the sine of the gantry angle. The dose distribution was calculated by the treatment planning system and measured using radiochromic film in a skull phantom for leaf gaps of 1.6, 2.1, and 2.6 mm. Cones with a diameter of 4 mm and 5 mm were measured for comparison. Output factor constancy was investigated using a parallel-plate chamber. RESULTS: The mean ratio of the measured-to-calculated dose was 0.99, 1.03, and 1.05 for 1.6, 2.1, and 2.6 mm leaf gaps, respectively. The diameter of the measured (calculated) 50% isodose line was 4.9 (4.6) mm, 5.2 (5.1) mm, and 5.5 (5.5) mm for the 1.6, 2.1, and 2.6 mm leaf gap, respectively. The measured diameter of the 50% isodose line was 4.5 and 5.7 mm for the 4 mm and 5 mm cones, respectively. The standard deviation of the parallel-plate chamber signal relative to a 10 cm × 10 cm field was less than 0.4%. The relative signal changed 32% per millimeter change in leaf gap, indicating that the parallel-plate chamber is sensitive to changes in gap width. CONCLUSIONS: The virtual cone is an efficient technique for treatment of small spherical targets. Patient-specific quality assurance measurements will not be necessary in routine clinical use. Integration directly into the treatment planning system will make planning using this technique extremely efficient.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Postoperative radiosurgery for the treatment of metastatic brain tumor: Evaluation of local failure and leptomeningeal disease.

In patients undergoing surgical resection of a metastatic brain tumor, whole brain radiation therapy reduces the risk of recurrence and neurologic death. Focal radiation has the potential to mitigate neurocognitive side effects. We present an institutional experience of postoperative radiosurgery for the treatment of brain metastases. A retrospective review of a prospectively maintained institutional radiosurgery database was performed for the years 2005-2015 identifying all adult patients treated with postoperative radiosurgery to the tumor bed. Primary endpoints include local recurrence and postoperative LMD. Kaplan-Meier curves and Cox regression were used to evaluate time to local recurrence and postoperative LMD. Ninety-one patients received adjuvant focal radiation for a brain metastasis. Median radiographic follow-up among patients who had not developed a local failure was 9 months. Of the 91 patients, 20 (22%) developed local recurrence and 32 (35%) experienced postoperative LMD. Freedom from local recurrence and LMD at 1 year was 84% and 69%, respectively. In multivariable models, predictors of local failure included the presence of more than one brain metastasis (HR = 2.65, p = .04) with a preoperative tumor diameter of >3 cm (HR = 4.16, p = .06) trending toward significance. There was a trend to a higher risk of LMD with >1 tumor (HR 2.07, p = .06) and breast cancer (HR 2.37, p = .07). More than one metastasis is an independent predictor of local and leptomeningeal failure following postoperative radiosurgery. The high rate of LMD was likely related to the liberal definition of LMD to include focal dural recurrences.