Preventing Shift from Pneumocephalus During Deep Brain Stimulation Surgery: Don't Give Up the 'Fork in the Brain'.

Clinical vignette: We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target. Clinical dilemma: Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory. Clinical solution: We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass. Gap in knowledge: Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement.

Active recharge biphasic stimulation for the intraoperative monopolar review in deep brain stimulation.

Introduction: Charge balancing is used in deep brain stimulation (DBS) to avoid net charge accumulation at the tissue-electrode interface that can result in neural damage. Charge balancing paradigms include passive recharge and active recharge. In passive recharge, each cathodic pulse is accompanied by a waiting period before the next stimulation, whereas active recharge uses energy to deliver symmetric anodic and cathodic stimulation pulses sequentially, producing a net zero charge. We sought to determine differences in stimulation induced side effect thresholds between active vs. passive recharge during the intraoperative monopolar review. Methods: Sixty-five consecutive patients undergoing DBS from 2021 to 2022 were retrospectively reviewed. Intraoperative monopolar review was performed with both active recharge and passive recharge for all included patients to determine side effect stimulation thresholds. Sixteen patients with 64 total DBS contacts met inclusion criteria for further analysis. Intraoperative monopolar review results were compared with the monopolar review from the first DBS programming visit. Results: The mean intraoperative active recharge stimulation threshold was 4.1 mA, while the mean intraoperative passive recharge stimulation threshold was 3.9 mA, though this difference was not statistically significant on t-test (p = 0.442). Mean stimulation threshold at clinic follow-up was 3.2 mA. In Pearson correlation, intraoperative passive recharge thresholds had stronger correlation with follow-up stimulation thresholds (Pearson r = 0.5281, p < 0.001) than intraoperative active recharge (Pearson r = 0.340, p = 0.018), however the difference between these correlations was not statistically significant on Fisher Z correlation test (p = 0.294). The mean difference between intraoperative passive recharge stimulation threshold and follow-up stimulation threshold was 0.8 mA, while the mean difference between intraoperative active recharge threshold and follow-up threshold was 1.2 mA. This difference was not statistically significant on a t-test (p = 0.134). Conclusions: Both intraoperative active recharge and passive recharge stimulation were well-correlated with the monopolar review at the first programming visit. No statistically significant differences were observed suggesting that either passive or active recharge may be utilized intraoperatively.

Risk factors for postoperative urinary retention after deep brain stimulation surgery: the role of the subthalamic nucleus.

OBJECTIVE: Deep brain stimulation (DBS) is a common procedure in neurosurgery used for the treatment of Parkinson's disease (PD) and essential tremor (ET) among other disorders. Lower urinary tract dysfunction is a common complication in PD, and this study aimed to evaluate the risk factors of postoperative urinary retention (POUR) after DBS surgery in patients with PD compared with patients with ET. Understanding the risk factors associated with this complication may help in the development of strategies to minimize its occurrence and improve patient outcomes. METHODS: The study was a retrospective analysis of patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. The surgical technique used has been described in previous articles and included a two-stage procedure, with stage 1 involving burr hole placement, microelectrode recording, and electrode implantation and stage 2 involving the placement of an implantable pulse generator (IPG). Data were collected on patient characteristics and surgical details and analyzed using univariate and mixed-linear models. Post hoc propensity score matching was used to confirm the association between subthalamic nucleus (STN)-DBS and POUR. RESULTS: The study included 350 patients (153 with PD and 197 with ET) who underwent 1086 DBS surgeries (lead implantations, IPG placement, and IPG replacements). The POUR rates were 16.6% (79/477), 5.2% (19/363), and 0.4% (1/246) for stage 1, stage 2, and IPG replacement procedures, respectively. Optimal mixed-effects logistic modeling revealed history of urinary retention (OR 9.3, p = 0.004), male sex (OR 2.7, p = 0.011), having an electrode placed or connected for the first time (OR 2.2, p = 0.014), anesthesia time (OR 1.5 for each 30-minute increase, p < 0.0001), preoperative opioid use (OR 1.4 for each additional 10 morphine milligram equivalents, p = 0.032), and Charlson Comorbidity Index (OR 1.4 per comorbidity, p = 0.017) to be significant risk factors for POUR. Having an electrode in the STN was found to be protective of POUR (propensity score-matched analysis: OR 0.2, p = 0.010). CONCLUSIONS: Most risk factors found to increase the risk of POUR in DBS are not modifiable but are still important to consider in preoperative planning. Opioid use reduction and shorter anesthesia time may be modifiable risk factors to weigh against their alternative. Targeting the STN during DBS may result in decreased rates of POUR. This highlights the potential for STN-targeted DBS in reducing POUR risk in PD and ET patients.

Identification and Management of Persistent Stimulation-Induced Dyskinesia Associated with STN DBS: The See-Saw Dilemma.

Clinical vignette: A 73-year-old woman with Parkinson's disease (PD) underwent implantation of bilateral subthalamic nucleus deep brain stimulators (STN-DBS) to address bilateral upper extremity medication-refractory tremor. Post-operatively, she experienced a "see-saw effect" where small increases in stimulation resulted in improvement in one symptom (tremor) with concurrent worsening in another (dyskinesia). Clinical dilemma: SID is usually considered a positive predictor of DBS outcome. However, there are cases where SID cannot be optimized. Lead location and pre-operative characteristics may contribute to this adverse effect. If the combination of programming and medication adjustments fails to resolve SID, what can be done to "rescue" the outcome? Clinical solution: Management of SID requires a gradual and steadfast programming approach. Post-operative lead localization can guide advanced programming and decision-making. Rescue surgical interventions may be considered. Gap in knowledge: In cases where SID is persistent despite deploying persistent optimization strategies, there is limited guidance on next steps.

Ventriculo-inferior-venacaval shunt salvage via endovascular surgery.

INTRODUCTION: Hydrocephalus treatment can be very challenging. While some hydrocephalic patients can be treated endoscopically, many will require ventricular shunting. Frequent shunt issues over a lifetime is not uncommon. Although most shunt malfunctions are of the ventricular catheter or valve, distal failures occur as well. A subset of patients will accumulate non-functioning distal drainage sites. CASE DESCRIPTION: We present a 27-year-old male with developmental delay who was shunted perinatally for hydrocephalus from intraventricular hemorrhage of prematurity. After failure of the peritoneum, pleura, superior vena cava (SVC), gallbladder, and endoscopy, an inferior vena cava (IVC) shunt was placed minimally-invasively via the common femoral vein. We believe this is only the eighth reported ventriculo-inferior-venacaval shunt. IVC occlusion years later was successfully treated with endovascular angioplasty and stenting followed by anticoagulation. To our knowledge, a ventriculo-inferior-venacaval shunt salvaged by endovascular surgery has not been previously described in the literature. CONCLUSION: After failure of the peritoneum, pleura, SVC, gallbladder, and endoscopy, IVC shunt placement is an option. Subsequent IVC occlusion can be rescued by endovascular angioplasty and stenting. Anticoagulation after stenting (and potentially after initial IVC placement) is advised.

Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease.

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus (N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor (N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes (P = 0.9) but a higher frequency (P = 0.009) and a higher number of peaks (P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes (P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease.

Connectomic analysis of unilateral dual-lead thalamic deep brain stimulation for treatment of multiple sclerosis tremor.

Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T1-weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = -0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.

Deep brain stimulation for the treatment of tremor.

This review article provides a brief historical perspective on the use of DBS for tremor, reviews the various etiologies for tremor that can be effectively managed with DBS therapy, discusses the DBS targets that have been used for suppression of tremor, and reviews in detail important aspects of DBS surgical technique, including significant technological advances over the past several years that, when applied, can substantially improve the outcomes of DBS for tremor. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

Past, Present, and Future of Deep Brain Stimulation: Hardware, Software, Imaging, Physiology and Novel Approaches.

Deep brain stimulation (DBS) has advanced treatment options for a variety of neurologic and neuropsychiatric conditions. As the technology for DBS continues to progress, treatment efficacy will continue to improve and disease indications will expand. Hardware advances such as longer-lasting batteries will reduce the frequency of battery replacement and segmented leads will facilitate improvements in the effectiveness of stimulation and have the potential to minimize stimulation side effects. Targeting advances such as specialized imaging sequences and "connectomics" will facilitate improved accuracy for lead positioning and trajectory planning. Software advances such as closed-loop stimulation and remote programming will enable DBS to be a more personalized and accessible technology. The future of DBS continues to be promising and holds the potential to further improve quality of life. In this review we will address the past, present and future of DBS.

Time for a New 3-D Image for Globus Pallidus Internus Deep Brain Stimulation Targeting and Programming.

Deep brain stimulation (DBS) is an effective neuromodulatory therapy for Parkinson's disease (PD). Early studies using globus pallidus internus (GPi) DBS for PD profiled the nucleus as having two functional zones. This concept disseminated throughout the neuromodulation community as the "GPi triangle". Although our understanding of the pallidum has greatly evolved over the past 20 years, we continue to reference the triangle in our clinical decision-making process. We propose a new direction, termed the spatial boundary hypothesis, to build upon the 2-dimensional outlook on GPi DBS. We believe an updated 3-D GPi model can produce more consistent, positive patient outcomes.

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor.

BACKGROUND: The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long-term reduction of benefit seen with VIM-DBS. OBJECTIVES: To compare clinical outcomes and DBS programming in the long-term between VIM and cZI neurostimulation in ET-DBS patients. MATERIALS AND METHODS: A retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow-up to 4 years after DBS. Student t-tests and analysis of variance (ANOVA) were used to compare variables between groups. RESULTS: Relative to baseline, an improvement in ON-DBS tremor scores was observed in both groups from 6 months to 4 years post-DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post-DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post-DBS. CONCLUSIONS: More ventral DBS contacts in the cZI region do improve tremor, however, VIM-DBS provided better long-term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results.

Postoperative lead migration in deep brain stimulation surgery: Incidence, risk factors, and clinical impact.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1) quantify the incidence of lead migration in a large series of DBS patients, 2) identify potential risk factors contributing to DBS lead migration, and 3) investigate the practical importance of this complication by correlating its occurrence with clinical outcomes. METHODS: A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT) acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating scales for all cases, and a comparison was made between outcomes of cases with lead migration versus those where migration of the lead did not occur. RESULTS: Data from 138 leads in 132 patients with initial and delayed lead localization CT scans were analyzed. The mean distance between initial and delayed DBS lead tip position was 2.2 mm and the mean change in intracranial lead length was 0.45 mm. Significant delayed migration (>3 mm) was observed in 17 leads in 16 patients (12.3% of leads, 12.1% of patients). Factors associated with lead migration were: technical error, repetitive dystonic head movement, and twiddler's syndrome. Outcomes were worse in dystonia patients with lead migration (p = 0.035). In the PD group, worse clinical outcomes trended in cases with lead migration. CONCLUSIONS: Over 10% of DBS leads in this large single center cohort were displaced by greater than 3 mm on delayed measurement, adversely affecting outcomes. Multiple risk factors emerged, including technical error during implantation of the DBS pulse generator and failure of lead fixation at the burr hole site. We hypothesize that a change in surgical technique and a more effective lead fixation device might mitigate this problem.

Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

BACKGROUND: Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. METHODS: We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov, number NCT00954421. FINDINGS: Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), -29·6% reduction; t=-0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. INTERPRETATION: Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. FUNDING: US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship.

Post-mortem Findings in Huntington's Deep Brain Stimulation: A Moving Target Due to Atrophy.

BACKGROUND: Deep brain stimulation (DBS) has been shown to be effective for Parkinson's disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington's disease (HD). CASE REPORT: A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. DISCUSSION: This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule.

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting.

OBJECTIVE: We conducted intraoperative measurements of tremor during DBS containing short pauses (⩽50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. METHODS: Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. RESULTS: All patterns of DBS decreased tremor relative to 'off'. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. CONCLUSIONS: The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. SIGNIFICANCE: Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor.

A magnetic resonance imaging, histological, and dose modeling comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus.

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.

Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.

Effective subthalamic nucleus deep brain stimulation sites may differ for tremor, bradykinesia and gait disturbances in Parkinson's disease.

BACKGROUND/AIMS: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD). This study investigates whether improvement for particular PD symptoms varies differentially with respect to stimulation location in the STN. METHODS: Ten PD patients treated with bilateral STN DBS were enrolled in the study. Each electrode contact was stimulated independently to assess for changes in tremor, bradykinesia, and gait. Electrode contacts were localized via MRI. A novel iterative volumetric analysis was used to search the contact space for stimulation regions corresponding to alleviation of specific symptoms. RESULTS: Tremor was best controlled with DBS applied to the more dorsal, anterior, and medial areas of the contact space. Improvement in bradykinesia was seen largely within the middle of the contact space. Gait improvement was observed with ventral contacts, likely bordering the ventral boundaries of the STN. CONCLUSION: The iterative volumetric analysis is a valuable tool in identifying anatomic regions responsive to DBS across a subject population treated for PD. In the subjects tested, overlapping efficacy for all symptoms was observed in the region of the STN, but anatomic variances in the responsiveness for tremor, bradykinesia, and gait were found.