Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

BACKGROUND: The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. METHODS: STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. RESULTS: Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P = 0.002 and P = 0.029, respectively, for 60 Hz; P < 0.001 and P < 0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P = 0.007) and attenuated high-beta power (19-27 Hz, P < 0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P < 0.001). Only 60-Hz DBS improved the regularity of angular range (P = 0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. CONCLUSIONS: These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

BACKGROUND: Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. METHODS: Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. RESULTS: Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). CONCLUSIONS: Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

Safety of elective enteral access in elderly patients: a comparative analysis of perioperative risk.

BACKGROUND: Elderly patients can experience torpid hospitalization that is often characterized by malnutrition. In this setting, enteral feeding may facilitate improvement in nutritional status. This study aimed to compare the perioperative outcomes between elderly (age of ≥65 years old) and nonelderly (age of <65 years old) patients undergoing elective enteral access placement. METHODS: Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care facility were retrospectively reviewed. Differences in baseline characteristics between nonelderly and elderly patients were adjusted using entropy-balanced weights. Subsequently, multivariate logistic and linear regression models were developed to evaluate the association between elderly status and outcomes of interest. RESULTS: Overall, 914 patients with enteral access met the inclusion criteria, of whom 471 (51.5%) were elderly. Elderly patients more commonly received percutaneous gastrostomy and had a higher burden of comorbidities as measured using the Charlson Comorbidity Index than nonelderly patients. Multivariate risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups. After adjustment, despite no significant association with inhospital mortality, reoperation, or time to feeding goals, elderly status was linked to an approximately 8-day reduction in length of stay (95% CI, -14.28 to -2.30; P = .007) and significantly lower odds of total parenteral nutrition (adjusted odds ratio [AOR], 0.59; 95% CI, 0.37-0.94; P = .026) and nonelective readmission (AOR, 0.65; 95% CI, 0.49-0.86; P = .003). In addition, elderly status was associated with significantly greater odds of nonhome discharge (AOR, 1.58; 95% CI, 1.17-2.13; P = .003). CONCLUSION: Despite having more comorbidities than their nonelderly counterparts, elderly patients experienced favorable nutritional and perioperative outcomes after enteral access placement.

Impact of Artificial Intelligence-Assisted Indication Selection on Appropriateness Order Scoring for Imaging Clinical Decision Support.

PURPOSE: The aim of this study was to assess appropriateness scoring and structured order entry after the implementation of an artificial intelligence (AI) tool for analysis of free-text indications. METHODS: Advanced outpatient imaging orders in a multicenter health care system were recorded 7 months before (March 1, 2020, to September 21, 2020) and after (October 20, 2020, to May 13, 2021) the implementation of an AI tool targeting free-text indications. Clinical decision support score (not appropriate, may be appropriate, appropriate, or unscored) and indication type (structured, free-text, both, or none) were assessed. The χ2 and multivariate logistic regression adjusting for covariables with bootstrapping were used. RESULTS: In total, 115,079 orders before and 150,950 orders after AI tool deployment were analyzed. The mean patient age was 59.3 ± 15.5 years, and 146,035 (54.9%) were women; 49.9% of orders were for CT, 38.8% for MR, 5.9% for nuclear medicine, and 5.4% for PET. After deployment, scored orders increased to 52% from 30% (P < .001). Orders with structured indications increased to 67.3% from 34.6% (P < .001). On multivariate analysis, orders were more likely to be scored after tool deployment (odds ratio [OR], 2.7, 95% CI, 2.63-2.78; P < .001). Compared with physicians, orders placed by nonphysician providers were less likely to be scored (OR, 0.80; 95% CI, 0.78-0.83; P < .001). MR (OR, 0.84; 95% CI, 0.82-0.87) and PET (OR, 0.12; 95% CI, 0.10-0.13) were less likely to be scored than CT (; P < .001). After AI tool deployment, 72,083 orders (47.8%) remained unscored, 45,186 (62.7%) with free-text-only indications. CONCLUSIONS: Embedding AI assistance within imaging clinical decision support was associated with increased structured indication orders and independently predicted a higher likelihood of scored orders. However, 48% of orders remained unscored, driven by both provider behavior and infrastructure-related barriers.

Transjugular intrahepatic portosystemic shunt for the management of symptomatic malignant pseudocirrhosis.

Background: Pseudocirrhosis is defined by radiologic changes of the liver parenchyma secondary to metastatic disease and/or cancer treatments, and portends a high rate of morbidity and mortality from sequelae of portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension; however, TIPS is relatively contraindicated in the setting of hepatic metastases. The study aims to determine the technical efficacy and clinical outcomes of patients undergoing TIPS for symptomatic pseudocirrhosis. Methods: Retrospective analysis of patients with hepatic malignancy who underwent TIPS between 2008 and 2020 at a single tertiary care center. Patients with imaging findings of pseudocirrhosis and without history of primary liver malignancy or confounding causes of cirrhosis were included. West Haven scores assessing hepatic encephalopathy were obtained from chart review. Technical success was defined as successful TIPS creation with reduction in the portosystemic gradient (PSG). Clinical success was defined as resolution of variceal bleeding and/or ascites. Results: Nine patients (4 female/5 male), average (± SD) age 61.2±9.5 years with metastatic pseudocirrhosis were included for analysis. Primary malignancy was colorectal adenocarcinoma (n=5), neuroendocrine tumor (n=3), and malignant endothelial hemangioendothelioma (n=1). Average Model for End Stage Liver Disease (MELD-Na) score was 15.7±3.7. Technical success was 8/9 (89%) with average PSG reduced from 23.5±11.0 to 6.5±2.8 mmHg (P=0.001). Clinical success was 6/9 (67%). Two patients required TIPS revision after initial clinical success. Mild-moderate HE occurred in 6/9 patients post TIPS (67%), with a highest West Haven score of 2. Time from TIPS to death for acute variceal bleeding and ascites was 4.9±4.2 and 12±16.5 months, respectively. Cause of death was disease progression (n=5), variceal bleeding (n=1), or unavailable (n=2). Conclusions: TIPS in the setting of malignant pseudocirrhosis can be created safely with similar clinical outcomes to TIPS performed for benign disease. Rates of low-grade hepatic encephalopathy may be higher amongst patients undergoing TIPS for pseudocirrhosis.

Changes in perfusion angiography after IVC filter placement and retrieval.

Inferior vena cava (IVC) filters are posited to effect flow dynamics, causing turbulence, vascular remodeling and eventual thrombosis; however, minimal data exists evaluating hemodynamic effects of IVC filters in vivo. The purpose of this study was to determine differences in hemodynamic flow parameters acquired with two-dimension (2D)-perfusion angiography before and after IVC filter placement or retrieval. 2D-perfusion images were reconstructed retrospectively from digital subtraction angiography from a cohort of 37 patients (13F/24M) before and after filter placement (n = 18) or retrieval (n = 23). Average dwell time was 239.5 ±â€…132.1 days. Changes in the density per pixel per second within a region of interest (ROI) were used to calculate contrast arrival time (AT), time-to-peak (TTP), wash-in-rate (WIR), and mean transit time (MTT). Measurements were obtained superior to, inferior to, and within the filter. Differences in hemodynamic parameters before and after intervention were compared, as well as correlation between parameters versus filter dwell time. A P value with Bonferroni correction of <.004 was considered statistically significant. After placement, there was no difference in any 2D-perfusion variable. After retrieval, ROIs within and inferior to the filter showed a significantly shorter TTP (1.7 vs 1.4 s, P = .004; 1.5 vs 1.3 s, P = .001, respectively) and MTT (1.7 vs 1.4 s, P = .003; 1.5 vs 1.2 s, P = .002, respectively). Difference in variables showed no significant correlation when compared to dwell time. 2D-perfusion angiography is feasible to evaluate hemodynamic effects of IVC filters in vivo. TTP and MTT within and below the filter after retrieval were significantly changed, without apparent correlation to dwell time, suggesting a functional hemodynamic delay secondary to filter presence.

Subthalamic oscillations and phase amplitude coupling are greater in the more affected hemisphere in Parkinson's disease.

OBJECTIVE: Determine the incidence of resting state oscillations in alpha/beta, high frequency (HFO) bands, and their phase amplitude coupling (PAC) in a large cohort in Parkinson's disease (PD). METHODS: Intra-operative local field potentials (LFPs) from subthalamic nucleus (STN) were recorded from 100 PD subjects, data from 74 subjects were included in the analysis. RESULTS: Alpha/beta oscillations were evident in >99%, HFO in 87% and PAC in 98% of cases. Alpha/beta oscillations (P<0.01) and PAC were stronger in the more affected (MA) hemisphere (P=0.03). Alpha/beta oscillations were primarily found in 13-20Hz (low beta). Beta and HFO frequencies with the greatest coupling, were positively correlated (P=0.001). Tremor attenuated alpha (P=0.002) and beta band oscillations (P<0.001). CONCLUSIONS: STN alpha/beta band oscillations and PAC were evident in ⩾98% cases and were greater in MA hemisphere. Resting tremor attenuated underlying alpha/beta band oscillations. SIGNIFICANCE: Beta band LFP power may be used to drive adaptive deep brain stimulation (aDBS), augmented by a kinematic classifier in tremor dominant PD.

Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease.

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson's disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony. Here we demonstrate for the first time that during intra-operative 60 Hz STN DBS, one or more bands of resting state neural synchrony were amplified in the STN in PD. We recorded intra-operative STN resting state local field potentials (LFPs) from twenty-eight STNs in seventeen PD subjects after placement of the DBS lead (model 3389, Medtronic, Inc.) before and during three randomized neurostimulation sets (130 Hz/1.35V, 130 Hz/2V, 60 Hz/2V). During 130 Hz/2V DBS, baseline (no DBS) STN alpha (8-12 Hz) and beta (13-35 Hz) band power decreased (N=14, P < 0.001 for both), whereas during 60 Hz/2V DBS, alpha band and peak frequency power increased (P = 0.012, P = 0.007, respectively). The effect of 60 Hz/2V DBS opposed that of power-equivalent (130 Hz/1.35V) DBS (alpha: P < 0.001, beta: P = 0.006). These results show that intra-operative 60 Hz STN DBS amplified whereas 130 Hz STN DBS attenuated resting state neural synchrony in PD; the effects were frequency-specific. We demonstrate that neurostimulation may be useful as a tool to selectively modulate resting state resonant bands of neural synchrony and to investigate its influence on motor and non-motor behaviors in PD and other neuropsychiatric diseases.