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Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Aims: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS., Methods: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics., Results: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores., Conclusion: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Desflurane and sevoflurane are commonly used during inhalational anaesthesia, but few studies have investigated their effects on deep cerebral neuronal activity. In addition, the association between subthalamic nucleus (STN) neurophysiology and general anaesthesia induced by volatile anaesthetics are not yet identified. This study aimed to identify differences in neurophysiological characteristics of the STN during comparable minimal alveolar concentration (MAC) desflurane and sevoflurane anaesthesia for deep brain stimulation (DBS) in patients with Parkinson's disease., Methods: Twelve patients with similar Parkinson's disease severity received desflurane (n=6) or sevoflurane (n=6) during DBS surgery. We obtained STN spike firing using microelectrode recording at 0.5-0.6 MAC and compared firing rate, power spectral density, and coherence., Results: Neuronal firing rate was lower with desflurane (47.4 [26.7] Hz) than with sevoflurane (63.9 [36.5] Hz) anaesthesia (P<0.001). Sevoflurane entrained greater gamma oscillation power than desflurane (62.9% [0.9%] vs 57.0% [1.5%], respectively; P=0.002). There was greater coherence in the theta band of the desflurane group compared with the sevoflurane group (13% vs 6%, respectively). Anaesthetic choice did not differentially influence STN mapping accuracy or the clinical outcome of DBS electrode implantation., Conclusions: Desflurane and sevoflurane produced distinct neurophysiological profiles in humans that may be associated with their analgesic and hypnotic actions., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome., Methods: A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up., Results: Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent., Conclusions: Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.

Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular-skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

Object: Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson's disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored., Methods: Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures., Results: The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05)., Conclusions: Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

Background/purpose: Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to produce long-term symptom improvement in Parkinson's disease. The aim of this study was to identify the target symptoms that show the most improvement at 1 year and at 5 years after STN-DBS., Methods: This was a 5-year cohort study of 41 consecutive patients treated with bilateral STN-DBS. Clinical evaluations were performed 1 month prior to surgery and 1 year and 5 years after surgery. The outcome measurements at 1 year and 5 years were the changes compared with the baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, III, and IV scores, the Hoehn and Yahr stage, and Schwab and England Activities of Daily Living (SEADL) scores in the conditions of off-medication/on-stimulation and off-medication/off-stimulation. Further analysis included changes in the levodopa equivalent daily dose., Results: When compared to the preoperative baseline off-medication condition, significant improvements were observed in the UPDRS parts I, II, III, and IV and SEADL (p < 0.001) scores in the off-medication/on-stimulation condition 1 year after STN-DBS. Five years after STN-DBS, improvements in UPDRS scores were observed only for parts II, III, and IV (p < 0.001). In the off-medication/off-stimulation condition, no significant improvement was observed. At 5 years, significant deteriorations were observed in scores for the UPDRS part III axial subitem (p = 0.005), UPDRS part I (p = 0.005), UPDRS part II (p < 0.001), and SEADL (p = 0.001)., Conclusion: The long-term effect of STN-DBS on motor function is promising, although the magnitude of its effectiveness varied over the 5-year period., (Copyright © 2013. Published by Elsevier B.V.)

Objective: Age of onset is considered a poor prognostic factor for subthalamic deep brain stimulation (STN-DBS) outcome in the case of Parkinson's disease (PD). The goal of current study is to identify the long-term impact of STN-DBS for young onset PD (YOPD) patients., Methods: 17 YOPD patients with a mean disease onset at 32.3 years were prospectively followed up at 1, 2, 5 and 7 years after STN-DBS. Unified Parkinson's disease rating scale (UPDRS) was evaluated in 4 combinations of Med/DBS on/off., Results: UPDRS part II-IV improved significantly 7 years after operation. While a slowly progressive worsening of levodopa response on part III, synergistic effect of medication and stimulation consistently improves motor disabilities. STN-DBS could remarkably reduce levodopa equivalent daily dose at 7 years. The morbidity rates were low. However, these patients seem to have more transient stimulation dyskinesia (47.1%) and dopamine dysregulation syndrome (11.8%) after surgery., Conclusions: STN-DBS remains effective to improve motor disabilities over 7 years for YOPD and is a safe procedure concerning cognitive outcome and morbidity. However, stimulation dyskinesia and dopamine dysregulation syndrome deserve attention for the causal relationship between DBS surgery and behavioral outcomes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The efficacy and feasibility of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) under general anesthesia (GA) has not been evaluated., Objective: We compared the outcome of patients under GA with those who were operated on under local anesthesia (LA)., Material and Methods: Thirty-three patients were assigned to the GA group (desflurane) and 19 patients were assigned to the LA group. Microelectrode recording (MER) was performed in both groups. The surgical outcomes of the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) after at least 12 months after surgery., Results: Postoperatively, there was no significant difference on the UPDRS scores in either groups. A significant deterioration in cognitive function in the GA group was observed (p = 0.017). The recorded electrode coordinates, the average tracts for the MER, and STN depth were comparable in both groups. The overall incidence of adverse effects did not show any difference except that the incidence of sialorrhea and dysarthria was significantly higher in the GA group., Conclusion: Desflurane GA was shown to be a good alternative anesthetic method for PD patients undergoing DBS. Although the motor outcomes were comparable, a significant cognitive decline may be seen in the GA group with a higher occurrence of stimulation side effects., (Copyright © 2011 S. Karger AG, Basel.)

Background/aims: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have long-term benefits in Parkinson's disease (PD). Through analyzing different variables, this study identified prognostic factors for the short- and long-term effects of STN-DBS., Methods: Thirty-six PD patients underwent bilateral STN-DBS. Clinical evaluations were performed 1 month before and 3 months after surgery, with additional follow-up examinations for a mean of 31.3 months., Results: There was a trend for long-term STN-DBS-induced improvements in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III measures to be greater in younger patients. Preoperative levodopa responsiveness only led to consistent UPDRS part III improvement from STN-DBS at 3 months, and this predictive value did not exist in the long term. The preoperative levodopa response of tremor and axial symptoms in motor disability predicted long-term DBS effect only. Preoperative cognitive function positively correlated with postoperative improvement from DBS in UPDRS part III during long-term follow-up only., Conclusions: The prognostic factors for STN-DBS benefit were different for short- and long-term follow-ups. Good prognostic factors for long-term STN-DBS for PD patients were good cognitive function and tremor dominance. Poor prognostic factors were related to older age and non-dopaminergic-responsive axial disability., (Copyright 2009 S. Karger AG, Basel.)

Object: The authors of this preliminary study investigated the outcome and feasibility of intraoperative microelectrode recording (MER) in patients with Parkinson disease (PD) undergoing deep brain stimulation of the subthalamic nucleus (STN) after anesthetic inhalation., Methods: The authors conducted a retrospective analysis of 10 patients with PD who received a desflurane anesthetic during bilateral STN electrode implantation. The MERs were obtained as an intraoperative guide for final electrode implantation and the data were analyzed offline. The functional target coordinates of the electrodes were compared preoperatively with estimated target coordinates., Results: Outcomes were evaluated using the Unified Parkinson's Disease Rating Scale 6 months after surgery. The mean improvement in total and motor Unified Parkinson's Disease Rating Scale scores was 54.27 +/- 17.96% and 48.85 +/- 16.97%, respectively. The mean STN neuronal firing rate was 29.7 +/- 14.6 Hz. Typical neuronal firing patterns of the STN and substantia pars nigra reticulata were observed in each patient during surgery. Comparing the functional target coordinates, the z axis coordinates were noted to be significantly different between the pre- and postoperative coordinates., Conclusions: The authors found that MER can be adequately performed while the patient receives a desflurane anesthetic, and the results can serve as a guide for STN electrode implantation. This may be a good alternative surgical method in patients with PD who are unable to tolerate deep brain stimulation surgery with local anesthesia.

Objective: The neuropsychological effects of chronic subthalamic nucleus (STN)-deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable. Whether these side effects result from the target per se or current diffusion into neighboring structures is uncertain. In this study, the relationship between clinical outcomes and coordinates of active contact are analyzed and compared between patients with and without neuropsychological sequelae., Methods: Thirty-eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. They were followed for at least 12 months. During the follow-up period, they were divided into two groups for comparison; Group A included patients with neuropsychological side effects and Group B was composed of patients without neuropsychological side effects. The position of the active contact of the electrode was defined with postoperative magnetic resonance imaging scans according to the midcommissural line. Active contact coordinates and clinical outcomes were compared for the two groups., Results: Among the 38 Parkinsonian patients who underwent STN-DBS, eight patients who had neuropsychological side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9 and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively. The mean coordinates of active contact in both Groups A and B were x = 10.1 and 10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2 mm, respectively, relative to the midcommissural point. A significant difference was observed on the y axis (P = 0.01)., Conclusion: When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.