Background： Subthalarnic nucleus deep brain stimulation （STN DBS） is effective against advanced Parkinson＇s disease （PD）, allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in ...Background： Subthalarnic nucleus deep brain stimulation （STN DBS） is effective against advanced Parkinson＇s disease （PD）, allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Meihods： Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson＇s Disease Rating Scale Part Ⅲ （UPDRS Ill）, Parkinson＇s Disease Questionnatire-39, Parkinson＇s Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Resulis： In the ＂oft＂ state （off medication）, DBS improved UPDRS Ill scores by 35.87% in 5 years, compared with preoperative baseline （P 〈 0.001 ）. In the ＂on＂ state （on medication）, motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% （P 〈 0.001 ） from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years （by 52.96%, P 〈 0.001 ）. The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 Its, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions： STN DBS is an effective intervention for PD, although with other studies, patients in our study required lower voltage and associated with a slightly diminished efficacy after 5 years. Compared medication for satisfactory symptom control.展开更多
Background The major neuropathological symptoms of Parkinson’s disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate ...Background The major neuropathological symptoms of Parkinson’s disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS). Methods Seven consecutive advanced PD patients (4 men and 3 women, mean age 64±4 years, mean H-Y disability rating 4.4±0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose ( 18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. Results STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P<0.05). Conclusion Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.展开更多
Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment usi...Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria： （1） at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; （2） pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and （3） adequate reporting of study results using means and standard deviations. Of -170 clinical studies identified, 25 cohort studies （including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment） and one meta- analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.展开更多
Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous ...Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous causes, hereditary neurologic syndromes or neurodegenerative disorders. Tardive dystonia is a special type of secondary dystonia due to exposure to certain medicines such as neuroleptics, with a chronic and persistent extrapyramidal symptoms.展开更多
Background Dystonia is one of the most challenging movement disorders to treat. Medications and surgeries are the two methods to control dystonic symptoms. For patients with dystonia in whom symptoms are inadequately ...Background Dystonia is one of the most challenging movement disorders to treat. Medications and surgeries are the two methods to control dystonic symptoms. For patients with dystonia in whom symptoms are inadequately controlled with pharmacologic measures, the use of deep brain stimulation （DBS） can improve symptoms and enhance functional capacity. The best candidate for DBS is believed to be primary generalized dystonia, especially the DYT-1 type. Here, we report 9 cases of secondary dystonia to explore the feasibility, indications and complications of DBS in the treatment of secondary dystonia. Methods From July 2003 to June 2006, nine patients with secondary dystonia underwent surgery at Beijing Tiantan Hospital. Among them, 2 were diagnosed as having tardive dystonia, 1 had posttraumatic dystonia, 3 had a history of perinatal anoxia, 1 had neonatal pathologic jaundice, and 2 had no exact contributory history; MRI showed bilateral lentiform nuclei degeneration in one patient. Six patients underwent bilateral subthalamic nucleus （STN）-DBS, two underwent unilateral STN-DBS, the other underwent left STN and fight globus pallidus internus（GPi）-DBS. Results With intraoperative microelectrode recording, the targeted nucleus was accurately localized. Tentative stimulation could decrease muscle tension to the same extent, but twisting was not obviously improved. Follow-up for 3 months to 3 years showed satisfactory results in 3 patients with tardive dystonia and posttraumatic dystonia and that Burke-Fahn-Marsden Dystonia Scale （BFMS） decreased by more than 90%. The improvement of symptoms was progressive along with time. The other 6 patients had slight to moderate improvement. None of them had severe surgery-related complications. One had lead fracture 16 months after surgery and the lead was then evacuated. Conclusions DBS could be an ideal treatment for patients with tardive and posttraumatic dystonia. For patients with perinatal anoxia and diffuse impairment in the basal ganglia, DBS seemed not to b展开更多
Deep brain stimulation has become a well-established symptomatic treatment for Parkinson＇s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on pat...Deep brain stimulation has become a well-established symptomatic treatment for Parkinson＇s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients＇ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.展开更多
Objective： This review examines the evidence that deep brain stimulation （DBS） has extensive impact on nonmotor symptoms （NMSs） of patients with Parkinson＇s disease （PD）. Data Sources： We retrieved informatio...Objective： This review examines the evidence that deep brain stimulation （DBS） has extensive impact on nonmotor symptoms （NMSs） of patients with Parkinson＇s disease （PD）. Data Sources： We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus （GPi）, subthalamic nucleus （STN）, and ventral intermediate thalamic nucleus. Study Selection： We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs： Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups： those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results： In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS： The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions： As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.展开更多
Background The subthalamic nucleus （STN） is widely recognized as one of the most important and commonly targeted nuclei in stereotactic and functional neurosurgery. The success of STN surgery depends on accuracy in ...Background The subthalamic nucleus （STN） is widely recognized as one of the most important and commonly targeted nuclei in stereotactic and functional neurosurgery. The success of STN surgery depends on accuracy in target determination. Construction of a digitaiized atlas of STN based on stereotactic MRI will play an instrumental role in the accuracy of anatomical localization. The aim of this study was to investigate the three-dimensional （3D） target location of STN in stereotactic space and construct a digitalized atlas of STN to accomplish the visualization of the STN on stereotactic MRI, thus providing clinical guidance on the precise anatomical localization of STN. Methods One hundred and twenty healthy people volunteered to be scanned by 1.5 Tesla MRI scanning with 1-mm-thick slice in the standard stereotactic space between 2005 and 2006. One adult male was selected for 3D reconstruction of STN. The process of 3D reconstruction included identification, manual segmentation, extraction, conservation and reconstruction. Results There was a significant correlation between the coordinates and age （P 〈0.05）. The volume of left STN was significantly larger than the right STN, and there was a significant negative correlation between volume and age （P 〈0.05） The surface of the STN nucleus after 3D reconstruction appeared smooth, natural and realistic. The morphological feature of STN on the individual brain could be visualized directly in 3D. The 3D reconstructed STN could be rotated, zoomed and displayed at any direction in the stereotactic space. The anteroposterior diameter of the STN nucleus was longer than the vertical and transverse diameters in 3D space. The 3D reconstruction of STN manifested typical structure of the ＂dual lens＂. Conclusions The visualization of individual brain atlas based on stereotactic MRI is feasible. However, software for automated segmentation, extraction and registration of MR images need to be further developed.展开更多
Depression is a frequent comorbid syndrome in Parkinson's disease. It is a difficult symptom to manage, as patients continuously receive antiparkinsonian medication and may also have to be treated for the ameliora...Depression is a frequent comorbid syndrome in Parkinson's disease. It is a difficult symptom to manage, as patients continuously receive antiparkinsonian medication and may also have to be treated for the amelioration of the side-effects of antiparkinsonian therapy. The first-line treatment for depression in Parkinson's disease is the use of selective serotonin reuptake inhibitors(SSRIs). The clinical efficacy of these medications in patients with Parkinson's disease is questionable. In fact, based on their mechanism of action, which requires at least a functional serotonergic system, it is predicted that SSRIs will have lower efficacy in patients with Parkinson's disease. Here, we consider the mechanism of action of SSRIs in the context of Parkinson's disease by investigating the fall in the levels of serotonergic markers and the inhibitory outcomes of antiparkinsonian treatment on serotonergic nerve activity. Because certain classes of antidepressant drugs are widely available, it is necessary to perform translational research to address different strategies used to manage depression in Parkinson's disease.展开更多
In this study, 23 asymmetrical Parkinson＇s disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified ...In this study, 23 asymmetrical Parkinson＇s disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson＇s disease patients presenting no severe axial symptoms and dyskinesias.展开更多
The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel micr...The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.展开更多
There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nuc...There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for op展开更多
Background Subthalamic deep brain stimulation （STN-DBS） has been shown to be effective in the treatment of Parkinson＇s disease. The site for permanent stimulation is still in debate. This study aimed to assess the ...Background Subthalamic deep brain stimulation （STN-DBS） has been shown to be effective in the treatment of Parkinson＇s disease. The site for permanent stimulation is still in debate. This study aimed to assess the position of active contacts in relation to the subthalamic nucleus. Methods We reviewed the location of 40 electrodes in 34 patients who underwent STN-DBS. The position of electrode was evaluated by postoperative magnetic resonance imaging （MRI）. The position of active contacts was compared with the subthalamic nucleus （STN） determined by intraoperative electrophysiological mapping and postoperative MRI. Results The average position of the 40 active contacts was （11.7±1.2） mm lateral, （0.6±1.3） mm anterior, and （0.7±1.4） mm vertical to the midcommissural point. The dorsal margin of the STN was （11.6±1.1） mm lateral, （0.2±1.1） mm anterior, and （1.3±1.1） mm vertical to the midcommissural point. When compared with the dorsal margin of the STN, the active contacts were located more dorsally （P=0.033） and anteriorly （P=-0.012）, no significant difference was found in the lateral direction （P=0.107）. When compared with the position of the STN, 26 （65%） of active contacts were located in the region dorsal to the STN, only 13 （32.5%） were located in the upper two-thirds portion of STN. Conclusions The site for permanent stimulation appears to be in the subthalamic region dorsal to the STN, close to the dorsal margin of the STN. Besides the dorsal portion of the STN, other structures such as fields of Forel H and zona incerta may also be involved in the therapeutic benefit of deep brain stimulation.展开更多
Deep brain stimulation of the subthalamic nucleus(STN)is an effective therapy for motor deficits in Parkinson’s disease(PD),but commonly causes weight gain in late-phase PD patients probably by increasing feeding mot...Deep brain stimulation of the subthalamic nucleus(STN)is an effective therapy for motor deficits in Parkinson’s disease(PD),but commonly causes weight gain in late-phase PD patients probably by increasing feeding motivation.It is unclear how STN neurons represent and modulate feeding behavior in different internal states.In the present study,we found that feeding caused a robust activation of STN neurons in mice(GCaMP6 signal increased by 48.4%±7.2%,n=9,P=0.0003),and the extent varied with the size,valence,and palatability of food,but not with the repetition of feeding.Interestingly,energy deprivation increased the spontaneous firing rate(8.5±1.5 Hz,n=17,versus 4.7±0.7 Hz,n=18,P=0.03)and the depolarization-induced spikes in STN neurons,as well as enhanced the STN responses to feeding.Optogenetic experiments revealed that stimulation and inhibition of STN neurons respectively reduced(by 11%±6%,n=6,P=0.02)and enhanced(by 36%±15%,n=7,P=0.03)food intake only in the dark phase.In conclusion,our results support the hypothesis that STN neurons are activated by feeding behavior,depending on energy homeostatic status and the palatability of food,and modulation of these neurons is sufficient to regulate food intake.展开更多
Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of thi...Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.展开更多
Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to ...Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is mo展开更多
Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic ...Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.展开更多
BACKGROUND： Although experimental studies have utilized high-frequency stimulation in animal models, few reports have focused on long-term subthalamic nucleus deep brain stimulation （STN DBS） in Parkinson＇s disea...BACKGROUND： Although experimental studies have utilized high-frequency stimulation in animal models, few reports have focused on long-term subthalamic nucleus deep brain stimulation （STN DBS） in Parkinson＇s disease （PD） animal models. OBJECTIVE： The present study simulated long-term DBS system and utilized microdialysis technology to study the influence of STN DBS on levels of extracellular dopamine （DA） and its metabolites, homovanillic acid （HVA） and dihydroxy phenyl acetic acid, in the corpus striatum of a hemiparkinsonian monkey model. DESIGN, TIME AND SETTING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. MATERIALS： 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindinewas （MPTP） purchased from Sigma, USA. Type-3389 DBS electrode and type-7246 pulse generator were provided by Medtronic, USA. METHODS： Hemiparkinsonism was induced in 2 male, adult Rhesus Macaque monkeys through unilateral internal carotid artery infusion of MPTP. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5 2.0 V pressure） was performed. MAIN OUTCOME MEASURES： Prior to, and 2 hours, 8 hours, 1 week, 1 month, and 2 months after DBS, samples were collected from the caudate nucleus and putamen using microdialysis technology Extracellular levels of DA and its metabolites were measured using high-performance liquid chromatography and electrochemical detection （HPLC-ECD） methods. RESULTS： At 8 hours, 1 week, 1 month, and 2 months after DBS, DA levels in the putamen and caudate nucleus were increased on the electrode-implanted side by 39%, 91%, 111%, and 114% and 31%, 91%, 106%, and 102%, respectively. The DA turnover rate （HVA/DA） was increased in the putamen and caudate nucleus by 186% and 91%, respectively, at 8 hours after DBS, while there wa展开更多
Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad- vanced Parkinson＇s disease. Subthalamic nucleus deep brain stimulation can dramatically improve the motor symptoms of car...Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad- vanced Parkinson＇s disease. Subthalamic nucleus deep brain stimulation can dramatically improve the motor symptoms of carefully selected patients with this disease. Surprisingly, some specific dimensions of quality of life, ＂psychological＂ aspects and social adjustment do not always improve, and they could sometimes be even worse. Patients and their families should fully understand that subthalamic nucleus deep brain stimulation can alter the motor status and time is needed to readapt to their new postoperative state and lifestyles. This paper reviews the literatures regarding effects of bilateral subthalamic nucleus deep brain stimulation on social adjustment, quality of life and coping strategies in patients with Parkinson＇s disease. The findings may help to understand the psychoso-cial maladjustment and poor improvement in quality of life in some Parkinson＇s disease patients.展开更多
Essential tremor （ET）, characterized by a postural and/or kinetic tremor and primarily manifested in theupper extremities, head, and other parts of the body, is one of the most common neurological disorders.1 The tr...Essential tremor （ET）, characterized by a postural and/or kinetic tremor and primarily manifested in theupper extremities, head, and other parts of the body, is one of the most common neurological disorders.1 The traditional target for the neurosurgical treatment of ET, the ventral intermedius nucleus （Vim） of the thalamus, has confirmed that chronic deep brain stimulation （DBS1 is an effective, standard, and primary procedure for ET. However, the loss of tremor suppression due to tolerance of chronic Vim stimulation, accompanied by other adverse effects, such as paresthesias, dysarthria, dysequilibrium, hyperhidrosis, and localized pain, has necessitated changes in the stimulation target in some patients.展开更多
文摘Background： Subthalarnic nucleus deep brain stimulation （STN DBS） is effective against advanced Parkinson＇s disease （PD）, allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Meihods： Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson＇s Disease Rating Scale Part Ⅲ （UPDRS Ill）, Parkinson＇s Disease Questionnatire-39, Parkinson＇s Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Resulis： In the ＂oft＂ state （off medication）, DBS improved UPDRS Ill scores by 35.87% in 5 years, compared with preoperative baseline （P 〈 0.001 ）. In the ＂on＂ state （on medication）, motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% （P 〈 0.001 ） from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years （by 52.96%, P 〈 0.001 ）. The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 Its, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions： STN DBS is an effective intervention for PD, although with other studies, patients in our study required lower voltage and associated with a slightly diminished efficacy after 5 years. Compared medication for satisfactory symptom control.
基金ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No 3 0 2 70 493 )
文摘Background The major neuropathological symptoms of Parkinson’s disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS). Methods Seven consecutive advanced PD patients (4 men and 3 women, mean age 64±4 years, mean H-Y disability rating 4.4±0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose ( 18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. Results STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P<0.05). Conclusion Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.
基金supported by National Natural Science Foundation of China(81071065)
文摘Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria： （1） at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; （2） pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and （3） adequate reporting of study results using means and standard deviations. Of -170 clinical studies identified, 25 cohort studies （including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment） and one meta- analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.
文摘Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous causes, hereditary neurologic syndromes or neurodegenerative disorders. Tardive dystonia is a special type of secondary dystonia due to exposure to certain medicines such as neuroleptics, with a chronic and persistent extrapyramidal symptoms.
文摘Background Dystonia is one of the most challenging movement disorders to treat. Medications and surgeries are the two methods to control dystonic symptoms. For patients with dystonia in whom symptoms are inadequately controlled with pharmacologic measures, the use of deep brain stimulation （DBS） can improve symptoms and enhance functional capacity. The best candidate for DBS is believed to be primary generalized dystonia, especially the DYT-1 type. Here, we report 9 cases of secondary dystonia to explore the feasibility, indications and complications of DBS in the treatment of secondary dystonia. Methods From July 2003 to June 2006, nine patients with secondary dystonia underwent surgery at Beijing Tiantan Hospital. Among them, 2 were diagnosed as having tardive dystonia, 1 had posttraumatic dystonia, 3 had a history of perinatal anoxia, 1 had neonatal pathologic jaundice, and 2 had no exact contributory history; MRI showed bilateral lentiform nuclei degeneration in one patient. Six patients underwent bilateral subthalamic nucleus （STN）-DBS, two underwent unilateral STN-DBS, the other underwent left STN and fight globus pallidus internus（GPi）-DBS. Results With intraoperative microelectrode recording, the targeted nucleus was accurately localized. Tentative stimulation could decrease muscle tension to the same extent, but twisting was not obviously improved. Follow-up for 3 months to 3 years showed satisfactory results in 3 patients with tardive dystonia and posttraumatic dystonia and that Burke-Fahn-Marsden Dystonia Scale （BFMS） decreased by more than 90%. The improvement of symptoms was progressive along with time. The other 6 patients had slight to moderate improvement. None of them had severe surgery-related complications. One had lead fracture 16 months after surgery and the lead was then evacuated. Conclusions DBS could be an ideal treatment for patients with tardive and posttraumatic dystonia. For patients with perinatal anoxia and diffuse impairment in the basal ganglia, DBS seemed not to b
基金supported by ERA-NET Neuron/German Federal Ministry of Education and Research(BMBF):TYMON 01EW141 to LW
文摘Deep brain stimulation has become a well-established symptomatic treatment for Parkinson＇s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients＇ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.
文摘Objective： This review examines the evidence that deep brain stimulation （DBS） has extensive impact on nonmotor symptoms （NMSs） of patients with Parkinson＇s disease （PD）. Data Sources： We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus （GPi）, subthalamic nucleus （STN）, and ventral intermediate thalamic nucleus. Study Selection： We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs： Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups： those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results： In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS： The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions： As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.
基金This study was supported by National Natural Science Foundation of China （No. 30770595） and Key Scientific and Technological Project in Heilongjiang Province （No. GB06C40302）.
文摘Background The subthalamic nucleus （STN） is widely recognized as one of the most important and commonly targeted nuclei in stereotactic and functional neurosurgery. The success of STN surgery depends on accuracy in target determination. Construction of a digitaiized atlas of STN based on stereotactic MRI will play an instrumental role in the accuracy of anatomical localization. The aim of this study was to investigate the three-dimensional （3D） target location of STN in stereotactic space and construct a digitalized atlas of STN to accomplish the visualization of the STN on stereotactic MRI, thus providing clinical guidance on the precise anatomical localization of STN. Methods One hundred and twenty healthy people volunteered to be scanned by 1.5 Tesla MRI scanning with 1-mm-thick slice in the standard stereotactic space between 2005 and 2006. One adult male was selected for 3D reconstruction of STN. The process of 3D reconstruction included identification, manual segmentation, extraction, conservation and reconstruction. Results There was a significant correlation between the coordinates and age （P 〈0.05）. The volume of left STN was significantly larger than the right STN, and there was a significant negative correlation between volume and age （P 〈0.05） The surface of the STN nucleus after 3D reconstruction appeared smooth, natural and realistic. The morphological feature of STN on the individual brain could be visualized directly in 3D. The 3D reconstructed STN could be rotated, zoomed and displayed at any direction in the stereotactic space. The anteroposterior diameter of the STN nucleus was longer than the vertical and transverse diameters in 3D space. The 3D reconstruction of STN manifested typical structure of the ＂dual lens＂. Conclusions The visualization of individual brain atlas based on stereotactic MRI is feasible. However, software for automated segmentation, extraction and registration of MR images need to be further developed.
基金Supported by"Centre National de la Recherche Scientifique"and the"conseil Régional d’Aquitaine"
文摘Depression is a frequent comorbid syndrome in Parkinson's disease. It is a difficult symptom to manage, as patients continuously receive antiparkinsonian medication and may also have to be treated for the amelioration of the side-effects of antiparkinsonian therapy. The first-line treatment for depression in Parkinson's disease is the use of selective serotonin reuptake inhibitors(SSRIs). The clinical efficacy of these medications in patients with Parkinson's disease is questionable. In fact, based on their mechanism of action, which requires at least a functional serotonergic system, it is predicted that SSRIs will have lower efficacy in patients with Parkinson's disease. Here, we consider the mechanism of action of SSRIs in the context of Parkinson's disease by investigating the fall in the levels of serotonergic markers and the inhibitory outcomes of antiparkinsonian treatment on serotonergic nerve activity. Because certain classes of antidepressant drugs are widely available, it is necessary to perform translational research to address different strategies used to manage depression in Parkinson's disease.
基金supported by the foundation of Science and Technology Commission of Shanghai Municipality,No.101195400
文摘In this study, 23 asymmetrical Parkinson＇s disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson＇s disease patients presenting no severe axial symptoms and dyskinesias.
基金funded by the National Natural Science Foundation of China(Nos.L2224042,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the Frontier Interdisciplinary Project of the Chinese Academy of Sciences(No.XK2022XXC003)+2 种基金the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of he Chinese Academy of Sciences(No.GJJSTD20210004).
文摘The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.
基金support by the National Nature Science Foundation of China,Nos.81830033,61761166004(both to JGZ)。
文摘There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for op
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30770746）.Acknowledgements： We thank Dr. QIAO Liang for reviewing and revising the manuscript.
文摘Background Subthalamic deep brain stimulation （STN-DBS） has been shown to be effective in the treatment of Parkinson＇s disease. The site for permanent stimulation is still in debate. This study aimed to assess the position of active contacts in relation to the subthalamic nucleus. Methods We reviewed the location of 40 electrodes in 34 patients who underwent STN-DBS. The position of electrode was evaluated by postoperative magnetic resonance imaging （MRI）. The position of active contacts was compared with the subthalamic nucleus （STN） determined by intraoperative electrophysiological mapping and postoperative MRI. Results The average position of the 40 active contacts was （11.7±1.2） mm lateral, （0.6±1.3） mm anterior, and （0.7±1.4） mm vertical to the midcommissural point. The dorsal margin of the STN was （11.6±1.1） mm lateral, （0.2±1.1） mm anterior, and （1.3±1.1） mm vertical to the midcommissural point. When compared with the dorsal margin of the STN, the active contacts were located more dorsally （P=0.033） and anteriorly （P=-0.012）, no significant difference was found in the lateral direction （P=0.107）. When compared with the position of the STN, 26 （65%） of active contacts were located in the region dorsal to the STN, only 13 （32.5%） were located in the upper two-thirds portion of STN. Conclusions The site for permanent stimulation appears to be in the subthalamic region dorsal to the STN, close to the dorsal margin of the STN. Besides the dorsal portion of the STN, other structures such as fields of Forel H and zona incerta may also be involved in the therapeutic benefit of deep brain stimulation.
基金the National Natural Science Foundation of China(81701100,81870891,and 81971038)the Fund for Jiangsu Province Specially-Appointed Professor(2016 and 2018)+3 种基金the Natural Science Foundation of Jiangsu Province,China(BK20171160)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(17KJA320007 and 18KJA320009)the Jiangsu Province Fund for Dominant Discipline(Anesthesiology)Academic Startup Packages from Xuzhou Medical University,China(D2017009 and D2017010)。
文摘Deep brain stimulation of the subthalamic nucleus(STN)is an effective therapy for motor deficits in Parkinson’s disease(PD),but commonly causes weight gain in late-phase PD patients probably by increasing feeding motivation.It is unclear how STN neurons represent and modulate feeding behavior in different internal states.In the present study,we found that feeding caused a robust activation of STN neurons in mice(GCaMP6 signal increased by 48.4%±7.2%,n=9,P=0.0003),and the extent varied with the size,valence,and palatability of food,but not with the repetition of feeding.Interestingly,energy deprivation increased the spontaneous firing rate(8.5±1.5 Hz,n=17,versus 4.7±0.7 Hz,n=18,P=0.03)and the depolarization-induced spikes in STN neurons,as well as enhanced the STN responses to feeding.Optogenetic experiments revealed that stimulation and inhibition of STN neurons respectively reduced(by 11%±6%,n=6,P=0.02)and enhanced(by 36%±15%,n=7,P=0.03)food intake only in the dark phase.In conclusion,our results support the hypothesis that STN neurons are activated by feeding behavior,depending on energy homeostatic status and the palatability of food,and modulation of these neurons is sufficient to regulate food intake.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81271518).
文摘Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(No.81371256,81171061,81361128012)Ministry of Education of Republic of China(BIBD-PXM2013-014226-07-000084)Seed Grant of International Alliance of Translational Neuroscience(PXM2014-014226-000015).
文摘Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is mo
基金Natural Science Foundation of Hainan Province (No.821RC682)。
文摘Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.
基金Supported by: the National Natural Science Foundation of China, No, 30471776
文摘BACKGROUND： Although experimental studies have utilized high-frequency stimulation in animal models, few reports have focused on long-term subthalamic nucleus deep brain stimulation （STN DBS） in Parkinson＇s disease （PD） animal models. OBJECTIVE： The present study simulated long-term DBS system and utilized microdialysis technology to study the influence of STN DBS on levels of extracellular dopamine （DA） and its metabolites, homovanillic acid （HVA） and dihydroxy phenyl acetic acid, in the corpus striatum of a hemiparkinsonian monkey model. DESIGN, TIME AND SETTING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. MATERIALS： 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindinewas （MPTP） purchased from Sigma, USA. Type-3389 DBS electrode and type-7246 pulse generator were provided by Medtronic, USA. METHODS： Hemiparkinsonism was induced in 2 male, adult Rhesus Macaque monkeys through unilateral internal carotid artery infusion of MPTP. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5 2.0 V pressure） was performed. MAIN OUTCOME MEASURES： Prior to, and 2 hours, 8 hours, 1 week, 1 month, and 2 months after DBS, samples were collected from the caudate nucleus and putamen using microdialysis technology Extracellular levels of DA and its metabolites were measured using high-performance liquid chromatography and electrochemical detection （HPLC-ECD） methods. RESULTS： At 8 hours, 1 week, 1 month, and 2 months after DBS, DA levels in the putamen and caudate nucleus were increased on the electrode-implanted side by 39%, 91%, 111%, and 114% and 31%, 91%, 106%, and 102%, respectively. The DA turnover rate （HVA/DA） was increased in the putamen and caudate nucleus by 186% and 91%, respectively, at 8 hours after DBS, while there wa
文摘Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad- vanced Parkinson＇s disease. Subthalamic nucleus deep brain stimulation can dramatically improve the motor symptoms of carefully selected patients with this disease. Surprisingly, some specific dimensions of quality of life, ＂psychological＂ aspects and social adjustment do not always improve, and they could sometimes be even worse. Patients and their families should fully understand that subthalamic nucleus deep brain stimulation can alter the motor status and time is needed to readapt to their new postoperative state and lifestyles. This paper reviews the literatures regarding effects of bilateral subthalamic nucleus deep brain stimulation on social adjustment, quality of life and coping strategies in patients with Parkinson＇s disease. The findings may help to understand the psychoso-cial maladjustment and poor improvement in quality of life in some Parkinson＇s disease patients.
基金This work was supported partly by the Beijing Health System Advanced Health Technology Talent Cultivation Plan, China （No. 2011-3-032） and the National Natural Science Foundation of China （No. 81071224）.
文摘Essential tremor （ET）, characterized by a postural and/or kinetic tremor and primarily manifested in theupper extremities, head, and other parts of the body, is one of the most common neurological disorders.1 The traditional target for the neurosurgical treatment of ET, the ventral intermedius nucleus （Vim） of the thalamus, has confirmed that chronic deep brain stimulation （DBS1 is an effective, standard, and primary procedure for ET. However, the loss of tremor suppression due to tolerance of chronic Vim stimulation, accompanied by other adverse effects, such as paresthesias, dysarthria, dysequilibrium, hyperhidrosis, and localized pain, has necessitated changes in the stimulation target in some patients.
