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 optimal therapeutic efficacy in Parkinson’s disease.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： Subthalamic nucleus deep brain stimulation （STN DBS） for Parkinson＇s disease （PD） has achieved good effects, but to date the mechanism of STN DBS remains poorly understood STN DBS may increase dopami...BACKGROUND： Subthalamic nucleus deep brain stimulation （STN DBS） for Parkinson＇s disease （PD） has achieved good effects, but to date the mechanism of STN DBS remains poorly understood STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE： To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography （SPECT） and position emission tomography （PET）. DESIGN, TIME AND SET＇rING： 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. METHODS： Hemiparkinsonism was induced in adult Rhesus Macaque monkeys, which exhibit similar characteristics of PD in humans, through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine. 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： The changes in dopamine transporter （DAT）, D2 receptor （D2R）, and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS： SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation, and D2R specific binding in the right corpus striatum gradually decreased near levels on the left （non-electrode-implanted） side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity, increased activities, and stable gait under chronic high-frequency stimulation. CONCLUSION： STN DBS increased striatal DAT, decreased D2R, and enhanced glucose metabolism, suggesting that chronic, high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum, a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.展开更多
Deep brain stimulation（DBS）is a well established electrophysiological treatment initially applied to treat medication-refractory motor symptoms in Parkinson＇s disease（PD）,and is now being explored for several neu...Deep brain stimulation（DBS）is a well established electrophysiological treatment initially applied to treat medication-refractory motor symptoms in Parkinson＇s disease（PD）,and is now being explored for several neurological and psychiatric disorders.The specific physiological mechanisms underlying the effectiveness of DBS are not fully understood.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
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
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 was no significant difference at 1 week, 1 month, and 2 months after DBS. CONCLUSION： Effective, chronic, high frequency DBS increased extracellular DA levels in the corpus striatum, which could be one of mechanisms involved in the effects of STN DBS.展开更多
Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining th...Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is consid- ered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson＇s disease （four men and two women, aged 37-65 years）, who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson＇s Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 ps and frequency at 130 Hz. Voltage adjust- ment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov （identifier： NCT01934881）.展开更多
Deep brain stimulation (DBS) has become an effective therapeutic option for neurological and psychiatric disorders such as Parkinson’s disease (PD), dystonia, and obsessive-compulsive disorder. The subthalamic nucleu...Deep brain stimulation (DBS) has become an effective therapeutic option for neurological and psychiatric disorders such as Parkinson’s disease (PD), dystonia, and obsessive-compulsive disorder. The subthalamic nucleus (STN) and internal globus pallidus (GPi) are by far the most commonly used targets for DBS in the treatment of PD. However, STN/GPi stimulation sometimes causes side effects, including motor fluctuations, cognitive declines, and worse emotional experience, which affect patients’ postoperative quality of life. Recent invasive electrophysiological studies are driven by the desire to better understand the mechanisms of therapeutic actions and side effects of STN/GPi stimulation. These studies investigated the function of the STN and GPi in motor, cognitive and affective processes by recording single- neuron firing patterns during the surgery or local field potentials after the surgery. Here we review the relevant studies to provide an integrative picture of the functional roles of the STN and GPi within the basal ganglia loops for motor, cognition, and emotion. Previous studies suggested that STN and GPi gamma oscillations encode the strength and speed of voluntary movements (execution), whereas beta oscillations reflect the effort and demand of potential movements (preparation). In the cognitive domain, oscillatory beta activity in the STN is involved when people have to stop an inappropriate action or to suppress salient but task-irrelevant information, whereas theta/delta activity is associated with the adjustment of decision thresholds and cost-benefit trade-off. In the affective domain, STN activity in the alpha band may represent the valence and arousal of emotional information.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS...Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.展开更多
BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state,...BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; （5） control （n = 10）, pentylenetetrazol administration, but no electrode was implanted; （6） blank control （n = 50）, administration of the same amount of physiological saline and chaotic electrical stimulation. MAIN OUTCOME MEASURES： Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours. RESULTS： Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats （P 〈 0.01）. Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups （P 〈 0.01）. Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades Ⅰ and Ⅳ epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group （P 〈 0.01）. CONCLUSION： Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.展开更多
Subthalamic nucleus deep brain stimulation (STN DBS) is an effective treatment for medically refractory Parkinson’s disease (PD). However, a minority of patients develop cognitive problems, particularly a decline of ...Subthalamic nucleus deep brain stimulation (STN DBS) is an effective treatment for medically refractory Parkinson’s disease (PD). However, a minority of patients develop cognitive problems, particularly a decline of executive function in the early period after STN DBS. Although this problem is usually transient, it may cause social maladjustment. We investigated factors affecting early decline of executive function after STN-DBS. Fifty-seven patients whose preoperative global cognitive screening was normal (MMSE score;28 or more) were enrolled in this study. Executive function was evaluated with the Trail-Making Test (TMT) preoperatively and 1-month after surgery. We considered a patient to have decline in executive function if the TMT (B-A) was prolonged more than 30 seconds after STN DBS. Among 57 patients, 25 patients were categorized as having decline of executive function. Univariate analysis revealed that high preoperative UPDRS III motor score in the medication-off period and a depressive state evaluated with BDI-II correlated significantly with decline in executive function. Multiple logistic regression analysis revealed that the only significant independent variable related to early decline of executive function was the preoperative BDI-II score. Postoperative factors such as active contact location or dopaminergic medication reduction had no relation with the decline of executive function. Even in cognitively well-selected patients, STN DBS causes early decline in executive function in a significant number of patients. Preoperative simple cognitive screening alone could not predict early decline in executive function. More detailed neuropsychological evaluation, including mood status, should be undertaken before surgery.展开更多
Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradu...Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day,mainstream scientific deep brain stimulation(DBS).We focus on the rise,fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy,which evoked stern criticism from both public and professionals,through to the development of modern day DBS-performed for patients suffering from severe,treatment resistant symptoms of obsessive-compulsive disorder(OCD),epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities,whilst simultaneously challenging any public/professional preconceptions of psychosurgery,which may indirectly be obstructing patient care.Additionally,we carried out a qualitative survey displayed in WordCloud Format,capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust,on“psychosurgery”,“prefrontal lobotomy”and“DBS”,which may well reflect wider public opinion.In summary,the article provides a brief,yet comprehensive overview of the controversial history of psychosurgery,present-day practice,and future trends of neurosurgery for psychiatric disorders.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
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
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 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
Background:Subthalamic nucleus deep brain stimulation(STN-DBS)is an effective treatment for Parkinson’s disease(PD),the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies,...Background:Subthalamic nucleus deep brain stimulation(STN-DBS)is an effective treatment for Parkinson’s disease(PD),the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies,however there were different conclusions about that through long-and short-term follow-ups.We aimed to investigate the factors which influence the predictive value of levodopa responsiveness,and discover more predictive factors of surgical outcomes.Methods:Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up.Clinical evaluations were performed 1 week before and 3 months after surgery.Results:STN-DBS significantly improved motor function of PD patients after 3 months;preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function;gender,disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement;the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement.Conclusions:The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients,patients with shorter disease duration or shorter motor fluctuations;PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms,especially in their later disease stage.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
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 optimal therapeutic efficacy in Parkinson’s disease.
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the National Natural Science Foundation of China,No.30471776
文摘BACKGROUND： Subthalamic nucleus deep brain stimulation （STN DBS） for Parkinson＇s disease （PD） has achieved good effects, but to date the mechanism of STN DBS remains poorly understood STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE： To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography （SPECT） and position emission tomography （PET）. DESIGN, TIME AND SET＇rING： 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. METHODS： Hemiparkinsonism was induced in adult Rhesus Macaque monkeys, which exhibit similar characteristics of PD in humans, through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine. 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： The changes in dopamine transporter （DAT）, D2 receptor （D2R）, and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS： SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation, and D2R specific binding in the right corpus striatum gradually decreased near levels on the left （non-electrode-implanted） side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity, increased activities, and stable gait under chronic high-frequency stimulation. CONCLUSION： STN DBS increased striatal DAT, decreased D2R, and enhanced glucose metabolism, suggesting that chronic, high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum, a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.
文摘Deep brain stimulation（DBS）is a well established electrophysiological treatment initially applied to treat medication-refractory motor symptoms in Parkinson＇s disease（PD）,and is now being explored for several neurological and psychiatric disorders.The specific physiological mechanisms underlying the effectiveness of DBS are not fully understood.
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.
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 was no significant difference at 1 week, 1 month, and 2 months after DBS. CONCLUSION： Effective, chronic, high frequency DBS increased extracellular DA levels in the corpus striatum, which could be one of mechanisms involved in the effects of STN DBS.
基金supported by the Science and Technology Foundation of Guangdong Province of China,No.2014A030304019the Natural Science Foundation of Guangdong Province of China,No.2015A030313164
文摘Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is consid- ered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson＇s disease （four men and two women, aged 37-65 years）, who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson＇s Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 ps and frequency at 130 Hz. Voltage adjust- ment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov （identifier： NCT01934881）.
基金the Thousand Young Talents Program (to Z.Y.)National Natural Science Foundation of China (31771216, to Z.Y.).
文摘Deep brain stimulation (DBS) has become an effective therapeutic option for neurological and psychiatric disorders such as Parkinson’s disease (PD), dystonia, and obsessive-compulsive disorder. The subthalamic nucleus (STN) and internal globus pallidus (GPi) are by far the most commonly used targets for DBS in the treatment of PD. However, STN/GPi stimulation sometimes causes side effects, including motor fluctuations, cognitive declines, and worse emotional experience, which affect patients’ postoperative quality of life. Recent invasive electrophysiological studies are driven by the desire to better understand the mechanisms of therapeutic actions and side effects of STN/GPi stimulation. These studies investigated the function of the STN and GPi in motor, cognitive and affective processes by recording single- neuron firing patterns during the surgery or local field potentials after the surgery. Here we review the relevant studies to provide an integrative picture of the functional roles of the STN and GPi within the basal ganglia loops for motor, cognition, and emotion. Previous studies suggested that STN and GPi gamma oscillations encode the strength and speed of voluntary movements (execution), whereas beta oscillations reflect the effort and demand of potential movements (preparation). In the cognitive domain, oscillatory beta activity in the STN is involved when people have to stop an inappropriate action or to suppress salient but task-irrelevant information, whereas theta/delta activity is associated with the adjustment of decision thresholds and cost-benefit trade-off. In the affective domain, STN activity in the alpha band may represent the valence and arousal of emotional information.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
文摘Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.
基金Research and Development Foundation of Fujian Medical University, No. FJGXY04041
文摘BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; （5） control （n = 10）, pentylenetetrazol administration, but no electrode was implanted; （6） blank control （n = 50）, administration of the same amount of physiological saline and chaotic electrical stimulation. MAIN OUTCOME MEASURES： Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours. RESULTS： Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats （P 〈 0.01）. Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups （P 〈 0.01）. Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades Ⅰ and Ⅳ epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group （P 〈 0.01）. CONCLUSION： Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.
文摘Subthalamic nucleus deep brain stimulation (STN DBS) is an effective treatment for medically refractory Parkinson’s disease (PD). However, a minority of patients develop cognitive problems, particularly a decline of executive function in the early period after STN DBS. Although this problem is usually transient, it may cause social maladjustment. We investigated factors affecting early decline of executive function after STN-DBS. Fifty-seven patients whose preoperative global cognitive screening was normal (MMSE score;28 or more) were enrolled in this study. Executive function was evaluated with the Trail-Making Test (TMT) preoperatively and 1-month after surgery. We considered a patient to have decline in executive function if the TMT (B-A) was prolonged more than 30 seconds after STN DBS. Among 57 patients, 25 patients were categorized as having decline of executive function. Univariate analysis revealed that high preoperative UPDRS III motor score in the medication-off period and a depressive state evaluated with BDI-II correlated significantly with decline in executive function. Multiple logistic regression analysis revealed that the only significant independent variable related to early decline of executive function was the preoperative BDI-II score. Postoperative factors such as active contact location or dopaminergic medication reduction had no relation with the decline of executive function. Even in cognitively well-selected patients, STN DBS causes early decline in executive function in a significant number of patients. Preoperative simple cognitive screening alone could not predict early decline in executive function. More detailed neuropsychological evaluation, including mood status, should be undertaken before surgery.
文摘Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day,mainstream scientific deep brain stimulation(DBS).We focus on the rise,fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy,which evoked stern criticism from both public and professionals,through to the development of modern day DBS-performed for patients suffering from severe,treatment resistant symptoms of obsessive-compulsive disorder(OCD),epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities,whilst simultaneously challenging any public/professional preconceptions of psychosurgery,which may indirectly be obstructing patient care.Additionally,we carried out a qualitative survey displayed in WordCloud Format,capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust,on“psychosurgery”,“prefrontal lobotomy”and“DBS”,which may well reflect wider public opinion.In summary,the article provides a brief,yet comprehensive overview of the controversial history of psychosurgery,present-day practice,and future trends of neurosurgery for psychiatric disorders.
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 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This study was funded by the National Nature Science Foundation of China(grant.no.81371421).
文摘Background:Subthalamic nucleus deep brain stimulation(STN-DBS)is an effective treatment for Parkinson’s disease(PD),the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies,however there were different conclusions about that through long-and short-term follow-ups.We aimed to investigate the factors which influence the predictive value of levodopa responsiveness,and discover more predictive factors of surgical outcomes.Methods:Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up.Clinical evaluations were performed 1 week before and 3 months after surgery.Results:STN-DBS significantly improved motor function of PD patients after 3 months;preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function;gender,disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement;the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement.Conclusions:The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients,patients with shorter disease duration or shorter motor fluctuations;PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms,especially in their later disease stage.
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.
