Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

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.

Voltage and Current Mode Vector Analyses of Correction Procedure Application to Clarke’s Matrix—Symmetrical Three-Phase Cases

Clarke’s matrix has been applied as a phase-mode transformation matrix to three-phase transmission lines substituting the eigenvector matrices. Considering symmetrical untransposed three-phase lines, an actual symmetrical three-phase line on untransposed conditions is associated with Clarke’s matrix for error and frequency scan analyses in this paper. Error analyses are calculated for the eigenvalue diagonal elements obtained from Clarke’s matrix. The eigenvalue off-diagonal elements from the Clarke’s matrix application are compared to the correspondent exact eigenvalues. Based on the characteristic impedance and propagation function values, the frequency scan analyses show that there are great differences between the Clarke’s matrix results and the exact ones, considering frequency values from 10 kHz to 1 MHz. A correction procedure is applied obtaining two new transformation matrices. These matrices lead to good approximated results when compared to the exact ones. With the correction procedure applied to Clarke’s matrix, the relative values of the eigenvalue matrix off-diagonal element obtained from Clarke’s matrix are decreased while the frequency scan results are improved. The steps of correction procedure application are detailed, investigating the influence of each step on the obtained two new phase-mode transformation matrices.

基于S3C2510和Nucleus的网络接口与驱动设计

本文介绍嵌入式微处理器S3C2510的网络接口,并使用RTL8201芯片为之设计了硬件接口电路;设计实现了基于Nu-cleus操作系统的驱动程序,完成以太网控制器的初始化设置、收/发中断例程和利用缓冲链表数据结构向TCP/IP协议层交换数据。运行实测表明接口工作性能稳定可靠,满足网络流媒体数据处理的要求。

嵌入式实时操作系统Nucleus PLUS在S3C2410A上移植的实现

本文在简要介绍嵌入式实时操作系统内核Nucleus PLUS和基于ARM920T内核的嵌入式微控制器S3C2410A后,详细地论述了Nucleus PLUS在S3C2410A上的移植过程和方法,最后指出了Nucleus PLUS在ARM9上移植的重点和难点。

Five-year follow-up of 23 asymmetrical Parkinson's disease patients treated with unilateral subthalamic nucleus stimulation

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.

Distribution of serotonin 5-HT_(2A) and 5-HT_7 receptors in the Onuf’s nucleus of the rat spinal cord

BACKGROUND：Motoneurons from the Onuf’s nucleus of the spinal cord, which innervate the striated muscle of the pelvic floor, play an important role in erection, ejaculation, and urine control. Serotonin （5-hydroxytryptamine, 5-HT） regulates motoneuron activity from the Onuf’s nucleus of the spinal cord. However, few studies exist that describe 5-HT receptor distribution in the Onuf’s nucleus. In addition, the nature of the effects of 5-HT receptor on the innervating striated muscle of the pelvic floor is controversial. OBJECTIVE： To investigate the distribution of serotonin 5-HT2A and 5-HT7 receptors in motoneurons of Onuf’s nucleus in the spinal cord of male rats, and to analyze the relationship of 5-HT2A and 5-HT7 receptor to central modulation of urogenital function. DESIGN, TIME AND SETTING： The neural morphology experiment was performed at the Ultramicro-structure Laboratory of Reproductive Medicine, Basic Medical College, Chongqing Medical University, China from April to December 2007. MATERIALS： Ten adult, Sprague Dawley rats （eight males and two females） were randomly divided into gender control group （n = 4, 50% male and 50% female） and a retrograde tracing group （n = 6, 100% male） Recombinant pseudorabies virus （PRV-152） was provided by Professor LW Enquist from Princeton University, USA. Rabbit anti-5-HT2A and 5-HT7 receptor antibodies were purchased from Diasorin, France. METHODS： In the gender control group, the spinal L5-6 segments were harvested, sliced, and then incubate antibodies specific against 5-HT2A or 5-HT7 receptors for immunohistochemical staining. In the retrograde tracing group, PRV-152 was separately injected into the right ischiocavernosus （ischiocavernosus subgroup, n = 3） and the right external urethral sphincter （external urethral sphincter subgroup, n = 3）. Four days after injection, L5-6 segments were harvested, sliced, and incubated with antibodies specific against 5-HT2A or 5-HT7 receptors for double-labeling immunofluorescence staining. MAIN OUTCOME MEASURES： Distribution analysis of 5-HT2A and 5-HT7 receptors in Onuf’s nucleus utilizing optical or laser confocal microscopy. RESULTS： 5-HT2A receptor immunoreactivity was revealed primarily in the medial region of the dorsolateral nucleus of Onuf’s nucleus. 5-HT7 receptor expression was observed in the lateral part of the dorso-lateral nucleus. 5-HT2A and 5-HT7 receptor expressions in the Onuf’s nucleus were significantly greater in male rats, compared to female rats. Double-labeling immunofluorescence demonstrated that 5-HT2A recepto were distributed primarily in the surrounding motoneurons innervating the ischiocavernosus, and 5-HT7 receptors were primarily expressed in motoneurons innervating the external urethral sphincter. CONCLUSION： Motoneurons innervating the ischiocavernosus and external urethral sphincter are located primarily in the medial and lateral region of the dorsolateral nucleus of L5-6 segments. The 5-HT2A receptor-innervating ischiocavernosus may be preferentially involved in the regulation of sexual reflex, and the 5-HT7 receptor-innervating external urethral sphincter may mainly join in regulating micturition reflex.

Chronic deep brain stimulation of the subthalamic nucleus in a monkey model of hemiparkinsonian Dynamic alterations of extracellular fluid dopamine levels in corpus striatum

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.

Five-Year Outcomes of Bilateral Subthalamic Nucleus Stimulation in Japanese Patients with Parkinson’s Disease

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.

Cholinergic input from the pedunculopontine nucleus to the cerebellum: implications for deep brain stimulation in Parkinson's disease

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.

External anal sphincter electromyography in multiple system atrophy:implications for diagnosis,clinical correlations,and novel insights into prognosis

Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.

Involvement of GABAergic pathway on inhibition of subthalamic nucleus high-frequency stimulation of spontaneous firing activity in substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

BACKGROUND： Subthalamic nucleus-high frequency stimulation （STN-HFS） plays an important role in the treatment of Parkinson＇s disease, but the mechanisms underlying STN-HFS remain unclear. Some studies have demonstrated that STN stimulation inhibits the firing activity of substantia nigra pars reticulata neurons. OBJECTIVE： To investigate the effects of different-frequency STN stimulation and microiontophoresis of gamma-aminobutyric acid （GABA） and its antagonist, bicuculline, on spontaneous firing activity in a rat model of Parkinson＇s disease, and to analyze the action pathway of high frequency stimulation in firing activity inhibition of substantia nigra pars reticulata neurons. DESIGN, TIME AND SETTING： This neuroelectrophysiological, animal experiment was performed at the Electrophysiology Laboratory of Liaoning Medical University, China from March to August 2008. MATERIALS： 6-hydroxydopamine （6-OHDA） （Sigma, USA）, A320R isolated stimulus and DAM80 preamplifier （World Precision Instruments, USA）, 6400A microiontophoresis apparatus （Dagan, USA）, and Spike 2 biological signal acquisition system （CED, UK） were used in this study. METHODS： A total of 20 Sprague Dawley rats were used to establish a Parkinson＇s disease model via injection of 6-OHDA into the right striatum. Electrical stimulation （0.06-ms width, 0.4-mA intensity 20-200-Hz frequency, 5-second train duration） was delivered to the subthalamic nucleus. Peripheral channels were separately filled with GABA （pH 3.5, 0.2 mol/L）, bicuculline （pH 4.0, 0.01 mol/L）, and NaCI （pH 7.0, 3 mol/L）. The electrode was positioned with a WK-2 microelectrode propulsion device, and was slowly inserted into the substantia nigra pars reticulata to record spontaneous firing activity of substantia nigra pars reticulata neurons. MAIN OUTCOME MEASURES： The number and firing rate of substantia nigra pars reticulata neurons which were either inhibited or excited were measured. RESULTS： Substantia nigra pars reticulata neurons were inhibited by STN stimulation. The proportion of inhibited substantia nigra pars reticulata neurons increased with increasing stimulation frequency. GABA had a tonic inhibitory effect on substantia nigra pars reticulata neurons. Microiontophoresis of bicuculline suppressed the inhibitory effect of STN-HFS on 67% （4/6） of substantia nigra pars reticulata neurons. CONCLUSION： STN-HFS ameliorated abnormal activity in substantia nigra pars reticulata neurons via the inhibitory effect of GABA treatment in a rat model of Parkinson＇s disease.

Deep brain stimulation of the subthalamic nucleus treats Parkinson's disease through enhancing metabolic activity of the corpus striatum Verification by single photon emission computed tomography and positron emission tomography

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.

Factors affecting early decline of executive function after subthalamic nucleus stimulation in Parkinson’s disease

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.

High-frequency Stimulation of Subthalamic Nucleus for Treatment of Parkinson's Disease

Degeneration and death of the neurons of the substantia nigra can cause a deficit in brain dopamine, leading to loss of movement control The subthalamic nucleus is a junction of basal ganglia neural circuit and can regulate the efferent information of basal ganglia and control motor activity. High-frequency stimulation of the subthalamic nucleus can alter dopamine levels as well as related factor expression in the corpus striatum and thereby improve the symptoms of Parkinson＇s disease.

Multiplicity of Solutions for a Class of Noncooperative Elliptic Systems

In this paper, we consider the following noncooperative elliptic systems where Ω is a bounded domain in RN with smooth boundary ∂Ω, λ,δ,γ are real parameters, and . We assume that F is subquadratic at zero with respect to the variables u,v. By using a variant Clark’s theorem, we obtain infinitely many nontrivial solutions (uk,vk) with as k → ∞. Compared with the existing literature, we do not need to assume the behavior of the nonlinearity ∇F at infinity.

Charke’s串联排队系统

本文主要是通过运用马尔可夫骨架过程来研究Charke's串联排队系统,并得到了其瞬时状态分布.

The treatment of Parkinson's disease with deep brain stimulation: current issues

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.

关于局部Lipschitz泛函的一个临界点存在定理

设X是Banach空间 ,C是X的闭子集。本文利用Ekeland变分原理的推广形式 ,研究X上的局部Lipschitz泛函在C中的临界点的存在性问题 。

Neurosurgery in Parkinson's disease:Social adjustment, quality of life and coping strategies

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.

Voltage adjustment improves rigidity and tremor in Parkinson's disease patients receiving deep brain stimulation

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）.