Effects of various frequency electrical stimulation of the dorsal raphe nucleus on spontaneous firing activities in the rat subthalamic nucleus★

BACKGROUND： Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus （STN） neurons in the rat brain. OBJECTIVE： To validate the effect of electrical stimulation to the dorsal raphe nucleus （DRN） on the neuronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies. DESIGN, TIME AND SETTING： Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design. MATERIALS： Twenty-four healthy male Sprague-Dawley （SD） rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Company （USA）; a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS： Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinson＇s disease, rats in the model group were injected with 4μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group received deep brain stimulation in same brain region without modeling. Electrical stimulation （width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds） was delivered to the DRN. MAIN OUTCOME MEASURES： The firing rates of STN neurons were observed by extracellular recording using a biological signal acquisition system. RESULTS： DRN-high-frequency stimulation （DRN-HFS） induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from （7.14±0.75） and （7.94 ± 0.61） Hz to （11.17 ±1.49） and （12.11 ± 1.05） Hz, respectively （P 〈 0.01）. Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dep     

Influence of deep brain stimulation of the subthalamic nucleus on cognitive function in patients with Parkinson＇s disease

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.     

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson’s disease

Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinsons disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in off UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a lesion-like effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.     

Quadruple deep brain stimulation in Huntington’s disease,targeting pallidum and subthalamic nucleus: case report and review of the literature

Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington’s disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55–66 % at 1–4 years, respectively, compared to presurgical state following GPi–STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi–STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect–adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi–STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option.     

Effect of Ganoderma lucidum spore on expression of insulin-like growth factor-1, nuclear factor-kappa B, and neuronal apoptosis in the epileptic rat brain*★

BACKGROUND：It has been reported that Ganoderma lucidum spore powder, a very well known Chinese traditional medicine, can affect immunoregulation, free radical scavenging, and anti-hypoxia responses. OBJECTIVE： To investigate the effect of Ganoderma lucidum spore powder on expression of insulin-like growth factor-1 （IGF-1）, nuclear factor-κB （NF-κB） and neuronal apoptosis in rats with pentylenetetrazol （PTZ）-induced epilepsy. DESIGN, TIME AND SETTING： A cellular and molecular biology experiment with randomized controlled study design was performed at the Central Laboratory of Basic Medical College of Jiamusi University from June to August 2005. MATERIALS： Thirty healthy, adult, male, Wistar rats were selected and randomly divided into 3 groups （10 rats per group）： control, epilepsy model, and Ganoderma lucidum spore powder. A sub-eclampsia PTZ dose （35 mg/kg） was intraperitoneally injected to induce epilepsy in the latter two groups. Wild Ganoderma lucidum spore powder （30 g/L） was provided by the wild Ganoderma lucidum plant nursery at Jiamusi, China. Immunohistochemical detection and terminal deoxynucleotidyl transferase-mediate dUTP nick end-labeling （TUNEL） kits were purchased from Wuhan Boster Biological Technology Co., Ltd., China. METHODS： Ganoderma lucidum spore powder was intragastrically administered at a dose of 10.0 mL/kg, once a day for 28 days. In the epilepsy and control groups, an equivalent volume of normal saline was intragastrically administered. MAIN OUTCOME MEASURES： Immunoreactivity for IGF-1 and NF-κB/P65 were detected by immunohistochemical staining. Neuronal apoptosis was detected using TUNEL methods. RESULTS： The hippocampus and cerebral cortex of rats with PTZ-induced epilepsy exhibited a higher number of apoptotic cells at high magnification （×400）, compared with the control group. Expression of IGF-1 and NF-κB were higher in the epilepsy group, compared with the control group （P 〈 0.01）. In Ganoderma lucidum spore-treated rats,     

Neuropsychological and psychiatric assessments following bilateral deep brain stimulation of the subthalamic nucleus in Japanese patients with Parkinson’s disease

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n = 13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at 1 and 6 months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the Verbal Fluency Test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p < 0.001) and HAM-A score (p = 0.004) showed significant improvement at 1 month post-surgery, but a significant decline was observed in the WCST total error (p = 0.005) and the semantic VFT score (p < 0.001). The phonetic VFT also showed a substantial decline (p = 0.015) at 1 month post-surgery. At 6 months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms.     

Changes in beta-endorphin neuron numbers and serum hormone levels in the arcuate nucleus of ovariectomized rats undergoing treadmill exercise★

BACKGROUND： The arcuate nucleus, when damaged in young rats, can lead to pathological changes in adults, such as osteoporosis. Ovariectomized rats suffer from osteoporosis at eight weeks following surgery and the number of β -endorphin immunoreactive neurons in the arcuate nucleus of the hypothalamus is significantly decreased. OBJECTIVE： To establish a rat model of osteoporosis using ovariectomy and to explore changes in the number of β-endorphin neurons and to correlate any such change with serum hormone levels in response to exercise or rest. DESIGN, TIME AND SETTING： The completely randomized block design, neural morphology study was performed at the Key Laboratory of Physiology, Guangdong Medical College, China between March 2004 and January 2005. MATERIALS： Sixteen healthy female rats were selected for ovariectomy. METHODS： Following model establishment, rats were assigned to either rest or exercise groups and each rat was housed individually. Rats in the exercise group underwent an exercise regimen using a treadmill. MAIN OUTCOME MEASURES： Eight weeks following exercise, radioimmunoassay was performed to detect serum growth hormone, estrogen and osteocalcin levels. Immunohistochemistry was used to measure changes in the number of β -endorphin neurons in the arcuate nucleus of the hypothalamus. Changes in bone metabolism were assessed using bone histomorphometry. RESULTS： In the exercise group, the β -endorphin immunoreactive neurons were high in number, darkly stained, and the nucleus was not obvious. In the rest group, the β -endorphin immunoreactive neurons were low in number and lightly stained. The number of β-endorphin immunoreactive neurons in the exercise group was higher compared with the rest group （t = 2.83, P 〈 0.05）. Estrogen levels were similar between the rest and exercise groups （P 〉 0.05）. Serum osteocalcin and growth hormone levels were significantly higher in the exercise group compared with the rest group （t = 2.78, 2.32, P 〈 0.05）. Compared with the     

Chaotic electrical stimulation of the subthalamic nucleus-mossy fiber sprouting, epileptic seizures, and brain electrical activity in pentylenetetrazol-kindled rats

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 μ A, 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.     

Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease.

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow-up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN-DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN-DBS beyond the first year after surgical procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse events which, however, were temporary.     

丘脑底核电刺激术治疗帕金森病的疗效

目的评估丘脑底核脑深部电刺激(STN-DBS)对帕金森病的临床疗效。方法回顾性分析应用STN-DBS手术治疗的32例帕金森病病人的临床资料,在术前、术后3个月分别采用统一帕金森病评定量表(UPDRS)、抑郁自评量表(SDS)和症状自评量表(SCL-90)进行随访评估、心理状况问卷调查和分析。结果脉冲发生器开启后,32例病人的UPDRS日常活动和运动功能在"关"状态,平均改善率为51.7%和60.9%;在"开"状态下,平均改善率21.4%和22.3%。20例病人术前SDS评分50分,其SCL-90的抑郁、焦虑、躯体化、人际敏感、敌对、恐怖和偏执7个因子显著高于中国常模(P0.05)。术前与术后SCL-90抑郁、躯体化、恐怖、焦虑、精神病性因子有显著性差异(P0.05),人际敏感、偏执、敌对和强迫等因子无显著性差异(P0.05)。结论 STN-DBS可以改善帕金森病病人的运动功能,提高日常生活能力,还可以明显改善帕金森病伴抑郁病人的心理状况,是安全有效的治疗方法。     

帕金森病患者丘脑底核电极植入术中位置判断和调整

目的探讨帕金森病患者脑深部刺激术（DBS）中丘脑底核（STN）电极植入位置准确性判断和调整。方法对137例帕金森病（PD）患者进行了丘脑底核DBS治疗,其中单侧68例,双侧69例。采用磁共振扫描,图像直接定位和坐标值定位相结合的方法计算靶点坐标,微电极记录细胞外放电。术中采用微毁损效应,观察刺激效果和副作用,X线透视和带立体定向头架MRI复查。结果绝大部分患者都能观察到电极植入的微毁损效应、电刺激效果和刺激副作用,术中X线透视和带立体定向头架MRI复查能观察到电极实际位置,并进行必要的调整。结论通过微毁损效应、电刺激效果和刺激副作用观察以及术中影像学检查能及时纠正电极位置偏差,减少二次手术,从而提高PD患者的DBS疗效。     

丘脑底核脑深部刺激术的参数设置及调整

目的 探讨帕金森病（PD）丘脑底核（STN）脑深部刺激术（DBS）术中、术后脉冲发生器的参数调整。方法 回顾采用STN—DBS治疗的62例帕金森病病人的病历资料．对病人术中及术后刺激参数的调整进行分析。结果 32例行单侧手术者均接受单极刺激；30例行双侧手术病人中，接受双侧双极刺激25例，双侧单极刺激2例．一侧单极刺激、另一侧双极刺激3例。7例触点调整均为上移。统一帕金森病评定量表（UPDRS）运动评分改善率双侧刺激优于单侧刺激。本组刺激参数为：电压双极14V．单极1～3．5V；脉宽60-120μs；频率180～190HZ。结论 STN—DBS术后病人采用适当刺激参数可获得安全可靠的疗效。电压调整对PD症状控制作用明显。脉宽及频率的调整相对较少；双侧刺激效果更佳。     

双侧丘脑底核电刺激治疗原发性帕金森病

目的 探讨双侧丘脑底核(STN)电刺激(DBS)对原发性帕金森病(PD)的治疗效果及手术方式。方法 应用MRI扫描、手术计划系统及微电极导向技术进行靶点定位,对15例病人行双侧丘脑底核电极植入及锁骨下刺激器植入,术后1～2周打开刺激器,术后1个月到2年随访评价。结果 全部15例病人术后肢体僵直、震颤及运动迟缓等症状明显缓解,UPDRS运动评分和日常生活能力评分均有显著下降(P<0.01),左旋多巴服用量也有不同程度的减少,无严重或永久并发症发生。结论 双侧STN电刺激手术治疗原发性PD,可全面改善病人症状,尤其是中线症状的改善更为明显;可通过调节刺激参数达到最佳治疗效果并避免副反应的发生;病人服药量减少,是一种安全有效的治疗方法。     

丘脑底核脑深部电刺激对帕金森病焦虑状况的影响

目的探讨双侧丘脑底核脑深部电刺激(STN-DBS)对帕金森病人焦虑状况的影响。方法设置双侧STN-DBS组及左旋多巴类药物治疗组,配对入组,每组有效病例各31例。采用汉密尔顿焦虑量表(HAMA)、焦虑状态-特质问卷(STAI)、帕金森病生活质量39问卷(PDQ-39)及统一帕金森病评定量表第Ⅲ部分(UPDRS-Ⅲ)对病人进行评估分析。结果与术前及药物治疗组相比,STN-DBS组术后状态焦虑(S-AI)评分明显降低(均P<0.05)。STN-DBS组UPDRS-Ⅲ评分与S-AI评分在术后4个月内相关(均P<0.05),电压、脉宽与特质焦虑(T-AI)和HAMA评分均相关(均P<0.05);术后电压和脉宽对T-AI和HAMA评分的标准回归方程成立,回归系数均显著(均P<0.05)。结论 STN-DBS在改善帕金森病人运动障碍的同时,在短期内可改善即时焦虑情绪。在治疗范围内,STN-DBS电压和脉宽越高,帕金森病人的特质焦虑情绪和焦虑症状越严重。     

Predict initial subthalamic nucleus stimulation outcome in Parkinson's disease with brain morphology

AimSubthalamic nucleus deep brain stimulation (STN‐DBS) has been reported to be effective in treating motor symptoms in Parkinson''s disease (PD), which may be attributed to changes in the brain network. However, the association between brain morphology and initial STN‐DBS efficacy, as well as the performance of prediction using neuroimaging, has not been well illustrated. Therefore, we aim to investigate these issues.MethodsIn the present study, 94 PD patients underwent bilateral STN‐DBS, and the initial stimulation efficacy was evaluated. Brain morphology was examined by magnetic resonance imaging (MRI). The volume of tissue activated in the motor STN was measured with MRI and computed tomography. The prediction of stimulation efficacy was achieved with a support vector machine, using brain morphology and other features, after feature selection and hyperparameter optimization.ResultsA higher stimulation efficacy was correlated with a thicker right precentral cortex. No association with subcortical gray or white matter volumes was observed. These morphological features could estimate the individual stimulation response with an r value of 0.5678, an R ² of 0.3224, and an average error of 11.4%. The permutation test suggested these predictions were not based on chance.ConclusionOur results indicate that changes in morphology are associated with the initial stimulation motor response and could be used to predict individual initial stimulation‐related motor responses.     

丘脑底核脑深部电刺激对帕金森病术后药物治疗的影响(附40例分析)

目的 观察帕金森病（PD）病人丘脑底核脑深部电刺激（STN—DBS）术后药物变化情况。探讨STN—DBS对帕金森病术后药物治疗的影响。方法 对接受STN—DBS手术治疗的40例帕金森病病人手术前后的药物服用剂量、药物引起的相关并发症等情况进行回顾性分析。结果 本组经6～49个月随访。多数病人在STN-DBS作用下因症状明显改善，于开机后的1-6个月间使用抗PD药物逐渐减量。最终的选择剂量可维持2年以上。开机后5例不再服用相关药物。25例药物较术前平均减少60％。7例药物用量与术前相同，3例行单侧STN—DBS者术后药物用量增加。药物相关并发症因术后药物用量的减少而得到明显缓解。结论 STN—DBS能够减少术后抗PD药物的用量。改善药物引起的相关并发症。