Effect of bilateral subthalamic deep brain stimulation on diphasic dyskinesia

OBJECTIVES: The goal of this study was to assess the effect of bilateral subthalamic deep brain stimulation (STN DBS) on levodopa-induced diphasic dyskinesia in patients with Parkinson disease (PD). PATIENTS AND METHODS: Six PD patients with diphasic dyskinesia were included in this study. Prior to surgery, the duration and severity of dyskinesia were determined in each patient, along with the Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Bilateral STN electrode implantation was performed during a single operation. RESULTS: The median duration of the follow-up period was 21.5 months (range 14-24 months). STN DBS had a beneficial effect on diphasic dyskinesia in all patients. At the last follow-up, 3 patients had no dyskinesia and 1 had only a small amount of peak-dose dyskinesia. One patient showed a reduction in the duration of diphasic dyskinesia, despite a lack of reduction in the total duration of dyskinesia. In the last patient, although the total duration of dyskinesia increased, the pattern of dyskinesia changed from severe painful disabling dyskinesia to the less severe peak-dose type of dyskinesia. There were no intraoperative or postoperative surgical complications. CONCLUSIONS: Bilateral STN DBS is good at reducing diphasic dyskinesia, and it can be a good therapeutic option for patients with diphasic dyskinesia.     

Neuronal Responses in the Globus Pallidus during Subthalamic Nucleus Electrical Stimulation in Normal and Parkinson's Disease Model Rats

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson''s disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.     

微电极导向核团毁损术和脑深部电刺激术治疗帕金森病的疗效分析

目的 观察微电极导向核团毁损术和脑深部电刺激术（DBS）治疗帕金森病的临床疗效。方法 对380例接受微电极导向立体定向核团毁损术和25例脑深部电刺激丘脑底核（STN—DBS）治疗的帕金森病患者进行随访和神经功能评估，分别获得术前、术后和DBS开启后1周、6个月、2年及5年的不同服药状态下统一帕金森病量表（UPDRS）评分资料，采用威尔科克森检验（Wilcoxontest），比较不同术后时间点UPDRS运动评分与术前评分的差异。结果 核团毁损术和DBS在术后1周、6个月及2年随访中均能明显改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。在5年随访时间点上仅DBS治疗组较术前比较仍显示差异性。而且DBS组患者术后左旋多巴服药的剂量较术前减少。核团毁损组总体并发症的发生率为5．8％，永久性并发症的发生率为1．2％。DBS组未发生严重并发症。结论 核团毁损术和DBS两者被证实是中晚期帕金森病安全、有效的治疗方法，能显著改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。STN—DBS较毁损术更具有独特的可控性、安全性和长效性。     

Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats

Rationale  Dyskinesia affects the majority of levodopa-treated parkinsonian patients within 5–10 years of treatment with levodopa. Clinical and preclinical observations suggest that an increase in serotoninergic transmission can contribute to the appearance of dyskinesias. It is thus conceivable that a modulation of synaptic dopamine (DA) levels induced by the inhibition of serotonin (5-HT) release, as a consequence of 5-HT_1A agonists administration, might alleviate dyskinesias. Objective  Since 5-HT_1A receptors are expressed in the subthalamic nucleus (STN), the aim of the present study was to assess the effect of the intrasubthalamic administration of sarizotan, a compound with full 5-HT_1A agonist properties, on levodopa-induced dyskinesias in the 6-hydroxydopamine (6-OHDA) model of parkinsonism. Materials and methods  Male Sprague–Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. A test of apomorphine was performed to evaluate dopamine depletion. One week later, a cannula was implanted in the STN. Animals were treated with levodopa (6 mg/kg, i.p., twice at day) for 22 consecutive days. On day 23, several doses (1 ng, 10 ng, or 1 μg) of sarizotan were administered through the cannula to the STN. The higher doses of sarizotan effectively attenuated all levodopa-induced dyskinesias including axial, limb, and orolingual subtypes. Conclusions  These results suggest that the STN is a target structure for the antidyskinetic action of sarizotan and indicate that drug-mediated modulation of STN activity may be an alternative option for the treatment of levodopa-induced dyskinesias in Parkinson’s disease.     

Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: A pilot study

Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.     

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.     

Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat

Responses of the subthalamic nucleus (STH) neurons to the stimulation of the sensorimotor cortex (Cx) were recorded in intact rats and in those which received lesions in the pallidum, the neostriatum, the brainstem, or the corpus callosum. Most of the STH units (78%) exhibited two excitatory peaks which were interrupted by a brief period of inhibition. Some of units which were located in the peripheral part of the STH tended to lack the brief inhibitory component and exhibited a long period of excitation. These excitations were followed by a long-lasting inhibitory period. Intracellular recording indicated that these responses were EPSPs interrupted by a short IPSP and a long period of disfacilitation of Cx inputs. A quinolinic acid lesion of the neostriatum and a knife cut of the brainstem failed to alter these responses, while an ibotenic acid lesion of the globus pallidus abolished the short inhibition seen in the midst on the excitation. Stimulation of contralateral Cx also evoked excitatory responses in the STH. The responses were completely eliminated by a parasagittal knife cut of the rostral part of the corpus callosum.     

Role of the subthalamo-nigral input in the control of amygdala-kindled seizures in the rat

The substantia nigra pars reticulata (SNpr) is a critical site for the control of epileptic seizures. Potentiation of the inhibitory GABAergic input from the striatum to the SNpr suppresses primary or secondary generalized seizures in the rat. The purpose of this study was to examine the possible involvement of the excitatory glutamatergic input from the subthalamic nucleus to the SNpr in the control of both the electroencephalographic and the motor components of amygdala-kindled seizures in the rat. Microinjections of either an N-methyl- -aspartate (NMDA) antagonist in the substantia nigra or a GABA_A agonist in the subthalamic nucleus, significantly reduced motor seizures but did not modified the afterdischarges. These results provide evidence for the involvement of the subthalamo-nigral projection in the modulation and the propagation of the motor components of amygdala-kindled seizures.     

双侧丘脑底核电刺激对帕金森病患者生活质量影响的研究

目的对给予丘脑底核(STN)电刺激治疗的帕金森病(PD)患者进行生活质量评估,以评价治疗的有效性及不同因素对生活质量的影响。方法41例接受双侧STN深部电刺激(DBS)治疗的PD患者分别于术前及术后12个月应用统一帕金森病评定量表(UPDRS)、Hoehn和Yahr分期、Schwab和England日常生活活动量表、医院焦虑和抑郁量表(HADS)评价其临床情况;帕金森病生活质量问卷(PDQ-39)评价生活质量,并对统计结果进行配对t检验和Spearman相关性检验。结果UPDRS评分中日常生活活动、运动检查、并发症均有明显改善(P<0.001),而精神、行为和情绪无明显改善。HADS量表结果显示患者的焦虑及抑郁评分均有明显改善(P<0.001)。PDQ-39评分中运动、日常生活活动、情绪状态、身体不适、总评分等项均有明显改善(P<0.001),羞耻感也有改善(P<0.05)。相关性检验的结果提示与PDQ-39总评分变化程度成相关性的因素依次为:UPDRS运动检查“关”期(P<0.001), Schwab和England日常生活活动量表“关”期(P<0.001),UPDRS日常生活活动“关”期(P<0.01),HADS-抑郁(P< 0.05)。结论脑深部电刺激能明显改善PD患者的生活质量。     

Monoballism revealing multiple sclerosis. Neuroradiological aspects

A 38-year-old woman suddenly showed signs of monoballism in the right upper limb. Examination of CSF showed 13 monocytes per mm³ and 28.7% of IgG in oligoclonal bands. MRI examination showed several high signal lesions in T₂-weighted images. One of these lesions was located in the left subthalamic region. Visual evoked potentials showed increased latencies for the P100 wave on the left eye. Two years later she experienced vertigo, diplopia, gait unsteadiness and left facial dysesthesia. This clinical syndrome almost completely regressed after 10 days of ACTH therapy (Synacthene). Diagnosis of multiple sclerosis was supported by radiological and neurophysiological investigations.