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临床试验/NCT05820425
NCT05820425招募中不适用

Local Fields Potentials of the Subthalamic Nucleus in Patients With Parkinson's Disease and Neuropsychiatric Fluctuations

University Hospital, Grenoble1 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2023年4月7日最近更新:
适应症

试验速览

阶段
不适用
状态
招募中
发起方
入组人数
12
试验地点
1
主要终点
The LFPs recordings from the STN correlating with the neuropsychiatric OFF and ON

研究概览

简要总结

Neuropsychiatric fluctuations are frequent and debilitating non-motor disorders in Parkinson's disease. Subthalamic stimulation is an effective treatment for motor and non-motor neuropsychiatric fluctuations in Parkinson's disease, which has also allowed to better characterize the electrophysiological activity of the subthalamic nucleus in patients with Parkinson's disease. Numerous studies have been carried out on electrophysiological activity correlated with motor disorders, showing that akinesia is correlated with an abnormal synchronization in the beta frequency band (13-30Hz) in the dorsal motor part of the subnucleus. thalamic. This abnormal synchronization is reduced when the akinesia improves with dopaminergic treatment. On the cognitive-behavioural non-motor side, electrophysiological studies are less numerous, but suggest an involvement of the subthalamic nucleus (with an abnormal synchronization in the lower frequency bands). Currently, the electrophysiological correlates of neuropsychiatric fluctuations are unknown. In addition, all studies on electrophysiological activity are carried out immediately after the intervention, and before the implantation of the pacemaker. It is unknown whether the electrophysiological correlates of motor and non-motor fluctuations change following their transient improvement observed in the setting of chronic stimulation of the subthalamic nucleus and chronic reduction of dopaminergic treatment. The new PERCEPT stimulators (Medtronic) available on the market make it possible to record long-term electrophysiological activity for the first time. With this study we want to define the electrophysiological markers of neuropsychiatric fluctuations and their change over time.

详细描述

In PD several studies have shown an abnormal synchronized activity in the beta band (13-30 Hz) in the motor dorsal STN, which correlates with bradykinesia. This abnormal activity is decreased by dopaminergic treatment and movement. In contrast, higher alpha activity is concentrated in the ventromedial part of the nucleus. Anatomically, it has been shown that the motor dorsal subthalamic nucleus is connected with the motor frontal cortex, whereas its non-motor ventral part is connected to the premotor and the prefrontal cortex.

More recently, an increasing attention has been focused on the key role of the STN in emotion and cognition in Parkinson's disease. Neuropsychiatric symptoms indeed represent a real burden for patients with PD and their caregivers. Patients might experience fatigue, depressive symptoms, anxiety, apathy, impulse control disorders, punding, hallucinations, and impaired cognition. Moreover, neuropsychiatric symptoms might fluctuate along the day. During the off state, patients might present with fatigue, lack of energy and motivation, low mood and slowness of thought, whereas during the on state they experience a sensation of well-being, high motivation, logorrhoea with easy flow of ideas, and good attention span and liveliness. Little is known about the electrophysiological correlates of such neuropsychiatric symptoms. An increase in the background activity and a reduced oscillatory activity in the alpha spectrum was observed in the ventral part of the right STN after vocal emotional stimuli. A change in the oscillatory activity in the alpha spectrum of the STN has been recorded after visual emotional stimuli. A theta activity in the ventral region of the STN has been recorded in PD patients with impulse control disorders while on medication.

Recently, a new tool, the neuropsychiatric fluctuations scale, has been developed. This scale, contrary to the other scales measuring the non-motor fluctuations, which are mainly retrospective, allows to measure the neuropsychiatric state of the patient at the very moment of the test. This is a critical advantage as patients can be anosognosic of their fluctuations. The neuropsychiatric fluctuations scale allows measuring the neuropsychiatric state of the patient "in real time", just as the MDS UPDRS assesses the motor condition.

At present, the electrophysiological marker of neuropsychiatric fluctuations in PD is unknown. Moreover, all electrophysiological data on STN activity comes from the postoperative phase and no data are available on their evolution over time.

The PERCEPT (Medtronic) allows to record STN activity not only in the immediate postoperative phase, but also in the medium and long-term follow-up, providing an excellent tool to investigate the electrophysiological activity of the subthalamic nucleus, and its changes over time.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
30 Years 至 75 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Age between 30 and 75 years
  • Diagnosis of Parkinson's disease with fluctuations and/or dyskinesias
  • Ability to collaborate and fill a questionnaire in the OFF state condition (this criterion will be assessed based on the results of the preoperative screening to retain indication for STN stimulation, which takes place whenever a PD patient has to undergo DBS surgery)
  • Surgery for bilateral STN stimulation with a Percept® (Medtronic) in the last 10 days
  • Absence of dementia (defined as MoCA score > 24)

排除标准

  • Active psychosis
  • Patients unable to provide an informed consent or under gardianship
  • Patients under judicial supervision or deprived of liberty
  • Pregnancy and breastfeeding

结局指标

主要结局

The LFPs recordings from the STN correlating with the neuropsychiatric OFF and ON

时间窗: at 1 year after surgery

Correlation will be performed within a general mixed effect model approach. The dependent variable will be the power spectral density (PSD, expressed as logpower (µV\^2)) of the subthalamic nucleus local field potentials estimated with the Welch method. The independant variable will be measured using the neuropsychiatric fluctuations scale score.

次要结局

未报告次要终点

研究者

发起方
University Hospital, Grenoble
申办方类型
Other
责任方
Sponsor

研究点 (1)

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