The Method And Accessory Device For Implanting A Curved Lead To Two Intracranial Targets

Object: Deep brain stimulation(DBS)is an effective treatment for movement disorders,as well as an important method to research the brain function.Based on Current researches,the multi-target DBS aimed at improving symptoms caused by different pathogenetic mechanisms related to different nuclei might be a promising direction in the future.However,the clinical researches of multi-target DBS are very rare,the clinical significance of multi-target DBS is still unknown,and it is difficult to implant a single lead into multiple targets simultaneously with the current method of lead implantation.Therefore,the major aims of current study are: 1.a meta-analysis is performed to assess the overall efficacy of pedunculopontine nucleus(PPN)DBS,subthalamic nucleus(STN)DBS and the combination of both in Parkinson' disease(PD)patients with motor and axial symptoms,and to assess whether the treatment effect of combined double targets(STN and PPN)would be better than single target DBS.2.a meta-analysis is performed to calculate the overall prevalence of freezing of gait(FOG)in all PD patients with different disease durations and severities.Because some PD axial symptoms,such as gait,do not always respond well to levodopa and STN-/globus pallidus internus(GPi)-DBS,multi-target DBS may be suitable for the PD patients with axial symptoms.The current study intends to use these two meta-analyzes to clarify in advance whether the multi-target DBS is be of significant clinical value.3.if the two meta-analyzes indicate that the multi-target DBS is clinically significant,we aim to proposes the method and auxiliary stereotaxic device for implanting a curved lead to human,such that a single curved lead can reach in sequence to any two intracranial targets.Maybe this new method can complement the current method of lead implantation.4.what's more,the method and auxiliary device for implanting a curved lead to rat/mice is also provided in order to expand the experimental techniques of brain function research.The current study is divided into four parts corresponding to the four aims.Based on the significances of the four aims,the manuscript will explain the related study of aim 3 and aim 4 firstly.Methods: Methods corresponding to the four aims are: 1.The meta-analysis was performed according to the guideline of Cochrane Handbook for Systematic Reviews of Interventions.MEDLINE/PubMed,EMBASE,and Cochrane Library were searched for studies published before September 1,2015.Search terms included various combinations of “subthalamic”,“pedunculopontine”,“deep brain stimulation” and “Parkinson”.All studies on comparison of clinical outcomes of PPN-DBS,STN-DBS and combined PPN-STN-DBS were analysed.Therapeutic outcomes of included studies were evaluated using motor scores and axial subscores in Unified Parkinson's Disease Rating Scale III(UPDRS III).2.The meta-analysis was performed according to the guideline of Preferred Reporting Items for Systematic Review and Meta-analysis Protocols.A systematic literature search was carried out using databases Medline/PubMed.The entire time scale was used up to July 10,2016.Search terms were “freezing of gait” and “Parkinson”.All studies reported the prevalence of freezing of gait in Parkinson's disease patients were accepted to further analysis.The prevalence of freezing of gait in Parkinson's disease and the prevalence of freezing of gait in patients with different disease durations and severities were calculated respectively.3.Mathematical model is built to determine the theoretical position of the “lead pathway plane” and the “curved lead pathway”.And the “curved lead pathway” method and auxiliary stereotaxic system that enables a single curved lead to reach any two intracranial targets were put forward subsequently.Then,the novel stereotaxic system was fabricated,and a three dimensional printed skull model with predetermined intracranial targets was fabricated and used as the subject to prove the accuracy of the novel method and stereotaxic system.4.Combined with the existing animal stereotaxic frame and the stereotaxic coordinate atlas of rat/mouse brain,mathematical model is built to determine the theoretical position of the “lead pathway plane” and the “curved lead pathway”.And the “curved lead pathway” method and auxiliary device that enables a single curved lead to reach any two intracranial targets of rat/mouse brain were put forward subsequently.Then the rat was used as subject,and the “right STN + right GP” or “right STN + left STN” were selected as combined targets,to prove the accuracy of the method and auxiliary device.For each rat in experimental groups,a curved lead was implanted;and for each rat in control groups,two straight leads were implanted aiming at two selected targets.After lead implantation,the Morris water maze test was used to evaluate spatial learning for the rats.Afer the Morris water maze test,rat brains were obtained,sectioned,and stained with hematoxylin-eosin to verify the lead placements.Results: Results corresponding to the above-mentioned aims and methods are: 1.STN-DBS reduced UPDRSIII scores(off-medication phases)to levels lower than PPN-DBS.However,the improvement of UPDRSIII axial subscores(on-medication phases)after PPN-DBS was greater than that after STN-DBS.UPDRSIII score change caused by combined PPN-STN-DBS were not significantly different from STN-DBS(on-and off-medication phases).Improvements in UPDRSIII axial subscores for combined PPN-STN-DBS were significantly greater than subthalamic DBS(on-and off-medication phases).2.eighteen studies fulfilled the quality criteria and included in this meta-analysis.The overall prevalence of FOG in PD was 40.8%(95%CI 34.7%-46.9%).Disease duration and severity are both the clinical features associated with the FOG.The mean FOG prevalence rates in PD patients with disease durations > 10 years,> 5 years,and < 5 years were 72.3%,56.2% and 23.1%.And FOG presented in 25.9% of PD patients with Hoehn and Yahr staging(H&Y)score ? 2.5,and in 70.6% of PD patients with H&Y score ? 2.5 averagely.3.the “curved lead pathway” method and auxiliary stereotaxic system that enables a single curved lead to reach any two targets of the brain were proposed,and the Excel algorithm needed to calculate the necessary parameters was designed.The preliminary application used the 3D skull model as subject indicated that the novel method and auxiliary stereotaxic system enables curved lead implantation with high accuracy.The average vector error of curved lead implantation was 0.70 ± 0.24 mm.4.the method and auxiliary device that could be used together with the animal stereotaxic frame and the stereotaxic coordinate atlas of rat/mouse brain were proposed,and the Excel algorithm needed to calculate the necessary parameters was designed.The preliminary application used the rats as subjects indicated that the novel method and auxiliary device could guide curved lead to reach the two selected targets with high accuracy.There were no differences between the experimental groups and control groups on the performance during Morris water maze tests.Conclusion: Two meta-analyzes in this study indicate that multi-target DBS is clinically significant and is a promising direction in the future research.The “curved lead pathway” method and auxiliary device that enable a single lead to reach any two intracranial targets might be a beneficial complement to the current method of lead implantation.The “curved lead pathway” method to implant a single curved lead to any two targets was proposed,the auxiliary devices and the Excel algorithm needed to calculate the necessary parameters were designed to realize such an implantation method in human and rat/mice.The preliminary application used the 3D skull model as subject indicated that the novel method and auxiliary stereotaxic system enables curved lead implantation with high accuracy.The average vector error of implanting a curved lead with the help of novel stereotaxic system was less than or equal to the vector error of implanting a straight lead using the current stereotaxic system.The preliminary application used the rats as subjects indicated that,curved lead implantation is relatively safe with an appropriately designed curved lead pathway.