Deep Brain Stimulation最新文献

Objectives

Participation is essential to DBS research, yet circumstances that affect diverse participation remain unclear. Here we evaluate factors impacting participation in an adaptive DBS study of Parkinson’s disease (PD) and dystonia.

Methods

Twenty participants were implanted with a sensing-enabled DBS device (Medtronic Summit RC+S) that allows neural data streaming in naturalistic settings and encouraged to stream as much as possible for the first five months after surgery. Using standardized baseline data obtained through neuropsychological evaluation, we compared neuropsychological and social variables to streaming hours.

Results

Marital status and irritability significantly impacted streaming hours (estimate=136.7, bootstrapped (^b) CI^b=45.0 to 249.0, p^b=0.016, and estimate=−95.1, CI^b=−159.9 to −49.2, p^b=0.027, respectively). These variables remained significant after multivariable analysis. Composite scores on verbal memory evaluations predicted the number of hours of data streamed (R²=0.284, estimate=67.7, CI^b=20.1 to 119.9, p^b=0.019).

Discussion

Verbal memory impairment, irritability, and lack of a caregiver may be associated with decreased participation. Further study of factors that impact research participation is critical to the sustained inclusion of diverse participants.

Participants in DBS clinical trials for major depressive and other psychiatric disorders may not have access to post-trial neuromodulation. Some commentators have claimed that this would be unfair to trial participants and effectively abandon them. Continued access to these devices could be justified only if there were a statistically significant difference in outcomes between active and sham stimulation and participants responded positively to active DBS. Clinicians and investigators have post-trial obligations to provide appropriate care and psychosocial support to patients and trial participants. Depending on trial outcomes and patient responses, lack of access to continued DBS may not be unfair to them or a form of abandonment.

Local field potentials (LFP) in the basal ganglia (BG) have attracted considerable research and clinical interest. The genesis of these signals has been a topic of extensive discourse, focusing on whether they are a manifestation of local synaptic activity or result from the propagation of electrical signals through tissue, as described by the Maxwell equations (volume conduction). To investigate this, we conducted simultaneous recordings of LFPs from two cortical areas— the dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1)—and various sites within the BG nuclei in an awake, non-task-engaged non-human primate (NHP). Employing innovative analytical techniques, we discerned significant cross-correlations indicative of potential connections, while filtering out non-significant correlations. This allowed us to differentiate between synaptic inputs and volume conduction. Our findings indicate two distinct propagation pathways of BG field potentials emanating from the M1 and the DLPFC, each characterized by different temporal delays. The results imply that these anatomical pathways are differentially influenced by the mechanisms of volume conduction and synaptic transmission. Notably, the M1 exhibits more functional links with non-zero-time delays to the BG structures, while the DLPFC-BG connections are marked by zero-time delays, suggesting a predominance of volume conduction effects. Consequently, investigations into the origins of BG LFP should account for the distinct anatomical pathways linking the cortex and the BG, as they differentially represent information flow and volume conductance.

Local field potentials (LFPs) are signals generated primarily by the result of the synchronous discharge of post-synaptic potentials. Detection of LFPs from intracranial electrodes sited within the basal ganglia has led to the recognition that there are specific features of the LFP that could serve as neurophysiological biomarkers of different disease states. For example, in Parkinson’s disease peaks in the beta frequency range of the power spectrum are known to correlate with the degree of bradykinesia and rigidity, whereas low frequency, alpha-theta peaks are increasingly considered a biomarker of dystonic activity. The introduction of newer deep brain stimulation (DBS) devices capable of simultaneous stimulation and LFP detection creates opportunities to investigate new strategies for treating patients with dystonia. This review aims to summarise the LFP findings seen in patients with dystonia undergoing DBS with a particular focus on the potential implications for future clinical practice and the development of adaptive DBS systems.

Neuropalliative care (NPC) is a relatively new subspeciality of neurology. Recent studies have demonstrated efficacy of NPC in Parkinson’s disease (PD). However, the implementation of NPC in deep brain stimulation (DBS) has yet to be addressed. Patients with PD being evaluated for and having undergone DBS potentially have unmet needs that may be best assessed and managed by neuropalliative neurologist. Specific areas include an in-depth psychosocial evaluation, exploration of patient and caregiver expectations, addressing caregiver needs, providing spiritual and marital support, and discussing advance directives.

Traditionally believed to be a non-genetic disease (sporadic or idiopathic), running of Parkinson Disease (PD) in families and early-onset PD patients have drawn attention to the role of genetics in PD. Variants associated with PD include rare, high penetrance pathogenic variants causing familial disease, and genetic risk factor variants driving PD risk in a significant minority in PD cases, and high frequency, low penetrance variants, which contribute a small increase of the risk of developing sporadic PD. Studying PD genetics is critical for a thorough understanding of the underlying mechanisms, given that PD is a clinically and pathologically heterogenous disease. Although the great majority of PD patients cannot be explained by a single mutation, the identification of risk loci, genes, and mutations has provided new insights into PD pathogenesis and paved the way for new studies. It is clear that we will need more data about the treatment outcomes of monogenic/complex PD. Knowledge of genetics has the potential to improve clinical trial design and to generate new and optimize existing therapeutic options for people with PD. The molecular PD research combined with detailed clinical data, is timely and will contribute to fill some of the gaps in PD genetics.

Background

The subthalamic nucleus (STN) deep brain stimulation (DBS) usually requires high energy stimulation in the treatment of Parkinson's disease (PD) with medically refractory tremor, which may lead to axial disturbances compromising the anti-tremor effect.

Methods

One patient with PD developed from essential tremor suffered from severe levodopa-unresponsive tremor. He received bilateral DBS surgery targeting the posterior subthalamic area (PSA) and dorsal STN simultaneously using one single lead. A conventional frontal approach was applicable. Using standard clinical scales and objective gait analysis, we explored and compared the efficacy of PSA DBS, STN DBS, and PSA-STN co-stimulation.

Results

No severe adverse event was documented in this case. At the 2-year follow-up, having comparable efficacy on rigidity and bradykinesia, PSA stimulation, compared with STN stimulation, provided greater improvement in the tremor sub-score of the MDS Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), the total score of the MDS UPDRS-III, and the score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) part A&B. In addition, some of the gait parameters (i.e., turning duration and cadence) were better under PSA stimulation.

Conclusion

Single-trajectory simultaneous PSA and STN DBS with conventional frontal approach is feasible and is highly effective in one case with PD suffering from medically refractory tremor. This case provides insight into DBS targets selection for treatment-refractory tremor-dominant PD and suggests the potential for PSA as a complementary or alternative target in these cases.

Deep brain stimulation (DBS) is a widely accepted and safe treatment for selected patients with movement disorders. Many medical centres prefer to perform DBS lead positioning using local anesthesia to enable microelectrode recordings (MER) and assess the therapeutic and side effects of stimulation. These steps allow for the precise identification of the borders and subdomains of the target nuclei using the electrophysiological properties. Additionally, they facilitate the evaluation of the therapeutic window and thereby improve the accuracy of final DBS lead placement. However, in some patients awake surgery can be challenging and, as a result, sedation or general anesthesia may be needed. Unfortunately, if not used properly this approach can lead to alterations in the electrophysiological signature and interfere with clinical testing, potentially affecting surgical outcomes. Consequently, the type and dose of anesthesia needs to be chosen carefully.

Deep brain stimulation (DBS) is a surgical treatment critical for alleviating symptoms of Parkinson's disease (PD), especially when medication fails to manage motor dysfunctions effectively. The accuracy of electrode placement in the subthalamic nucleus (STN) is critical for the procedure's success. The long-standing debate between electrophysiological recording (MER) and imaging-based targeting remains at the forefront of neurosurgical discussions. MER has traditionally been used to enhance the precision of DBS targeting, indicated by changes in local field potentials (LFPs), which correlate with Parkinsonian motor symptoms such as rigidity, bradykinesia, and tremor. However, the necessity of MER has been questioned due to advances in imaging techniques and the potential risks associated with the practice, including hemorrhage and cognitive decline post-surgery. A critical appraisal of the literature reveals mixed opinions, with recent meta-analyses showing no significant increase in hemorrhage risks with MER but demonstrating a modest increase in adverse cognitive outcomes using multiple electrodes. Despite improved imaging modalities enabling more accurate radiological targeting, MER remains a favored technique among surgeons for its direct feedback on electrode placement. Additionally, the aspect of conducting surgery under awake conditions versus general anesthesia is reviewed, considering the anxiety and discomfort associated with awake surgery against the limitations of performing electrophysiological recordings under general anesthesia. The current consensus underscores the importance of accurate electrode placement, achievable through a combination of MER, test stimulation, and intraoperative imaging, while also acknowledging the growing confidence in image-guided procedures performed under general anesthesia. This review highlights the need for individualized approaches considering patient-specific risks and the evolving landscape of DBS surgery.