MRI-guided DBS of STN under general anesthesia for Parkinson's disease: results and microlesion effect analysis.

BACKGROUND: The efficacy of the subthalamic nucleus (STN) stimulation for Parkinson's disease has been widely established. The microlesion effect (MLE) due to deep brain stimulation (DBS) electrode implantation has been reputed to be a good predictor for long-term efficacy of the procedure but its analysis in asleep implantation is still unclear. We thus analyzed MLE rate in our strategy of targeting the STN on MRI under general anesthesia and its correlation with our long-term results. METHOD: We retrospectively analyzed 32 consecutive parkinsonian patients implanted with a DBS targeting the STN bilaterally under general anesthesia between October 2013 and December 2020. Targeting was performed after head frame and localizer placement using a stereotactic peroperative robotic 3D fluoroscopy (Artis Zeego, Siemens) fused with preoperative CT and MRI data. We collected intraoperative data, postoperative occurrence of MLE, modification of Unified Parkinson Disease Rating Scale item III (UPDRS III) postoperatively and at subsequent visit, as well as reduction of medication. RESULTS: The mean operative time was 223 min. No permanent complication occurred. MLE was observed in 90.7%. The mean follow-up time was 17 months. The UPDRS III for the off medication/on stimulation condition improved by 64.8% from baseline. The mean dose reduction of Prolopa after the surgical procedure was 31.3%. CONCLUSIONS: Direct targeting of STN under general anesthesia based on preoperative CT and MRI data fused with a preoperative 3D fluoroscopy is safe. It allows for a high rate of postoperative MLE (90.7%) and results in prolonged clinical improvement.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease.

INTRODUCTION: We aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS). METHODS: We followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF. RESULTS: Subjective sleep latency was significantly decreased (P=0.033) and sleep duration was increased (P=0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P=0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P=0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P=0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P=0.038) and 3rd (P=0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P=0.017) and REM sleep (P=0.041) were negatively correlated with UPDRS scores at post-operative 1st year. CONCLUSION: Disturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.

An Eye on the First Surgical Side: Appreciating the Potential Impacts of a Second DBS Lead on Ipsilateral Symptoms.

Clinical Vignette: A 63-year-old man with severe essential tremor underwent staged bilateral ventralis intermedius (Vim) deep brain stimulation (DBS). Left Vim DBS resulted in improved right upper extremity tremor control. Months later, the addition of right Vim DBS to the other brain hemisphere was associated with acute worsening of the right upper extremity tremor. Clinical Dilemma: In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can disrupt previously achieved benefit. Clinical Solution: DBS programming, including an increase in left Vim DBS amplitude, re-established and enhanced bilateral tremor control. Gap in Knowledge: The mechanisms underlying changes in ipsilateral tremor control following a second lead implantation are unknown. In this case, worsening and subsequent improvement after optimization highlight the potential impact of DBS implantation on the ipsilateral side. Expert Commentary: After staged bilateral Vim DBS, clinicians should keep an eye on the first or original DBS side and carefully monitor for emergent side effects or worsening in tremor. Ipsilateral effects resulting from DBS implantation present a reprogramming opportunity with a potential to further optimize clinical outcomes. Highlights: This case report highlights the potential for ipsilateral tremor worsening following staged bilateral DBS and provides valuable insights into troubleshooting and reprogramming strategies. The report emphasizes the importance of vigilant monitoring and individualized management in optimizing clinical outcomes for patients undergoing staged bilateral DBS for essential tremor.

Surgical Concepts and Long-term Outcomes of Thalamic Deep Brain Stimulation in Patients with Severe Tourette Syndrome: A Single-center Experience.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by tic movements. Deep brain stimulation (DBS) may be a treatment option for severe cases refractory to medical and behavioral therapies. In this study, we reviewed the surgical techniques used for DBS in patients with severe TS and its clinical outcomes and sought to determine the optimal surgical procedure and current issues based on our experience and the literature. A total of 14 patients, consisting of 13 men and 1 woman, who underwent centromedian thalamic DBS and were followed up for a mean duration of 2.3 ± 1.0 years, participated in this study. The mean Yale Global Tic Severity Scale severity score significantly improved from 41.4 ± 7.0 at baseline to 19.8 ± 11.4 at 6 months (P = 0.01) and 12.7 ± 6.2 at the last follow-up (P < 0.01). Moreover, the mean Yale Global Tic Severity Scale impairment score significantly improved from 47.1 ± 4.7 at baseline to 23.1 ± 11.1 at 6 months (P < 0.01) and 7.6 ± 2.9 at the last follow-up (P < 0.01). However, there were problems with continuous postoperative monitoring (three cases were lost to follow-up) and surgery-related adverse events, including one case each of lead misplacement and a delayed intracerebral hemorrhage due to severe self-injurious tics. This study aimed to highlight not only the clinical efficacy of DBS for TS but also its challenges. Clinicians should understand the three-dimensional brain anatomy so that they can perform precise surgical procedures, avoid adverse events, and achieve favorable outcomes of DBS for TS.

Microlesion Effect Induced by Electrode Implantation in the Posteroventral Globus Pallidus Interna for Severe Dystonic Tics.

Background: Tourette syndrome (TS) is a neurologic condition characterized by motor and phonic tics. Dystonic tics, including blepharospasm, are considered atypical or unusual in severe TS. Case Report: We report a severe case of TS with facial dystonic tics resembling blepharospasm in which the microlesion effect and a sustained therapeutic effect was observed with bilateral globus pallidus interna (GPi) deep brain stimulation (DBS). Discussion: Bilateral GPi DBS can be beneficial for blepharospasm-like tics and severe symptoms of TS. The improvements seen can be explained by the microlesion effect induced by DBS lead placement in the GPi.

Reorganization of motor network in patients with Parkinson's disease after deep brain stimulation.

AIMS: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis. METHODS: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated. RESULTS: The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. CONCLUSION: The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.

Subthalamic nucleus dynamics track microlesion effect in Parkinson's disease.

Parkinson's Disease (PD) is characterized by the temporary alleviation of motor symptoms following electrode implantation (or nucleus destruction), known as the microlesion effect (MLE). Electrophysiological studies have explored different PD stages, but understanding electrophysiological characteristics during the MLE period remains unclear. The objective was to examine the characteristics of local field potential (LFP) signals in the subthalamic nucleus (STN) during the hyperacute period following implantation (within 2 days) and 1 month post-implantation. 15 patients diagnosed with PD were enrolled in this observational study, with seven simultaneous recordings of bilateral STN-LFP signals using wireless sensing technology from an implantable pulse generator. Recordings were made in both on and off medication states over 1 month after implantation. We used a method to parameterize the neuronal power spectrum to separate periodic oscillatory and aperiodic components effectively. Our results showed that beta power exhibited a significant increase in the off medication state 1 month after implantation, compared to the postoperative hyperacute period. Notably, this elevation was effectively attenuated by levodopa administration. Furthermore, both the exponents and offsets displayed a decrease at 1 month postoperatively when compared to the hyperacute postoperative period. Remarkably, levodopa medication exerted a modulatory effect on these aperiodic parameters, restoring them back to levels observed during the hyperacute period. Our findings suggest that both periodic and aperiodic components partially capture distinct electrophysiological characteristics during the MLE. It is crucial to adequately evaluate such discrepancies when exploring the mechanisms of MLE and optimizing adaptive stimulus protocols.

Sleep outcomes and related factors in Parkinson's disease after subthalamic deep brain electrode implantation: a retrospective cohort study.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves sleep qualities in Parkinson's disease (PD) patients; however, it remains elusive whether STN-DBS improves sleep by directly influencing the sleep circuit or alleviates other cardinal symptoms such as motor functions, other confounding factors including stimulation intensity may also involve. Studying the effect of microlesion effect (MLE) on sleep after STN-DBS electrode implantation may address this issue. Objective: To examine the influence of MLE on sleep quality and related factors in PD, as well as the effects of regional and lateral specific correlations with sleep outcomes after STN-DBS electrode implantation. Study Design: Case-control study; Level of evidence, 3. Data Sources and Methods: In 78 PD patients who underwent bilateral STN-DBS surgery in our center, we compared the sleep qualities, motor performances, anti-Parkinsonian drug dosage, and emotional conditions at preoperative baseline and postoperative 1-month follow-up. We determined the related factors of sleep outcomes and visualized the electrodes position, simulated the MLE-engendered volume of tissue lesioned (VTL), and investigated sleep-related sweet/sour spots and laterality in STN. Results: MLE improves sleep quality with Pittsburgh Sleep Quality Index (PSQI) by 13.36% and Parkinson's Disease Sleep Scale-2 (PDSS-2) by 17.95%. Motor (P = 0.014) and emotional (P = 0.001) improvements were both positively correlated with sleep improvements. However, MLE in STN associative subregions, as an independent factor, may cause sleep deterioration (r = 0.348, P = 0.002), and only the left STN showed significance (r = 0.327, P = 0.004). Sweet spot analysis also indicated part of the left STN associative subregion is the sour spot indicative of sleep deterioration. Conclusion: The MLE of STN-DBS can overall improve sleep quality in PD patients, with a positive correlation between motor and emotional improvements. However, independent of all other factors, the MLE in the STN associative subregion, particularly the left side, may cause sleep deterioration.

The Relevance of Intraoperative Clinical and Accelerometric Measurements for Thalamotomy Outcome.

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertion effect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

Altered Spontaneous Neural Activity and Functional Connectivity in Parkinson's Disease With Subthalamic Microlesion.

BACKGROUND: Transient improvement in motor symptoms are immediately observed in patients with Parkinson's disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood. PURPOSE: We utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS. METHOD: Overall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients. RESULT: Relative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN). CONCLUSION: The subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.

Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem.

During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.