Outcome Of Deep Brain Stimulation Research Articles

Intraoperative electrophysiological monitoring determines the final electrode position for pallidal stimulation in dystonia patients.

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for refractory dystonia. Neuroradiological target and stimulation electrode trajectory planning with intraoperative microelectrode recordings (MER) and stimulation are used. With improving neuroradiological techniques, the need for MER is in dispute mainly because of the suspected risk of hemorrhage and the impact on clinical post DBS outcome. The aim of the study is to compare the preplanned GPi electrode trajectories with final trajectories selected for electrode implantation after electrophysiological monitoring and to discuss the factors potentially responsible for differences between preplanned and final trajectories. Finally, the potential association between the final trajectory selected for electrode implantation and clinical outcome will be analyzed. Forty patients underwent bilateral GPi DBS (right-sided implants first) for refractory dystonia. The relationship between preplanned and final trajectories (MicroDrive system) was correlated with patient (gender, age, dystonia type and duration) and surgery characteristics (anesthesia type, postoperative pneumocephalus) and clinical outcome measured using CGI (Clinical Global Impression parameter). The correlation between the preplanned and final trajectories together with CGI was compared between patients 1-20 and 21-40 for the learning curve effect. The trajectory selected for definitive electrode implantation matched the preplanned trajectory in 72.5% and 70% on the right and left side respectively; 55% had bilateral definitive electrodes implanted along the preplanned trajectories. Statistical analysis did not confirm any of the studied factors as predictor of the difference between the preplanned and final trajectories. Also no association between CGI and final trajectory selected for electrode implantation in the right/left hemisphere has been proven. The percentages of final electrodes implanted along the preplanned trajectory (the correlation between anatomical planning and intraoperative electrophysiology results) did not differ between patients 1-20 and 21-40. Similarly, there were no statistically significant differences in CGI (clinical outcome) between patients 1-20 and 21-40. The final trajectory selected after electrophysiological study differed from the preplanned trajectory in a significant percentage of patients. No predictor of this difference was identified. The anatomo-electrophysiological difference was not predictive of the clinical outcome (as measured using CGI parameter).

Long-term outcomes of deep brain stimulation for treatment-resistant schizophrenia: Exploring potential targets

BackgroundSchizophrenia is a complex and disabling disorder. Around 30% of patients have treatment-resistant schizophrenia (TRS). ObjectiveThis study summarizes the outcomes after three years follow-up of the first series of patients with TRS treated with deep brain stimulation (DBS) and discuss surgical, clinical and imaging analysis. MethodsEight patients with TRS treated with DBS in the nucleus accumbens (NAcc) or the subgenual cingulate gyrus (SCG) were included. Symptoms were rated with the PANSS scale and normalized using the illness density index (IDI). A reduction in IDI-PANSS of ≥25% compared to baseline was the criterion of good response. The volume of activated tissue was calculated to perform a connectomic analysis for each patient. An estimation of the tracts and cortical areas modulated was generated. ResultsFive women and three men were analyzed. After 3 years’ follow-up, positive symptoms improved in 50% of the SCG group and 75% of the NAcc group (p = 0.06), and general symptoms improved in 25% and 50% respectively (p = 0.06). The SCG group showed activation of the cingulate bundle and modulation of orbitofrontal and frontomesial regions; in contrast, the NAcc group showed activation of the ventral tegmental area projections pathway and modulation of regions associated with the “default mode network” (precuneus) and Brodmann areas 19 and 20. ConclusionsThese results showed a trend toward improvement for positive and general symptoms in patients with TRS treated with DBS. The connectomic analysis will help us understand the interaction of this treatment with the disease to pursue future trial designs.

Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome.

By studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy. We selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei. Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox-Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%. ANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.

Patient feedback and psychosocial outcomes of deep brain stimulation in people with obsessive–compulsive disorder

Severe and refractory psychiatric patients can experience complex and profound changes in symptomology, functioning and well-being from deep brain stimulation (DBS) therapy. Currently, the efficacy of DBS is assessed by clinician rated scales of primary symptoms, yet this does not capture the multitude of DBS mediated changes or represent the patient perspective. We aimed to elucidate the patient perspective in psychiatric DBS application by investigating 1) symptomatic, and 2) psychosocial changes, 3) therapeutic expectations and satisfaction, 4) decision-making capacity, and 5) clinical care recommendations from treatment refractory obsessive–compulsive disorder (OCD) DBS patients. Participants enrolled in an open label clinical trial of DBS therapy for OCD who had reached clinical response were invited to participate in a follow up survey. Participants completed a 1) feedback survey relating to goals, expectations, and satisfaction of therapy, and 2) self-report questionnaires on psychosocial functioning including quality of life, cognitive insight, locus of control, rumination, cognitive flexibility, impulsivity, affect, and well-being. Greatest change was reported for quality of life, rumination, affect and cognitive flexibility. Participants reported realistic expectations, high satisfaction, adequate pre-operative education and decision-making capacity; and advocated for greater access to DBS care and more widespread support services. This is the first identified investigation on psychiatric patient perspectives of functioning and therapeutic outcomes following DBS. Insights from the study have implications for informing psychoeducation, clinical practices, and neuroethical debates. We encourage a greater patient-centred and biopsychosocial approach in evaluating and managing OCD DBS patients, by considering personally meaningful goals and addressing symptomatic and psychosocial recovery.

Therapeutic Outcomes of Directional Deep Brain Stimulation in Essential Tremor Patients (P7-11.007)

<h3>Objective:</h3> Analyzing directional deep brain stimulation (DBS) outcomes in Essential Tremor (ET) patients using the Abbott Infinity and Boston Scientific Vercise Systems. <h3>Background:</h3> Stimulation of the Ventralis Intermedius nucleus of the thalamus (VIM) effectively suppresses tremors in patients with ET. Data on the long-lasting benefits of directional current delivery remains limited. <h3>Design/Methods:</h3> Tremor was evaluated in 9 ET patients implanted with directional DBS leads using the Fahn-Tolosa-Marin Tremor Scale (FTM). One patient was subsequently diagnosed with parkinsonism. In our sample 7 patients were implanted bilaterally and 2 unilaterally, 7 implanted with Abbott Infinity and 2 with the Boston Scientific Vercise system. FTM assessments were obtained preoperatively and 7 to 16 months following device activation. <h3>Results:</h3> On average patients exhibited tremors for 23.3 ±17.9 years. Mean age at surgery was 67.2 ±11.0 years. Preoperatively FTM scores ranged from 36 to 88 points with a mean of 51.3 ±15.9, while 11.6 ±2.9 months post device activation FTM scores ON stimulation ranged 7 to 31 points and averaged 15.9±8.2. FTM scores ON stimulation at postoperative follow-up decreased by 66% when compared with FTM scores at baseline. Medication reduction or discontinuation was observed in 71% of patients who were prescribed tremor suppressing medications at baseline. Segmented DBS contacts were used in 15 of the 16 directional leads. <h3>Conclusions:</h3> Tremor control using directional DBS leads in ET patients is evident by reduction in FTM scores approximately 1 year following DBS activation, especially in the setting of medication reduction. Future analysis of clinical outcomes in a larger cohort and investigation of directional DBS lead parameters is necessary to thoroughly understand and optimize directional current stimulation. <b>Disclosure:</b> The institution of Ms. Shub has received research support from Abbott and Boston Scientific . Dr. Smith has nothing to disclose. Dr. Zesiewicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Uniqure. Dr. Zesiewicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Retrotope. Dr. Zesiewicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reata. Dr. Zesiewicz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Zesiewicz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Steniment. Dr. Zesiewicz has received intellectual property interests from a discovery or technology relating to health care. Teresita Malapira has nothing to disclose. Yarema B Bezchlibnyk has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PMT Corporation. Yarema B Bezchlibnyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Yarema B Bezchlibnyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Yarema B Bezchlibnyk has received personal compensation in the range of $0-$499 for serving as a Consultant for Medtronic.

Influence of Body Mass Index (BMI) and Blood Pressure (BP) on Deep Brain Stimulation (DBS) Outcomes in Parkinson’s disease (PD) Patients (P4-11.003)

<h3>Objective:</h3> PD literature supports a complex relationship between preoperative obesity, BP abnormalities, and post-DBS cognitive and motor outcomes. This study aims to improve on evidence associating BMI and BP with cognitive, emotional, and quality-of-life outcomes post-DBS. <h3>Background:</h3> Previous studies indicate obesity and hypertension increase intra-/ post-operative complications. Up to 65% of PD patients may be overweight or obese, with obese patients having less axial motor improvement and worsened cognitive function six months post-DBS. PD patients have also demonstrated increased BP fluctuations compared to healthy controls. <h3>Design/Methods:</h3> PD patients [n=28, Mage=62.6(8.8), 75% male, Medu=16.1(3.0), 92.9% STN) underwent pre-/post-DBS assessment (global cognition, language, memory, attention, processing speed, visuospatial ability) and emotional screenings via TeleNP. Systolic (M=130.0; SD=19.5) and diastolic (M=74.4; SD=16.0) BP (SBP, DBP), weight, and height were measured pre-DBS surgery. BMI was computed (M=27.3; SD=6.1). Logistic regression was used to predict neurocognitive performance using BMI, SBP, and DBP. <h3>Results:</h3> BMI, SBP, and DBP predicted decline in verbal reasoning in post-, compared to pre-, DBS testing, but not other assessed domains. Model coefficient estimates of 0.40 [<i>p</i>=.02, OR=1.5 (95% CI [1.07, 2.10])] for BMI, 0.13 [<i>p</i>=.04, OR=1.13 (95% CI [1.01, 1.28])] for SBP, and −0.15 [<i>p</i>=.08, OR=0.86 (95% CI [0.73, 1.02])] for DBP were indicated. Model fit was robust [X²(3)=14.2, <i>p</i>=.003]. While holding BP constant: each unit increase in BMI predicted a 50% increase in odds of verbal reasoning decline (one-half <i>SD</i> or more), and a unit increase in SBP (or decrease in DBP) predicted a 13% increase in odds (or, respectively, a 14% decrease in odds) of verbal reasoning decline. Post-DBS patient classification using BMI and BP predictors yield a .882 specificity and a .857 sensitivity. <h3>Conclusions:</h3> BMI, SBP, and DBP should be considered in predicting DBS surgical outcomes, particularly on verbal reasoning tasks. This small sample requires replication but is consistent with existing literature. <b>Disclosure:</b> Miss See has nothing to disclose. Dr. Harcourt has nothing to disclose. Annelly Buré-Reyes has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Luca has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Luca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Jonathan Jagid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic Inc. The institution of Jonathan Jagid has received research support from Boston Scientific. The institution of Jonathan Jagid has received research support from Medtronic Inc. Bonnie Levin has nothing to disclose. Ms. Bullock has nothing to disclose. The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson’s Foundation. The institution of Dr. Haq has received research support from NIMH. Dr. Haq has a non-compensated relationship as a consultant with Medtronics that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Boston Scientific that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Abbott that is relevant to AAN interests or activities. Dr. Sarno has nothing to disclose.

Clinical Utility of Home-to-Home Tele-neuropsychology (TeleNP) in the Assessment of Post-Operative Deep Brain Stimulation (DBS) Outcomes in Parkinson’s disease (PD) Patients (P10-11.012)

<h3>Objective:</h3> The coronavirus pandemic facilitated widespread implementation of tele-neuropsychological assessment of DBS candidates due to physical distancing and safety requirements. Our prior work has demonstrated preoperative home-to-home TeleNP feasibility and patient satisfaction in determining candidacy for DBS in PD patients. To our knowledge the implementation and feasibility of TeleNP in assessing postoperative outcomes have not been assessed. <h3>Background:</h3> Neurologists work closely with neuropsychologists who evaluate postoperative cognitive, behavioral, and mood outcomes in PD patients. For PD patients with barriers to accessing care, home-to-home TeleNP post-DBS management provides a much-needed resource to increase care access. <h3>Design/Methods:</h3> PD patients [<i>n</i>=28, <i>M</i>_age=62.6(8.8), 75% male, <i>M</i>_edu=16.1(3.0), 46.4% Hispanic, 64.3% pretested in English<b>/</b>35.7% in Spanish, 92.9% STN), underwent pre- and post-cognitive (global cognition, language, memory, attention, processing speed, visuospatial ability) and emotional assessments via home-to-home TeleNP between May 2020 and March 2022. PD patients underwent either in-person (n=23) or TeleNP (n=5) evaluation pre-DBS and in-person (<i>n</i>=1) or home-to-home TeleNP (<i>n</i>=27) assessments post-surgery. Paired t-tests were conducted to assess differences between pre and post assessments. <h3>Results:</h3> To date, 28 candidates completed both pre- and post-DBS neuropsychological assessment. Significant differences in semantic fluency (Animals: <i>t</i>(53)=3.89, <i>d</i>=.53, <i>m</i><i>_z-d</i>_iff=0.6), short- and long-delay verbal recall (CVLT: <i>t</i>(43)=2.95, <i>d</i>=.44, <i>m</i><i>_z-d</i>_iff=0.4 and <i>t</i>(47)=3.13, <i>d</i>=.45, <i>m</i><i>_z-d</i>_iff=0.4 respectively), and processing speed (SDMT: <i>t</i>(23)=3.57, <i>d</i>=.73, <i>m</i><i>_z-d</i>_iff=0.8) were noted at <i>p</i>&lt;.005 (Bonferroni-adjusted for family-wise error), where <i>m</i><i>_z-d</i>_iff represents <i>z</i>-score decrease from pre- to post-test. In contrast, no significant change was noted in orientation, naming, phonemic fluency, working memory, executive functioning, verbal reasoning, depression, anxiety, or PD symptom dysfunction (PDQ-39). <h3>Conclusions:</h3> TeleNP is a feasible platform for comprehensively assessing short- and long-term outcomes in PD patients post-DBS in English and Spanish. Remote care reduces the risk of patients being lost to follow-up by offering time- and cost advantages to those who have physical or transportation limitations or are living in remote areas. <b>Disclosure:</b> Ms. Bullock has nothing to disclose. Dr. Harcourt has nothing to disclose. Dr. Rodriguez has nothing to disclose. Annelly Buré-Reyes has nothing to disclose. Dr. Luca has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Luca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Jonathan Jagid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic Inc. The institution of Jonathan Jagid has received research support from Boston Scientific. The institution of Jonathan Jagid has received research support from Medtronic Inc. Bonnie Levin has nothing to disclose. Miss See has nothing to disclose. The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson’s Foundation. The institution of Dr. Haq has received research support from NIMH. Dr. Haq has a non-compensated relationship as a consultant with Medtronics that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Boston Scientific that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Abbott that is relevant to AAN interests or activities. Dr. Sarno has nothing to disclose.

Should we offer deep brain stimulation to Parkinson's disease patients with GBA mutations?

Parkinson's disease (PD) patients who are carriers of glucosylceramidase β1 (GBA1) gene mutations typically have an earlier age at onset and a more aggressive disease course, with a higher burden of neuropsychological issues. The use of deep brain stimulation (DBS) in PD patients with disabling motor fluctuations and absence of dementia is a widespread therapeutic option, often with good results in terms of improvement in activities of daily living and quality of life. Although all PD patients, when fulfilling the common selection criteria for DBS, can benefit from this intervention, some studies have raised attention toward the fact that PD patients who are carriers of GBA1 variants may have a worse DBS outcome possibly due to an accelerated progression of cognitive decline. From this viewpoint, we summarize the current literature, highlighting the knowledge gaps and proposing suggestions for further research as well as for clinical practice in this timeframe of uncertainty related to using DBS in PD patients who are carriers of GBA1 variants.

Personal recovery associated with deep brain stimulation for treatment-resistant depression: A constructivist grounded theory study.

WHAT IS KNOWN ON THE SUBJECT?: Major depressive disorder is the most prevalent of all mental illnesses. 10%-20% of patients with depression and 1% of the population overall have treatment-resistant depression (TRD). DBS is an emerging investigational treatment for TRD with documented clinical efficacy and safety. The framework of the recovery model includes both clinical and personal recovery. Personal recovery is a self-process in which hope, empowerment and optimism are embraced to overcome the impact of mental illness on one's sense of self. Although clinical and functional outcomes of DBS for TRD have been well documented in the previous studies, personal recovery as an outcome has been explored only in a handful of studies. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first qualitative study exploring personal recovery from DBS treatment specific to the target of subcallosal cingulate cortex in patients with TRD. Since the existing literature on personal recovery in DBS studies is limited, the contribution of this paper is crucial to this field. For individuals who responded to deep brain stimulation clinically, neither participants nor family believed it cured their depression, but rather there was a significant decrease in the severity of symptoms of depression. A holistic-oriented framework (that includes personal recovery) is significant for those individuals with TRD undergoing DBS. Personal and clinical recovery are two different constructs, and individuals may experience one or the other or both. The experience of participants who responded to deep brain stimulation recognized that the recovery from depression is a process of reconstructing self. This process involved a period of adjustment that evoked a deeper self-awareness, re-engagement with daily living and newfound gratitude in living. Individuals transitioned from an emotionally driven life to one where future goals were considered. Supportive relationships were instrumental in this process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A deep brain stimulation intervention for treatment-resistant depression offered individuals an opportunity for personal recovery where a reconstruction of self occurred. Personal recovery can be considered as an outcome in conjunction with clinical and functional outcomes in future DBS trials for TRD. The relevance of personal recovery in the prevention of relapses needs further investigation. To advocate for care and services that facilitate the process of recovery from depression, it is important to understand the personal dimensions and experience of recovery that may influence the process. To develop recovery-oriented interventions to help patients and families in recovery post-deep brain stimulation, further understanding of support and negotiating relationships during this life-altering experience is needed. ABSTRACT: Introduction Multiple trials of antidepressant treatments in patients with depression pose a major challenge to the mental health system. Deep brain stimulation (DBS) is an emerging and promising investigational treatment to reduce depressive symptoms in individuals with treatment-resistant depression (TRD). The clinical and functional outcomes of DBS for TRD have been well documented in previous studies; however, studies of personal recovery as an outcome of DBS specific to the target of subcallosal cingulate cortex in patients with TRD are limited. Aim To explore the processes of personal recovery in patients with treatment-resistant depression following subcallosal cingulate-deep brain stimulation. Method Participants were 18 patients with TRD who participated in the subcallosal cingulate (SCC)-DBS trial and 11 family members. They also participated in add-on individual cognitive behavioural therapy during the trial. A qualitative constructivist grounded theory approach was used to conceptualize the personal recovery process of patients and families. Results While every participant and their families' journey were unique following the deep brain stimulation intervention, a theoretical model of Balancing to Establish a Reconstructed Self emerged from the data. The themes underlying the model were (1) Balancing to Establish a Reconstructed Self: A Whole-Body Experience, (2) The Liminal Space in-between: Balancing with Cautious Optimism, (3) Hope: Transitioning from Emotion-Focussed Living to Goal-Oriented Planning and (4) Support: Negotiating Relationships. Discussion This is the first study examining recovery from patients' perspectives as an outcome of SCC-DBS intervention for TRD. The study shows that personal recovery is a gradual and continual process of reconstruction of the self, developing through supportive relationships. Clinical and personal recovery are two distinct constructs, and individuals may experience one or the other or both. Most patients who do respond clinically experience improvement in terms of having optimism and hope. Some patients, however, respond with significant symptom reduction but are not able to achieve personal recovery to experience joy or hope for improved quality of living. Implications for Practice Strategies for personal recovery for both patients and family need to be considered during and post deep brain stimulation intervention. Nurses working with these patients and families may benefit from education, training and support to assess and engage in conversations about their recovery process.

510 Prospective, Multicenter, International Outcomes Study of Deep Brain Stimulation for Essential Tremor

INTRODUCTION: Essential Tremor (ET) treatment is focused on medical management of motor symptoms and includes pharmacotherapy and ventral intermediate nucleus (VIM) thalamotomy, which is being largely replaced by thalamic Deep Brain Stimulation (DBS) as the surgical treatment of choice. DBS of the VIM thalamus is recommended as a therapeutic option for appropriate subjects with ET (Elble RJ., et al. Expert Rev Neurother. 2018). METHODS: This is a prospective, on-label, multi-center, international DBS outcomes study conducted at up to 50 implanting centers. All participants are implanted with a multiple-source, constant-current directional DBS system (Vercise, Boston Scientific). Subjects are followed for up to 3-years post implantation where their overall improvement in quality of life and ET symptoms are evaluated. Clinical endpoints evaluated at baseline and follow-up timepoints include: The Essential Tremor Rating Assessment Scale (TETRAS), Quality of Life in Essential Tremor Questionnaire (QUEST), Fahn-Tolosa-Marin Rating Scale (TRS), and Global Impression of Change. Adverse events also collected. RESULTS: To date, 18-implanted subjects with a mean disease duration of 15.1 ± 14.6-years and a baseline QUEST Summary Index score of 35.0 ± 12.4. At 6-months post-DBS, a clinically significant improvement in quality of life (∆ = 19.5-point change in QUEST SI score) was reported. In addition, a mean 9-hours of tremor reduction was noted (14-hours at Baseline, 6.9-hours at 6-months) in a typical day at 6-months. All subjects (100%) reported mild disability, and no subject reported moderate or marked disability (89% at baseline) as reported by TRS at 6 months. CONCLUSIONS: This work represents the first comprehensive, large scale collection of real-world outcomes and evaluation of safety and effectiveness of a multiple-source, constant-current DBS system capable of providing directionality for use in treatment of Essential Tremor.

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region

Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease.

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus (N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor (N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes (P = 0.9) but a higher frequency (P = 0.009) and a higher number of peaks (P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes (P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease.

Deep brain stimulation in Lesch-Nyhan syndrome: a systematic review.

Given the good results of deep brain stimulation (DBS) in the treatment of movement disorders, DBS was initially tried to treat Lesch-Nyhan syndrome (LNS) with the aim to alleviate LNS-related dystonia. Some cases have reported clinical results of DBS in LNS thus far. This systematic review was conducted to comprehensively summarize cases of LNS treated with DBS and evaluate the efficacy and safety of DBS in LNS. Eight publications covering 12 LNS patients were included in this review. DBS improved dystonia of the LNS to varying degrees. All the included cases achieved partial or complete control of self-injurious behavior (SIB). Overall, DBS is a promising treatment for both motor and behavior disorders of LNS patients, but the results reported thus far have varied widely, especially for motor outcomes. The ultimate clinical benefits in LNS patients were still unpredictable. DBS-related complications were rather common, which raised questions about the safety of the procedure in LNS. More research is needed to further clarify the safety and effectiveness of this treatment.

Commentary: Targeting Accuracy and Clinical Outcomes of Awake versus Asleep Interventional Magnetic Resonance Imaging-Guided Deep Brain Stimulation for Parkinson's Disease: The University of California, San Francisco Experience.

*Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA; ‡Neurology Service, Jesse Brown Veterans Administration Medical Center, Chicago, Illinois, USA Correspondence: Konstantin V. Slavin, MD, Department of Neurosurgery, University of Illinois at Chicago, 912 South Wood St M/C 799, Chicago, IL60612, USA. Email: [email protected]

The mortality of patients with Parkinson's disease with deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in improving motor function in patients with Parkinson's disease (PD). This study aimed to investigate mortality associated with bilateral STN DBS in patients with PD and to assess the factors associated with mortality and causes of death after DBS. We reviewed the medical records of 257 patients with PD who underwent bilateral STN DBS at the Movement Disorder Center at Seoul National University Hospital between March 2005 and November 2018. Patients were evaluated preoperatively, at 3, 6, and 12 months after surgery and annually thereafter. The cause and date of death were obtained from interviews with caregivers or from medical certificates at the last follow-up. Of the 257 patients with PD, 48 patients (18.7%) died, with a median time of death of 11.2 years after surgery. Pneumonia was the most common cause of death. Older age of disease onset, preoperative falling score while on medication, and higher preoperative total levodopa equivalent daily dose were associated with a higher risk of mortality in time-dependent Cox regression analysis. These results confirm the mortality outcome of STN DBS in patients with advanced PD.

Towards biomarker-based optimization of deep brain stimulation in Parkinson's disease patients.

Subthalamic deep brain stimulation (DBS) is an established therapy to treat Parkinson's disease (PD). To maximize therapeutic outcome, optimal DBS settings must be carefully selected for each patient. Unfortunately, this is not always achieved because of: (1) increased technological complexity of DBS devices, (2) time restraints, or lack of expertise, and (3) delayed therapeutic response of some symptoms. Biomarkers to accurately predict the most effective stimulation settings for each patient could streamline this process and improve DBS outcomes. To investigate the use of evoked potentials (EPs) to predict clinical outcomes in PD patients with DBS. In ten patients (12 hemispheres), a monopolar review was performed by systematically stimulating on each DBS contact and measuring the therapeutic window. Standard imaging data were collected. EEG-based EPs were then recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. Linear mixed models were used to assess how well both EPs and image-derived information predicted the clinical data. Evoked potential peaks at 3 ms (P3) and at 10 ms (P10) were observed in nine and eleven hemispheres, respectively. Clinical data were well predicted using either P3 or P10. A separate model showed that the image-derived information also predicted clinical data with similar accuracy. Combining both EPs and image-derived information in one model yielded the highest predictive value. Evoked potentials can accurately predict clinical DBS responses. Combining EPs with imaging data further improves this prediction. Future refinement of this approach may streamline DBS programming, thereby improving therapeutic outcomes. ClinicalTrials.gov, identifier NCT04658641.

Gender-specific outcomes of deep brain stimulation for Parkinson’s disease — results from a single movement disorder center

Introduction and goalThe investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson’s disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve therapeutic counseling.MethodsWe analyzed clinical outcome parameters of 203 patients with PD that underwent DBS surgery targeting the subthalamic nucleus (STN) at our movement disorder center. A total of 27.6% of patients were female and 72.4% male. Motor and non-motor scores were compared before and 1 year after DBS surgery (1y FU) using Wilcoxon signed-rank tests and gender specific outcomes were analyzed with chi-square tests.ResultsAt 1y FU, we found significant improvement in UPDRS II, UPDRS III (35.78 ± 36.14% MedOFF vs. StimON-MedOFF), UPDRS IV, depression (BDI-II), and health-related disability as (ADL) that showed no gender-specific differences. No significant change was revealed for UPDRS I, QUIP, and DemTect for the entire cohort. However, when analyzing both groups separately, only women improved in general cognition (plus 1.26 ± 3.03 DemTect points, p = 0.014*), whereas only men ameliorated in depression (minus 1.97 ± 6.92 BDI-II points, p = 0.002**) and impulsivity (minus 2.80 ± 7.27 QUIP points, p = 0.004**). Chi-square tests, however, revealed no significant differences between genders.Conclusion and outlookSTN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in non-motor-domains like cognition, depressive symptoms, and impulsivity. To explore this in more detail, larger cohorts need to be investigated in multicenter trials.

Morphologic brain network predicts levodopa responsiveness in Parkinson disease.

The levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines recommend that patients with an improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-III score > 33% in the LCT receive DBS treatment. However, LCT results are affected by many factors, and only provide information on the immediate effectiveness of dopamine. The aim of the present study was to investigate the relationship between LCT outcome and brain imaging features of PD patients to determine whether the latter can be used to identify candidates for DBS. A total of 38 PD patients were enrolled in the study. Based on improvement in UPDRS-III score in the LCT, patients were divided into low improvement (PD-LCT-L) and high improvement (PD-LCT-H) groups. Each patient's neural network was reconstructed based on T1-weighted magnetic resonance imaging data using the Jensen-Shannon divergence similarity estimation method. The network was established with the multiple kernel support vector machine technique. We analyzed differences in individual morphologic brain networks and their global and local metrics to determine whether there were differences in the connectomes of PD-LCT-L and PD-LCT-H groups. The 2 groups were similar in terms of demographic and clinical characteristics. Mean ± SD levodopa responsiveness was 26.52% ± 3.47% in the PD-LCT-L group (N = 13) and 58.66% ± 4.09% in the PD-LCT-H group (N = 25). There were no significant differences between groups in global and local metrics. There were 43 consensus connections that were affected in both groups; in PD-LCT-L patients, most of these connections were decreased whereas those related to the dorsolateral superior frontal gyrus and left cuneus were significantly increased. Morphologic brain network assessment is a valuable method for predicting levodopa responsiveness in PD patients, which can facilitate the selection of candidates for DBS.

Relationship Between Iron Distribution in Deep Gray Matter Nuclei Measured by Quantitative Susceptibility Mapping and Motor Outcome After Deep Brain Stimulation in Patients With Parkinson's Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor deficits in advanced Parkinson's disease (PD) patients, but the degree of motor improvement varies across individuals. PD pathology involves the changes of iron spatial distribution in the deep gray matter nuclei. To explore the relationship between the iron spatial distribution and motor improvement among PD patients who underwent STN-DBS surgery in three regions: substantia nigra (SN), STN, and dentate nucleus (DN). Prospective. Forty PD patients (49.7 ± 8.8 years, 22 males/18 females) who underwent bilateral STN-DBS. A 3 T preoperative three-dimensional spoiled bipolar-readout multi-echo gradient recalled echo and two-dimensional fast spin echo sequences. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) scores were assessed 2-3 days before and 6 months after STN-DBS. The first- and second-order texture features in regions of interest were measured on susceptibility maps. Intraclass correlation coefficient was used to determine the consistency of the region of interest volumes delineated by the two raters. Pearson or Spearman's correlation coefficients were used to assess the relationship between motor improvement after DBS and texture features. A P-value <0.05 was considered statistically significant. MDS-UPDRS III scores were reduced by 59.9% after STN-DBS in 40 PD patients. Motor improvement correlated with second-order texture parameters in the SN including angular second moment (r=-0.449), correlation (rho=0.326), sum of squares (r=0.402), sum of entropy (rho=0.421), and entropy (r=0.410). Additionally, DBS outcome negatively correlated with mean susceptibility values in the DN (r=-0.400). PD patients with a more homogeneous iron distribution throughout the SN or a higher iron concentration in the DN responded worse to STN-DBS. 2 TECHNICAL EFFICACY: Stage 1.

Mortality of Deep Brain Stimulation and Risk Factors in Patients With Parkinson's Disease: A National Cohort Study in Korea.

This study aimed to investigate 1) long-term outcomes of deep brain stimulation (DBS), such as mortality after DBS as well as the causes of death, 2) demographic and socioeconomic factors influencing mortality, and 3) comorbidities affecting mortality after DBS in patients with Parkinson's disease (PD). This study analyzed the National Health Insurance Service-National Health Information Database. Data on patients with PD diagnosis codes from 2002 to 2019 were extracted and analyzed. Data on the causes of death were obtained by linking the causes of death to data from Statistics Korea. The Kaplan-Meier method with the log-rank test was used for survival analysis. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and their 95% confidence intervals. Regarding comorbidities such as PD dementia and fracture, which did not satisfy the assumption for the proportional HR, time-dependent Cox analysis with the Mantel-Byar method was used. From 2005 to 2017, among 156,875 patients diagnosed with PD in Korea, 1,079 patients underwent DBS surgery, and 251 (23.3%) had died by 2019. The most common cause of death (47.1%) was PD. In the multivariate Cox regression analysis, the higher the age at diagnosis and surgery, the higher the mortality rate. The men and medical aid groups had significantly higher mortality rates. PD dementia and fracture were identified as risk factors for mortality. Older age at diagnosis and surgery, being male, the use of medical aid, and the comorbidity of dementia and fractures were associated with a higher risk of mortality after DBS in patients with PD. Neurologists should consider these risk factors in assessing the prognosis of PD patients undergoing DBS.