Focal Subthalamic Atrophy after Long-Term Deep Brain Stimulation in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Gelpi E
PROVIDER: S-EPMC8453839 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. METHODS:Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ?6 months but ?4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. RESULTS:As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. CONCLUSIONS:This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
| S-EPMC4103427 | biostudies-literature
Project description:Patients aged 65 years and older are not traditionally considered optimal candidates for subthalamic deep brain stimulation (STN-DBS), mainly for their presumed increased incidence of surgical complications. The aim of this study was to assess STN-DBS surgery safety in relation to age.A total of 107 consecutive patients undergoing bilateral STN-DBS at our institution between 2002 and 2014 were retrospectively stratified according to age in two groups (Young group < 65 years old; Elderly group ≥ 65 years old;). Rate of short-term surgical complications (within 90 days) was reviewed and compared between the two groups.Pre-operative baseline data were comparable between the two groups. The 90-days post-operative mortality rate was 0%. Overall incidence of complications related to surgery was 6,54%. In the Elderly group we observed 3 post-operative intra-cerebral haematomas (7,89%), 1 requiring urgent surgical evacuation. In the Young group we observed 2 post-operative asymptomatic intra-cerebral haematomas (2,89%) and 2 wound infections (2,89%), 1 requiring system removal. No others surgical complications were noticed in both groups.Chronological age ≥ 65 years old should not be considered alone as exclusion criteria to STN-DBS surgery.
| S-EPMC4595247 | biostudies-other
Project description:BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson's disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording.MethodsA cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5?years, with a subgroup of 12 patients being followed for 8-11?years. Motor status was evaluated using part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes.ResultsSTN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8?years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8?years respectively.ConclusionsOur data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.
| S-EPMC4451170 | biostudies-literature
Project description:Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.
| S-EPMC3413674 | biostudies-literature
Project description:Parkinson's disease (PD) is a complex multisystem disorder with motor and non-motor symptoms (NMS). NMS may have an even greater impact on quality of life than motor symptoms. Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor fluctuations and quality of life, whereas the effects on different NMS have been less examined. Sleep disturbances and autonomic dysfunction are among the most prevalent NMS. We here report the efficacy of STN-DBS on sleep disturbances and autonomic dysfunction. In the parent trial, 60 patients were included in a single-center randomized prospective study, with MDS-UPDRS III and PDQ-39 as primary endpoints at 12 months of STN-DBS. Preplanned assessments at baseline and postoperatively at 3 and 12 months also included Parkinson's Disease Sleep Scale (PDSS); Scopa-Aut; and MDS-UPDRS I, II, and IV. We found that STN-DBS had a significant and lasting positive effect on overall sleep quality, nocturnal motor symptoms and restlessness, and daytime dozing. Several aspects of autonomic dysfunction were also improved at 3 months postoperatively, although at 12 months only thermoregulation (sudomotor symptoms) remained significantly improved. We could not identify preoperative factors that predicted improvement in PDSS or Scopa-Aut. There was a close relationship between improved autonomic symptoms and improved quality of life after 1 year. NMS and especially sleep and autonomic dysfunction deserve more focus to improve patient outcomes further.
| S-EPMC7560751 | biostudies-literature
Project description:Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state (18)F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ?11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.
| S-EPMC3137472 | biostudies-literature
Project description:Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken. We examined this matter in a consecutive sample of 64 persons with Parkinson's disease undertaking subthalamic deep brain stimulation. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with emergent, clinically-significant symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to putative limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated specific subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms. Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency task at 6-weeks (p?=?0.023) and 13-weeks postoperatively (p?=?0.0017). A cluster of subthalamic voxels associated with inhibitory errors was identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion (p?=?0.0026) and stimulation within the right associative subregion (p?=?0.0009). At 13-weeks, clinically-significant symptoms were associated with the distance to the right (p?=?0.0027) and left (p?=?0.0084) associative subregions and stimulation within the right associative subregion (p?=?0.0026). Discrete clusters of subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. When a classifier was trained on these data, clinically-significant symptoms were predicted with an accuracy of 79%. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.
| S-EPMC5988013 | biostudies-literature
Project description:Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.
| S-EPMC8421387 | biostudies-literature
Project description:ObjectivesFirstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.MethodsHigh angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.ResultsAll patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.InterpretationThese findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
| S-EPMC6581538 | biostudies-literature
Project description:Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and proven treatment option for patients with advanced Parkinson's disease (PD). Long-term outcomes (>5 years) have demonstrated sustained improvement in objective motor symptoms; however, few studies have evaluated patient-centered outcomes other than quality of life (QOL). A locally developed DBS-patient-centered outcomes questionnaire was administered to PD patients >5 years post-DBS. All questions were scored on a ten-point scale, whereby 0 represented the most 'positive' answer and 10 the most 'negative' answer. Pre-operative scales were repeated at the time of survey. Fifty-two patients (mean 8.2 ± 2.6 years post-DBS) were included. Satisfaction was high with median score (range) of 1/10 (0-8) at the time of survey. Patients endorsed having made the correct decision by undergoing DBS, with a score of 0 (0-10), would choose to have DBS again, with a score of 0 (0-10), and would recommend DBS to others, with a score of 0 (0-10). Pre-operative expectation target was set at a high level with a score of 2 (0-10). Parkinson's Disease QOL (PDQ-39) Questionnaire Summary Index (SI) scores were, mean (SD), 2.1 (18.2) above baseline (p = 0.44). Those with worsening in PDQ-39-SI scores had less satisfaction with DBS (rs = 0.57, p ? 0.0001). This is the first study to assess long-term patient satisfaction with STN DBS. We are currently collecting data prospectively to confirm the results of these preliminary findings.
| S-EPMC5924396 | biostudies-literature