Neuropsychiatric Side Effects of Deep Brain Stimulation in Parkinson’s Disease

2012 ◽  
pp. 159-173 ◽  
Author(s):  
Christine Daniels ◽  
Jens Volkmann
Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2235-2254 ◽  
Author(s):  
Philip E Mosley ◽  
Saee Paliwal ◽  
Katherine Robinson ◽  
Terry Coyne ◽  
Peter Silburn ◽  
...  

Abstract Subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease treats motor symptoms and improves quality of life, but can be complicated by adverse neuropsychiatric side-effects, including impulsivity. Several clinically important questions remain unclear: can ‘at-risk’ patients be identified prior to DBS; do neuropsychiatric symptoms relate to the distribution of the stimulation field; and which brain networks are responsible for the evolution of these symptoms? Using a comprehensive neuropsychiatric battery and a virtual casino to assess impulsive behaviour in a naturalistic fashion, 55 patients with Parkinson’s disease (19 females, mean age 62, mean Hoehn and Yahr stage 2.6) were assessed prior to STN-DBS and 3 months postoperatively. Reward evaluation and response inhibition networks were reconstructed with probabilistic tractography using the participant-specific subthalamic volume of activated tissue as a seed. We found that greater connectivity of the stimulation site with these frontostriatal networks was related to greater postoperative impulsiveness and disinhibition as assessed by the neuropsychiatric instruments. Larger bet sizes in the virtual casino postoperatively were associated with greater connectivity of the stimulation site with right and left orbitofrontal cortex, right ventromedial prefrontal cortex and left ventral striatum. For all assessments, the baseline connectivity of reward evaluation and response inhibition networks prior to STN-DBS was not associated with postoperative impulsivity; rather, these relationships were only observed when the stimulation field was incorporated. This suggests that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure and that stimulation acts to mediate impulsivity through differential recruitment of frontostriatal networks. Notably, a distinction could be made amongst participants with clinically-significant, harmful changes in mood and behaviour attributable to DBS, based upon an analysis of connectivity and its relationship with gambling behaviour. Additional analyses suggested that this distinction may be mediated by the differential involvement of fibres connecting ventromedial subthalamic nucleus and orbitofrontal cortex. These findings identify a mechanistic substrate of neuropsychiatric impairment after STN-DBS and suggest that tractography could be used to predict the incidence of adverse neuropsychiatric effects. Clinically, these results highlight the importance of accurate electrode placement and careful stimulation titration in the prevention of neuropsychiatric side-effects after STN-DBS.


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e029652 ◽  
Author(s):  
Dan Piña-Fuentes ◽  
Martijn Beudel ◽  
Simon Little ◽  
Peter Brown ◽  
D L Marinus Oterdoom ◽  
...  

IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson’s disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson’s disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.


2017 ◽  
Vol 89 (7) ◽  
pp. 687-691 ◽  
Author(s):  
Allen L Ho ◽  
Rohaid Ali ◽  
Ian D Connolly ◽  
Jaimie M Henderson ◽  
Rohit Dhall ◽  
...  

ObjectiveNo definitive comparative studies of the efficacy of ‘awake’ deep brain stimulation (DBS) for Parkinson’s disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques.MethodsWe conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up. There were 145 studies, 16 of which were under general anaesthesia. Data were pooled using an inverse-variance weighted, random effects meta-analytic model for observational data.ResultsThere was no significant difference in mean target error between local and general anaesthesia, but there was a significantly less mean number of DBS lead passes with general anaesthesia (p=0.006). There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia (p<0.001). There were no significant differences in Unified Parkinson’s Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, p=0.022).ConclusionsOur meta-analysis demonstrates that while DBS under general anaesthesia may lead to lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS or prefer the asleep alternative.


2020 ◽  
Vol 91 (8) ◽  
pp. e6.1-e6
Author(s):  
Peter Brown

Professor Peter Brown is Professor of Experimental Neurology and Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. Prior to 2010 he was a Professor of Neurology at University College London.For decades we have had cardiac pacemakers that adjust their pacing according to demand and yet therapeutic adaptive stimulation approaches for the central nervous system are still not clinically available. Instead, to treat patients with advanced Parkinson’s disease we stimulate the basal ganglia with fixed regimes, unvarying in frequency or intensity. Although effective, this comes with side-effects and in terms of sophistication this treatment approach could be compared to having central heating system on all the time, regardless of temperature. This talk will describe recent steps being taken to define the underlying circuit dysfunction in Parkinson’s and to improve deep brain stimulation by controlling its delivery according to the state of pathological activity.Evidence is growing that motor symptoms in Parkinson’s disease are due, at least in part, to excessive synchronisation between oscillating neurons. Recordings confirm bursts of oscillatory synchronisation in the basal ganglia centred around 20 Hz. The bursts of 20 Hz activity are prolonged in patients withdrawn from their usual medication and the dominance of these long duration bursts negatively correlates with motor impairment. Longer bursts attain higher amplitudes, indicative of more pervasive oscillatory synchronisation within the neural circuit. In contrast, in heathy primates and in treated Parkinson’s disease bursts tend to be short. Accordingly, it might be best to use closed-loop controlled deep brain stimulation to selectively terminate longer, bigger, pathological beta bursts to both save power and to spare the ability of underlying neural circuits to engage in more physiological processing between long bursts. It is now possible to record and characterise bursts on-line during stimulation of the same site and trial adaptive stimulation. Thus far, this has demonstrated improvements in efficiency and side-effects over conventional continuous stimulation, with at least as good symptom control in Parkinsonian patients.


Neurosurgery ◽  
2010 ◽  
Vol 66 (5) ◽  
pp. E1029-E1029 ◽  
Author(s):  
Jong Hyun Kim ◽  
Taek-Hyun Kwon ◽  
Seong-Beom Koh ◽  
Jung Youl Park

Abstract OBJECTIVE Deep brain stimulation is an alternative treatment for advanced Parkinson's disease. Levodopa medications are usually discontinued the night before surgery to localize the optimal response site to intraoperative macrostimulation. However, abrupt withdrawal of medication may result in side effects. We report a case of parkinsonism-hyperpyrexia syndrome (PHS), a rare complication resulting from discontinuation of antiparkinsonian medication, after a deep brain stimulation (DBS) procedure for bilateral subthalamic-nucleus (STN). CLINICAL PRESENTATION A 66-year-old woman with an 11-year history of idiopathic Parkinson's disease was admitted for DBS. She had experienced wearing-off symptoms, severe peak-dose dyskinesia, and medication-induced side effects. Antiparkinsonian medication was discontinued 2 days before surgery because of severe drug-related complications. DBS for bilateral STN was performed uneventfully, but the patient was unconscious with fever, tachycardia, and hypertension after surgery. INTERVENTION Levodopa and dopamine agonist replacement by nasogastric tube and hydration were immediately administered with conservative treatment for the hypertension, tachycardia, and fever. The patient's serum creatine kinase level increased to 786 U/L 3 days after the surgery and then decreased gradually as the patient's consciousness improved. CONCLUSION Physicians should be aware of the possibility of PHS after a deep brain stimulation procedure. If the patient shows unexplained changes in consciousness with hyperpyrexia after surgery, PHS should be considered and adequate treatment should be given immediately to prevent death.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lauren E. Schrock ◽  
Remi Patriat ◽  
Mojgan Goftari ◽  
Jiwon Kim ◽  
Matthew D. Johnson ◽  
...  

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for Parkinson’s disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead “anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) produces similar clinical efficacy.” These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson’s disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla (7 T) magnetic resonance imaging (MRI) data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories.


2021 ◽  
Author(s):  
Quirin David Strotzer ◽  
Zacharias Kohl ◽  
Judith Maria Anthofer ◽  
Rupert Faltermeier ◽  
Nils-Ole Schmidt ◽  
...  

2008 ◽  
Vol 20 (4) ◽  
pp. 182-192 ◽  
Author(s):  
Linton J. Meagher ◽  
Ralf Ilchef ◽  
Paul Silberstein ◽  
Raymond J. Cook ◽  
Daniel Wasson ◽  
...  

Objective:To provide a comprehensive review and evaluation of the literature pertaining to the psychiatric sequelae of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD).Methods:A structured search of the EMBASE, PsychINFO and MEDLINE databases was performed on articles published since the first use of STN DBS in 1993 for PD until March 2007. Non-human studies were excluded, along with studies reporting on unilateral DBS and studies reporting on the use of STN DBS for indications other than idiopathic PD. Ninety-seven articles were selected for inclusion in the review.Results:Patients with advanced PD have a high rate of psychiatric morbidity. STN DBS has been shown to be an effective treatment for the control of motor symptoms in advanced PD. Neurobehavioural side-effects are, however, relatively common following STN DBS. Side-effects include impaired executive function and verbal fluency, depression, hypomania, apathy, postoperative delirium, anxiety disorders and psychotic symptoms, especially hallucinations. The alteration in dopaminergic medication following surgery as well as the direct effect of STN stimulation both appear to contribute to the short-term and long-term postoperative psychiatric complications. Methodological issues that limit the applicability of the current literature in this field are highlighted.Conclusions:STN DBS is an effective treatment for the motor symptoms of advanced PD. However, further research is needed to assess the extent to which STN DBS contributes to or exacerbates psychiatric morbidity over and above that associated with advanced PD. Careful neuropsychiatric evaluation and monitoring are required in this patient group.


Author(s):  
Fadi Almahariq ◽  
Goran Sedmak ◽  
Vladimira Vuletić ◽  
Domagoj Dlaka ◽  
Darko Orešković ◽  
...  

Abstract Introduction In 33 consecutive patients with Parkinson's disease (PD) undergoing awake deep brain stimulation (DBS) without microelectrode recording (MER), we assessed and validated the precision and accuracy of direct targeting of the subthalamic nucleus (STN) using preoperative magnetic resonance imaging (MRI) and stereotactic computed tomography (CT) image fusion combined with immediate postoperative stereotactic CT and postoperative MRI, and we report on the side effects and clinical results up to 6 months' follow-up. Materials and Methods Preoperative nonstereotactic MRI and stereotactic CT images were merged and used for planning the trajectory and final lead position. Immediate postoperative stereotactic CT and postoperative nonstereotactic MRI provided the validation of the final electrode position. Changes in the Unified Parkinson's Disease Rating Scale III (UPDRS III) scores and the levodopa equivalent daily doses (LEDD) and appearance of adverse side effects were assessed. Results The mean Euclidian distance (ED) error between the planned position and the final position of the lead in the left STN was 1.69 ± 0.82 mm and that in the right STN was 2.12 ± 1.00. The individual differences between planned and final position in each of the three coordinates were less than 2 mm. The UPDRS III scores improved by 75% and LEDD decreased by 45%. Few patients experienced complications, such as postoperative infection (n = 1), or unwanted side effects, such as emotional instability (n = 1). Conclusion Our results confirm that direct targeting of an STN on stereotactic CT merged with MRI could be a valid method for placement the DBS electrode. The magnitude of our targeting error is comparable with the reported errors when using MER and other direct targeting approaches.


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