Physiology of dystonia: Human studies.

In this chapter, we discuss neurophysiological techniques that have been used in the study of dystonia. We examine traditional disease models such as inhibition and excessive plasticity and review the evidence that these play a causal role in pathophysiology. We then review the evidence for sensory and peripheral influences within pathophysiology and look at an emergent literature that tries to probe how oscillatory brain activity may be linked to dystonia pathophysiology

Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

Introduction. Neuropsychiatric symptoms in Parkinson's disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's disease (SEND-PD) has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson's disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9 ± 3.1 (range from 0 to 16). The neuropsychiatric MDS-UPDRS part IA score was 2.9 ± 3 (range from 0 to 14). The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was r s = 0.93 (all, P < 0.001). Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.S

Acute effects of adaptive Deep Brain Stimulation in Parkinson's disease

Background: Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson's disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed. Methods: To determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson's Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT). Results: Mean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS. Conclusion: Beta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy

Adaptive Deep Brain Stimulation for Parkinson’s Disease and Dystonia

Deep brain stimulation (DBS) is a neurosurgical treatment, in which electrodes are implanted in deep regions of the brain. This procedure can be used to treat patients with movement disorders, such as Parkinson’s disease (PD) and dystonia. The implanted electrodes deliver electrical pulses, that help to control the main disease symptoms. Until recently, stimulation could only be continuously applied, without taking into account daily symptom fluctuations. Adaptive DBS (aDBS) is an upgrade of this treatment. With aDBS, the stimulation delivered is regulated (in real time), based on the severity of symptoms. To indicate when and how stimulation should be delivered, brain oscillations are used as feedback signal. These oscillations are able to reflect the clinical state of the patients. By dynamically adjusting the stimulation according to the needs of each patient, aDBS might be able to provide a better symptom control. In addition to this, aDBS could prevent the occurrence of side effects caused by excessive stimulation. This thesis investigates the intraoperative efficacy of aDBS in patients with PD and dystonia at the University Medical Center Groningen, The Netherlands. The first part of this thesis describes the characteristics of the signals that can be used to estimate the severity of symptoms in these patients. The second and third parts of the thesis evaluate the immediate effects of aDBS in patients with PD and dystonia, respectively. The main conclusions are that aDBS is effective for PD, and feasible for dystonia. This opens the possibility to further investigate aDBS outside the hospital

Adaptive deep brain stimulation as advanced Parkinson's disease treatment (ADAPT study): protocol for a pseudo-randomised clinical study

INTRODUCTION: Adaptive 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 ANALYSIS: This 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 DISSEMINATION: This 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 NUMBER: NTR 5456; Pre-results

Diving into the subcortex: The potential of chronic subcortical sensing for unravelling basal ganglia function and optimization of deep brain stimulation

Subcortical structures are a relative neurophysiological ‘terra incognita’ owing to their location within the skull. While perioperative subcortical sensing has been performed for more than 20 years, the neurophysiology of the basal ganglia in the home setting has remained almost unexplored. However, with the recent advent of implantable pulse generators (IPG) that are able to record neural activity, the opportunity to chronically record local field potentials (LFPs) directly from electrodes implanted for deep brain stimulation opens up. This allows for a breakthrough of chronic subcortical sensing into fundamental research and clinical practice. In this review an extensive overview of the current state of subcortical sensing is provided. The widespread potential of chronic subcortical sensing for investigational and clinical use is discussed. Finally, status and future perspectives of the most promising application of chronic subcortical sensing —i.e., adaptive deep brain stimulation (aDBS)— are discussed in the context of movement disorders. The development of aDBS based on both chronic subcortical and cortical sensing has the potential to dramatically change clinical practice and the life of patients with movement disorders. However, several barriers still stand in the way of clinical implementation. Advancements regarding IPG and lead technology, physiomarkers, and aDBS algorithms as well as harnessing artificial intelligence, multimodality and sensing in the naturalistic setting are needed to bring aDBS to clinical practice