Deep Brain Stimulation for Orthostatic Tremor: An Observational Study.

BACKGROUND: Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. OBJECTIVE: To evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects. METHODS: Nine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. RESULTS: Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS. CONCLUSION: Vim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.

Subhairline Electroencephalography for the Detection of Large Vessel Occlusion Stroke.

BACKGROUND: Endovascular thrombectomy is standard treatment for patients with anterior circulation large vessel occlusion stroke (LVO-a). Prehospital identification of these patients would enable direct routing to an endovascular thrombectomy-capable hospital and consequently reduce time-to-endovascular thrombectomy. Electroencephalography (EEG) has previously proven to be promising for LVO-a stroke detection. Fast and reliable electrode application, however, can remain a challenge. A potential alternative is subhairline EEG. We evaluated the diagnostic accuracy of subhairline EEG for LVO-a stroke detection. METHODS AND RESULTS: We included adult patients with a suspected stroke or known LVO-a stroke and symptom onset time <24 hours. A single 3-minute EEG recording was performed at the emergency department, before endovascular thrombectomy, using 9 self-adhesive electrodes placed on the forehead and behind the ears. We evaluated the diagnostic accuracies of EEG features quantifying frequency band power and brain symmetry (pairwise derived Brain Symmetry Index) for LVO-a stroke detection using receiver operating characteristic analysis. EEG data were of sufficient quality for analysis in 51/52 (98%) included patients. Of these patients, 16 (31%) had an LVO-a stroke, 16 (31%) a non-LVO-a ischemic stroke, 5 (10%) a transient ischemic attack, and 14 (27%) a stroke mimic. Median symptom-onset-to-EEG-time was 266 (interquartile range 130-709) minutes. The highest diagnostic accuracy for LVO-a stroke detection was reached by the pairwise derived Brain Symmetry Index in the theta frequency band (area under the receiver operating characteristic curve 0.90; sensitivity 86%; specificity 83%). CONCLUSIONS: Subhairline EEG could detect LVO-a stroke with high diagnostic accuracy and had high data reliability. These data suggest that subhairline EEG is potentially suitable as a prehospital stroke triage instrument.

Prehospital Detection of Large Vessel Occlusion Stroke With EEG.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time to EVT by allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic accuracy of dry electrode EEG for the detection of LVO-a stroke in the prehospital setting. METHODS: ELECTRA-STROKE was an investigator-initiated, prospective, multicenter, diagnostic study, performed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed by the attending ambulance nurse) and symptom onset <24 hours. A single dry electrode EEG recording (8 electrodes) was performed by ambulance personnel. Primary endpoint was the diagnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1, or proximal M2 occlusion) detection among patients with EEG data of sufficient quality, expressed as the area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results. RESULTS: Between August 2020 and September 2022, 311 patients were included. The median EEG duration time was 151 (interquartile range [IQR] 151-152) seconds. For 212/311 (68%) patients, EEG data were of sufficient quality for analysis. The median age was 74 (IQR 66-81) years, 90/212 (42%) were women, and the median baseline NIH Stroke Scale was 1 (IQR 0-4). Six (3%) patients had an LVO-a stroke, 109/212 (51%) had a non-LVO-a ischemic stroke, 32/212 (15%) had a transient ischemic attack, 8/212 (4%) had a hemorrhagic stroke, and 57/212 (27%) had a stroke mimic. AUC of the theta/alpha ratio was 0.80 (95% CI 0.58-1.00). Of the secondary endpoints, the pairwise derived Brain Symmetry Index in the delta frequency band had the highest diagnostic accuracy (AUC 0.91 [95% CI 0.73-1.00], sensitivity 80% [95% CI 38%-96%], specificity 93% [95% CI 88%-96%], positive likelihood ratio 11.0 [95% CI 5.5-21.7]). DISCUSSION: The data from this study suggest that dry electrode EEG has the potential to detect LVO-a stroke among patients with suspected stroke in the prehospital setting. Toward future implementation of EEG in prehospital stroke care, EEG data quality needs to be improved. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT03699397. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients with suspected acute stroke.

Magnetoencephalography to measure the effect of contact point-specific deep brain stimulation in Parkinson's disease: A proof of concept study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for disabling fluctuations in motor symptoms in Parkinson's disease (PD) patients. However, iterative exploration of all individual contact points (four in each STN) by the clinician for optimal clinical effects may take months. OBJECTIVE: In this proof of concept study we explored whether magnetoencephalography (MEG) has the potential to noninvasively measure the effects of changing the active contact point of STN-DBS on spectral power and functional connectivity in PD patients, with the ultimate aim to aid in the process of selecting the optimal contact point, and perhaps reduce the time to achieve optimal stimulation settings. METHODS: The study included 30 PD patients who had undergone bilateral DBS of the STN. MEG was recorded during stimulation of each of the eight contact points separately (four on each side). Each stimulation position was projected on a vector running through the longitudinal axis of the STN, leading to one scalar value indicating a more dorsolateral or ventromedial contact point position. Using linear mixed models, the stimulation positions were correlated with band-specific absolute spectral power and functional connectivity of i) the motor cortex ipsilateral tot the stimulated side, ii) the whole brain. RESULTS: At group level, more dorsolateral stimulation was associated with lower low-beta absolute band power in the ipsilateral motor cortex (p = .019). More ventromedial stimulation was associated with higher whole-brain absolute delta (p = .001) and theta (p = .005) power, as well as higher whole-brain theta band functional connectivity (p = .040). At the level of the individual patient, switching the active contact point caused significant changes in spectral power, but the results were highly variable. CONCLUSIONS: We demonstrate for the first time that stimulation of the dorsolateral (motor) STN in PD patients is associated with lower low-beta power values in the motor cortex. Furthermore, our group-level data show that the location of the active contact point correlates with whole-brain brain activity and connectivity. As results in individual patients were quite variable, it remains unclear if MEG is useful in the selection of the optimal DBS contact point.

Differences in Olivo-Cerebellar Circuit and Cerebellar Network Connectivity in Essential Tremor: a Resting State fMRI Study.

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid-filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is "disconnected" from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group.

ELECTRA-STROKE: Electroencephalography controlled triage in the ambulance for acute ischemic stroke-Study protocol for a diagnostic trial.

Background: Endovascular thrombectomy (EVT) is the standard treatment for large vessel occlusion stroke of the anterior circulation (LVO-a stroke). Approximately half of EVT-eligible patients are initially presented to hospitals that do not offer EVT. Subsequent inter-hospital transfer delays treatment, which negatively affects patients' prognosis. Prehospital identification of patients with LVO-a stroke would allow direct transportation of these patients to an EVT-capable center. Electroencephalography (EEG) may be suitable for this purpose because of its sensitivity to cerebral ischemia. The hypothesis of ELECTRA-STROKE is that dry electrode EEG is feasible for prehospital detection of LVO-a stroke. Methods: ELECTRA-STROKE is an investigator-initiated, diagnostic study. EEG recordings will be performed in patients with a suspected stroke in the ambulance. The primary endpoint is the diagnostic accuracy of the theta/alpha ratio for the diagnosis of LVO-a stroke, expressed by the area under the receiver operating characteristic (ROC) curve. EEG recordings will be performed in 386 patients. Discussion: If EEG can be used to identify LVO-a stroke patients with sufficiently high diagnostic accuracy, it may enable direct routing of these patients to an EVT-capable center, thereby reducing time-to-treatment and improving patient outcomes. Clinical trial registration: ClinicalTrials.gov, identifier: NCT03699397.

Detection of large vessel occlusion stroke with electroencephalography in the emergency room: first results of the ELECTRA-STROKE study.

BACKGROUND: Prehospital detection of large vessel occlusion stroke of the anterior circulation (LVO-a) would enable direct transportation of these patients to an endovascular thrombectomy (EVT) capable hospital. The ongoing ELECTRA-STROKE study investigates the diagnostic accuracy of dry electrode electroencephalography (EEG) for LVO-a stroke in the prehospital setting. To determine which EEG features are most useful for this purpose and assess EEG data quality, EEG recordings are also performed in the emergency room (ER). Here, we report data of the first 100 patients included in the ER. METHODS: Patients presented to the ER with a suspected stroke or known LVO-a stroke underwent a single EEG prior to EVT. Diagnostic accuracy for LVO-a stroke of frequency band power, brain symmetry and phase synchronization measures were evaluated by calculating receiver operating characteristic curves. Optimal cut-offs were determined as the highest sensitivity at a specificity of ≥ 80%. RESULTS: EEG data were of sufficient quality for analysis in 65/100 included patients. Of these, 35/65 (54%) had an acute ischemic stroke, of whom 9/65 (14%) had an LVO-a stroke. Median onset-to-EEG-time was 266 min (IQR 121-655) and median EEG-recording-time was 3 min (IQR 3-5). The EEG feature with the highest diagnostic accuracy for LVO-a stroke was theta-alpha ratio (AUC 0.83; sensitivity 75%; specificity 81%). Combined, weighted phase lag index and relative theta power best identified LVO-a stroke (sensitivity 100%; specificity 84%). CONCLUSION: Dry electrode EEG is a promising tool for LVO-a stroke detection, but data quality needs to be improved and validation in the prehospital setting is necessary. (TRN: NCT03699397, registered October 9 2018).

OptimisAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies (ADAPT study): a protocol for a prospective diagnostic accuracy study of multimodality testing in patients suspected of a treatable idiopathic inflammatory myopathy.

INTRODUCTION: Idiopathic inflammatory myopathies (IIMs) excluding inclusion body myositis (IBM) are a group of heterogeneous autoimmune disorders characterised by subacute-onset and progressive proximal muscle weakness, which are frequently part of a multisystem autoimmune disorder. Reaching the diagnosis can be challenging, and no gold standard for the diagnosis of IIM exists. Diagnostic modalities include serum creatine kinase activity, muscle imaging (MRI or ultrasound (US)), electromyography (EMG), myositis autoantibody testing and muscle biopsy. Several diagnostic criteria have been developed for IIMs, varying in reported sensitivity and specificity. HYPOTHESIS: We hypothesise that an evidence-based diagnostic strategy, using fewer and preferably the least invasive diagnostic modalities, can achieve the accuracy of a complete panel of diagnostic tests, including MRI, US, EMG, myositis-specific autoantibody testing and muscle biopsy. METHODS AND ANALYSIS: The OptimizAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies study is a prospective diagnostic accuracy study with an over-complete study design. 100 patients suspected of an IIM excluding IBM will be included. A reference diagnosis will be assigned by an expert panel using all clinical information and all results of all ancillary tests available, including 6 months of follow-up. Several predefined diagnostic strategies will be compared against the reference diagnosis to find the optimal diagnostic strategy. ETHICS AND DISSEMINATION: Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, The Netherlands (2019-814). The results will be distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: Netherlands trial register; NL8764.

Detection of Large Vessel Occlusion Stroke in the Prehospital Setting: Electroencephalography as a Potential Triage Instrument.

A reliable and fast instrument for prehospital detection of large vessel occlusion (LVO) stroke would be a game-changer in stroke care, because it would enable direct transportation of LVO stroke patients to the nearest comprehensive stroke center for endovascular treatment. This strategy would substantially improve treatment times and thus clinical outcomes of patients. Here, we outline our view on the requirements of an effective prehospital LVO detection method, namely: high diagnostic accuracy; fast application and interpretation; user-friendliness; compactness; and low costs. We argue that existing methods for prehospital LVO detection, including clinical scales, mobile stroke units and transcranial Doppler, do not fulfill all criteria, hindering broad implementation of these methods. Instead, electroencephalography may be suitable for prehospital LVO detection since in-hospital studies have shown that quantification of hypoxia-induced changes in the electroencephalography signal have good diagnostic accuracy for LVO stroke. Although performing electroencephalography measurements in the prehospital setting comes with challenges, solutions for fast and simple application of this method are available. Currently, the feasibility and diagnostic accuracy of electroencephalography in the prehospital setting are being investigated in clinical trials.

GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients.

Background: Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or ß-adrenergic blockers. Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls. Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity. Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.

SSEP amplitudes add information for prognostication in postanoxic coma.

OBJECTIVE: To investigate whether somatosensory evoked potential (SSEP) amplitude adds information for prediction of poor outcome in postanoxic coma. METHODS: In this retrospective cohort study we included adult patients admitted after cardiac arrest between January 2010 and June 2018 who remained in coma and had SSEP recorded for prognostication. Outcome was dichotomized in poor (Cerebral Performance Category (CPC) 4-5) and good (CPC 1-3) at ICU discharge. Sensitivity of bilaterally absent N20 potential was calculated. In case the N20 potential was not bilaterally absent, the amplitude contralateral to stimulation side (baseline-N20, N20-P25, and maximum) was determined. At a specificity of 100%, SEPP amplitude sensitivities were determined for poor outcome. RESULTS: SSEP recordings were performed in 197 patients of whom 57 had bilaterally absent N20 potentials. From 140 patients, 16 (11%) had a good outcome. The sensitivity for poor outcome of bilaterally absent N20 was 31%. At a specificity of 100%, contralateral amplitude thresholds were 0.34 µV (baseline-N20), 0.99 µV (N20-P25) and 1.0 µV (maximum), corresponding to a sensitivity for poor outcome of 38%, 44% and 40%. Combination of bilaterally absent N20 and a N20-P25 threshold below 0.99 µV yielded a sensitivity of 62%. CONCLUSIONS: Our results confirm that very low cortical SSEP amplitudes are highly predictive of poor outcome in patients with postanoxic coma. Adding 'N20-P25 threshold amplitude' to the 'bilaterally absent N20' criterion, increased sensitivity substantially.

[Clinical course of COVID-19 in the Netherlands: an overview of 2607 patients in hospital during the first wave]. / Klinisch beloop van covid-19 in Nederland.

OBJECTIVE: To systematically collect clinical data from patients with a proven COVID-19 infection in the Netherlands. DESIGN: Data from 2579 patients with COVID-19 admitted to 10 Dutch centers in the period February to July 2020 are described. The clinical data are based on the WHO COVID case record form (CRF) and supplemented with patient characteristics of which recently an association disease severity has been reported. METHODS: Survival analyses were performed as primary statistical analysis. These Kaplan-Meier curves for time to (early) death (3 weeks) have been determined for pre-morbid patient characteristics and clinical, radiological and laboratory data at hospital admission. RESULTS: Total in-hospital mortality after 3 weeks was 22.2% (95% CI: 20.7% - 23.9%), hospital mortality within 21 days was significantly higher for elderly patients (> 70 years; 35, 0% (95% CI: 32.4% - 37.8%) and patients who died during the 21 days and were admitted to the intensive care (36.5% (95% CI: 32.1% - 41.3%)). Apart from that, in this Dutch population we also see a risk of early death in patients with co-morbidities (such as chronic neurological, nephrological and cardiac disorders and hypertension), and in patients with more home medication and / or with increased urea and creatinine levels. CONCLUSION: Early death due to a COVID-19 infection in the Netherlands appears to be associated with demographic variables (e.g. age), comorbidity (e.g. cardiovascular disease) but also disease char-acteristics at admission.

Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson's disease.

BACKGROUND: Notwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. OBJECTIVE: We studied whether apathy in DBS-treated PD patients could be a stimulation effect. METHODS: In 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. RESULTS: Average apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. CONCLUSIONS: The present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.

Motor effects of deep brain stimulation correlate with increased functional connectivity in Parkinson's disease: An MEG study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established symptomatic treatment in Parkinson's disease, yet its mechanism of action is not fully understood. Locally in the STN, stimulation lowers beta band power, in parallel with symptom relief. Therefore, beta band oscillations are sometimes referred to as "anti-kinetic". However, in recent studies functional interactions have been observed beyond the STN, which we hypothesized to reflect clinical effects of DBS. Resting-state, whole-brain magnetoencephalography (MEG) recordings and assessments on motor function were obtained in 18 Parkinson's disease patients with bilateral STN-DBS, on and off stimulation. For each brain region, we estimated source-space spectral power and functional connectivity with the rest of the brain. Stimulation led to an increase in average peak frequency and a suppression of absolute band power (delta to low-beta band) in the sensorimotor cortices. Significant changes (decreases and increases) in low-beta band functional connectivity were observed upon stimulation. Improvement in bradykinesia/rigidity was significantly related to increases in alpha2 and low-beta band functional connectivity (of sensorimotor regions, the cortex as a whole, and subcortical regions). By contrast, tremor improvement did not correlate with changes in functional connectivity. Our results highlight the distributed effects of DBS on the resting-state brain and suggest that DBS-related improvements in rigidity and bradykinesia, but not tremor, may be mediated by an increase in alpha2 and low-beta functional connectivity. Beyond the local effects of DBS in and around the STN, functional connectivity changes in these frequency bands might therefore be considered as "pro-kinetic".

Defining the Dorsal STN Border Using 7.0-T MRI: A Comparison to Microelectrode Recordings and Lower Field Strength MRI.

BACKGROUND: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson's disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. OBJECTIVE: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. DESIGN/METHODS: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. RESULTS: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un-distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range -4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. CONCLUSION: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation.

Distance to white matter tracts is associated with deep brain stimulation motor outcome in Parkinson's disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in patients with Parkinson's disease (PD). However, the underlying mechanism of tremor suppression is not well understood. Stimulation of white matter tracts, such as the dentatorubrothalamic tract (DRT), might be involved. Also, side effects, including dysarthria, might result from (unwanted) stimulation of white matter tracts in proximity to the STN. The aim of this study was to establish an association between stimulation effect on tremor and dysarthria and stimulation location relative to relevant white matter tracts. METHODS: In 35 PD patients in whom a bilateral STN DBS system was implanted, the authors established clinical outcome measures per electrode contact. The distance from each stimulation location to the center of the DRT, corticopontocerebellar tract, pyramidal tract (PT), and medial lemniscus was determined using diffusion-weighted MRI data. Clinical outcome measures were subsequently related to the distances to the white matter tracts. RESULTS: Patients with activated contacts closer to the DRT showed increased tremor improvement. Proximity of activated contacts to the PT was associated with dysarthria. CONCLUSIONS: Proximity to specific white matter tracts is associated with tremor outcome and side effects in DBS. This knowledge can help to optimize both electrode placement and postsurgical electrode contact selection. Presurgical white matter tract visualization may improve targeting and DBS outcome. These findings are of interest not only for treatment in PD, but potentially also for other (movement) disorders.