Subthalamic dynamic neural states correlate with motor symptoms in Parkinson’s Disease

ObjectiveThis study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson’s Disease (PD).MethodsThe resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms.ResultsThe proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia.ConclusionsThis study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD.SignificanceThis study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD.     

Male and female Gaelic games coaches’ and referees’ experiences,knowledge and views on sports-related concussion

ObjectivesConcern regarding identification and management of sports-related concussion (SRC) in the community sports of Gaelic games exists. This study aimed to examine Gaelic games coaches’ and referees’ previous SRC experiences, knowledge of and attitudes on SRC and views on SRC education.DesignCross-sectional study;SettingOnline survey instrument.ParticipantsIrish male and female Gaelic games coaches (n = 144) and referees (n = 110).Main outcome measuresDemographics, SRC previous experience, SRC knowledge, attitudes towards SRC reporting and previous and future interest in SRC education.ResultsMost coaches (70.1%) and referees (74.5%) previously dealt with a suspected SRC event. In the most recent SRC event, coaches predominantly removed the player from play (97.0%) and referees frequently informed medical staff (97.1%) or coaches present (96.3%). Coaches and referees were predominantly (>90%) able to identify common SRC signs and symptoms such as dizziness, nausea, confusion, poor balance and headache. Coaches and referees displayed positive attitudes towards removing players from play regardless of game importance.ConclusionsGood knowledge of common SRC symptoms were displayed, however their ability to recognise false signs and symptoms was limited. Widespread promotion of Gaelic games SRC education across all stakeholders is warranted and should target the misconceptions highlighted in this study.     

Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A point of view

Parkinson disease (PD) is a complex heterogeneous neurodegenerative disorder. Association studies have revealed numerous genetic risk loci and variants, and about 5–10% suffer from a monogenic form. Because the presentation and course of PD is unique to each patient, personalized symptomatic treatment should ideally be offered to treat the most disabling motor and non-motor symptoms. Indeed, clinical milestones and treatment complications that appear during disease progression are influenced by the genetic imprint. With recent advances in PD, more patients live longer to become eligible for device-aided therapies, such as apomorphine continuous subcutaneous infusion, levodopa duodenal gel infusion, and deep brain stimulation surgery, each with its own inclusion and exclusion criteria, advantages and disadvantages. Because genetic variants influence the expression of particular clinical profiles, factors for better or worse outcomes for device-aided therapies may then be proactively identified. For example, mutations in PRKN, LRRK2 and GBA express phenotypes that favor suitability for different device therapies, although with marked differences in the therapeutic window; whereas multiplications of SNCA express phenotypes that make them less desirable for device therapies.     

侧裂区病变周围水肿对术中脑膨出的影响

目的 探讨侧裂区病变周围水肿对术中急性脑膨出的影响。方法 回顾性分析2016年3月至2020年9月手术治疗的68例侧裂区病变的临床资料。结果 68例中，无-轻度周围水肿25例，中-重度周围水肿43例。中-重度周围水肿术中脑膨出发生率（60.5%，26/43）明显高于无-轻度周围水肿（24.0%，6/25；P<0.05）。多因素logistic回归分析表明，中-重度水肿是侧裂区病变发生术中脑膨出的独立危险因素（OR=3.07; 95% CI 1.06~14.52；P=0.040）。结论 周围周水肿是引起侧裂区病变术中急性脑膨出的重要原因，临床应充分重视，采取有效措施缓解周围水肿，可以有效避免或减少术中脑膨出。     

Prediction of AF in Heart Failure With Preserved Ejection Fraction: Incremental Value of Left Atrial Strain

ObjectivesThis study sought to identify the factors associated with incident atrial fibrillation (AF) in a well-characterized heart failure with preserved ejection fraction (HFpEF) population, with special focus on left atrial (LA) strain.BackgroundAF is associated with HFpEF, with adverse consequences. Effective risk evaluation might allow the initiation of protective strategies.MethodsClinical evaluation and echocardiography, including measurements of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA volume index (LAVI), were obtained in 170 patients with symptomatic HFpEF (mean age, 65 ± 8 years), free of baseline AF. AF was identified by standard 12-lead electrocardiogram, review of relevant medical records (including Holter documentation), and surveillance with a portable single-lead electrocardiogram device over 2 weeks. Results were validated in the 103 patients with HFpEF from the Karolinska-Rennes (KaRen) study.ResultsOver a median follow-up of 49 months, incident AF was identified in 39 patients (23%). Patients who developed AF were older; had higher clinical risk scores, brain natriuretic peptide, creatinine, LAVI, and LV mass; lower LA strain and exercise capacity; and more impaired LV diastolic function. PACS, PALS, and LAVI were the most predictive parameters for AF (area under receiver-operating characteristic curve: 0.76 for PACS, 0.71 for PALS, and 0.72 for LAVI). Nested Cox regression models showed that the predictive value of PACS and PALS was independent from and incremental to clinical data, LAVI, and E/e’ ratio. Classification and regression trees analysis identified PACS ≤12.7%, PALS ≤29.4%, and LAVI >34.3 ml/m² as discriminatory nodes for AF, with a 33-fold greater hazard of AF (p < 0.001) in patients categorized as high risk. The classification and regression trees algorithm discriminated high and low AF risk in the validation cohort.ConclusionsPACS and PALS provide incremental predictive information about incident AF in HFpEF. The inclusion of these LA strain components to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.     

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

BackgroundTemporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear.ObjectiveWe developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain.MethodsThe electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head.ResultsAmplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABA_b) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ∼5 V/m (corresponding to ∼13 mA at the scalp surface), whereas, 1 kHz carrier frequency ∼60 V/m (∼160 mA) and 2 kHz carrier frequency ∼80 V/m (∼220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants.ConclusionThe TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABA_b) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Utility of Deep Brain Stimulation Telemedicine for Patients With Movement Disorders During the COVID-19 Outbreak in China

ObjectiveTo explore the utility of deep brain stimulation (DBS) telemedicine in the management of patients with movement disorders from January 2019 to March 2020, covering the main period of the COVID-19 outbreak in China.Materials and MethodsWe obtained data from 40 hospitals around China that employed DBS tele-programming for their outpatients with Parkinson’s disease or dystonia from January 2019 to March 2020. Data were obtained on the number and nature of patients’ DBS health care service requests, reasons for their requests, the number of DBS telemedicine sessions subsequently completed, safety issues, and the patients’ satisfaction with the DBS tele-programing parameter adjustments made.ResultsThere were 909 DBS tele-programming health service requests (from 196 patients) completed during the study period. The results showed: 1) the number of DBS telemedicine sessions requested and the number of patients examined increased during the COVID-19 outbreak in February and March 2020 when compared with the monthly numbers in 2019; 2) the most common reason for the patients’ health service requests was poor symptom control; 3) the most common DBS tele-programming adjustment made was voltage change; 4) overall, most (89%) DBS tele-programming adjustment sessions were experienced by the patients as satisfactory; and 5) significant adverse events and unexpected treatment interruptions caused by connection failure or other hardware- or software-related problems did not occur.ConclusionsDBS telemedicine could have a unique role to play in maintaining the delivery of DBS treatment and medical care to outpatients with movement disorders during the COVID-19 pandemic.