Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) ...that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.
Neuroimaging advances in Parkinson's disease Rispoli, Vittorio; Schreglmann, Sebastian R; Bhatia, Kailash P
Current opinion in neurology,
08/2018, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Neuroimaging in Parkinson's disease is an evolving field, providing in-vivo insights into the structural and biochemical changes of the condition, although its diagnosis remains clinical. Here, we ...aim to summarize the most relevant recent advances in neuroimaging in Parkinson's disease to assess the underlying disease process, identify a biomarker of disease progression and guide or monitor therapeutic interventions.
The clinical applications of imaging technology increasingly allow to quantify pigments (iron, neuromelanin) on MRI, proteins (tau), cell markers (phosphodiesterases, microglia) and neurotransmitter receptors (dopamine, serotonin, noradrenalin, cholin) via PET protocols, activity maps by resting-state and task-dependent functional MRI, as well as microstructural changes (free water) through diffusion-based assessments. Their application provides increasing insight on the temporal and spatial dynamics of dopaminergic and other neurotransmitter systems as well as anatomical structures and circuits in Parkinson's disease. An expanding list of PET tracers increases the yield of functional studies.
This review summarizes the most recent, relevant advances in neuroimaging technology in Parkinson's disease. In particular, the combination of different imaging techniques seems promising to maximize the scope of future work, which should, among others, aim at identifying the best imaging marker of disease progression.
OBJECTIVE:To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET).
METHODS:This ...was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS. Motor symptoms, manual dexterity, cognition, and quality of life were assessed before intervention and at 48 hours and 1, 3, and 6 months after intervention. Rating of standardized video recordings was blinded for evaluation time points. Primary outcome was the change in unilateral hand tremor score of the treated hand.
RESULTS:Six patients received MRIgFUS ablation of the CTT contralateral to the treated hand. Repeated-measures comparison determined a statistically significant 83% reduction (before vs 6 months after intervention mean ± SD; absolute reduction; 95% confidence interval) in the unilateral treated hand subscore (14.3 ± 4.9 vs 2.5 ± 2.6; 11.8; 8.4–15.2; p < 0.001), while quality of life improved by 52% (50.5 ± 19.4 vs 24.8 ± 11.4; 25.7; 3.5–47.28; p = 0.046). Measures for manual dexterity, attention and coordination, and overall cognition were unchanged. Transient side effects (n = 3) were ipsilateral hand clumsiness and mild gait instability for up to 3 months.
CONCLUSIONS:Unilateral MRIgFUS lesioning of the CTT was highly efficacious in reducing contralateral hand tremor in ET without affecting fine motor function and dexterity over 6 months of follow-up. Adverse effects were mild and transient.
CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that for patients with ET, transcranial MRIgFUS ablation of the cerebellothalamic tract improves tremor.
IMPORTANCE: Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce. OBJECTIVE: To determine whether nocturnal ...administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale ESS score >10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12). INTERVENTIONS: Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed. MAIN OUTCOMES AND MEASURES: Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale–2), and objective variables of nighttime sleep (polysomnography). RESULTS: Among 12 patients in the intention-to-treat population (10 men, 2 women; mean SD age, 62 11.1 years; disease duration, 8.4 4.6 years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, −4.2 points ; 95% CI, −5.3 to −3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P < .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment. CONCLUSIONS AND RELEVANCE: This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02111122
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use ...Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.
Background
Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain ...disorders.
Methods
In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH (N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16).
Results
In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula.
Conclusions
Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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