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  • Long term correlation of subthalamic beta band activity with motor impairment in patients with Parkinson's disease.

    9 February 2018

    OBJECTIVES: To investigate the long term association of subthalamic beta activity with parkinsonian motor signs. METHODS: We recruited 15 patients with Parkinson's disease undergoing subthalamic DBS for local field potential recordings after electrode implantation, and at 3 and 8months post-operatively using the implantable sensing enabled Activa PC+S (Medtronic). Three patients dropped out leaving 12 patients. Recordings were conducted ON and OFF levodopa at rest. Beta (13-35Hz) peak amplitudes were extracted, compared across time points and correlated with UPDRS-III hemibody scores. RESULTS: Peaks in the beta frequency band (13-35Hz) in the OFF medication state were found in all hemispheres. Mean beta activity was significantly suppressed by levodopa at all recorded time points (P<0.007) and individual beta power amplitude correlated with parkinsonian motor impairment across time points and dopaminergic states (pooled data; ρ=0.25, P<0.001). CONCLUSIONS: Our results indicate that beta-activity is correlated with parkinsonian motor signs over a time period of 8months. SIGNIFICANCE: Beta-activity may be a chronically detectable biomarker of symptom severity in PD that should be further evaluated under ongoing DBS.

  • Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

    9 February 2018

    Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and interhemispheric synchronization. This may compromise information coding capacity and thereby motor processing. Dopaminergic activity limits this uncontrolled beta synchronization by terminating long duration beta bursts, with positive consequences on network state and motor symptoms.

  • Arterial spin labeling for the measurement of cerebral perfusion and angiography.

    14 February 2018

    Arterial spin labeling (ASL) is an MRI technique that was first proposed a quarter of a century ago. It offers the prospect of non-invasive quantitative measurement of cerebral perfusion, making it potentially very useful for research and clinical studies, particularly where multiple longitudinal measurements are required. However, it has suffered from a number of challenges, including a relatively low signal-to-noise ratio, and a confusing number of sequence variants, thus hindering its clinical uptake. Recently, however, there has been a consensus adoption of an accepted acquisition and analysis framework for ASL, and thus a better penetration onto clinical MRI scanners. Here, we review the basic concepts in ASL and describe the current state-of-the-art acquisition and analysis approaches, and the versatility of the method to perform both quantitative cerebral perfusion measurement, along with quantitative cerebral angiographic measurement.

  • Density-weighted concentric rings k-space trajectory for 1 H magnetic resonance spectroscopic imaging at 7 T.

    14 February 2018

    It has been shown that density-weighted (DW) k-space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW-MRSI that samples k-space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW-CRTs were compared against a radially equidistant (RE) CRT and an echo-planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW-CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal-to-noise ratio (SNR). High-quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in-plane resolution of 7.5 × 7.5 mm2 in 8 min 3 s. Due to hardware limitations, high-spatial-resolution spectra with an in-plane resolution of 5 × 5 mm2 and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW-CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW-CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW-CRT method allowed for reliable metabolic mapping of eight metabolites including N-acetylaspartylglutamate, γ-aminobutyric acid and glutathione with Cramér-Rao lower bounds below 50%, using an LCModel analysis. Finally, high-quality metabolic mapping of a whole brain slice using DW-CRT was achieved with a high in-plane resolution of 5 × 5 mm2 in a healthy subject. These findings demonstrate that our DW-CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.

  • The Intracranial-B2LEED3S Score and the Risk of Intracranial Hemorrhage in Ischemic Stroke Patients Under Antiplatelet Treatment.

    28 January 2018

    BACKGROUND: Chronic antiplatelet therapy in the post-acute phase of non-cardioembolic ischemic stroke is limited by the risk of intracranial hemorrhage (ICH) complications. METHODS: We developed an ICH risk score based on the PERFORM trial cohort (n = 19,100), which included patients with a non-cardioembolic ischemic stroke or transient ischemic attack, and externally validated this score in one contemporary trial of very similar size and inclusion criteria, the PRoFESS trial (n = 20,332 patients). Outcome was ICH over 2 years. A Cox proportional-hazard regression analysis identified risk factors. Discrimination was quantified with c-statistics and calibration was assessed by comparing predicted and observed ICH risk in PERFORM and PRoFESS. RESULTS: ICH occurred within 2 years in 263 (1.4%) patients in PERFORM trial and in 246 (1.2%) patients in PRoFESS trial. A 13-point score based on 9 items (Intracranial-B2LEED3S score - low body mass index, blood pressure, lacune, elderly, Asian ethnicity, coronary artery or cerebrovascular disease history, dual antithrombotic agent or oral anticoagulant, gender) was derived from the PERFORM trial. In PERFORM, the observed 2-year ICH risk varied from 0.75% in low-risk (score ≤2) to 2.44% in high-risk patients (score ≥5) with an acceptable calibration but a low discrimination both in PERFORM (c-statistic 0.64, 95% CI 0.61-0.68) and on external validation in PRoFESS (0.58, 95% CI 0.55-0.62). CONCLUSION: The Intracranial-B2LEED3S score helps identify patients who are at a high risk of bleeding. However, other variables need to be identified to improve the score (e.g., microbleeds) (Clinical Trial Registration Information ISRCTN66157730). URL: http://www.isrctn.com/ISRCTN66157730?totalResults=5&amp;pageSize=10&amp;page=1&amp;searchType=basic-search&amp;offset=3&amp;q=&amp;filters=conditionCategory%3ACirculatory+System%2CrecruitmentCountry%3ATaiwan%2CrecruitmentCountry%3AAustria&amp;sort=.

  • Specificities of Ischemic Stroke Risk Factors in Arab-Speaking Countries.

    25 December 2017

    BACKGROUND: Stroke is largely preventable, and therefore, a better understanding of risk factors is an essential step in reducing the population stroke rate and resulting disease burden in Arab countries. SUMMARY: We performed 2 separate analyses in 2 similar populations of patients with noncardioembolic ischemic stroke. This first involved 3,635 patients in the Outcomes in Patients with TIA and Cerebrovascular disease (OPTIC) registry (followed for 2 years), with baseline collection of the usual risk factors and 5 socioeconomic variables (unemployment status, residence in rural area, living in fully serviced accommodation, no health-insurance coverage, and low educational level). The second involved patients in the PERFORM trial (n = 19,100 followed up for 2 years), with baseline collection of the usual risk factors and 1 socioeconomic variable (low educational level). The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death. Stroke risk factors were more prevalent in patients in Arab countries. The incidence of major cardiovascular events (MACE; age- and gender-adjusted) was higher in Arab countries (OPTIC, 18.5 vs. 13.3%; PERFORM, 18.4 vs. 9.7%; both p ≤ 0.0001). These results remained significant after adjustment on risk factors and were attenuated in OPTIC after further adjustment on socioeconomic variables (hazard ratio 1.24; 95% CI 0.98-1.55; p = 0.07). Key Messages: Patients with ischemic stroke living in Arab countries had a lower mean socioeconomic status, a much higher prevalence of diabetes mellitus, and a higher rate of MACE compared with patients from non-Arab countries. This finding is partly explained by a higher prevalence of risk factors and also by a high prevalence of poverty and low educational level.

  • Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

    6 December 2017

    BACKGROUND AND PURPOSE: This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. METHODS: The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS: Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. CONCLUSIONS: The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.