The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society.

We describe high-specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society.

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Robust, effective treatments for Parkinson's freezing of gait remain elusive. Our previous study revealed beneficial effects of highfrequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson's disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset of 30 patients with freezing of gait (verum group: N = 20; sham group: N = 10) who participated the aforementioned rTMS study underwent another scan after the treatments. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. Results showed that the freezing of gait biomarker was negatively correlated with Freezing of Gait Questionnaire score (r = −0.6723, p < 0.0001); while the Parkinson's disease biomarker was negatively correlated with MDS-UPDRS motor score (r = −0.7281, p < 0.0001). After the rTMS treatment, both the freezing of gait biomarker (0.326 ± 0.125 vs. 0.486 ± 0.193, p = 0.0071) and Parkinson's disease biomarker (0.313 ± 0.126 vs. 0.379 ± 0.155, p = 0.0378) were significantly improved in the verum group; whereas no significant biomarker changes were found in the sham group. Our findings indicate that high-frequency rTMS over the supplementary motor area confers the beneficial effect jointly through normalizing abnormal brain functional connectivity patterns specifically associated with freezing of gait, in addition to normalizing overall disrupted connectivity patterns seen in Parkinson's disease.

Introduction. The sequence effect (SE) is a reason contributing to freezing of gait (FOG) in Parkinson’s disease (PD) patients. There is no effective treatment for the SE. The objective of the current study is to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the SE in PD patients with FOG. Methods. 28 PD patients with FOG received either real or sham 10-Hz rTMS over the supplementary motor area (SMA). The effects of rTMS on the SE, FOG, and some gait parameters were evaluated. Results. rTMS did not improve the SE. Real rTMS had beneficial effects on FOG and some gait parameters, and this effect lasted for at least four weeks. Conclusions. High-frequency rTMS over the SMA cannot alleviate the SE in PD patients with FOG. rTMS has a long-lasting beneficial effect on FOG; however, this effect is not achieved by improving the SE but may be through improving some other gait parameters.

Freezing of gait (FOG) is a common and debilitating symptom in Parkinson’s disease (PD). The current study investigated alterations of resting-state spontaneous brain activity in PD patients with FOG. A total of 29 patients with FOG, 28 patients without FOG and 31 controls were included. All subjects underwent resting-state functional MRI, and the amplitude of low-frequency fluctuation (ALFF) was calculated to measure the spontaneous brain activity. Between-group differences and correlations with FOG severity (both subjective and objective measures) were analyzed. Compared to those without FOG, patients with FOG showed increased ALFF in right anterior cingulate cortex (ACC) and left inferior parietal lobule (IPL), as well as decreased ALFF in right superior frontal gyrus (SFG), bilateral cerebellum and left thalamus. Correlation analyses demonstrated that ALFF within the right SFG, right ACC and bilateral pallidum were positively correlated with FOG; while ALFF within the thalamus, putamen, cerebellum and sensorimotor regions were negatively correlated. Our results indicate that FOG is associated with dysfunction within frontal-parietal regions, along with increased inhibitory outputs from basal ganglia. Additionally, altered activity of cerebellum implicates its role in the pathophysiology of FOG. These findings provide further insight into the underlying neural mechanisms of FOG in PD patients.

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Background: Remote ischemic preconditioning (RIPC) of the limb has been shown to induce ischemic tolerance in basic and clinical studies that focused on sustained large artery occlusion rather than small vessel disease (SVD). This study aimed to evaluate the protective effects of brief repetitive limb RIPC on patients with cerebral SVD. Methods: Seventeen patients with cerebral SVD were enrolled. Patients underwent 5 ischemia-reperfusion cycles of preconditioning/sham preconditioning on both upper limbs twice a day for 1 year. Cerebral hemodynamic indexes, brain lesions, cognitive functions and assessment outcomes of dizziness handicap inventory (DHI) were analyzed. Results: In the RIPC group, the mean flow velocity (MFV) of the left middle cerebral artery (MCA) was accelerated (57.33 (52.33-61.34) vs. 51.33 (48.83-58.33), respectively; p = 0.038), and the post-treatment DHI score was reduced (18 (13-19) vs. 34 (21-45), respectively; p = 0.043). The post-treatment volume of the white matter lesions (WMLs) was also reduced (4.19 (2.96-7.25) vs. 6.06 (4.67-10.95), respectively; p = 0.050). There was no remarkable difference between the 2 groups either before or after treatment. Conclusion: The present study indicates that RIPC has potential beneficial effects on cerebral SVD by increasing the MFV of MCA, decreasing the DHI score as well as the volume of WMLs in patients with SVD.