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The article discusses a study on the influence of ictal cutaneous allodynia (CA) on the response to treatment with occipital transcutaneous electrical stimulation (OTES) in chronic migraine (CM) and chronic tension-type headache (CTTH). The study involved 160 patients with CM or CTTH who were treated with real or sham OTES. The results showed a significant difference responders in real OTES compared with patents in sham OTES.

Introduction: Distinguishing tremor-dominant Parkinson's disease (tPD) from essential tremor with rest tremor (rET) can be challenging and often requires dopamine imaging. This study aimed to differentiate between these two diseases through a machine learning (ML) approach based on rest tremor (RT) electrophysiological features and structural MRI data., Methods: We enrolled 72 patients including 40 tPD patients and 32 rET patients, and 45 control subjects (HC). RT electrophysiological features (frequency, amplitude, and phase) were calculated using surface electromyography (sEMG). Several MRI morphometric variables (cortical thickness, surface area, cortical/subcortical volumes, roughness, and mean curvature) were extracted using Freesurfer. ML models based on a tree-based classification algorithm termed XGBoost using MRI and/or electrophysiological data were tested in distinguishing tPD from rET patients., Results: Both structural MRI and sEMG data showed acceptable performance in distinguishing the two patient groups. Models based on electrophysiological data performed slightly better than those based on MRI data only (mean AUC: 0.92 and 0.87, respectively; p = 0.0071). The top-performing model used a combination of sEMG features (amplitude and phase) and MRI data (cortical volumes, surface area, and mean curvature), reaching AUC: 0.97 ± 0.03 and outperforming models using separately either MRI ( p = 0.0001) or EMG data ( p = 0.0231). In the best model, the most important feature was the RT phase., Conclusion: Machine learning models combining electrophysiological and MRI data showed great potential in distinguishing between tPD and rET patients and may serve as biomarkers to support clinicians in the differential diagnosis of rest tremor syndromes in the absence of expensive and invasive diagnostic procedures such as dopamine imaging., Competing Interests: BV was employed by Biotecnomed S.c.a.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aracri, Quattrone, Bianco, Sarica, De Maria, Calomino, Crasà, Nisticò, Buonocore, Vescio, Vaccaro and Quattrone.)

Radiomics represents an innovative approach to medical image analysis, enabling comprehensive quantitative evaluation of radiological images through advanced image processing and Machine or Deep Learning algorithms. This technique uncovers intricate data patterns beyond human visual detection. Traditionally, executing a radiomic pipeline involves multiple standardized phases across several software platforms. This could represent a limit that was overcome thanks to the development of the matRadiomics application. MatRadiomics, a freely available, IBSI-compliant tool, features its intuitive Graphical User Interface (GUI), facilitating the entire radiomics workflow from DICOM image importation to segmentation, feature selection and extraction, and Machine Learning model construction. In this project, an extension of matRadiomics was developed to support the importation of brain MRI images and segmentations in NIfTI format, thus extending its applicability to neuroimaging. This enhancement allows for the seamless execution of radiomic pipelines within matRadiomics, offering substantial advantages to the realm of neuroimaging.

Background: Postural instability (PI) is a common disabling symptom in Parkinson's disease (PD), but little is known on its pathophysiological basis., Objective: In this study, we aimed to identify the brain structures associated with PI in PD patients, using different MRI approaches., Methods: We consecutively enrolled 142 PD patients and 45 control subjects. PI was assessed using the MDS-UPDRS-III pull-test item (PT). A whole-brain regression analysis identified brain areas where grey matter (GM) volume correlated with the PT score in PD patients. Voxel-based morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) were also used to compare unsteady (PT ≥ 1) and steady (PT = 0) PD patients. Associations between GM volume in regions of interest (ROI) and several clinical features were then investigated using LASSO regression analysis., Results: PI was present in 44.4% of PD patients. The whole-brain approach identified the bilateral inferior frontal gyrus (IFG) and superior temporal gyrus (STG) as the only regions associated with the presence of postural instability. VBM analysis showed reduced GM volume in fronto-temporal areas (superior, middle, medial and inferior frontal gyrus, and STG) in unsteady compared with steady PD patients, and the GM volume of these regions was selectively associated with the PT score and not with any other motor or non-motor symptom., Conclusions: This study demonstrates a significant atrophy of fronto-temporal regions in unsteady PD patients, suggesting that these brain areas may play a role in the pathophysiological mechanisms underlying postural instability in PD. This result paves the way for further studies on postural instability in Parkinsonism., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Most patients with idiopathic REM sleep behavior disorder (iRBD) present peculiar repetitive leg jerks during sleep in their clinical spectrum, called periodic leg movements (PLMS). The clinical differentiation of iRBD patients with and without PLMS is challenging, without polysomnographic confirmation. The aim of this study is to develop a new Machine Learning (ML) approach to distinguish between iRBD phenotypes. Heart rate variability (HRV) data were acquired from forty-two consecutive iRBD patients (23 with PLMS and 19 without PLMS). All participants underwent video-polysomnography to confirm the clinical diagnosis. ML models based on Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) were trained on HRV data, and classification performances were assessed using Leave-One-Out cross-validation. No significant clinical differences emerged between the two groups. The RF model showed the best performance in differentiating between iRBD phenotypes with excellent accuracy (86%), sensitivity (96%), and specificity (74%); SVM and XGBoost had good accuracy (81% and 78%, respectively), sensitivity (83% for both), and specificity (79% and 72%, respectively). In contrast, LR had low performances (accuracy 71%). Our results demonstrate that ML algorithms accurately differentiate iRBD patients from those without PLMS, encouraging the use of Artificial Intelligence to support the diagnosis of clinically indistinguishable iRBD phenotypes.

Background: Differentiating Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) from PSP-Parkinsonism (PSP-P) may be extremely challenging. In this study, we aimed to distinguish these two PSP phenotypes using MRI structural data., Methods: Sixty-two PSP-RS, 40 PSP-P patients and 33 control subjects were enrolled. All patients underwent brain 3 T-MRI; cortical thickness and cortical/subcortical volumes were extracted using Freesurfer on T1-weighted images. We calculated the automated MR Parkinsonism Index (MRPI) and its second version including also the third ventricle width (MRPI 2.0) and tested their classification performance. We also employed a Machine learning (ML) classification approach using two decision tree-based algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) with different combinations of structural MRI data in differentiating between PSP phenotypes., Results: MRPI and MRPI 2.0 had AUC of 0.88 and 0.81, respectively, in differentiating PSP-RS from PSP-P. ML models demonstrated that the combination of MRPI and volumetric/thickness data was more powerful than each feature alone. The two ML algorithms showed comparable results, and the best ML model in differentiating between PSP phenotypes used XGBoost with a combination of MRPI, cortical thickness and subcortical volumes (AUC 0.93 ± 0.04). Similar performance (AUC 0.93 ± 0.06) was also obtained in a sub-cohort of 59 early PSP patients., Conclusion: The combined use of MRPI and volumetric/thickness data was more accurate than each MRI feature alone in differentiating between PSP-RS and PSP-P. Our study supports the use of structural MRI to improve the early differential diagnosis between common PSP phenotypes, which may be relevant for prognostic implications and patient inclusion in clinical trials., (© 2023. The Author(s).)

Rest tremor (RT) is observed in subjects with Parkinson's disease (PD) and Essential Tremor (ET). Electromyography (EMG) studies have shown that PD subjects exhibit alternating contractions of antagonistic muscles involved in tremors, while the contraction pattern of antagonistic muscles is synchronous in ET subjects. Therefore, the RT pattern can be used as a potential biomarker for differentiating PD from ET subjects. In this study, we developed a new wearable device and method for differentiating alternating from a synchronous RT pattern using inertial data. The novelty of our approach relies on the fact that the evaluation of synchronous or alternating tremor patterns using inertial sensors has never been described so far, and current approaches to evaluate the tremor patterns are based on surface EMG, which may be difficult to carry out for non-specialized operators. This new device, named "RT-Ring", is based on a six-axis inertial measurement unit and a Bluetooth Low-Energy microprocessor, and can be worn on a finger of the tremulous hand. A mobile app guides the operator through the whole acquisition process of inertial data from the hand with RT, and the prediction of tremor patterns is performed on a remote server through machine learning (ML) models. We used two decision tree-based algorithms, XGBoost and Random Forest, which were trained on features extracted from inertial data and achieved a classification accuracy of 92% and 89%, respectively, in differentiating alternating from synchronous tremor segments in the validation set. Finally, the classification response (alternating or synchronous RT pattern) is shown to the operator on the mobile app within a few seconds. This study is the first to demonstrate that different electromyographic tremor patterns have their counterparts in terms of rhythmic movement features, thus making inertial data suitable for predicting the muscular contraction pattern of tremors.

Objective: We aimed to identify the brain structures associated with postural instability (PI) in Progressive Supranuclear Palsy (PSP)., Methods: Forty-seven PSP patients and 45 control subjects were enrolled in this study. PI was assessed using the items 27 and 28 of the PSP rating scale (postural instability score, PIS). PSP patients were compared with controls using voxel-based morphometry (VBM). In PSP patients, LASSO regression model was used to investigate associations between VBM-based Region-Of-Interest grey matter (GM) volumes and different categories of the PSP rating scale. A whole-brain multi-regression analysis was also used to identify brain areas where GM volumes correlated with the PIS in PSP patients., Results: VBM analysis showed widespread GM atrophy (fronto-temporal-parietal-occipital regions, limbic lobes, insula, cerebellum, and basal ganglia) in PSP patients compared with control subjects. In PSP patients, LASSO regression analysis showed associations of the right cerebellar lobules IV-V with ocular motor category score, and the left Rolandic area with bulbar category score, while the right inferior frontal gyrus (IFG) was negatively correlated with the PIS. The whole-brain multi-regression analysis identified the right IFG as the only area significantly associated with the PIS., Conclusions: In our study, two different approaches demonstrated that the IFG volume was associated with PIS in PSP patients, suggesting that this area may play a role in the pathophysiological mechanisms underlying PI. Our findings may have important implications for developing optimal Transcranial Magnetic Stimulation protocols targeting IFG in parkinsonism with postural disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and purpose: Growing evidence suggests that Machine Learning (ML) models can assist the diagnosis of neurological disorders. However, little is known about the potential application of ML in diagnosing idiopathic REM sleep behavior disorder (iRBD), a parasomnia characterized by a high risk of phenoconversion to synucleinopathies. This study aimed to develop a model using ML algorithms to identify iRBD patients and test its accuracy. Methods: Data were acquired from 32 participants (20 iRBD patients and 12 controls). All subjects underwent a video-polysomnography. In all subjects, we measured the components of heart rate variability (HRV) during 24 h recordings and calculated night-to-day ratios (cardiac autonomic indices). Discriminating performances of single HRV features were assessed. ML models based on Logistic Regression (LR), Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) were trained on HRV data. The utility of HRV features and ML models for detecting iRBD was evaluated by area under the ROC curve (AUC), sensitivity, specificity and accuracy corresponding to optimal models. Results: Cardiac autonomic indices had low performances (accuracy 63-69%) in distinguishing iRBD from control subjects. By contrast, the RF model performed the best, with excellent accuracy (94%), sensitivity (95%) and specificity (92%), while XGBoost showed accuracy (91%), specificity (83%) and sensitivity (95%). The mean triangular index during wake (TIw) was the best discriminating feature between iRBD and HC, with 81% accuracy, reaching 84% accuracy when combined with VLF power during sleep using an LR model. Conclusions: Our findings demonstrated that ML algorithms can accurately identify iRBD patients. Our model could be used in clinical practice to facilitate the early detection of this form of RBD.

Background: Imaging studies investigating cerebellar gray matter (GM) in essential tremor (ET) showed conflicting results. Moreover, no large study explored the cerebellum in ET patients with resting tremor (rET), a syndrome showing enhanced blink reflex recovery cycle (BRrc)., Objective: To investigate cerebellar GM in ET and rET patients using voxel-based morphometry (VBM) analysis., Methods: Seventy ET patients with or without resting tremor and 39 healthy controls were enrolled. All subjects underwent brain 3 T-MRI and BRrc recording. We compared the cerebellar GM volumes between ET (n = 40) and rET (n = 30) patients and controls through a VBM analysis. Moreover, we investigated possible correlations between cerebellar GM volume and R2 component of BRrc., Results: rET and ET patients had similar disease duration. All rET patients and none of ET patients had enhanced BRrc. No differences in the cerebellar volume were found when ET and rET patients were compared to each other or with controls. By considering together the two tremor syndromes in a large patient group, the VBM analysis showed bilateral clusters of reduced GM volumes in Crus II in comparison with controls. The linear regression analysis in rET patients revealed a cluster in the left Crus II where the decrease in GM volume correlated with the R2BRrc increase., Conclusion: Our study suggests that ET and rET are different tremor syndromes with similar mild cerebellar gray matter involvement. In rET patients, the left Crus II may play a role in modulating the brainstem excitability, encouraging further studies on the role of cerebellum in these patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH) share several clinical and radiological features, making the differential diagnosis challenging. In this study, we aimed to differentiate between these two diseases using a machine learning approach based on cortical thickness and volumetric data., Methods: Twenty-three iNPH patients, 50 PSP patients and 55 control subjects were enrolled. All participants underwent a brain 3T-MRI, and cortical thickness and volumes were extracted using Freesurfer 6 on T1-weighted images and compared among groups. Finally, the performance of a machine learning approach with random forest using the extracted cortical features was investigated to differentiate between iNPH and PSP patients., Results: iNPH patients showed cortical thinning and volume loss in the frontal lobe, temporal lobe and cingulate cortex, and thickening in the superior parietal gyrus in comparison with controls and PSP patients. PSP patients only showed mild thickness and volume reduction in the frontal lobe, compared to control subjects. Random Forest algorithm distinguished iNPH patients from controls with AUC of 0.96 and from PSP patients with AUC of 0.95, while a lower performance (AUC 0.76) was reached in distinguishing PSP from controls., Conclusion: This study demonstrated a more severe and widespread cortical involvement in iNPH than in PSP, possibly due to the marked lateral ventricular enlargement which characterizes iNPH. A machine learning model using thickness and volumetric data led to accurate differentiation between iNPH and PSP patients, which may help clinicians in the differential diagnosis and in the selection of patients for shunt procedures., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The clinical differential diagnosis between Parkinson's disease (PD) and progressive supranuclear palsy (PSP) is often challenging. The description of milder PSP phenotypes strongly resembling PD, such as PSP-Parkinsonism, further increased the diagnostic challenge and the need for reliable neuroimaging biomarkers to enhance the diagnostic certainty. This review aims to summarize the contribution of a relatively simple and widely available imaging technique such as MR planimetry in the differential diagnosis between PD and PSP, focusing on the recent advancements in this field. The development of accurate MR planimetric biomarkers, together with the implementation of automated algorithms, led to robust and objective measures for the differential diagnosis of PSP and PD at the individual level. Evidence from longitudinal studies also suggests a role of MR planimetry in predicting the development of the PSP clinical signs, allowing to identify PSP patients before they meet diagnostic criteria when their clinical phenotype can be indistinguishable from PD. Finally, promising evidence exists on the possible association between MR planimetric measures and the underlying pathology, with important implications for trials with new disease-modifying target therapies.

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging., Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0) algorithm to distinguish PSP-P from PD and to validate its diagnostic performance in two large independent cohorts., Methods: We enrolled 676 participants: a training cohort (n = 346; 43 PSP-P, 194 PD, and 109 control subjects) from our center and an independent testing cohort (n = 330; 62 PSP-P, 171 PD, and 97 control subjects) from an international research group. We developed a new in-house algorithm for MRPI 2.0 calculation and assessed its performance in distinguishing PSP-P from PD and control subjects in both cohorts using receiver operating characteristic curves., Results: The automated MRPI 2.0 showed excellent performance in differentiating patients with PSP-P from patients with PD and control subjects both in the training cohort (area under the receiver operating characteristic curve [AUC] = 0.93 [95% confidence interval, 0.89-0.98] and AUC = 0.97 [0.93-1.00], respectively) and in the international testing cohort (PSP-P versus PD, AUC = 0.92 [0.87-0.97]; PSP-P versus controls, AUC = 0.94 [0.90-0.98]), suggesting the generalizability of the results. The automated MRPI 2.0 also accurately distinguished between PSP-P and PD in the early stage of the diseases (AUC = 0.91 [0.84-0.97]). A strong correlation (r = 0.91, P < 0.001) was found between automated and manual MRPI 2.0 values., Conclusions: Our study provides an automated, validated, and generalizable magnetic resonance biomarker to distinguish PSP-P from PD. The use of the automated MRPI 2.0 algorithm rather than manual measurements could be important to standardize measures in patients with PSP-P across centers, with a positive impact on multicenter studies and clinical trials involving patients from different geographic regions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Rest tremor (RT) can be observed in several positions (seated, standing, lying down) but it is unknown whether the tremor features may vary across them. This study aimed to compare the RT electrophysiological features across different positions in tremor-dominant Parkinson's disease (PD) and essential tremor plus (ET with RT, rET)., Methods: We consecutively enrolled 90 tremor-dominant PD and 24 rET patients. The RT presence was evaluated in three positions: with the patient seated, the arm flexed at 90°, the forearm supported against gravity, and the hand hanging down from the chair armrest (hand-hanging position), in lying down supine and in standing position. RT electrophysiological features (amplitude, frequency, burst duration, pattern) were compared between the two patient groups and across the different positions., Results: All PD and rET patients showed RT in hand-hanging position. Supine and standing RT were significantly more common in PD (67.8% and 75.6%, respectively) than in rET patients (37.5% and 45.8%, respectively). RT amplitude, frequency and pattern were significantly different between groups in hand-hanging position whereas only pattern was significantly different between PD and rET in both standing and supine positions. In each patient group, all RT electrophysiological features did not significantly vary across different recording positions (p > 0.05)., Discussion: In our study, PD and rET showed RT in hand-hanging, supine, and standing positions. RT pattern was the only electrophysiological feature significantly different between PD and rET patients in all these positions, enabling clinicians to perform the RT analysis for diagnostic purposes in different tremor positions., (© 2022. Fondazione Società Italiana di Neurologia.)

Introduction: Progressive supranuclear palsy (PSP) patients show reduced amplitude and velocity of vertical saccades, but saccadic abnormalities have also been reported in Parkinson's disease (PD). We investigated amplitude and velocity of vertical saccades in PSP and PD patients, to establish the best video-oculographic (VOG) parameters for PSP diagnosis., Methods: Fifty-one PSP patients, 113 PD patients and 40 controls were enrolled. The diagnosis was performed on a clinico-radiological basis (MR Parkinsonism index [MRPI] and MRPI 2.0). We used VOG to assess the diagnostic performances of saccadic amplitude, peak velocity, and their product (AxV) in upward or downward direction and in vertical gaze (upward and downward averaged) in distinguishing PSP from PD patients. The vestibulo-ocular reflex, necessary to establish the supranuclear nature of ocular dysfunction, was evaluated clinically., Results: PSP patients showed significantly reduced amplitude and peak velocity of ocular saccades in upward and downward directions compared to PD and healthy subjects. In PD patients, upward gaze amplitude was lower than in controls. In vertical gaze, the peak velocity showed 99.1% specificity and 54.7% sensitivity for PSP classification. The AxV product showed high specificity (94.7%) and sensitivity (84.3%) and yielded higher accuracy (91.5%) than velocity and amplitude used alone in distinguishing PSP from PD., Conclusion: Our study demonstrates that the peak velocity of vertical saccades was a very low sensitive parameter and cannot be used alone for PSP diagnosis. A new index combining amplitude and peak velocity in vertical gaze seems the most suitable video-oculographic biomarker for differentiating PSP from PD and controls., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The R2 component of blink reflex recovery cycle (R2BRrc) is a simple neurophysiological tool to detect the brainstem hyperexcitability commonly occurring in several neurological diseases such as Parkinson's disease and atypical parkinsonisms. In our study, we investigated for the first time the usefulness of R2BRrc to assess brainstem excitability in patients with idiopathic Normal Pressure Hydrocephalus (iNPH) in comparison with healthy subjects., Methods: Eighteen iNPH patients and 25 age-matched control subjects were enrolled. R2BRrc was bilaterally evaluated at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500 and 750 ms in all participants. We investigated the diagnostic performance of R2BRrc in differentiating iNPH patients from control subjects using ROC analysis. Midbrain area and Magnetic Resonance Hydrocephalic Index (MRHI), an MRI biomarker for the diagnosis of iNPH, were measured on T1-weighted MR images, and correlations between R2BRrc values and MRI measurements were investigated., Results: Fourteen (78%) of 18 iNPH patients showed an enhanced R2BRrc at ISIs 100-150-200 ms, while no control subjects had abnormal R2BRrc. The mean amplitude of bilateral R2BRrc at the shortest ISIs (100-150-200 ms) showed high accuracy in differentiating iNPH patients from controls (AUC = 0.89). R2BRrc values significantly correlated with midbrain area and MRHI values., Conclusions: This study represents the first evidence of brainstem hyperexcitability in iNPH patients. Given its low cost and wide availability, R2BRrc could be a useful tool for selecting elderly subjects with mild gait and urinary dysfunction who should undergo an extensive diagnostic workup for the diagnosis of NPH., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Deep grey nuclei of the human brain accumulate minerals both in aging and in several neurodegenerative diseases. Mineral deposition produces a shortening of the transverse relaxation time which causes hypointensity on magnetic resonance (MR) imaging. The physician often has difficulties in determining whether the incidental hypointensity of grey nuclei seen on MR images is related to aging or neurodegenerative pathology. We investigated the hypointensity patterns in globus pallidus, putamen, caudate nucleus, thalamus and dentate nucleus of 217 healthy subjects (ages, 20-79 years; men/women, 104/113) using 3T MR imaging. Hypointensity was detected more frequently in globus pallidus (35.5%) than in dentate nucleus (32.7%) and putamen (7.8%). A consistent effect of aging on hypointensity (p < 0.001) of these grey nuclei was evident. Putaminal hypointensity appeared only in elderly subjects whereas we did not find hypointensity in the caudate nucleus and thalamus of any subject. In conclusion, the evidence of hypointensity in the caudate nucleus and thalamus at any age or hypointensity in the putamen seen in young subjects should prompt the clinician to consider a neurodegenerative disease., (© 2021. Fondazione Società Italiana di Neurologia.)

Introduction: Parkinson's disease (PD), a progressive neurodegenerative disease, can be misdiagnosed with atypical conditions such as Progressive Supranuclear Paralysis (PSP) due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. The aim was to identify a set of differential exosomal miRNAs biomarkers, which may aid in diagnosis., Methods: We analyzed the serum level of 188 miRNAs in a discovery set, by using RTqPCR based TaqMan assay, in a small cohort of healthy controls, PD and PSP patients. Subsequently, the differentially expressed miRNAs, between PSP and PD patients, were further tested in a larger and independent cohort of 33 healthy controls, 40 PD and 20 PSP patients. The most accurate diagnostic exosomal miRNAs classifiers were identified in a logistic regression model., Results: A statistically significant set of three exosomal miRNAs: miR-21-3p, miR-22-3p and miR-223-5p, discriminated PD from HC (area under the curve of 0.75), and a set of three exosomal miRNAs, miR-425-5p, miR-21-3p, and miR-199a-5p, discriminated PSP from PD with good diagnostic accuracy (area under the curve of 0.86). Finally, the classifier that best discriminated PSP from PD consisted of six exosomal miRNAs (area under the curve = 0.91), with diagnostic sensitivity and specificity of 0.89 and 0.90, respectively., Conclusions: Based on our analysis, these data showed that exosomal miRNAs could act as biomarkers to differentiate between PSP and PD., (Copyright © 2021. Published by Elsevier Ltd.)

Tremor is an impairing symptom associated with several neurological diseases. Some of such diseases are neurodegenerative, and tremor characterization may be of help in differential diagnosis. To date, electromyography (EMG) is the gold standard for the analysis and diagnosis of tremors. In the last decade, however, several studies have been conducted for the validation of different techniques and new, non-invasive, portable, or even wearable devices have been recently proposed as complementary tools to EMG for a better characterization of tremors. Such devices have proven to be useful for monitoring the efficacy of therapies or even aiding in differential diagnosis. The aim of this review is to present systematically such new solutions, trying to highlight their potentialities and limitations, with a hint to future developments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vescio, Quattrone, Nisticò, Crasà and Quattrone.)

Background: Enlargement of the third ventricle has been reported in atypical parkinsonism. We investigated whether the measurement of third ventricle width could distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP)., Methods: We assessed a new MR T1-weighted measurement (third ventricle width/internal skull diameter) in a training cohort of 268 participants (98 PD, 73 PSP, 98 controls from our center) and in a testing cohort of 291 participants (82 de novo PD patients and 133 controls from the Parkinson's Progression Markers Initiative, 76 early-stage PSP from an international research group). PD diagnosis was confirmed after a 4-year follow-up. Diagnostic performance of the third ventricle/internal skull diameter was assessed using receiver operating characteristic curve with bootstrapping; the area under the curve of the training cohort was compared with the area under the curve of the testing cohort using the De Long test., Results: In both cohorts, third ventricle/internal skull diameter values did not differ between PD and controls but were significantly lower in PD than in PSP patients (P < 0.0001). In PD, third ventricle/internal skull diameter values did not change significantly between baseline and follow-up evaluation. Receiver operating characteristic analysis accurately differentiated PD from PSP in the training cohort (area under the curve, 0.94; 95% CI, 91.1-97.6; cutoff, 5.72) and in the testing cohort (area under the curve, 0.91; 95% CI, 87.0-97.0; cutoff,: 5.88), validating the generalizability of the results., Conclusion: Our study provides a new reliable and validated MRI measurement for the early differentiation of PD and PSP. The simplicity and generalizability of this biomarker make it suitable for routine clinical practice and for selection of patients in clinical trials worldwide. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Involuntary tremor at rest is observed in patients with Parkinson's disease (PD) or essential tremor (ET). Electromyography (EMG) studies have shown that phase displacement between antagonistic muscles at prevalent tremor frequency can accurately differentiate resting tremor in PD from that detected in ET. Currently, phase evaluation is qualitative in most cases. The aim of this study is to develop and validate a new mobile tool for the automated and quantitative characterization of phase displacement (resting tremor pattern) in ambulatory clinical settings. A new low-cost, wearable mobile device, called µEMG, is described, based on low-end instrumentation amplifiers and simple digital signal processing (DSP) capabilities. Measurements of resting tremor characteristics from this new device were compared with standard EMG. A good level of agreement was found in a sample of 21 subjects (14 PD patients with alternating resting tremor pattern and 7 ET patients with synchronous resting tremor pattern). Our results demonstrate that tremor analysis using µEMG is easy to perform and it can be used in routine clinical practice for the automated quantification of resting tremor patterns. Moreover, the measurement process is handy and operator-independent.

Background: Idiopathic normal pressure hydrocephalus and PSP share several clinical and radiological features, making differential diagnosis, at times, challenging., Objectives: To differentiate idiopathic normal pressure hydrocephalus from PSP using MR volumetric and linear measurements., Methods: Twenty-seven idiopathic normal pressure hydrocephalus patients, 103 probable PSP patients, and 43 control subjects were consecutively enrolled. Automated ventricular volumetry was performed using Freesurfer 6 on MR T 1 -weighted images. Linear measurements, such as callosal angle and a new measure, termed MR Hydrocephalic Index, were calculated on MR T 1 -weighted images. Receiver operating characteristic analyses were used for differentiating between patient groups. Generalizability and reproducibility of the results were validated, dividing each participant group in two cohorts used as training and testing subsets., Results: Ventricular volumes and linear measurements (callosal angle and Magnetic Resonance Hydrocephalic Index) revealed greater ventricular enlargement in patients with idiopathic normal pressure hydrocephalus than in PSP patients and controls. PSP patients had ventricular volume larger than controls. Automated ventricular volumetry and Magnetic Resonance Hydrocephalic Index were the most accurate measures (98.5%) in differentiating patients with idiopathic normal pressure hydrocephalus from PSP patients, whereas callosal angle misclassified several PSP patients and showed low positive predictive value (70.0%) in differentiating between these two diseases. All measurements accurately differentiated idiopathic normal pressure hydrocephalus patients from controls. Accuracy values obtained in the training set (automated ventricular volumetry, 98.4%; Magnetic Resonance Hydrocephalic Index, 98.4%; callosal angle, 87.5%) were confirmed in the testing set., Conclusions: Our study demonstrates that AVV and Magnetic Resonance Hydrocephalic Index were the most accurate measures for differentiation between idiopathic normal pressure hydrocephalus and PSP patients. Magnetic Resonance Hydrocephalic Index is easy to measure and can be used in clinical practice to prevent misdiagnosis and ineffective shunt procedures in idiopathic normal pressure hydrocephalus mimics. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full-night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability-polysomnographic study included 16 never-treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full-night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high-frequency and low-frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea-hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single-night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea-hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice., (© 2019 European Sleep Research Society.)

Introduction: We investigated the disease progression rate in patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P) in comparison with Parkinson disease (PD) patients, using MRPI (Magnetic Resonance Parkinsonism Index), and MRPI 2.0., Methods: Fifteen PSP-RS patients (disease duration, y, mean ± SD: 2.5 ± 1.1), 16 PSP-P patients (disease duration, y, mean ± SD: 6.5 ± 3.2) and 19 PD patients (disease duration, y, mean ± SD: 3.2 ± 2.3) were enrolled. All patients underwent clinical assessment and MRI at baseline, 1-year, and 2-year follow-up. MRPI, MRPI 2.0 and clinical scores over 1 and 2-years were used to evaluate disease progression rate, and to calculate sample sizes required to power placebo-controlled trials., Results: All groups showed increased clinical motor scores over time whereas only PSP groups had increased MRPI and MRPI 2.0 values over T1 and T2 intervals. The percentage increase over 1 and 2-years of MRPI and MRPI 2.0 values was significantly higher in PSP groups than in PD group, and in PSP-RS than in PSP-P patients while no difference between patient groups was observed when clinical motor scores were considered. Sample size estimates showed that MRPI 2.0 performed better than MRPI and clinical scales. Treatment trials with MRPI 2.0 could be performed over 2-years both in PSP-RS and PSP-P with a sample size per treatment arm of 89 and 170 patients, respectively., Conclusions: Our results demonstrate that MRPI 2.0 was more powerful than MRPI and clinical motor scales in evaluating PSP progression, and in providing the best sample size estimates for clinical trials., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Apomorphine is a dopamine agonist used in Parkinson's disease (PD), which matches levodopa in terms of the magnitude of effect on the cardinal motor features, such as tremor and bradykinesia. The beneficial effect of this treatment on PD patients with tremor-dominant has widely been demonstrated, although the underlying neural correlates are unknown. We sought to examine the effects of apomorphine on topological characteristics of resting-state functional connectivity networks in tremor-dominant PD (tdPD) patients., Methods: Sixteen tdPD patients were examined using a combined electromyography-functional magnetic resonance imaging approach. Patients were scanned twice following either placebo (subcutaneous injection of 1 mL saline solution) or 1 mg of apomorphine injection. Graph analysis methods were employed to investigate the modular organization of functional connectivity networks before and after drug treatment., Results: After injection of apomorphine, evident reduction of tremor symptoms was mirrored by a significant increase in overall connectivity strength and reorganization of the modular structure of the basal ganglia and of the fronto-striatal module. Moreover, we found an increase in the centrality of motor and premotor regions. No differences were found between pre- and post-placebo sessions., Conclusion: These results provide new evidence about the effects of apomorphine at a large-scale neural network level showing that drug treatment modifies the brain functional organization of tdPD, increasing the overall resting-state functional connectivity strength, the segregation of striato-frontal regions and the integrative role of motor areas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

According to embodied cognition, processing language with motor content involves a simulation of this content by the brain motor system. Patients with brain lesions involving the motor system are characterized by deficits in action verbs processing in the absence of dementia. We sought to assess whether action verbs interfere with the motor behavior of patients with Parkinson's disease (PD) having tremor dominant symptoms. PD tremor is considered to result from dysfunction of cortical-subcortical motor circuits driven by dopamine depletion. In addition, PD tremor is reduced during active movement execution. Therefore, likewise movement execution, the motor simulation of bodily actions predicted by the embodiment may show to be effective in modifying tremor by interfering with a dysfunctional motor system. Here, we asked to simply read and repeat words expressing a hand-related bodily action. Abstract verbs served as control. Changes in tremor kinematics were evaluated using a monoaxial accelerometer. Seventeen PD patients with rest tremor of the upper limbs were enrolled. Tremor amplitude was significantly smaller when reading action verbs as compared to abstract verbs. We provide empirical evidence supporting the embodied cognition theory by showing that circuits mediating tremor of PD patients are distinctively affected by processing action language., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We investigated the imaging counterpart of two functional domains (ocular motor dysfunction and postural instability) in progressive supranuclear palsy (PSP) patients classified according to the new clinical diagnostic criteria., Methods: Forty-eight patients with probable PSP-Richardson's syndrome (PSP-RS), 30 with probable PSP-parkinsonism (PSP-P), 37 with Parkinson's disease (PD), and 38 controls were enrolled. For each functional domain, PSP patients were stratified by two certainty levels: vertical supranuclear gaze palsy (O1) and slowness of vertical saccades (O2) for ocular motor dysfunction; early unprovoked falls and tendency to fall on the pull-test for postural instability. Voxel-based morphometry (VBM), whole-brain fractional anisotropy (FA) and MR planimetric measurements were analysed and compared across patient groups., Results: O1 was present in 64%, and O2 in 36% of all PSP patients. All PSP-RS patients showed early unprovoked falls. TBSS whole-brain analysis revealed that superior cerebellar peduncles (SCPs) were the only structures with significantly lower FA values in PSP-RS compared with PSP-P patients. PSP/O1 patients had lower FA values in midbrain than PSP/O2 patients. By contrast, VBM revealed no differences in grey matter volume between PSP patient groups. MR Planimetric measurements confirmed atrophy of midbrain and SCPs, in line with DTI findings., Conclusions: Our study demonstrates that SCPs were significantly more damaged in patients with PSP-RS in comparison with PSP-P patients, thus suggesting the role of SCPs in developing postural instability. Midbrain damage was less severe in O2 than in O1 patients, suggesting that the degree of vertical ocular dysfunction reflects the severity of midbrain atrophy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Several evidences demonstrated the role of white matter (WM) lesions in the pathogenesis of Vascular Parkinsonism (VP), a clinical entity characterized by parkinsonism, postural instability, marked gait difficulty and poor response to levodopa. However, the involvement of normal appearing white matter (NAWM) in VP still remains unknown. This study aimed to investigate the microstructural integrity of NAWM in VP compared to Parkinson's disease (PD) and controls using neuroimaging approach., Methods: Magnetic resonance imaging data were acquired from 50 participants (15 VP, 20 PD and 15 controls). Diffusion tensor imaging (DTI) and Tract-based spatial statistics (TBSS) were performed to assess microstructural NAWM changes. In order to evaluate the relationship between specific fiber tract involvement and clinical picture, diffusion alterations were correlated with clinical features., Results: Compared to PD patients and controls, significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in NAWM of corpus callosum, internal and external capsule, and corona radiata were present in VP. By contrast, DTI metrics were normal in NAWM-PD and controls. A significant correlation was found between FA and MD of anterior third of corpus callosum and clinical variables (postural instability, freezing-of-gait and symmetry of parkinsonism)., Conclusions: This study improves the knowledge on WM pathology in VP, as our results demonstrate that NAWM damage occurs in VP, but not in PD nor in controls. NAWM damage might relate to clinical picture and suggest that non-clearly-visible WM alterations may contribute to the physiopathology of this vascular disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: REM sleep behavior disorder (RBD) is an important risk factor for the dementia development and for the deterioration of autonomic functions in patients with Parkinson's Disease. RBD has also been reported in patients with Essential Tremor (ET). However, its clinical significance in ET remains still unknown. We aimed to investigate clinical, neuropsychological and cardiac autonomic scintigraphic differences between ET patients with and without RBD. Methods: To assess RBD symptoms, RBD Single-Question has been administered in a cohort of 55 patients with a clinical diagnosis of ET. Patients with clinical RBD underwent polysomnography (PSG) confirmation. All patients completed a battery of neuropsychological assessment of memory, executive function, attention, language, and visuospatial function. Cardiac MIBG scintigraphy was performed in order to measure the cardiac autonomic innervation. Results: Ten ET patients (18%) had a PSG-confirmed RBD (ET RBD+ ). Compared to ET patients without RBD (ET RBD- ), significantly reduced scores on memory domain tests such as Rey auditory verbal learning test immediate recall ( p = 0.015) and Rey auditory verbal learning test delayed recall ( p = 0.004) and phonemic fluency test ( p = 0.028) were present in ET RBD+ . By contrast, no other significant clinical difference has emerged from the comparison between two ET groups. Similarly, ET RBD+ patients have cardiac MIBG tracer uptake in the normal value range as occurred in those with ET RBD- . Conclusions: This study improves the knowledge on clinical significance of RBD symptoms in ET patients. Our preliminary findings demonstrate that presence of RBD in ET is associated with neurocognitive impairment, but not with cardiac autonomic dysfunction. Further longitudinal studies are needed to investigate whether ET patients with RBD will develop a frank dementia over the time.

Objective: To identify the pressure-related features of isolated cerebrospinal fluid hypertension (ICH) in order to differentiate headache sufferers with ICH from those with primary headache disorder. Methods: In this prospective study, patients with refractory chronic headaches and suspected of having cerebrospinal fluid-pressure elevation without papilledema or sixth nerve palsy, together with controls, underwent 1-h lumbar cerebrospinal fluid pressure monitoring via a spinal puncture needle. Results: We recruited 148 consecutive headache patients and 16 controls. Lumbar cerebrospinal fluid pressure monitoring showed high pressure and abnormal pressure pulsations in 93 (63 %) patients with headache: 37 of these patients with the most abnormal pressure parameters (opening pressure above 250 mm H 2 O, mean pressure 301 mm H 2 O, mean peak pressure 398 mm H 2 O, and severe abnormal pressure pulsations) had the most severe headaches and associated symptoms (nocturnal headache, postural headache, transient visual obscuration); 56 patients with the less abnormal pressure parameters (opening pressure between 200 and 250 mm H 2 O, mean pressure 228 mm H 2 O, mean peak pressure 316 mm H 2 O, and abnormal pressure pulsations) had less severe headaches and associated symptoms. Conclusions: Nocturnal and postural headache, and abnormal pressure pulsations are the more common pressure-related features of ICH in patients with chronic headache. Abnormal pressure pulsations may be considered a marker of ICH in chronic headache.

Introduction: Essential tremor-Parkinson's disease (ET-PD) syndrome is a clinical condition in which individuals with a long-lasting history of Essential tremor (ET) eventually develop Parkinson's disease (PD). The aim of the study was to investigate the accuracy performances of clinical, neurophysiological, and imaging biomarkers in differentiating patients affected by ET-PD syndrome from patients with ET or PD., Methods: Nineteen patients affected by ET-PD syndrome, 48 ET patients, and 37 tremor-dominant PD (t-PD) patients were included. Electrophysiological studies, including blink-reflex recovery cycle and tremor parameters analyses, were performed in all groups. Nigro-striatal and cardiac sympathetic denervation were also investigated. Sensitivity, specificity and accuracy of clinical, electrophysiological, and radiological features in differentiating ET-PD syndrome from ET and PD were calculated., Results: ET-PD patients had significantly lower rigidity (p = 0.007) and higher postural/kinetic tremor (p = 0.007) scores, in comparison to t-PD patients. ET-PD patients, differently from PD patients, had a synchronous pattern of resting tremor and, differently from ET patients, had abnormal blink-reflex recovery cycle. ET-PD patients also showed reduced nigro-striatal and cardiac sympathetic uptakes, albeit to a lesser extent than in PD patients. The highest accuracy values were found for the synchronous pattern of resting tremor (97.1%) in distinguishing ET-PD from PD, and for presence of abnormal blink-recovery cycle (100%) in distinguishing ET-PD syndrome from ET., Conclusion: Our study demonstrates that some electrophysiological parameters, such as a synchronous resting tremor pattern and the abnormal blink-recovery cycle were the most accurate biomarkers in distinguishing patient with ET-PD syndrome from those with ET or those with PD., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD., Methods: Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images., Results: The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients., Conclusion: The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: The aim of our study was to investigate the effect of apomorphine and placebo on resting tremor in tremor-dominant Parkinson's disease (tPD) patients., Methods: Fifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received apomorphine. On each day, the patients underwent three electrophysiological recording sessions: T0, T1, and T2: before, 30 min, and 60 min after the treatment respectively. Electrophysiological changes in tremor amplitude were evaluated using a triaxial accelerometer., Results: Placebo was effective in improving resting tremor in all tPD patients (p = 0.009) at T1, but not at T2. Eight out of 15 tPD patients (53.3%) responded to placebo with an at least 70% reduction in tremor amplitude compared to the basal condition (responders). By contrast, seven out of 15 tPD patients (46.7%) did not show any variation in tremor amplitude after placebo administration (non-responders). Apomorphine induced a marked reduction in tremor amplitude at 30 min and 60 min in all investigated tPD patients. Of note, the decrease in tremor amplitude in placebo responders was similar to that achieved with dopaminergic stimulation induced by apomorphine., Conclusions: Our study demonstrates that placebo was very effective in reducing resting tremor in about half of patients with tPD. The decrease in tremor amplitude in placebo responders was similar to that induced by apomorphine. The cerebral mechanisms underlying the placebo effect on resting tremor need further investigations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Heart rate variability (HRV) is commonly used to assess autonomic functions and responses to environmental stimuli. It is usually derived from electrocardiographic signals; however, in the last few years, photoplethysmography has been successfully used to evaluate beat-to-beat time intervals and to assess changes in the human heart rate under several conditions. The present work describes a simple design of a photoplethysmograph, using a wearable earlobe sensor. Beat-to-beat time intervals were evaluated as the time between subsequent pulses, thus generating a signal representative of heart rate variability, which was compared to RR intervals from classic electrocardiography. Twenty-minute pulse photoplethysmography and ECG recordings were taken simultaneously from 10 healthy individuals. Ten additional subjects were recorded for 24 h. Comparisons were made of raw signals and on time-domain and frequency-domain HRV parameters. There were small differences between the inter-beat intervals evaluated with the two techniques. The current findings suggest that our wearable earlobe pulse photoplethysmograph may be suitable for short and long-term home measuring and monitoring of HRV parameters., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate circadian fluctuations and night/day ratio of Heart Rate Variability (HRV) spectral components in patients with obstructive sleep apnea (OSA) in comparison with controls., Participants and Methods: This is a simultaneous HRV-polysomnographic (PSG) study including 29 patients with OSA and 18 age-sex-matched controls. Four patients with OSA dropped out. All participants underwent PSG and HRV analysis. We measured the 24-hour fluctuations and the night/day ratio of low frequency (LF) and high frequency (HF) spectral components of HRV in all subjects and controls. The LF night/day ratio was termed the cardiac sympathetic index while the HF night/day ratio was termed the cardiac parasympathetic index., Results: All twenty-five OSA patients were PSG positive (presence of OSA) while 18 controls were PSG negative (absence of OSA). There was no significant difference in LF and HF 24-hour fluctuation values between OSA patients and controls. In OSA patients, LF and HF values were significantly higher during night-time than day time recordings (p<0.001). HF night/day ratio (cardiac parasympathetic index) accurately (100%) differentiated OSA patients from controls without an overlap of individual values. The LF night/day ratio (cardiac sympathetic index) had sensitivity of 84%, specificity of 72.2% and accuracy of 79.1% in distinguishing between groups., Conclusions: The cardiac parasympathetic index accurately differentiated patients with OSA from controls, on an individual basis.

In this work, we investigated motor network structure in patients affected by essential tremor (ET) with or without resting tremor, using probabilistic tractography of the cerebello-thalamo-basal ganglia-cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with resting tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT-SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello-thalamo-basal ganglia-cortical loop. All patients with ET, regardless of the presence of resting tremor, had normal DAT-SPECT, but showed significantly decreased connectivity in the cerebello-thalamo-precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by resting tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello-thalamo-precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.

Objective: To investigate heart rate variability (HRV) in patients with Essential Tremor (ET) in comparison with patients with Parkinson's Disease (PD)., Methods: This is a cross sectional control study including 10 patients with ET, 10 patients with PD and 10 age-sex-matched controls. In patients and controls, we measured the components of HRV analysis in the frequency domain during a daytime period of 12-h. Selected HRV variables were low-frequency (LF) and high-frequency (HF), conventionally considered to be influenced by the sympathetic system and the parasympathetic system respectively., Results: HRV variables, in patients with ET, were significantly different from those detected in PD patients and similar to those of controls while in PD patients, they were significantly different from those of controls. At cut off level of 654 ms 2 , LF component correctly distinguished ET patients versus PD with sensitivity, specificity, PPV and accuracy of 100%. By contrast, at cut off level of 737 ms 2 , HF component showed sensitivity, specificity, PPV and accuracy of 80%, 100%, 100%, and 86.67% respectively. DAT-SPECT and cardiac MIBG uptake were both normal in ET patients whereas they were markedly decreased in those with PD., Conclusions: In our study, the LF component of HRV analysis distinguishes ET patients from those with PD on an individual basis, thus representing a valid help in everyday clinical practice for differentiation between these patients in absence of scintigraphic investigations., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: To identify a biomarker for predicting the appearance of vertical supranuclear gaze palsy (VSGP) in patients affected by progressive supranuclear palsy-parkinsonism (PSP-P)., Methods: Twenty-four patients with PSP-P were enrolled in the current study. Patients were clinically followed up every 6 months until the appearance of VSGP or the end of the follow-up (4 years). Participants underwent MRI at baseline and at the end of follow-up. Magnetic resonance parkinsonism index (MRPI), an imaging measure useful for diagnosing PSP, was calculated., Results: Twenty-one patients with PSP-P completed follow-up, and 3 patients dropped out. Eleven of 21 patients with PSP-P developed VSGP after a mean follow-up period of 28.5 months (range 6-48 months), while the remaining 10 patients with PSP-P did not develop VSGP during the 4-year follow-up period. At baseline, patients with PSP-P who later developed VSGP had MRPI values significantly higher than those of patients not developing VSGP without overlapping values between the 2 groups. MRPI showed a higher accuracy (100%) in predicting VSGP than vertical ocular slowness (accuracy 33.3%) or postural instability with or without vertical ocular slowness (accuracy 71.4% and 42.9%, respectively)., Conclusions: Our study demonstrates that MRPI accurately predicted, on an individual basis, the appearance of VSGP in patients with PSP-P, thus confirming clinical diagnosis in vivo., (© 2016 American Academy of Neurology.)

Objective: To compare circadian autonomic fluctuations in patients with Parkinson's Disease (PD) with or without REM sleep behavior disorder (RBD) by using heart rate variability (HRV) analysis., Methods: This is a case-control study including 20 PD patients with RBD (PD-RBD) and 20 PD patients without RBD (PD). In all patients, we measured the components of HRV in the frequency domain during 24-h with daytime and night time recordings. Selected variables considered were low-frequency (LF) influenced by the sympathetic system and high-frequency (HF) influenced by the parasympathetic system. Moreover, we calculated night-to-day ratio for both LF (cardiac sympathetic index) and HF (cardiac parasympathetic index) spectral components. Video-polysomnography was performed in all patients to diagnose RBD., Results: Both nocturnal LF and HF spectral power values were significantly higher in PD-RBD patients than in PD patients (P < 0.001 and P = 0.004 respectively). Moreover, in PD-RBD patients LF and HF values were higher at night than during the day while no difference between night time and daytime values was observed in patients with PD. Cardiac sympathetic index value was significantly higher in PD-RBD patients (median 1.83, range 1.65-3.66) than in PD patients (median 0.93, range 0.44-1.3) without overlap of individual values between groups (accuracy 100%). By contrast, cardiac parasympathetic index had sensitivity of 45% and specificity of 100% for differentiating between PD groups., Conclusions: Cardiac sympathetic index distinguishes PD-RBD patients from those with PD on an individual basis, thus representing a valid help in everyday clinical practice for screening of RBD in PD patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: We tested whether a change in head/neck position initiates head deviation in drug-naïve patients with cervical dystonia and to identify the electrophysiological and neuroanatomical correlates of dystonic head rotation., Methods: Twenty-five consecutive drug-naïve patients with cervical dystonia and 25 healthy controls underwent the simultaneous surface electromyographic (EMG) recording of sternocleidomastoid (SCM) muscle contractions during head/neck position changes, blink reflex recovery cycle (BRrc), DAT-SPECT, and advanced structural neuroimaging analysis using voxel-based morphometry (VBM)., Results: Surface EMG recordings of SCM muscle activity during changes in head/neck position demonstrated an insignificant asymmetric low amplitude of the SCM muscle contractions in the horizontal position in both patients and controls, but an asymmetric high amplitude in SCM muscle contractions leading to abnormal head movements in vertical positions in patients with cervical dystonia. All controls had a symmetric low increase in amplitude of SCM muscle contractions in response to changes in head/neck position. VBM analysis in 19 patients showed abnormal decreases of gray matter (GM) volume in the bilateral motor (localized in the homunculus of the head) and premotor cortices when compared to controls. In addition, the side of these neuroanatomical changes was asymmetrically related to abnormal head deviations in these patients. All subjects had normal results during BRrc and DAT-SPECT., Conclusions: The passage from inactive horizontal position to active vertical head/neck posture initiates head deviation in drug-naïve patients with cervical dystonia, and the anatomical correlates of this dystonic head rotation is a restricted abnormal pattern of GM changes in the motor cortices., (Copyright © 2015 Elsevier Ltd. All rights reserved.)