Publications by authors named "Andrea Quattrone"

55 Publications

Exosomal miRNA as peripheral biomarkers in Parkinson's disease and progressive supranuclear palsy: A pilot study.

Parkinsonism Relat Disord 2021 Nov 24;93:77-84. Epub 2021 Nov 24.

Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto, 88100, Catanzaro, Italy; Neuroscience Research Center, University Magna Graecia, 88100, Catanzaro, Italy. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2021.11.020DOI Listing
November 2021

Mutation analysis of the ATP13A2 gene in patients with PD and MSA from Italy.

J Neurol Sci 2021 Nov 16;430:120031. Epub 2021 Oct 16.

Institute for Biomedical Research and Innovation, National Research Council, Mangone, CS, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2021.120031DOI Listing
November 2021

Corticospinal tract abnormalities and ventricular dilatation: A transdiagnostic comparative tractography study.

Neuroimage Clin 2021 Oct 19;32:102862. Epub 2021 Oct 19.

Neuroscience Research Center, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy; Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, 88100 Catanzaro, Italy. Electronic address:

Background: Microstructural alterations of corticospinal tract (CST) have been found in idiopathic normal pressure hydrocephalus (iNPH). No study, however, investigated the effect of ventricular dilatation on CST in Progressive Supranuclear Palsy (PSP).

Objective: The aim of this study was to investigate CST diffusion profile in a large cohort of PSP patients with and without ventricular dilatation.

Methods: Twenty-three iNPH patients, 87 PSP patients and 26 controls were enrolled. Evans index (EI) and ventricular volume (VV) were measured in all patients. CST tractography was performed to calculate FA, MD, AxD and RD in six different anatomical regions: medulla oblungata (MO), pons (P), cerebral peduncle (CP), posterior limb of internal capsule (PLIC), corona radiata (CR), subcortical white matter (SWM). ANCOVA was used for comparing CST diffusion profiles between the groups and association between CST microstructural metrics and measures of ventricular dilatation (EI and VV) was assessed.

Results: Thirty-three PSP patients had ventricular dilatation (EI > 0.30, PSP-vd) while 54 PSP patients had normal ventricular system (EI ≤ 0.30, PSP-wvd). iNPH patients had the most marked FA and AxD increase in PLIC and CR of CST followed by PSP-vd, PSP-wvd and controls; RD was altered only in iNPH. A strong correlation was found between CST diffusion metrics and EI or VV.

Conclusions: Our findings confirm the microstructural changes of CST in iNPH patients and demonstrate for the first time similar alterations in PSP-vd patients, suggesting a crucial role of ventricular dilatation in the mechanical compression of CST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536776PMC
October 2021

Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease.

J Parkinsons Dis 2021 Oct 7. Epub 2021 Oct 7.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.

Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation.

Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases.

Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017).

Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking.

Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JPD-212851DOI Listing
October 2021

Rest Tremor Pattern Predicts DaTscan ( I-Ioflupane) Result in Tremulous Disorders.

Mov Disord 2021 Sep 28. Epub 2021 Sep 28.

Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28797DOI Listing
September 2021

Aceruloplasminemia: a multimodal imaging study in an Italian family with a novel mutation.

Neurol Sci 2021 Sep 24. Epub 2021 Sep 24.

Institute of Molecular Bioimaging and Physiology, National Research Council, Rome, Italy.

Objective: Structural abnormalities in thalami and basal ganglia, in particular the globus pallidus (GP), are a neuroimaging hallmark of hereditary aceruloplasminemia (HA), yet few functional imaging data exit in HA carriers. This study investigated the iron-related structural and functional abnormalities in an Italian HA family.

Methods: Multimodal imaging was used including structural 3 T MRI, functional imaging (SPECT imaging with I-ioflupane (DAT-SPECT), cardiac I metaiodobenzylguanidine (I-MIBG) scintigraphy, and F-fluorodeoxyglucose (F-FDG)-PET imaging). In the proband, MRI and scintigraphic evaluations were performed at baseline, 2 and 4 years (structural imaging), and 2 years of follow-up period (functional imaging).

Results: We investigated two cousins carrying a novel splicing homozygous mutation in intron 6 (IVS6 + 1 G > A) of CP gene. Interestingly, MRI features in both subjects were characterized by marked iron accumulation in the thalami and basal ganglia nuclei, while GP was not affected. MRI performed in the proband at 2 and 4 years of follow-up confirmed progressive neurodegeneration of the thalami and basal ganglia without the involvement of GP. Functional imaging showed reduced putaminal DAT uptake in both cousins, whereas cardiac MIBG and FDG uptakes performed in the proband were normal. Longitudinal scintigraphic investigations did not show significant changes over the time.

Conclusions: For HA carriers, our findings demonstrate that GP was spared by iron accumulation over the time. The nigrostriatal presynaptic dopaminergic system was damaged while the cardiac sympathetic system remained longitudinally preserved, thus expanding the imaging features of this rare inherited disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05613-4DOI Listing
September 2021

Progressive supranuclear palsy with marked ventricular dilatation mimicking normal pressure hydrocephalus.

Neurol Sci 2021 Sep 9. Epub 2021 Sep 9.

Neuroscience Research Center, University "Magna Graecia", Catanzaro, Italy.

Background: Progressive supranuclear palsy (PSP) patients can show ventricular enlargement mimicking normal pressure hydrocephalus (NPH). The aim of this study was to distinguish PSP patients with marked ventricular dilatation (PSP-vd) from those with normal ventricular system and to evaluate the coexistence of NPH in PSP-vd patients.

Methods: One hundred three probable PSP patients, 18 definite NPH patients, and 41 control subjects were enrolled in the study. Evans index (EI) > 0.32 associated with callosal angle (CA) < 100° was used to identify PSP-vd patients. Automated ventricular volumetry (AVV) and Magnetic Resonance Hydrocephalic Index (MRHI) were performed on T1-weighted MR images to evaluate the presence of NPH in PSP-vd patients.

Results: Twelve (11.6%) out of 103 PSP patients had both abnormal EI and CA values (PSP-vd). In two of these 12 patients, AVV and MRHI values suggested PSP + NPH. In the remaining 10 PSP-vd patients, AVV and MRHI values were higher than PSP patients with normal ventricular system and controls, but lower than PSP + NPH and NPH patients, suggesting a non-hydrocephalic ventricular enlargement.

Discussion: Our study provides evidence that the combination of EI and CA biomarkers allowed to identify PSP patients with marked ventricular dilatation mimicking NPH. Only a few of these patients had PSP + NPH. Recognition of these PSP patients with enlarged ventricles can positively impact the care of this disease, helping clinicians to identify patients with PSP + NPH who could benefit from shunt procedure and avoid surgery in those with enlarged ventricles without NPH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05594-4DOI Listing
September 2021

Hyper-religiosity and visual hallucinations in a patient with frontotemporal dementia carrying a double variant in GRN gene.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Aug 26:1-4. Epub 2021 Aug 26.

Neuroscience Centre, Magna Graecia University, Catanzaro, Italy, and.

: Hyper-religiosity has been reported in patients affected by frontotemporal dementia (FTD) with asymmetrical, predominantly right-sided frontotemporal atrophy. : We report a FTD patient carrying a double genetic variant (p.Cys139Arg and c.*78C > T) in the progranulin (GRN) gene who showed an unusual clinical phenotype characterized by hyper-religiosity behavior and visual hallucinations with exclusively religious content. Noteworthy, this patient exhibited a slow clinical and radiological rate of disease progression and a predominantly left-sided frontotemporal atrophy. : The simultaneous presence of these GRN variants in our FTD patient with predominant atrophy in the left (dominant) hemisphere could determine the unusual phenotype with hyper-religiosity and visual hallucinations with exclusively religious content and influence the slow rate of disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21678421.2021.1946087DOI Listing
August 2021

Semi-automated assessment of the principal diffusion direction in the corpus callosum: differentiation of idiopathic normal pressure hydrocephalus from neurodegenerative diseases.

J Neurol 2021 Aug 24. Epub 2021 Aug 24.

Neuroscience Research Center, University "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.

Background: Idiopathic normal pressure hydrocephalus (iNPH) shares clinical and radiological features with progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). Corpus callosum (CC) involvement in these disorders is well established on structural MRI and diffusion tensor imaging (DTI), but alterations overlap and lack specificity to underlying tissue changes.

Objective: We propose a semi-automated approach to assess CC integrity in iNPH based on the spatial distribution of DTI-derived principal diffusion direction orientation (V1).

Methods: We processed DTI data from 121 subjects (Site1: iNPH = 23, PSP = 27, controls = 14; ADNI: AD = 35, controls = 22) to obtain V1, fractional anisotropy (FA) and mean diffusivity (MD) maps. To increase the estimation accuracy of DTI metrics, analyses were restricted to the midsagittal CC portion (± 6 slices from midsagittal plane). Group-wise comparison of normalized altered voxel count in midsagittal CC was performed using Kruskal-Wallis tests, followed by post hoc comparisons (Bonferroni-corrected p < 0.05). ROC analysis was used to evaluate the diagnostic power of DTI alterations compared to callosal volume.

Results: We found specific changes of V1 distribution in CC splenium of iNPH compared to AD and PSP, while MD and FA showed patterns of alterations common to all disorders. ROC curves showed that, compared to splenial volume, V1 represented the most accurate marker of iNPH diagnosis versus AD and PSP.

Conclusions: Our results provide evidence that V1 is a powerful biomarker for distinguishing patients with iNPH from patients with AD or PSP. Indeed, our findings also provide more specific insight into the pathophysiological mechanisms that underlie tissue damage across iNPH and its mimics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-021-10762-9DOI Listing
August 2021

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Schizophr Res 2021 10 14;236:69-79. Epub 2021 Aug 14.

Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473991PMC
October 2021

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Transl Psychiatry 2021 08 10;11(1):423. Epub 2021 Aug 10.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355107PMC
August 2021

Roles of Non-Coding RNAs as Novel Diagnostic Biomarkers in Parkinson's Disease.

J Parkinsons Dis 2021;11(4):1475-1489

Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto, Catanzaro, Italy.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JPD-212726DOI Listing
January 2021

Blink reflex recovery cycle distinguishes patients with idiopathic normal pressure hydrocephalus from elderly subjects.

J Neurol 2021 Jul 2. Epub 2021 Jul 2.

Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-021-10687-3DOI Listing
July 2021

Microstructural changes in normal-appearing white matter in male sleep apnea patients are reversible after treatment: A pilot study.

J Neurosci Res 2021 Oct 1;99(10):2646-2656. Epub 2021 Jul 1.

Division of Neuroscience, Sleep Disorders Center, San Raffaele Scientific Institute, Milan, Italy.

Visually appreciable white matter (WM) changes have been described in obstructive sleep apnea (OSA). However, few data exist on the involvement of silent WM abnormalities. This prospective study investigated the microstructural integrity of normal-appearing white matter (NAWM) in male OSA patients before and after continuous positive airway pressure (CPAP) treatment, using a neuroimaging approach. Magnetic resonance imaging (MRI) was acquired from 32 participants (16 severe never-treated OSA and 16 controls). Diffusion tensor imaging (DTI) and Tract-Based Spatial Statistics (TBSS) were used to assess the microstructural NAWM changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In order to evaluate the efficacy of the therapy, OSA patients underwent MRI evaluations at baseline and after 3 months of treatment (follow-up). CPAP treatment significantly increased the FA in NAWM of the brain stem, corpus callosum and bilateral internal capsule of OSA patients at follow-up compared to baseline (p < 0.05, TFCE-corrected). OSA patients also showed increases in AD in the corpus callosum, superior corona radiata, and internal capsule of the right hemisphere (p < 0.05, TFCE-corrected) after CPAP treatment. A significant negative correlation was found between the FA of the corona radiata, corpus callosum, internal capsule, limbic structures, and neuropsychological scores at follow-up evaluation. No significant differences were found in MD and RD of NAWM in our patients after treatment. Our results demonstrate that FA and AD of NAWM in major tracts such as the corpus callosum and the internal capsule increased significantly after CPAP treatment, as a potential beneficial effect of ventilatory therapy. The recovery of NAWM alterations might also be related to the improvement in the neurocognitive profile, suggesting that nonclearly visible WM alterations may contribute to the physiopathology of OSA-related cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.24858DOI Listing
October 2021

Wearable Devices for Assessment of Tremor.

Front Neurol 2021 11;12:680011. Epub 2021 Jun 11.

Neuroimaging Unit, Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.680011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226078PMC
June 2021

Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort.

J Neurol Sci 2021 08 24;427:117509. Epub 2021 May 24.

Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy. Electronic address:

Background: Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes.

Objectives: To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients.

Methods: A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria.

Results: Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age ± SD 65.6 ± 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)].

Conclusions: Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2021.117509DOI Listing
August 2021

Defining Populations for Neuroprotective Interventions: The Prodromal Stage of α-Synucleinopathies.

Mov Disord 2021 07 25;36(7):1553. Epub 2021 May 25.

Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28664DOI Listing
July 2021

Incidental evidence of hypointensity in brain grey nuclei on routine MR imaging: when to suspect a neurodegenerative disorder?

Neurol Sci 2021 May 1. Epub 2021 May 1.

Neuroscience Centre, Magna Graecia University, Catanzaro, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05292-1DOI Listing
May 2021

Diagnostic and therapeutic potential of exosomal miRNAs in Alzheimer's disease.

Neural Regen Res 2021 Nov;16(11):2217-2218

Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto; Neuroscience Research Center, University Magna Graecia, 88100 Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.310674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354126PMC
November 2021

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration.

JAMA Netw Open 2021 03 1;4(3):e211290. Epub 2021 Mar 1.

Memory and Aging Center, Department of Neurology, University of California, San Francisco.

Importance: The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking.

Objective: To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI).

Design, Setting, And Participants: In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020.

Main Outcomes And Measures: The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration.

Results: Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001).

Conclusions And Relevance: Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.1290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953307PMC
March 2021

Development and Validation of a New Wearable Mobile Device for the Automated Detection of Resting Tremor in Parkinson's Disease and Essential Tremor.

Diagnostics (Basel) 2021 Jan 29;11(2). Epub 2021 Jan 29.

Neuroimaging Unit, Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), 88100 Catanzaro, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11020200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911899PMC
January 2021

Aging effect on head motion: A Machine Learning study on resting state fMRI data.

J Neurosci Methods 2021 03 25;352:109084. Epub 2021 Jan 25.

Institute of Bioimaging and Molecular Physiology (IBFM), National Research Council, Catanzaro, Italy. Electronic address:

Background: Resting-state-fMRI is a technique used to explore the functional brain architecture in term of brain networks and their interactions. However, the robustness of Resting-state-fMRI analysis is negatively affected by physiological noise caused by subject head motion. The aim of our study was to provide new knowledge about the effect of normal aging on the head motion signals.

New Method: For the first time, we proposed a method for evaluating the most sensitive head motion parameters linked to subjects'aging. We enrolled 14-young(9females; mean-age = 28 ± 4.07) and 14-elderly(9females; mean-age = 66 ± 5.19) subjects. Along three axes(X,Y,Z), we extracted six motions parameters which reflected the head's movements to characterize translations(x,y,z) and rotations(angles phi,theta,psi). We performed:1)univariate analysis for comparing the groups and correlation to investigate the relationship between age and movement parameters; 2)Support-Vector-Machine, using bootstrap and calculating the feature importance.

Results: Statistical analyses showed significant association between the aging and some motion's parameters(rotation psi; translations y and z). These results were also confirmed by multivariate analysis with Support-Vector-Machine that presented an AUC of 90 %.

Comparison To Existing Methods: The proposed method shows that normal aging produces significant increase in head motion parameters, highlighting the critical effect of motion on resting data analyses in particular considering psi, y and z movements. To our knowledge and at the present, this represents the first study investigating the accurate characterization of motion parameters in aging.

Conclusions: Our results have a high impact to improve healthy control recruitment and appropriately decreasing the risk of signal distortion, according to the age of enrolled subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneumeth.2021.109084DOI Listing
March 2021

Opicapone-induced reversible myopathy in a patient with advanced Parkinson's disease and familial hyperCKemia.

Neurol Sci 2021 06 25;42(6):2583-2585. Epub 2021 Jan 25.

Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Magna Graecia University, Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05071-yDOI Listing
June 2021

Reply to: "MRI Linear Measurements in Normal Pressure Hydrocephalus Versus Progressive Supranuclear Palsy".

Mov Disord 2020 11;35(11):2122

Neuroscience Research Center, University "Magna Graecia", Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28337DOI Listing
November 2020

Diagnostic accuracy of MR planimetry in clinically unclassifiable parkinsonism.

Parkinsonism Relat Disord 2021 01 24;82:87-91. Epub 2020 Nov 24.

Department of Neurology, Medical University of Innsbruck, Austria; Neuroimaging Core Facility, Medical University Innsbruck, Innsbruck, Austria. Electronic address:

Introduction: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages.

Methods: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up.

Results: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0.

Conclusions: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3V width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2020.11.019DOI Listing
January 2021

Neuropsychological assessment could distinguish among different clinical phenotypes of progressive supranuclear palsy: A Machine Learning approach.

J Neuropsychol 2021 Sep 24;15(3):301-318. Epub 2020 Nov 24.

Neuroscience Research Center, Magna Graecia University, Catanzaro, Italy.

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive neurodegenerative disease. Richardson's syndrome (PSP-RS) and predominant parkinsonism (PSP-P) are characterized by wide range of cognitive and behavioural disturbances, but these variants show similar cognitive pattern of alterations, leading difficult differential diagnosis. For this reason, we explored with an Artificial Intelligence approach, whether cognitive impairment could differentiate the phenotypes. Forty Parkinson's disease (PD) patients, 25 PSP-P, 40 PSP-RS, and 34 controls were enrolled following the consensus criteria diagnosis. Participants were evaluated with neuropsychological battery for cognitive domains. Random Forest models were used for exploring the discriminant power of the cognitive tests in distinguishing among the four groups. The classifiers for distinguishing diseases from controls reached high accuracies (86% for PD, 95% for PSP-P, 99% for PSP-RS). Regarding the differential diagnosis, PD was discriminated from PSP-P with 91% (important variables: HAMA, MMSE, JLO, RAVLT_I, BDI-II) and from PSP-RS with 92% (important variables: COWAT, JLO, FAB). PSP-P was distinguished from PSP-RS with 84% (important variables: JLO, WCFST, RAVLT_I, Digit span_F). This study revealed that PSP-P, PSP-RS and PD had peculiar cognitive deficits compared with healthy subjects, from which they were discriminated with optimal accuracies. Moreover, high accuracies were reached also in differential diagnosis. Most importantly, Machine Learning resulted to be useful to the clinical neuropsychologist in choosing the most appropriate neuropsychological tests for the cognitive evaluation of PSP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnp.12232DOI Listing
September 2021

A New MRI Measure to Early Differentiate Progressive Supranuclear Palsy From De Novo Parkinson's Disease in Clinical Practice: An International Study.

Mov Disord 2021 03 5;36(3):681-689. Epub 2020 Nov 5.

Neuroscience Research Center, University "Magna Graecia", Catanzaro, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330364PMC
March 2021

Reduced Striatal DAT Uptake Normalizes After Shunt in Normal-Pressure Hydrocephalus.

Mov Disord 2021 01 12;36(1):261-262. Epub 2020 Oct 12.

Neuroscience Research Center, University "Magna Graecia,", Catanzaro, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28336DOI Listing
January 2021

Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer's Disease.

Pharmaceuticals (Basel) 2020 Sep 12;13(9). Epub 2020 Sep 12.

Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto, 88100 Catanzaro, Italy.

Alzheimer's disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer's disease, also taking a look at their potential clinical value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph13090243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559720PMC
September 2020
-->