440 results on '"Pacchetti, C."'
Search Results
152. Influence Of L-5Ht With And Without Carbidopa On Plasma B-Endorphin And Pain Reflex In Man
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Sandrini, G., primary, Facchinetti, F., additional, Calvani, M., additional, Costa, A., additional, Pacchetti, C., additional, and Nappi, G., additional
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- 1987
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153. Electroretinographic and visual evoked potential abnormalities in myotonic dystrophy
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Sandrini, G, primary, Gelmi, C, additional, Rossi, V, additional, Bianchi, P.E, additional, Alfonsi, E, additional, Pacchetti, C, additional, Verri, A.P, additional, and Nappi, G, additional
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- 1986
- Full Text
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154. Efficacy Of Cyclandelate In Migraine Prophylaxis
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Sandrini, G., primary, Savoini, G., additional, Cavallini, A., additional, Pacchetti, C., additional, Micieli, G., additional, and Nappi, G., additional
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- 1987
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155. Rubber Composition for Outer Covers of Pneumatic Tires
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Pacchetti, C, primary
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- 1915
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156. IS TOLOSA—HUNT SYNDROME A LIMITED FORM OF WEGENER'S GRANULOMATOSIS? REPORT OF TWO CASES WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES.
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MONTECUCCO, C., CAPORALI, R., PACCHETTI, C., and TURLA, M.
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Two patients with recurrent painful ophthalmoplegia due to granulomatous involvement of the intracavernous sinus (Tolosa-Hunt syndrome) had circulating anti-neutrophil cytoplasmic antibodies with a granular cytoplasmic immunofluorescence pattern during a flare-up of the disease. The presence of these antibodies suggests that Tolosa-Hunt syndrome might be regarded as a localized form of Wegener's granulomatosis. [ABSTRACT FROM PUBLISHER]
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- 1993
- Full Text
- View/download PDF
157. Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson Disease
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Giancarlo Germani, Arianna Faggioli, Roberta Zangaglia, Marina I Pan, Paolo Vitali, Fulvia Palesi, Claudio Pacchetti, Pietro Francaviglia, Brigida Minafra, Claudia A. M. Wheeler-Kingshott, Nicoletta Anzalone, Vitali, P., Pan, M. I., Palesi, F., Germani, G., Faggioli, A., Anzalone, N., Francaviglia, P., Minafra, B., Zangaglia, R., Pacchetti, C., and Wheeler-Kingshott, C. A. M. G.
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Male ,business.industry ,Parkinson Disease ,Substantia nigra ,Mean age ,Disease ,Middle Aged ,Magnetic Resonance Imaging ,Volumetric measurement ,Mean difference ,Substantia Nigra ,Clinical diagnosis ,Healthy control ,Humans ,Medicine ,Female ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Nuclear medicine ,business ,Prospective cohort study ,Aged - Abstract
Background Magnetization transfer-prepared T1-weighted MRI can depict a hyperintense subregion of the substantia nigra involved in the degeneration process of Parkinson disease. Purpose To evaluate quantitative measurement of substantia nigra volume by using MRI to support clinical diagnosis and staging of Parkinson disease. Materials and Methods In this prospective study, a high-spatial-resolution magnetization transfer-prepared T1-weighted volumetric sequence was performed with a 3-T MRI machine between January 2014 and October 2015 for participants with de novo Parkinson disease, advanced Parkinson disease, and healthy control participants. A reproducible semiautomatic quantification analysis method that entailed mesencephalic intensity as an internal reference was used for hyperintense substantia nigra volumetry normalized to intracranial volume. A general linear model with age and sex as covariates was used to compare the three groups. Results Eighty participants were evaluated: 20 healthy control participants (mean age ± standard deviation, 56 years ± 11; 11 women), 29 participants with de novo Parkinson disease (64 years ± 10; 19 men), and 31 participants with advanced Parkinson disease (60 years ± 9; 16 women). Volumetric measurement of hyperintense substantia nigra from magnetization transfer-prepared T1-weighted MRI helped differentiate healthy control participants from participants with advanced Parkinson disease (mean difference for ipsilateral side, 64 mm3 ± 14, P < .001; mean difference for contralateral side, 109 mm3 ± 14, P < .001) and helped distinguish healthy control participants from participants with de novo Parkinson disease (mean difference for ipsilateral side, 45 mm3 ± 15, P < .01; mean difference for contralateral side, 66 mm3 ± 15, P < .001) and participants with de novo Parkinson disease from those with advanced Parkinson disease (mean difference for ipsilateral side, 20 mm3 ± 13, P = .40; mean difference for contralateral side, 43 mm3 ± 13, P = .004). Conclusion Magnetization transfer-prepared T1-weighted MRI volumetry of the substantia nigra helped differentiate the stages of Parkinson disease. © RSNA, 2020 Online supplemental material is available for this article.
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- 2020
158. Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies
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Marta Lancione, Graziella Donatelli, Eleonora Del Prete, Nicole Campese, Daniela Frosini, Matteo Cencini, Mauro Costagli, Laura Biagi, Giacomo Lucchi, Michela Tosetti, Massimiliano Godani, Dario Arnaldi, Michele Terzaghi, Federica Provini, Claudio Pacchetti, Pietro Cortelli, Enrica Bonanni, Roberto Ceravolo, Mirco Cosottini, Lancione M., Donatelli G., Del Prete E., Campese N., Frosini D., Cencini M., Costagli M., Biagi L., Lucchi G., Tosetti M., Godani M., Arnaldi D., Terzaghi M., Provini F., Pacchetti C., Cortelli P., Bonanni E., Ceravolo R., and Cosottini M.
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REM behavior disorder ,Iron Overload ,Synucleinopathies ,Cognitive Neuroscience ,Parkinson's disease ,Iron ,Prodromal Symptoms ,Parkinson Disease ,Biomarker ,REM Sleep Behavior Disorder ,Prodromal Symptom ,Neurology ,Disease Progression ,Humans ,Quantitative susceptibility mapping ,Iron deposition ,Neurodegeneration ,Biomarkers ,Human - Abstract
Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.
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- 2022
159. A multinational consensus on dysphagia in Parkinson's disease:screening, diagnosis and prognostic value
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Enrico Alfonsi, Maggie-Lee Huckabee, Giovanni Abbruzzese, Marco Benazzo, Shaheen Hamdy, Leonardo Lopiano, Pietro Cortelli, Chiara Ferrari, Fabrizio Stocchi, Cristina Montomoli, Rosario Marchese Ragona, Francesca Valentino, Giovanni Ruoppolo, Anthony H.V. Schapira, Filippo Barbiera, Roberto Eleopra, Mariangela Rondanelli, Nicole Pizzorni, Giuseppe Cosentino, Cristina Tassorelli, Antonio Schindler, Giorgio Sandrini, Ronald F. Pfeiffer, Angelo Antonini, Emilia Michou, Claudio Pacchetti, Antonio Occhini, Pere Clavé, Domenico A. Restivo, Mauro Zamboni, Stefano Masiero, Roberta Zangaglia, Eduardo Tolosa, Mario Zappia, Micol Avenali, Giulia Bertino, Eduardo Elias Benarroch, Emanuele Cereda, Cosentino G., Avenali M., Schindler A., Pizzorni N., Montomoli C., Abbruzzese G., Antonini A., Barbiera F., Benazzo M., Benarroch E.E., Bertino G., Cereda E., Clave P., Cortelli P., Eleopra R., Ferrari C., Hamdy S., Huckabee M.-L., Lopiano L., Marchese Ragona R., Masiero S., Michou E., Occhini A., Pacchetti C., Pfeiffer R.F., Restivo D.A., Rondanelli M., Ruoppolo G., Sandrini G., Schapira A.H.V., Stocchi F., Tolosa E., Valentino F., Zamboni M., Zangaglia R., Zappia M., Tassorelli C., and Alfonsi E.
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medicine.medical_specialty ,Parkinson's disease ,Neurology ,dysphagia ,deglutition disorders ,swallowing disorders ,Clinical Neurology ,Deglutition disorders ,Dysphagia ,Swallowing disorders ,Deglutition ,Humans ,Italy ,Prognosis ,Quality of Life ,Deglutition Disorders ,Parkinson Disease ,Disease ,PHARYNGEAL DYSPHAGIA ,Severity assessment ,Quality of life ,QUALITY-OF-LIFE ,MANOMETRIC ABNORMALITIES ,medicine ,otorhinolaryngologic diseases ,Intensive care medicine ,ASPIRATION PNEUMONIA ,Deglutition disorder ,Neuroradiology ,Science & Technology ,CLINICAL-ASSESSMENT ,business.industry ,Consensus conference ,OROPHARYNGEAL DYSPHAGIA ,medicine.disease ,DYSFUNCTION ,PENETRATION-ASPIRATION ,Neurosciences & Neurology ,Neurology (clinical) ,medicine.symptom ,business ,Life Sciences & Biomedicine ,VOLUNTARY COUGH - Abstract
Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.
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- 2021
160. Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment
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Giovanna Calandra-Buonaura, Enrico Alfonsi, Luca Vignatelli, Eduardo E. Benarroch, Giulia Giannini, Alex Iranzo, Phillip A. Low, Paolo Martinelli, Federica Provini, Niall Quinn, Eduardo Tolosa, Gregor K. Wenning, Giovanni Abbruzzese, Pamela Bower, Angelo Antonini, Kailash P. Bhatia, Jacopo Bonavita, Maria Teresa Pellecchia, Nicole Pizzorni, François Tison, Imad Ghorayeb, Wassilios G. Meissner, Tetsutaro Ozawa, Claudio Pacchetti, Nicolò Gabriele Pozzi, Claudio Vicini, Antonio Schindler, Pietro Cortelli, Horacio Kaufmann, Calandra Buonaura G., Alfonsi E., Vignatelli L., Benarroch E.E., Giannini G., Iranzo A., Low P.A., Martinelli P., Provini F., Quinn N., Tolosa E., Wenning G.K., Abbruzzese G., Bower P., Antonini A., Bhatia K.P., Bonavita J., Pellecchia M.T., Pizzorni N., Tison F., Ghorayeb I., Meissner W.G., Ozawa T., Pacchetti C., Pozzi N.G., Vicini C., Schindler A., Cortelli P., and Kaufmann H.
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0301 basic medicine ,Consensus development conference ,Dysphagia ,Multiple system atrophy ,Prognosis ,Deglutition Disorders ,Humans ,Multiple System Atrophy ,nervous system diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,nervous system ,stomatognathic system ,otorhinolaryngologic diseases ,Neurology (clinical) ,Geriatrics and Gerontology ,030217 neurology & neurosurgery - Abstract
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.
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- 2021
161. Should We Consider Deep Brain Stimulation Discontinuation in Late-Stage Parkinson's Disease?
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Tommaso Tufo, Margherita Fabbri, Romito Luigi, Linda Borellini, Nicola Modugno, Andrea Bruno, Elisa Montanaro, Leonardo Lopiano, Gianluca Ardolino, Filippo Cogiamanian, Paola Berchialla, Carlo Alberto Artusi, Maurizio Zibetti, Antonella Peppe, Carla Piano, Mario Giorgio Rizzone, Brigida Minafra, Claudio Pacchetti, Giulia Giannini, Alberto Romagnolo, Roberto Eleopra, Giovanna Calandra-Buonaura, Alessandro Stefani, Francesco Bove, Pietro Cortelli, Fabbri M., Zibetti M., Rizzone M.G., Giannini G., Borellini L., Stefani A., Bove F., Bruno A., Calandra Buonaura G., Modugno N., Piano C., Peppe A., Ardolino G., Romagnolo A., Artusi C.A., Berchialla P., Montanaro E., Cortelli P., Luigi R., Eleopra R., Minafra B., Pacchetti C., Tufo T., Cogiamanian F., and Lopiano L.
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0301 basic medicine ,medicine.medical_specialty ,caregivers ,Parkinson's disease ,Deep brain stimulation ,medicine.medical_treatment ,Deep Brain Stimulation ,Stimulation ,Settore MED/05 ,deep brain stimulation ,dementia ,late stage ,Parkinson’s disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Subthalamic Nucleus ,Internal medicine ,medicine ,Humans ,Adverse effect ,caregiver ,business.industry ,Parkinsonism ,Parkinson Disease ,medicine.disease ,Dysphagia ,nervous system diseases ,Discontinuation ,030104 developmental biology ,Treatment Outcome ,Neurology ,England ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson’s disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of “poor stimulation responders” among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. Methods: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale
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- 2020
162. Expert recommendations for diagnosing cervical, oromandibular, and limb dystonia
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Alberto Albanese, Giovanni Fabbrini, Marcello Esposito, Claudio Pacchetti, Francesco Bono, Giovanni Defazio, Roberta Pellicciari, Anna Rita Bentivoglio, Giovanni Abbruzzese, Alfredo Berardelli, Francesca Morgante, Marcello Romano, Laura Fadda, Mario Coletti Moja, Paolo Girlanda, Cesa Scaglione, Leonardo Lopiano, Defazio, G., Albanese, A., Pellicciari, R., Scaglione, C. L., Esposito, M., Morgante, F., Abbruzzese, G., Bentivoglio, A. R., Bono, F., Coletti Moja, M., Fabbrini, G., Girlanda, P., Lopiano, L., Pacchetti, C., Romano, M., Fadda, L., and Berardelli, A.
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Neurology ,Pseudodystonia ,Blepharospasm ,Dermatology ,Limb dystonia ,Neurologist ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Diagnosis ,otorhinolaryngologic diseases ,medicine ,Movement Disorder ,Humans ,Neurologists ,030212 general & internal medicine ,Sensory trick ,Expert Testimony ,Laryngeal dystonia ,Torticollis ,Neuroradiology ,Dystonia ,Movement Disorders ,business.industry ,General Medicine ,Focal dystonia ,Dystonic Disorder ,Dystonic Disorders ,Italy ,2708 ,Neurology (clinical) ,Psychiatry and Mental Health ,medicine.disease ,nervous system diseases ,Settore MED/26 - NEUROLOGIA ,Psychiatry and Mental health ,diagnosis ,focal dystonia ,pseudodystonia ,neurology (clinical) ,psychiatry and mental health ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Diagnosi ,Human - Abstract
Background: Diagnosis of focal dystonia is based on clinical grounds and is therefore open to bias. To date, diagnostic guidelines have been only proposed for blepharospasm and laryngeal dystonia. To provide practical guidance for clinicians with less expertise in dystonia, a group of Italian Movement Disorder experts formulated clinical diagnostic recommendations for cervical, oromandibular, and limb dystonia. Methods: A panel of four neurologists generated a list of clinical items related to the motor phenomenology of the examined focal dystonias and a list of clinical features characterizing neurological/non-neurological conditions mimicking dystonia. Thereafter, ten additional expert neurologists assessed the diagnostic relevance of the selected features and the content validity ratio was calculated. The clinical features reaching a content validity ratio > 0.5 contributed to the final recommendations. Results: The recommendations retained patterned and repetitive movements/postures as the core feature of dystonia in different body parts. If present, a sensory trick confirmed diagnosis of dystonia. In the patients who did not manifest sensory trick, active exclusion of clinical features related to conditions mimicking dystonia (features that would be expected to be absent in dystonia) would be necessary for dystonia to be diagnosed. Discussion: Although reliability, sensitivity, and specificity of the recommendations are yet to be demonstrated, information from the present study would hopefully facilitate diagnostic approach to focal dystonias in the clinical practice and would be the basis for future validated diagnostic guidelines.
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- 2018
163. Monitoring subthalamic oscillations for 24 hours in a freely moving Parkinson's disease patient
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Alberto Priori, Paolo Rampini, Roberto Cilia, Mattia Arlotti, Domenico Servello, Ioannis U. Isaias, Gianni Pezzoli, Massimiliano Todisco, Nicolò Gabriele Pozzi, Marco Prenassi, Brigida Minafra, Sara Marceglia, Sergio Barbieri, Claudio Pacchetti, Jens Volkmann, Chiara Palmisano, Andrea Canessa, Arlotti, M., Palmisano, C., Minafra, B., Todisco, M., Pacchetti, C., Canessa, A., Pozzi, N. G., Cilia, R., Prenassi, M., Marceglia, S., Priori, A., Rampini, P., Barbieri, S., Servello, D., Volkmann, J., Pezzoli, G., and Isaias, I. U.
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medicine.medical_specialty ,Parkinson's disease ,Monitoring ,business.industry ,Deep Brain Stimulation ,Brain Waves ,Female ,Humans ,Middle Aged ,Monitoring, Ambulatory ,Parkinson Disease ,Subthalamic Nucleus ,Implantable Neurostimulators ,Brain Wave ,Letters: New Observations ,medicine.disease ,Physical medicine and rehabilitation ,Neurology ,Subthalamic Nucleu ,Ambulatory ,Medicine ,Neurology (clinical) ,business ,Human - Abstract
Adaptive deep brain stimulation (DBS) devices aim to personalize stimulation delivery by following the current state of symptom-specific neural signals during different activities of daily living (walking, sleeping, etc.). This approach is not yet suitable for clinical practice, and groundwork is needed. The first essential steps for establishing adaptive DBS comprise the capacity for measurements in chronically implanted patients (to avoid the “stunning effect”) and for prolonged recordings not corrupted by artifacts.
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- 2019
164. REM and NREM sleep enactment behaviors in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies.
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Ratti PL, Terzaghi M, Minafra B, Repetto A, Pasotti C, Zangaglia R, Pacchetti C, and Manni R
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- 2012
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165. Stridor in multiple system atrophy: Consensus statement on diagnosis, prognosis, and treatment
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Nicole Pizzorni, Jacopo Bonavita, Claudio Vicini, Pietro Cortelli, Nicolò Gabriele Pozzi, Kailash P. Bhatia, Maria Teresa Pellecchia, François Tison, Federica Provini, Eduardo E. Benarroch, Phillip A. Low, Wassilios G. Meissner, Giovanna Calandra-Buonaura, Horacio Kaufmann, Giulia Giannini, Angelo Antonini, Paolo Martinelli, Tetsutaro Ozawa, Antonio Schindler, Alex Iranzo, Niall Quinn, Claudio Pacchetti, Luca Vignatelli, Giovanni Abbruzzese, Eduardo Tolosa, Pamela Bower, Imad Ghorayeb, Gregor K. Wenning, Enrico Alfonsi, Cortelli P., Calandra-Buonaura G., Benarroch E.E., Giannini G., Iranzo A., Low P.A., Martinelli P., Provini F., Quinn N., Tolosa E., Wenning G.K., Abbruzzese G., Bower P., Alfonsi E., Ghorayeb I., Ozawa T., Pacchetti C., Pozzi N.G., Vicini C., Antonini A., Bhatia K.P., Bonavita J., Kaufmann H., Pellecchia M.T., Pizzorni N., Schindler A., Tison F., Vignatelli L., and Meissner W.G.
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medicine.medical_specialty ,Stridor ,medicine.medical_treatment ,Consensus Development Conferences as Topic ,Laryngoscopy ,multiple system atrophy ,consensus statement ,Humans ,Multiple System Atrophy ,Prognosis ,Respiratory Sounds ,Treatment Outcome ,NO ,03 medical and health sciences ,0302 clinical medicine ,MSA ,medicine ,otorhinolaryngologic diseases ,030212 general & internal medicine ,Continuous positive airway pressure ,Respiratory sounds ,Intensive care medicine ,Views & Reviews ,medicine.diagnostic_test ,Cerebellar ataxia ,business.industry ,Parkinsonism ,medicine.disease ,Dysphagia ,stridor ,3. Good health ,medicine.anatomical_structure ,Rima glottidis ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor is an additional feature for MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified.
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- 2019
166. Deep brain stimulation in Parkinson's disease: A multicentric, long-term, observational pilot study
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Luca Weis, E. Caputo, Nicolò Gabriele Pozzi, Filippo Tamma, Claudio Pacchetti, Andrea Marcante, Elisa Bianchi, Caterina F. Bagella, Francesco Lena, Sara Marceglia, Leonardo Lopiano, Emma Scelzo, Ettore Beghi, Serena Angrisano, Manuela Pilleri, Maurizio Zibetti, Angelo Antonini, Manuela Rosa, Francesco Massaro, Luigi Romito, Alberto Priori, Marco Santilli, Nicola Modugno, Scelzo, E., Beghi, E., Rosa, M., Angrisano, S., Antonini, A., Bagella, C., Bianchi, E., Caputo, E., Lena, F., Lopiano, L., Marcante, A., Marceglia, S., Massaro, F., Modugno, N., Pacchetti, C., Pilleri, M., Pozzi, N. G., Romito, L. M., Santilli, M., Tamma, F., Weis, L., Zibetti, M., and Priori, A.
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Male ,Pediatrics ,medicine.medical_specialty ,Parkinson's disease ,Deep brain stimulation ,Dementia ,Falls ,Non-motor symptoms ,Urinary symptoms ,Urinary system ,medicine.medical_treatment ,Deep Brain Stimulation ,Urinary incontinence ,Pilot Projects ,Non-motor symptom ,03 medical and health sciences ,0302 clinical medicine ,Fall ,medicine ,Nocturia ,Humans ,030212 general & internal medicine ,Prospective cohort study ,Aged ,Retrospective Studies ,business.industry ,Parkinson Disease ,Middle Aged ,medicine.disease ,Hospitalization ,Neurology ,Case-Control Studies ,Cohort ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background The impact of deep brain stimulation (DBS) on cognitive and urinary disorders, falls, and eventually hospitalizations and mortality in Parkinson's disease (PD) is still debated. Objective We compared the rates of dementia, mild cognitive impairment (MCI), urinary incontinence, nocturia, falls, hospitalizations, and mortality in a cohort of PD patients undergoing DBS with a cohort of medically-treated patients chosen as controls. Methods We conducted a retrospective pilot study in six Italian DBS centers. 91 PD patients receiving DBS and 91 age- and gender-matched controls receiving the best medical treatment alone with a minimum follow-up of one year were enrolled. Clinical data were collected from baseline to the last follow-up visit using an ad-hoc developed web-based system. Results The risk of dementia was similar in the two groups while patients in the surgical cohort had lower rates of MCI, urinary incontinence, nocturia, and falls. In contrast, the risk of hospital admissions related to PD was higher in the surgical cohort. However, when excluding hospitalizations related to DBS surgery, the difference between the two cohorts was not significant. The surgical cohort had a lower number of hospitalizations not related to PD. The risk of death was similar in the two groups. Conclusion Despite a higher risk of hospitalization, patients receiving DBS had a lower rate of MCI, urinary incontinence, nocturia and falls, without evidence of an increased risk of dementia and mortality. Although these findings need to be confirmed in prospective studies, they seem to suggest that DBS may play a significant role in the management of non-motor symptoms and common complications of advanced PD.
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- 2018
167. Factors influencing psychological well-being in patients with Parkinson's disease
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Claudio Pacchetti, Roberto Ceravolo, Fabrizio Stocchi, Giovanni Fabbrini, Giovanni Abbruzzese, Margherita Canesi, Gianni Pezzoli, Alessandra Nicoletti, Mario Zappia, Marco D'Amelio, Pietro Cortelli, Maria Francesca De Pandis, Alessandro Tessitore, Giovanni Mostile, Nicoletti, Alessandra, Mostile, Giovanni, Stocchi, Fabrizio, Abbruzzese, Giovanni, Ceravolo, Roberto, Cortelli, Pietro, Dâ amelio, Marco, De Pandis, Maria F., Fabbrini, Giovanni, Pacchetti, Claudio, Pezzoli, Gianni, Tessitore, Alessandro, Canesi, Margherita, Zappia, Mario, Nicoletti, A., Mostile, G., Stocchi, F., Abbruzzese, G., Ceravolo, R., Cortelli, P., D'Amelio, M., De Pandis MF, Fabbrini, G., Pacchetti, C., Pezzoli, G., Tessitore, A., Canesi, M., and Zappia, M.
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Genetics and Molecular Biology (all) ,Male ,Parkinson's disease ,Emotions ,Poison control ,Social Sciences ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Biochemistry ,Severity of Illness Index ,Aged ,Depression ,Fatigue ,Female ,Humans ,Italy ,Middle Aged ,Parkinson Disease ,Psychiatric Status Rating Scales ,Quality of Life ,Surveys and Questionnaires ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Quality of life ,Medicine and Health Sciences ,Medicine ,Psychology ,Surveys and Questionnaire ,030212 general & internal medicine ,lcsh:Science ,Depression (differential diagnoses) ,Multidisciplinary ,Movement Disorders ,Neurodegenerative Diseases ,Psychiatric Status Rating Scale ,humanities ,Neurology ,Physical Sciences ,Statistics (Mathematics) ,Clinical psychology ,Research Article ,Human ,Research and Analysis Methods ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Severity of illness ,Injury prevention ,Mental Health and Psychiatry ,Statistical Methods ,parkinson's disease, quality of life ,Analysis of Variance ,business.industry ,Mood Disorders ,lcsh:R ,Beck Depression Inventory ,Biology and Life Sciences ,medicine.disease ,Health Care ,Psychological well-being ,lcsh:Q ,business ,Sleep Disorders ,030217 neurology & neurosurgery ,Mathematics - Abstract
Background Both motor and non-motor symptoms could contribute to significant deterioration of psychological well-being in patients with Parkinson's disease (PD). However, its assessment has been only indirectly evaluated using tools based on health-related quality of life (HRQoL), such as the PDQ-39 scale. Objectives To evaluate psychological well-being in PD using a specific tool of assessment, the Psychological Well-being Scale (PWS), and its clinical correlates. Methods This article reports data of patients' perception of health state, as measured by means of the PWS, from an epidemiological, cross-sectional study conducted in Italian PD patients (FORTE Study). We tested possible relationship between well-being and clinical characteristics including fatigue, depression, sleep disruption and HRQoL. Results 272 patients completed the PWS questionnaire. Significant and clinically-relevant correlations were found between PWS total score and Parkinson's Fatigue Scale, Beck Depression Inventory, UPDRS Section I, PD Sleep Scale and PDQ-39 for HRQoL scores. Only clinically negligible correlations were found between PWS and motor scores. Conclusions Non-motor symptoms have a significant impact on psychological well-being in PD patients.
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- 2017
168. TRANSCRANIAL DIRECT CURRENT STIMULATION FOR TREATMENT OF FREEZING OF GAIT IN PARKINSON’S DISEASE. A CROSS-OVER STUDY
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Giuseppe Cosentino, Claudio Pacchetti, Francesca Valentino, Filippo Brighina, Giorgio Sandrini, Brigida Fierro, Nicolò Gabriele Pozzi, Marco D'Amelio, Giovanni Savettieri, Valentino, F, Cosentino, G, Brighina, F, Pozzi, N, Sandrini, G, Fierro, B, Savettieri, G, Pacchetti, C, and D'Amelio, M
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medicine.medical_specialty ,Parkinson's disease ,Transcranial direct-current stimulation ,Freezing of gait ,business.industry ,medicine.medical_treatment ,medicine.disease ,Crossover study ,Gait (human) ,Physical medicine and rehabilitation ,Neurology ,medicine ,Neurology (clinical) ,business - Published
- 2013
169. Subthalamic local field potentials after seven-year deep brain stimulation in Parkinson's disease
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Domenico Servello, Roberta Zangaglia, Giorgio Carrabba, E. Scelzo, Sara Marceglia, Manuela Rosa, Filippo Cogiamanian, Claudia Menghetti, Gaia Giannicola, Claudio Pacchetti, Alberto Priori, Lorenzo Rossi, Giannicola, G, Rosa, M, Servello, D, Menghetti, C, Carrabba, G, Pacchetti, C, Zangaglia, R, Cogiamanian, F, Scelzo, E, Marceglia, S, Rossi, L, Priori, A, Giannicola, Gaia, Rosa, Manuela, Servello, Domenico, Menghetti, Claudia, Carrabba, Giorgio, Pacchetti, Claudio, Zangaglia, Roberta, Cogiamanian, Filippo, Scelzo, Emma, Marceglia, SARA RENATA FRANCESCA, Rossi, Lorenzo, and Priori, Alberto
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Male ,Neurology ,Parkinson's disease ,medicine.medical_treatment ,Deep Brain Stimulation ,Action Potentials ,Stimulation ,Local field potential ,Audiology ,Subthalamic nucleus ,Chronic stimulation ,education.field_of_study ,Local field potentials ,Subthalamus ,Subthalamic nucleu ,Parkinson Disease ,Middle Aged ,Adaptive ,surgical procedures, operative ,medicine.anatomical_structure ,Cardiology ,Female ,Low frequency activity ,Psychology ,therapeutics ,Beta activity ,Deep brain stimulation ,Adult ,Aged ,Follow-Up Studies ,Humans ,Developmental Neuroscience ,Human ,medicine.medical_specialty ,AdaptiveBeta activityChronic stimulationDeep brain stimulationLocal field potentialsLow frequency activityBeta activityParkinson's diseaseSubthalamic nucleus ,Population ,Follow-Up Studie ,Internal medicine ,medicine ,Action Potential ,education ,Subthalamu ,medicine.disease ,nervous system diseases ,nervous system - Abstract
Studies describing subthalamic (STN) local field potentials (LFPs) recorded during deep brain stimulation (DBS) in patients with Parkinson's disease (PD), within the first month after DBS electrode implant, show that DBS modulates specific STN oscillations: whereas low-frequency (LF) oscillations (2-7Hz) increase, beta oscillations (8-30 Hz) variably decrease. No data show whether LFPs remain stable for longer than one month after DBS surgery. Having long-term information is essential especially for use as a long-term feedback control signal for adaptive DBS systems. To evaluate how STN activity behaves years after prolonged chronic stimulation in PD we studied STN LFPs at rest without DBS and during ongoing DBS, in 11 parkinsonian patients 7 years (7.54 +/- 1.04) after STN electrode implantation for DBS (hyperchronic group) and in 16 patients 3 days after STN electrode implantation (acute group). STN LF and beta-band LFPs recorded at rest at 7 years contained almost the same information as those recorded at 3 days. STN recordings showed similar LFP responses to DBS in the acute and hyperchronic stages: whereas during ongoing DBS the LF power band increased for the whole population, beta activity decreased only in nuclei with significant beta activity at baseline. The LF/beta power ratio in all nuclei changed in both study groups, suggesting that this variable might be an even more informative marker of PD than the single LF and beta bands. Because STN LFP activity patterns and STN LFP responses to DBS stay almost unchanged for years after DBS electrode implantation they should provide a consistent feedback control signal for adaptive DBS. (c) 2012 Elsevier Inc. All rights reserved.
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- 2012
170. Time dependent Subthalamic Local Field Potential Changes after DBS Surgery in Parkinson's disease
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Simona Mrakic-Sposta, Lorenzo Rossi, Domenico Servello, Mauro Porta, Roberta Zangaglia, Manuela Rosa, Marco Sassi, Sara Marceglia, Alberto Priori, Claudio Pacchetti, Guglielmo Foffani, Rosa, M, Marceglia, S, Servello, D, Foffani, G, Rossi, L, Sassi, M, Mrakic-Sposta, S, Zangaglia, R, Pacchetti, C, Porta, M, and Priori, A.
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Male ,Parkinson's disease ,Time Factors ,genetic structures ,medicine.medical_treatment ,Deep Brain Stimulation ,Statistics as Topic ,Local Field Potentials ,Local field potential ,Basal ganglia ,Evoked Potentials ,Tomography ,Spectrum Analysi ,Local Field Potential ,Impedance ,Parkinson Disease ,Electrode/tissue interface ,Subthalamic Nucleus ,Aged ,Analysis of Variance ,Biophysics ,Electric Stimulation ,Female ,Humans ,Magnetic Resonance Imaging ,Middle Aged ,Spectrum Analysis ,Subthalamus ,Tomography, X-Ray Computed ,Neurology ,Developmental Neuroscience ,X-Ray Computed ,Subthalamic nucleus ,medicine.anatomical_structure ,Subthalamic Nucleu ,Evoked Potential ,Human ,medicine.medical_specialty ,Deep brain stimulation ,Time Factor ,Central nervous system ,Central nervous system disease ,medicine ,business.industry ,Subthalamu ,medicine.disease ,Surgery ,Electrophysiology ,Biophysic ,business - Abstract
Local field potentials (LFPs) recorded through electrodes implanted in patients with Parkinson's disease (PD) for deep brain stimulation (DBS) provided physiological information about the human basal ganglia. However, LFPs were always recorded 2–7 days after electrode implantation (“acute” condition). Because changes in the tissue surrounding the electrode occur after DBS surgery and could be relevant for LFPs, in this work we assessed whether impedance and LFP pattern are a function of the time interval between the electrode implant and the recordings. LFPs and impedances were recorded from 11 patients with PD immediately after (T-0h), 2 h after (T-2h), 2 days after (T-48h), and 1 month after (T-30d, “chronic” condition) surgery. Impedances at T-0h were significantly higher than at all the other time intervals (T-2h, p = 0.0005; T-48h, p = 0.0002; T-30d, p = 0.003). Correlated with this change (p = 0.005), the low-frequency band (2-7 Hz) decreased at all time intervals (p = 0.0005). Conversely, the low- (8–20 Hz) and the high-beta (21–35 Hz) bands increased in time (low-beta, p = 0.003; high beta, p = 0.022), but did not change between T-48h and T-30d. Our results suggest that DBS electrode impedance and LFP pattern are a function of the time interval between electrode implant and LFP recordings. Impedance decrease could be related to changes in the electrode/tissue interface and in the low-frequency band. Conversely, beta band modulations could raise from the adaptation of the neural circuit. These findings confirm that results from LFP analysis in the acute condition can be extended to the chronic condition and that LFPs can be used in novel closed-loop DBS systems.
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- 2010
171. Apomorphine Subcutaneous Infusion Likely Induced Acute Thrombocytopenia in a Patient with Parkinson's Disease and Motor Fluctuations.
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Pocora MM, Avenali M, Croce MG, Ferrari F, Valentino F, Pacchetti C, Tassorelli C, and Zangaglia R
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- 2024
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172. Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.
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Imarisio A, Yahyavi I, Gasparri C, Hassan A, Avenali M, Di Maio A, Buongarzone G, Galandra C, Picascia M, Filosa A, Monti MC, Pacchetti C, Errico F, Rondanelli M, Usiello A, and Valente EM
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- Humans, Male, Aged, Female, Aged, 80 and over, Frailty blood, Serine blood, Glycine blood, Biomarkers blood, Cognitive Dysfunction blood, Frail Elderly
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Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty., (© 2024. The Author(s).)
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- 2024
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173. Functional Study of SNCA p.V15A Variant: Further Linking α-Synuclein and Glucocerebrosidase.
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Avenali M, Cerri S, Palmieri I, Ongari G, Stiuso R, Buongarzone G, Tassorelli C, Biagini T, Valente M, Cereda C, Mazza T, Gana S, Pacchetti C, and Valente EM
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Background: SNCA p.V15A was reported in five families. In vitro models showed increased aggregation and seeding activity, mitochondrial damage, and apoptosis. Mutant flies had reduced flying ability and survival., Objectives: To clinically and functionally evaluate SNCA p.V15A in a large Italian family with Parkinson's disease (PD)., Methods: Genetic diagnosis was reached through next-generation sequencing. Pathogenicity was assessed by molecular dynamics simulation and biochemical studies on peripheral blood mononuclear cells (PBMCs)., Results: Five siblings carried SNCA p.V15A; three developed bradykinetic-rigid PD in their 50s with rapid motor progression and variable cognitive impairment. A fourth sibling had isolated mood disturbance, whereas the fifth was still unaffected at age 47. The mutant protein showed decreased stability and an unstable folded structure. Proband's PBMCs showed elevated total and phosphorylated α-synuclein (α-syn) levels and significantly reduced glucocerebrosidase activity., Conclusion: This study demonstrates accumulation of α-syn
V15A in PBMCs and strengthens the link between α-syn pathophysiology and glucocerebrosidase dysfunction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)- Published
- 2024
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174. Comparing Essential Tremor with and without Soft Dystonic Signs and Tremor Combined with Dystonia: The TITAN Study.
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Erro R, Lazzeri G, Terranova C, Paparella G, Gigante AF, De Micco R, Magistrelli L, Di Biasio F, Valentino F, Moschella V, Pilotto A, Esposito M, Olivola E, Malaguti MC, Ceravolo R, Dallocchio C, Spagnolo F, Nicoletti A, De Rosa A, Di Giacopo R, Sorrentino C, Padovani A, Altavista MC, Pacchetti C, Marchese R, Contaldi E, Tessitore A, Misceo S, Bologna M, Rizzo V, Franco G, and Barone P
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- Humans, Male, Female, Middle Aged, Aged, Tremor diagnosis, Tremor physiopathology, Adult, Aged, 80 and over, Severity of Illness Index, Essential Tremor physiopathology, Essential Tremor diagnosis, Essential Tremor complications, Dystonia diagnosis, Quality of Life
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Background: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high., Objectives: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD)., Methods: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life., Results: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor., Conclusions: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity., (© 2024 International Parkinson and Movement Disorder Society.)
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- 2024
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175. Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort.
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Avenali M, Zangaglia R, Cuconato G, Palmieri I, Albanese A, Artusi CA, Bozzali M, Calandra-Buonaura G, Cavallieri F, Cilia R, Cocco A, Cogiamanian F, Colucci F, Cortelli P, Di Fonzo A, Eleopra R, Giannini G, Imarisio A, Imbalzano G, Ledda C, Lopiano L, Malaguti MC, Mameli F, Minardi R, Mitrotti P, Monfrini E, Spagnolo F, Tassorelli C, Valentino F, Valzania F, Pacchetti C, and Valente EM
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- Humans, Retrospective Studies, Italy, Parkinson Disease genetics, Parkinson Disease therapy, Parkinson Disease complications, Deep Brain Stimulation, Dyskinesias therapy, Dementia complications
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Background: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce., Objective: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort., Methods: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS., Results: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up., Conclusions: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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176. Blood D-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease.
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Imarisio A, Yahyavi I, Avenali M, Di Maio A, Buongarzone G, Galandra C, Picascia M, Filosa A, Gasparri C, Monti MC, Rondanelli M, Pacchetti C, Errico F, Valente EM, and Usiello A
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- Humans, Serine metabolism, Dopamine metabolism, Levodopa therapeutic use, Amino Acids, Glutamic Acid, Aging, Parkinson Disease drug therapy, Parkinson Disease metabolism
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We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D-/Total serine may represent a valuable biochemical signature of PD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Enza Maria Valente reports financial support was provided by Cariplo Foundation. Enza Maria Valente reports financial support was provided by Ministry of Health. Alessandro Usiello reports financial support was provided by Minister of University and Research. Micol Avenali reports a relationship with Aligning Science Across Parkinson's that includes: board membership. Micol Avenali reports a relationship with Bial that includes: speaking and lecture fees. Micol Avenali reports a relationship with Zambon SpA that includes: speaking and lecture fees. Micol Avenali reports a relationship with Ministry of Health that includes: funding grants. Enza Maria Valente reports a relationship with Aligning Science Across Parkinson's that includes: board membership and funding grants. Enza Maria Valente reports a relationship with Ministry of Health that includes: funding grants. Enza Maria Valente reports a relationship with Telethon Foundation that includes: funding grants. Enza Maria Valente reports a relationship with Pierfranco and Luisa Mariani Foundation that includes: funding grants. Enza Maria Valente reports a relationship with European Commission (Era-net Neuron) that includes: funding grants. Enza Maria Valente is Associate Editor of Journal of Medical Genetics; is Genetics Section Editor of Pediatric Research, of The Cerebellum, and of Neurological Sciences; is member of the Editorial Board of Movement Disorders Clinical Practice. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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177. Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases.
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Servello D, Galbiati TF, Iess G, Minafra B, Porta M, and Pacchetti C
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- Humans, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage etiology, Seizures etiology, Electrodes, Implanted adverse effects, Retrospective Studies, Parkinson Disease therapy, Deep Brain Stimulation adverse effects, Deep Brain Stimulation methods, Brain Edema etiology
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Background: The number of deep brain stimulation (DBS) procedures is rapidly rising as well as the novel indications. Reporting adverse events related to surgery and to the hardware used is essential to define the risk-to-benefit ratio and develop novel strategies to improve it., Objective: To analyze DBS complications (both procedure-related and hardware-related) and further assess potential predictive factors., Methods: Five hundred seventeen cases of DBS for Parkinson's disease were performed between 2006 and 2021 in a single center (mean follow-up: 4.68 ± 2.86 years). Spearman's Rho coefficient was calculated to search for a correlation between the occurrence of intracerebral hemorrhage (ICH) and the number of recording tracks. Multiple logistic regression analyzed the probability of developing seizures and ICH given potential risk factors. Kaplan-Meier curves were performed to analyze the cumulative proportions of hardware-related complications., Results: Mortality rate was 0.2%, while permanent morbidity 0.6%. 2.5% of cases suffered from ICH which were not influenced by the number of tracks used for recordings. 3.3% reported seizures that were significantly affected by perielectrode brain edema and age. The rate of perielectrode brain edema was significantly higher for Medtronic's leads compared to Boston Scientific's (Χ
2 (1)= 5.927, P= 0.015). 12.2% of implants reported Hardware-related complications, the most common of which were wound revisions (7.2%). Internal pulse generator models with smaller profiles displayed more favorable hardware-related complication survival curves compared to larger designs (X2 (1)= 8.139, P= 0.004)., Conclusion: Overall DBS has to be considered a safe procedure, but future research is needed to decrease the rate of hardware-related complications which may be related to both the surgical technique and to the specific hardware's design. The increased incidence of perielectrode brain edema associated with certain lead models may likewise deserve future investigation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)- Published
- 2023
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178. Safety and efficacy of venglustat in GBA1-associated Parkinson's disease: an international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.
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Giladi N, Alcalay RN, Cutter G, Gasser T, Gurevich T, Höglinger GU, Marek K, Pacchetti C, Schapira AHV, Scherzer CR, Simuni T, Minini P, Sardi SP, and Peterschmitt MJ
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- Adult, Humans, Treatment Outcome, Double-Blind Method, Parkinson Disease drug therapy
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Background: Variants in the GBA1 gene, which encodes lysosomal acid glucocerebrosidase, are among the most common genetic risk factors for Parkinson's disease and are associated with faster disease progression. The mechanisms involved are unresolved but might include accumulation of glucosylceramide. Venglustat is a brain-penetrant glucosylceramide synthase inhibitor that, in previous studies, reduced amounts of the glycosphingolipid. We aimed to assess the safety, efficacy, and target engagement of venglustat in people with early-stage Parkinson's disease carrying pathogenic GBA1 variants., Methods: MOVES-PD part 2 was a randomised, double-blinded, placebo-controlled phase 2 study done at 52 centres (academic sites, specialty clinics, and general neurology centres) in 16 countries. Eligible adults aged 18-80 years with Parkinson's disease (Hoehn and Yahr stage ≤2) and one or more GBA1 variants were randomly assigned using an interactive voice-response system (1:1) to 52 weeks of treatment with oral venglustat (15 mg/day) or matching placebo. Investigators, site personnel, participants, and their caregivers were masked to treatment allocation. The primary outcome measure was the change from baseline to 52 weeks in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III combined score (a higher score indicates greater impairment), and it was analysed in a modified intention-to-treat population (ie, all randomly assigned participants with a baseline and at least one post-baseline measurement during the treatment period). This study was registered with ClinicalTrials.gov (NCT02906020) and is closed to recruitment., Findings: Between Dec 15, 2016, and May 27, 2021, 221 participants were randomly assigned to venglustat (n=110) or placebo (n=111). The least squares mean change in MDS-UPDRS parts II and III combined score was 7·29 (SE 1·36) for venglustat (n=96) and 4·71 (SE 1·27) for placebo (n=105); the absolute difference between groups was 2·58 (95% CI -1·10 to 6·27; p=0·17). The most common treatment-emergent adverse events (TEAEs) were constipation and nausea (both were reported by 23 [21%] of 110 participants in the venglustat group and eight [7%] of 111 participants in the placebo group). Serious TEAEs were reported for 12 (11%) participants in each group. There was one death in the venglustat group owing to an unrelated cardiopulmonary arrest and there were no deaths in the placebo group., Interpretation: In people with GBA1-associated Parkinson's disease in our study, venglustat had a satisfactory safety profile but showed no beneficial treatment effect compared with placebo. These findings indicate that glucosylceramide synthase inhibition with venglustat might not be a viable therapeutic approach for GBA1-associated Parkinson's disease., Funding: Sanofi., Competing Interests: Declaration of interests AHVS declares research support from the UK Medical Research Council, Michael J Fox Foundation (MJFF), Aligning Science Across Parkinson's, and Cure Parkinson's; consulting fees from AvroBio, Auxilius, Coave, Destin, Enterin, Escape Bio, Genilac, and Sanofi; and speaking fees from the Prada Foundation. CRS declares research support from American Parkinson's Disease Foundation, MJFF, US National Institutes of Health (NIH), and US Department of Defense; consulting fees from Sanofi; a patent pending for sphingolipid biomarkers with Brigham and Women's Hospital and Sanofi; scientific advisory board participation for American Parkinson's Disease Foundation; other financial interests from Lysosomal Therapies, MJFF, NIH, Opko, Pfizer, Proteome Sciences, Sanofi, and US Department of Defense; and non-financial interests from Google. GC is an employee of Pythagoras; and declares compensation for consulting and advisory board participation from Alexion, Antisense Therapeutics, Biodelivery Sciences International, Biogen, Clinical Trial Solutions, Genentech, GW Pharmaceuticals, Immunic, Klein Buendel, MedImmune–Viela Bio, MedDay, Merck Serono, NeuroGenesis, Osmotica Pharmaceuticals, Perception Neurosciences, Reckover Pharmaceuticals, Recursion-CereXis Pharmaceuticals, Regeneron, Roche, SAb Biotherapeutics, Sanofi, and TG Therapeutics; data safety monitoring board participation for AI Therapeutics, AMO Pharmaceuticals, Applied Therapeutics, AstraZeneca, AveXis Pharmaceuticals, BioLineRx, BrainStorm Cell Therapeutics, Bristol Myers Squibb-Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Mapi Pharma, Merck–Pfizer, Mitsubishi Tanabe Pharma, Neurim, Novartis, Ophazyme, Opko Biologics, Reata Pharmaceuticals, Sanofi, Teva Pharmaceuticals, and VielaBio; and protocol review committee participation for the US National Heart, Lung, and Blood Institute. GUH declares compensation for consulting and advisory board participation from AbbVie, Alzprotect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Retrotope, Roche, Sanofi, UCB, and Weston Brain Institute; speaker honoraria from AbbVie, Biogen, Roche, Teva, UCB, and Zambon; data safety monitoring or advisory board participation for Alzprotect and Kainos Medicine; and is a patent holder for treatment of synucleinopathies (US patent number US 10,918,628 B2: EP 17 787 904.6–1109). KM declares consulting fees from Calico, Coave Therapeutics, Invicro, Lundbeck, Lysosomal Therapeutics, MJFF, NeuroDerm, Neuron23, OrbiMed, Roche, Takeda, and UBC. MJP, PM, and SPS are employees of Sanofi and might hold shares, stock options, or both, in the company. NG declares research support from Biogen, EU, Ionis, Israel Science Foundation, MJFF, and US National Parkinson Foundation; consulting fees from AbbVie, Biogen, BOL, Denali Therapeutics, NeuroDerm, Sanofi, and Sionara; speaker honoraria from AbbVie, Movement Disorders Society, and Sanofi; advisory board participation for Biogen, Denali Therapeutics, NeuroDerm, Sanofi, and Sionara; and stock ownership for BOL Pharma, GaitBetter, Lysosomal Therapeutics, and Vibrant. RNA declares research support from NIH, MJFF, Parkinson's Foundation, and US Department of Defense; and consulting fees from AVROBIO, Caraway, Gain Therapeutics, GlaxoSmithKline, Janssen, Merck, Ono Therapeutics, Sanofi, and Takeda. TGa declares research support from the EU, German Research Foundation, German Federal Ministry of Education and Research, Helmholtz Association, and MJFF; speaker honoraria from Bayer, BlueRock Therapeutics, and Coave Therapeutics; compensation for consulting and advisory board participation for MedUpdate, Novartis, Teva, and UCB; and advisory board participation for the EU. TGu declares grants from International Movement Disorders Society; consulting fees from AbbVie, NeuroDerm, Medison, Teva, and TrueMed; honoraria from AbbVie, Medison, and Teva; travel support from AbbVie, Boston Scientific, Medison, and Medtronic; unpaid advisory role or membership for Ezra Le’Marpeh Parkinson's rehabilitation programme, Israeli Huntington Disease Association, Israeli Movement Disorders Society, and Tikvah for Parkinson; stock options for Cytora; previous medical writing assistance from AbbVie and Teva; and planned patents for automated speech analysis and vocal Parkinson's disease biomarkers. TS declares research support from Biogen, MJFF, NeuroDerm, US National Institute of Neurological Disorders and Stroke, Parkinson's Foundation, and Roche; and consulting fees from Acadia, Anavex, Allergan, NeroDerm, MJFF, PhotoPharmics, Revance, Sanofi, Sunovion, Voyager, and US WorldMeds. CP declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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179. Gender differences in microRNA expression in levodopa-naive PD patients.
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Vallelunga A, Iannitti T, Somma G, Russillo MC, Picillo M, De Micco R, Vacca L, Cilia R, Cicero CE, Zangaglia R, Lazzeri G, Galantucci S, Radicati FG, De Rosa A, Amboni M, Scaglione C, Tessitore A, Stocchi F, Eleopra R, Nicoletti A, Pacchetti C, Di Fonzo A, Volontè MA, Barone P, and Pellecchia MT
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- Humans, Male, Female, Levodopa therapeutic use, Sex Factors, Biomarkers, MicroRNAs genetics, Parkinson Disease drug therapy, Parkinson Disease genetics
- Abstract
Gender is an important factor influencing epidemiological and clinical features of Parkinson's disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman's correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment., (© 2023. The Author(s).)
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- 2023
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180. Correction to: Gender differences in microRNA expression in levodopa‑naive PD patients.
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Vallelunga A, Iannitti T, Somma G, Russillo MC, Picillo M, De Micco R, Vacca L, Cilia R, Cicero CE, Zangaglia R, Lazzeri G, Galantucci S, Radicati FG, De Rosa A, Amboni M, Scaglione C, Tessitore A, Stocchi F, Eleopra R, Nicoletti A, Pacchetti C, Di Fonzo A, Volontè MA, Barone P, and Pellecchia MT
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- 2023
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181. Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.
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Cilia R, Cereda E, Piatti M, Pilotto A, Magistrelli L, Golfrè Andreasi N, Bonvegna S, Contaldi E, Mancini F, Imbalzano G, De Micco R, Colucci F, Braccia A, Bellini G, Brovelli F, Zangaglia R, Lazzeri G, Russillo MC, Olivola E, Sorbera C, Cereda V, Pinto P, Sucapane P, Gelosa G, Meloni M, Pistoia F, Sessa M, Canesi M, Modugno N, Pacchetti C, Brighina L, Pellecchia MT, Ceravolo R, Sensi M, Zibetti M, Comi C, Padovani A, Zecchinelli AL, Di Fonzo A, Tessitore A, Morgante F, and Eleopra R
- Abstract
Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches., Objectives: To estimate LED of safinamide 50 and 100 mg., Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg ( N = 130), safinamide 50 mg ( N = 144), or rasagiline 1 mg ( N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B ( N = 129)., Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED., Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2023
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182. Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies.
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Lancione M, Donatelli G, Del Prete E, Campese N, Frosini D, Cencini M, Costagli M, Biagi L, Lucchi G, Tosetti M, Godani M, Arnaldi D, Terzaghi M, Provini F, Pacchetti C, Cortelli P, Bonanni E, Ceravolo R, and Cosottini M
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- Biomarkers, Disease Progression, Humans, Iron, Prodromal Symptoms, Iron Overload diagnostic imaging, Parkinson Disease diagnostic imaging, Parkinson Disease pathology, REM Sleep Behavior Disorder diagnostic imaging, REM Sleep Behavior Disorder pathology, Synucleinopathies
- Abstract
Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD., Competing Interests: Declaration of Competing Interest Mirco Cosottini received a speaker honorarium from GE Healthcare. All other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2022
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183. Troubleshooting Gait Disturbances in Parkinson's Disease With Deep Brain Stimulation.
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Pozzi NG, Palmisano C, Reich MM, Capetian P, Pacchetti C, Volkmann J, and Isaias IU
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Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson's disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management., 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 © 2022 Pozzi, Palmisano, Reich, Capetian, Pacchetti, Volkmann and Isaias.)
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- 2022
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184. A multinational consensus on dysphagia in Parkinson's disease: screening, diagnosis and prognostic value.
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Cosentino G, Avenali M, Schindler A, Pizzorni N, Montomoli C, Abbruzzese G, Antonini A, Barbiera F, Benazzo M, Benarroch EE, Bertino G, Cereda E, Clavè P, Cortelli P, Eleopra R, Ferrari C, Hamdy S, Huckabee ML, Lopiano L, Marchese Ragona R, Masiero S, Michou E, Occhini A, Pacchetti C, Pfeiffer RF, Restivo DA, Rondanelli M, Ruoppolo G, Sandrini G, Schapira AHV, Stocchi F, Tolosa E, Valentino F, Zamboni M, Zangaglia R, Zappia M, Tassorelli C, and Alfonsi E
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- Deglutition, Humans, Italy, Prognosis, Quality of Life, Deglutition Disorders diagnosis, Deglutition Disorders etiology, Parkinson Disease complications, Parkinson Disease diagnosis
- Abstract
Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD., Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: Eighty-five papers were used to inform the Panel's statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions., Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD., (© 2021. The Author(s).)
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- 2022
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185. Parkinsonism and cerebrospinal fluid disorders.
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Youn J, Todisco M, Zappia M, Pacchetti C, and Fasano A
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- Brain, Cerebral Aqueduct surgery, Cerebrospinal Fluid, Cerebrospinal Fluid Shunts, Humans, Hydrocephalus, Normal Pressure diagnostic imaging, Hydrocephalus, Normal Pressure epidemiology, Parkinsonian Disorders diagnostic imaging, Parkinsonian Disorders therapy
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Background: Although various motor manifestations can be seen in patients with cerebrospinal fluid (CSF) disorders, such as hydrocephalus or intracranial hypotension, the clinical presentation with parkinsonism is not clearly elucidated., Methods: We searched the literature for studies describing the occurrence of parkinsonism in subjects with normal pressure hydrocephalus (NPH), obstructive hydrocephalus, and intracranial hypotension. We analyzed the clinical presentation (particularly with respect to bradykinesia, rigidity, rest tremor, and gait disturbance/postural instability) as well as the response to treatment., Results: Parkinsonism was most commonly reported in NPH patients. Although gait disturbance/postural instability is a well-known motor symptom of NPH, other cardinal signs include upper limb involvement or asymmetric presentation. As for obstructive hydrocephalus, parkinsonism was mainly observed in subjects with aqueductal stenosis and more often after shunt surgery. Patients with NPH or obstructive hydrocephalus rarely improved with levodopa therapy, while most subjects only improved with shunt surgery. Although the mechanism is still controversial, a functional involvement of nigrostriatal pathway has been hypothesized based on imaging studies and case reports. Brain imaging is also helpful for atypical cases of intracranial hypotension presenting with parkinsonism. Parkinsonism improved after treatment in such cases as well., Conclusions: Studies exploring the relationship between CSF disorders and parkinsonism are mainly descriptive and their quality is generally poor. However, considering that these disorders can be treated, clinicians' awareness of the differential diagnosis is important and future studies better exploring the underlying pathophysiological mechanisms are warranted. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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186. Diagnostic accuracy of quantitative susceptibility mapping in multiple system atrophy: The impact of echo time and the potential of histogram analysis.
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Lancione M, Cencini M, Costagli M, Donatelli G, Tosetti M, Giannini G, Zangaglia R, Calandra-Buonaura G, Pacchetti C, Cortelli P, and Cosottini M
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- Brain diagnostic imaging, Brain Mapping, Humans, Iron analysis, Magnetic Resonance Imaging, Multiple System Atrophy diagnostic imaging
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The non-invasive quantification of iron stores via Quantitative Susceptibility Mapping (QSM) could play an important role in the diagnosis and the differential diagnosis of atypical Parkinsonisms. However, the susceptibility (χ) values measured via QSM depend on echo time (TE). This effect relates to the microstructural organization within the voxel, whose composition can be altered by the disease. Moreover, pathological iron deposition in a brain area may not be spatially uniform, and conventional Region of Interest (ROI)-based analysis may fail in detecting alterations. Therefore, in this work we evaluated the impact of echo time on the diagnostic accuracy of QSM on a population of patients with Multiple System Atrophy (MSA) of either Parkinsonian (MSAp) or cerebellar (MSAc) phenotypes. In addition, we tested the potential of histogram analysis to improve QSM classification accuracy. We enrolled 32 patients (19 MSAp and 13 MSAc) and 16 healthy controls, who underwent a 7T MRI session including a gradient-recalled multi-echo sequence for χ mapping. Nine histogram features were extracted from the χ maps computed for each TE in atlas-based ROIs covering deep brain nuclei, and compared among groups. Alterations of susceptibility distribution were found in the Putamen, Substantia Nigra, Globus Pallidus and Caudate Nucleus for MSAp and in the Substantia Nigra and Dentate Nucleus for MSAc. Increased iron deposition was observed in a larger number of ROIs for the two shortest TEs and the standard deviation, the 75
th and the 90th percentile were the most informative features yielding excellent diagnostic accuracy with area under the ROC curve > 0.9. In conclusion, short TEs may enhance QSM diagnostic performances, as they can capture variations in rapidly-decaying contributions of high χ sources. The analysis of histogram features allowed to reveal fine heterogeneities in the spatial distribution of susceptibility alteration, otherwise undetected by a simple evaluation of ROI χ mean values., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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187. Consensus on the treatment of dysphagia in Parkinson's disease.
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Schindler A, Pizzorni N, Cereda E, Cosentino G, Avenali M, Montomoli C, Abbruzzese G, Antonini A, Barbiera F, Benazzo M, Benarroch E, Bertino G, Clavè P, Cortelli P, Eleopra R, Ferrari C, Hamdy S, Huckabee ML, Lopiano L, Marchese-Ragona R, Masiero S, Michou E, Occhini A, Pacchetti C, Pfeiffer RF, Restivo DA, Rondanelli M, Ruoppolo G, Sandrini G, Schapira A, Stocchi F, Tolosa E, Valentino F, Zamboni M, Zangaglia R, Zappia M, Tassorelli C, and Alfonsi E
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- Consensus, Humans, Italy, Deglutition Disorders etiology, Deglutition Disorders therapy, Parkinson Disease complications, Parkinson Disease therapy
- Abstract
Background: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD., Objective: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed., Conclusions: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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188. Neurophysiological evaluation of visual function in iRBD: potential role in stratifying RBD conversion risk.
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Terzaghi M, Romani A, Ranzani M, Callieco R, Avantaggiato F, Cremascoli R, Picascia M, Pilati L, Arnaldi D, Rustioni V, Sartori I, Zangaglia R, Pacchetti C, Colnaghi S, and Versino M
- Subjects
- Evoked Potentials, Visual, Follow-Up Studies, Humans, Neurodegenerative Diseases, Parkinson Disease, REM Sleep Behavior Disorder
- Abstract
Study Objectives: To evaluate neurophysiological alterations of visual function in idiopathic REM sleep Behavior Disorder (iRBD) both as markers and predictors of neurodegenerative disorders., Methods: In a longitudinal follow-up study of 46 consecutive iRBD patients (follow-up duration 8.4 ± 3.4 years), the baseline parameters in luminance-contrast pattern (VEPp), red-green color (VEPc) and motion-onset (VEPm) Visual Evoked Potentials in iRBD were compared to early (ePD) and advanced (aPD) Parkinson's Disease subjects. Parameters of latency and amplitude of iRBD converters to neurodegenerative disease were compared with those of the non-converters., Results: The VEP P100 mean latency values for both eyes and for both stimulation checks (30' and 15') were significantly longer in all the three groups of patients as compared to controls; moreover latencies were longer in aPD than in the iRBD group who did not differ from the ePD group. The same held true when we analyzed the number of abnormal subjects belonging to each diagnostic group with a higher number of abnormal subjects in the aPD group compared to both the ePD and in iRBD groups. Chromatic and motion potentials were not different from controls and did not differ in the 3 diagnostic groups. The iRBD subjects who converted to a neurodegenerative disorder showed longer P100 latencies and a higher occurrence of VEPp abnormalities than those who did not convert. Again chromatic and motion VEPs were not different depending on conversion., Conclusions: In iRBD patients the detection of an abnormal VEPp should be considered as a red flag for possible synnucleinopathy, eventually contributing in stratifying the risk of phenoconversion., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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189. Profiling the Biochemical Signature of GBA-Related Parkinson's Disease in Peripheral Blood Mononuclear Cells.
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Avenali M, Cerri S, Ongari G, Ghezzi C, Pacchetti C, Tassorelli C, Valente EM, and Blandini F
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- Glucosylceramidase genetics, Humans, Leukocytes, Mononuclear, Mutation genetics, alpha-Synuclein genetics, Parkinson Disease genetics
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Background: GBA mutations are the commonest genetic risk factor for Parkinson's disease (PD) and also impact disease progression., Objective: The objective of this study was to define a biochemical profile that could distinguish GBA-PD from non-mutated PD., Methods: 29 GBA-PD, 37 non-mutated PD, and 40 controls were recruited; α-synuclein levels in plasma, exosomes, and peripheral blood mononuclear cells were analyzed, GCase and main GCase-related lysosomal proteins in peripheral blood mononuclear cells were measured., Results: Assessment of plasma and exosomal α-synuclein levels did not allow differentiation between GBA-PD and non-mutated PD; conversely, measurements in peripheral blood mononuclear cells clearly distinguished GBA-PD from non-mutated PD, with the former group showing significantly higher α-synuclein levels, lower GCase activity, higher LIMP-2, and lower Saposin C levels., Conclusion: We propose peripheral blood mononuclear cells as an easily accessible and manageable model to provide a distinctive biochemical profile of GBA-PD, potentially useful for patient stratification or selection in clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2021
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190. Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment.
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Calandra-Buonaura G, Alfonsi E, Vignatelli L, Benarroch EE, Giannini G, Iranzo A, Low PA, Martinelli P, Provini F, Quinn N, Tolosa E, Wenning GK, Abbruzzese G, Bower P, Antonini A, Bhatia KP, Bonavita J, Pellecchia MT, Pizzorni N, Tison F, Ghorayeb I, Meissner WG, Ozawa T, Pacchetti C, Pozzi NG, Vicini C, Schindler A, Cortelli P, and Kaufmann H
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- Humans, Deglutition Disorders diagnosis, Deglutition Disorders etiology, Deglutition Disorders therapy, Multiple System Atrophy complications
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Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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191. PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype.
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Palmieri I, Valente M, Farina LM, Gana S, Minafra B, Zangaglia R, Pansarasa O, Sproviero D, Costa A, Pacchetti C, Pichiecchio A, Gagliardi S, and Cereda C
- Subjects
- Alleles, Brain diagnostic imaging, Brain pathology, DNA Mutational Analysis, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Molecular, Phenotype, Presenilin-1 chemistry, Protein Conformation, Cerebral Amyloid Angiopathy diagnosis, Cerebral Amyloid Angiopathy genetics, Cognitive Dysfunction diagnosis, Cognitive Dysfunction genetics, Mutation, Presenilin-1 genetics
- Abstract
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aβ) aggregates. Aβ aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein ( APP ) gene. However, mutations after codon 200 in the presenilin 1 ( PSEN1 ) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1 . With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.
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- 2021
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192. Is DAT imaging abnormality in normal pressure hydrocephalus always suggestive of degeneration?
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Del Gamba C, Bruno A, Frosini D, Volterrani D, Migaleddu G, Benedetto N, Perrini P, Pacchetti C, Cosottini M, Bonuccelli U, and Ceravolo R
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- Brain diagnostic imaging, Brain metabolism, Brain surgery, Dopamine Plasma Membrane Transport Proteins metabolism, Female, Humans, Substantia Nigra metabolism, Tomography, Emission-Computed, Single-Photon, Tropanes, Hydrocephalus, Normal Pressure complications, Hydrocephalus, Normal Pressure diagnostic imaging, Hydrocephalus, Normal Pressure surgery, Parkinsonian Disorders
- Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage.
123 I-FP-CIT-SPECT was believed to be helpful in this regard, however its role in predicting surgical outcome has been disputed. We illustrate a patient presented with gait disturbance, urinary incontinence, and asymmetrical parkinsonian signs, who underwent a 3T brain MRI and a123 I-FP-CIT-SPECT. VPS was performed. The patient repeated a123 I-FP-CIT-SPECT, 18 months after the operation, and was clinically followed up for 24 months. Our patient displayed clinical and radiological criteria for iNPH and an abnormal asymmetrical uptake in123 I-FP-CIT-SPECT, consistent with her asymmetrical parkinsonism. However, the organization of the substantia nigra studied with iron-sensitive sequences in 3T brain MRI scan appeared intact. The patient revealed an improvement both clinically and in123 I-FP-CIT-SPECT at postsurgical follow-up. Our report suggests that abnormal123 I-FP-CIT-SPECT may not necessarily reveal an overlap with neurodegenerative parkinsonism; its partial reversibility may suggest that the mechanical effect exerted on the striatum by ventriculomegaly ultimately leads to downregulation of dopaminergic transporters which may improve after VPS.- Published
- 2021
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193. Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus.
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Pozzi NG, Brumberg J, Todisco M, Minafra B, Zangaglia R, Bossert I, Trifirò G, Ceravolo R, Vitali P, Isaias IU, Fasano A, and Pacchetti C
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- Corpus Striatum diagnostic imaging, Corpus Striatum metabolism, Dopamine, Dopamine Plasma Membrane Transport Proteins metabolism, Humans, Tomography, Emission-Computed, Single-Photon, Tropanes, Hydrocephalus, Normal Pressure diagnostic imaging, Motor Disorders
- Abstract
Background: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear., Objectives: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls., Methods: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [
123 I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up., Results: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus., Conclusions: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)- Published
- 2021
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194. AQP4 autoantibodies in patients with idiopathic normal pressure hydrocephalus.
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Gastaldi M, Todisco M, Carlin G, Scaranzin S, Zardini E, Minafra B, Zangaglia R, Pichiecchio A, Reindl M, Jarius S, Pacchetti C, and Franciotta D
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- Adult, Aged, Aged, 80 and over, Biomarkers blood, Biomarkers cerebrospinal fluid, Female, Humans, Hydrocephalus, Normal Pressure diagnostic imaging, Male, Middle Aged, Prospective Studies, Aquaporin 4 blood, Aquaporin 4 cerebrospinal fluid, Autoantibodies blood, Autoantibodies cerebrospinal fluid, Hydrocephalus, Normal Pressure blood, Hydrocephalus, Normal Pressure cerebrospinal fluid
- Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder with unknown etiology. A selective depletion of aquaporin 4 (AQP4) has been shown in iNPH patients. We collected serum and cerebrospinal fluid (CSF) from 43 iNPH patients and 35 with other neurodegenerative conditions, and serum from 43 healthy subjects. All samples were tested for AQP4-IgG/IgA/IgM antibodies using a live cell-based assay. No patients or controls had serum/CSF AQP4-IgG/IgA. One/43 iNPH patient and 0/43 controls tested positive for serum AQP4-IgM. The AQP4-IgM-positive iNPH patient had no clinico-radiological distinctive features. AQP4 antibodies are unlikely to play a role in iNPH pathogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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195. GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort.
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Petrucci S, Ginevrino M, Trezzi I, Monfrini E, Ricciardi L, Albanese A, Avenali M, Barone P, Bentivoglio AR, Bonifati V, Bove F, Bonanni L, Brusa L, Cereda C, Cossu G, Criscuolo C, Dati G, De Rosa A, Eleopra R, Fabbrini G, Fadda L, Garbellini M, Minafra B, Onofrj M, Pacchetti C, Palmieri I, Pellecchia MT, Petracca M, Picillo M, Pisani A, Vallelunga A, Zangaglia R, Di Fonzo A, Morgante F, and Valente EM
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- Dissection, Genotype, Glucosylceramidase genetics, Humans, Italy epidemiology, Mutation genetics, Phenotype, Parkinson Disease epidemiology, Parkinson Disease genetics
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Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear., Objectives: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time., Methods: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed., Results: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity., Conclusions: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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196. NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease.
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Terzaghi M, Minafra B, Zangaglia R, Picascia M, Pozzi N, Cremascoli R, Arnaldi D, Versino M, Sinforiani E, Rustioni V, Pacchetti C, and Manni R
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- Arousal, Humans, Sleep, Cognitive Dysfunction etiology, Parkinson Disease complications, REM Sleep Behavior Disorder
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Background: Sleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders., Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD., Methods: Clinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54)., Results: Arousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387-95% CI 1.395-8.220, p = 0.007)., Conclusion: Arousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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197. Long-term effectiveness of levodopa-carbidopa intestinal gel on motor and non-motor symptoms in advanced Parkinson's disease: results of the Italian GLORIA patient population.
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Antonini A, Marano P, Gusmaroli G, Modugno N, Pacchetti C, Sensi M, Melzi G, Bergmann L, Zibetti M, and Lopiano L
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- Antiparkinson Agents adverse effects, Drug Combinations, Gels, Humans, Italy, Levodopa adverse effects, Quality of Life, Carbidopa, Parkinson Disease drug therapy
- Abstract
Introduction: The GLORIA registry included 375 advanced Parkinson's disease (PD) patients and evaluated the efficacy and safety of a 24-month levodopa-carbidopa intestinal gel (LCIG) treatment in routine medical care. This analysis focuses on the Italian population, 60 patients treated with LCIG in 7 specialised PD care centres., Methods: Hours of "Off" and "On" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV items 39 and 32. Motor fluctuations, dyskinesia, non-motor symptoms, quality of life and safety were evaluated., Results: Overall, 42 (70%) out of 60 patients completed the registry. LCIG treatment reduced "Off" time (- 3.3 ± 2.7 h at month 24 (M24), P < 0.0001), increased "On" time with dyskinesia (- 2.6 ± 5.2 h at M12, P = 0.0160), and improved UPDRS II and UPDRS III total scores at M24 (- 4.5 ± 10.6, P = 0.0333 and - 4.9 ± 11.7, P = 0.0229, respectively), Non-Motor Symptom Scale (NMSS) total score (- 21.8 ± 28.5, P < 0.0001) and Parkinson's Disease Questionnaire-8 item (PDQ-8) total score (- 12.5 ± 23.9, P = 0.0173) versus previous oral therapy. Adverse drug reactions (ADR) possibly or probably related to treatment were reported in 16 (28.6%) patients. Decreased weight (7.1%), polyneuropathy (7.1%) and abdominal pain (5.4%) were the most frequent ADRs while device malfunction (5.4%) and medical device change (5.4%) were the most reported device complaints., Conclusions: LCIG improved motor fluctuations, non-motor symptoms and quality of life over 24 months while tolerability was consistent with the established safety profile.
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- 2020
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198. Reproducibility and reaction time of swallowing as markers of dysphagia in parkinsonian syndromes.
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Cosentino G, Tassorelli C, Prunetti P, Todisco M, De Icco R, Avenali M, Minafra B, Zangaglia R, Valentino F, Pacchetti C, Bertino G, Mauramati S, Fresia M, and Alfonsi E
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- Aged, Aged, 80 and over, Deglutition Disorders physiopathology, Electromyography, Female, Humans, Male, Middle Aged, Parkinsonian Disorders physiopathology, Pharynx physiopathology, Reproducibility of Results, Deglutition physiology, Deglutition Disorders etiology, Parkinsonian Disorders complications, Reaction Time physiology
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Objective: To investigate reproducibility and reaction time of oropharyngeal swallowing in patients with Parkinson's disease (PD) and atypical parkinsonisms (APs)., Methods: We enrolled 19 patients with PD, 30 with APs, and 20 healthy subjects. Presence and severity of dysphagia were assessed with clinical and fiberoptic endoscopic evaluations of swallowing. Reproducibility of the oral and pharyngeal phases of swallowing were respectively assessed by calculating the 'similarity index' of the electromyography activity of the submental/suprahyoid muscles and of the laryngeal-pharyngeal mechanogram during consecutive swallows. These were performed both 'on command' and spontaneously. The swallowing reaction time was also recorded., Results: Reproducibility of the oral phase of swallowing was reduced in patients with dysphagia, mainly when swallowing 'on command'. Swallowing reaction time was prolonged in dysphagic patients. These electrophysiological parameters did not vary among different parkinsonian syndromes and correlated with dysphagia severity., Conclusions: Increased variability of oral swallowing automatisms and abnormal sensorimotor integration may be of relevance for the pathophysiology of dysphagia in parkinsonian syndromes., Significance: The electrophysiological assessment represents a valuable tool to investigate swallowing alterations in parkinsonian syndromes. It may also provide useful insights into clinical severity and pathophysiology of dysphagia, giving clues for the choice of the best therapeutic approach., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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199. Lumboperitoneal shunt in idiopathic normal pressure hydrocephalus: a prospective controlled study.
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Todisco M, Picascia M, Pisano P, Zangaglia R, Minafra B, Vitali P, Rognone E, Pichiecchio A, Ceravolo R, Vanacore N, Fasano A, and Pacchetti C
- Subjects
- Humans, Magnetic Resonance Imaging, Neuroimaging, Neuropsychological Tests, Prospective Studies, Hydrocephalus, Normal Pressure diagnostic imaging, Hydrocephalus, Normal Pressure surgery
- Abstract
Objective: In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS)., Methods: We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up., Results: Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group., Conclusions: LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.
- Published
- 2020
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200. Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson Disease.
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Vitali P, Pan MI, Palesi F, Germani G, Faggioli A, Anzalone N, Francaviglia P, Minafra B, Zangaglia R, Pacchetti C, and Gandini Wheeler-Kingshott CAM
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- Aged, Female, Humans, Male, Middle Aged, Parkinson Disease pathology, Prospective Studies, Substantia Nigra anatomy & histology, Substantia Nigra pathology, Magnetic Resonance Imaging methods, Parkinson Disease diagnostic imaging, Substantia Nigra diagnostic imaging
- Abstract
Background Magnetization transfer-prepared T1-weighted MRI can depict a hyperintense subregion of the substantia nigra involved in the degeneration process of Parkinson disease. Purpose To evaluate quantitative measurement of substantia nigra volume by using MRI to support clinical diagnosis and staging of Parkinson disease. Materials and Methods In this prospective study, a high-spatial-resolution magnetization transfer-prepared T1-weighted volumetric sequence was performed with a 3-T MRI machine between January 2014 and October 2015 for participants with de novo Parkinson disease, advanced Parkinson disease, and healthy control participants. A reproducible semiautomatic quantification analysis method that entailed mesencephalic intensity as an internal reference was used for hyperintense substantia nigra volumetry normalized to intracranial volume. A general linear model with age and sex as covariates was used to compare the three groups. Results Eighty participants were evaluated: 20 healthy control participants (mean age ± standard deviation, 56 years ± 11; 11 women), 29 participants with de novo Parkinson disease (64 years ± 10; 19 men), and 31 participants with advanced Parkinson disease (60 years ± 9; 16 women). Volumetric measurement of hyperintense substantia nigra from magnetization transfer-prepared T1-weighted MRI helped differentiate healthy control participants from participants with advanced Parkinson disease (mean difference for ipsilateral side, 64 mm
3 ± 14, P < .001; mean difference for contralateral side, 109 mm3 ± 14, P < .001) and helped distinguish healthy control participants from participants with de novo Parkinson disease (mean difference for ipsilateral side, 45 mm3 ± 15, P < .01; mean difference for contralateral side, 66 mm3 ± 15, P < .001) and participants with de novo Parkinson disease from those with advanced Parkinson disease (mean difference for ipsilateral side, 20 mm3 ± 13, P = .40; mean difference for contralateral side, 43 mm3 ± 13, P = .004). Conclusion Magnetization transfer-prepared T1-weighted MRI volumetry of the substantia nigra helped differentiate the stages of Parkinson disease. © RSNA, 2020 Online supplemental material is available for this article.- Published
- 2020
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