30 results on '"Artusi CA"'
Search Results
2. The still under-investigated role of cognitive deficits in PML diagnosis
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Scarpazza, Cristina, De Rossi, Nicola, Moiola, Lucia, Gerevini, Simonetta, Cosottini, Mirco, Capra, Ruggero, Mattioli, Flavia, Amato, Maria Pia, Artusi, Carlo Alberto, Bandini, Fabio, Barcella, Valeria, Bertolotto, Antonio, Bresciamorra, Vincenzo, Capobianco, Marco, Cavaletti, Guido, Cavalla, Paola, Centonze, Diego, Clerico, Marinella, Cordioli, Cinzia, D'Aleo, Giangaetano, de Riz, Marilena, Deotto, Luciano, Durelli, Luca, Falcini, Mario, Ferrari, Ernesta, Fusco, Maria Luisa, Gasperini, Claudio, Ghezzi, Angelo, Grimaldi, Luigi, Guidotti, Mario, Laroni, Alice, Lugaresi, Alessandra, Naldi, Paola, Pane, Chiara, Perrone, Patrizia, Pizzorno, Matteo, Pozzilli, Carlo, Prosperini, Luca, Rezzonico, Monica, Rovaris, Marco, Salemi, Giuseppe, Salvetti, Marco, Santuccio, Giuseppe, Scarpini, Elio, Sessa, Edoardo, Solaro, Claudio, Tabiadon, Giulia, Tortorella, Carla, Trojano, Maria, Valentino, Paola, Scarpazza C, De Rossi N, Gerevini S, Cosottini M, Capra R, Mattioli F, Amato MP, Artusi CA, Bandini F, Barcella V, Bertolotto A, Bresciamorra V, Capobianco M, Cavaletti G, Cavalla P, Centonze D, Clerico M, Cordioli C, D’Aleo G, de Riz M, Deotto L, Durelli L, Falcini M, Ferrari E, Fusco ML, Gasperini C, Ghezzi A, Grimaldi L, Guidotti M, Laroni A, Lugaresi A, Naldi P, Pane C, Perrone P, Pizzorno M, Pozzilli C, Prosperini L, Rezzonico M, Rovaris M, Salemi G, Salvetti M, Santuccio G, Scarpini E, Sessa E, Solaro C, Tabiadon G, Tortorella C, Trojano M, Valentino P., Scarpazza, C, De Rossi, N, Moiola, L, Gerevini, S, Cosottini, M, Capra, R, Mattioli, F, Amato, M, Artusi, C, Bandini, F, Barcella, V, Bertolotto, A, Bresciamorra, V, Capobianco, M, Cavaletti, G, Cavalla, P, Centonze, D, Clerico, M, Cordioli, C, D'Aleo, G, de Riz, M, Deotto, L, Durelli, L, Falcini, M, Ferrari, E, Fusco, M, Gasperini, C, Ghezzi, A, Grimaldi, L, Guidotti, M, Laroni, A, Lugaresi, A, Naldi, P, Pane, C, Perrone, P, Pizzorno, M, Pozzilli, C, Prosperini, L, Rezzonico, M, Rovaris, M, Salemi, G, Salvetti, M, Santuccio, G, Scarpini, E, Sessa, E, Solaro, C, Tabiadon, G, Tortorella, C, Trojano, M, and Valentino, P
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0301 basic medicine ,cognition ,medicine.medical_specialty ,Pediatrics ,italian database ,natalizumab ,neuropsychological impairment ,progressive multifocal leukoencephalopathy ,neurology (clinical) ,neurology ,immunology ,immunology and allergy ,Neurology ,Settore MED/17 - Malattie Infettive ,Asymptomatic ,Apraxia ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Dementia ,Psychiatry ,Cognitive deficit ,Progressive multifocal leukoencephalopathy ,Neuropsychology ,Cognition ,Progressive multifocal leukoencephalopathy Natalizumab Cognition Neuropsychological impairment Italian database ,medicine.disease ,030104 developmental biology ,Italian database ,Natalizumab ,Neuropsychological impairment ,Cognition, Italian database, Natalizumab, Neuropsychological impairment, Progressive multifocal leukoencephalopathy ,Immunology and Allergy ,Immunology ,Neurology (clinical) ,Settore MED/26 - Neurologia ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery - Abstract
Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment.
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- 2017
3. Botulinum Toxin for Axial Postural Abnormalities in Parkinson's Disease: A Systematic Review.
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Gandolfi M, Artusi CA, Imbalzano G, Camozzi S, Crestani M, Lopiano L, Tinazzi M, and Geroin C
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- Humans, Neuromuscular Agents therapeutic use, Spinal Curvatures drug therapy, Posture, Parkinson Disease drug therapy, Botulinum Toxins therapeutic use
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Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
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- 2024
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4. Unveiling the Unpredictable in Parkinson's Disease: Sensor-Based Monitoring of Dyskinesias and Freezing of Gait in Daily Life.
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Zampogna A, Borzì L, Rinaldi D, Artusi CA, Imbalzano G, Patera M, Lopiano L, Pontieri F, Olmo G, and Suppa A
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Background: Dyskinesias and freezing of gait are episodic disorders in Parkinson's disease, characterized by a fluctuating and unpredictable nature. This cross-sectional study aims to objectively monitor Parkinsonian patients experiencing dyskinesias and/or freezing of gait during activities of daily living and assess possible changes in spatiotemporal gait parameters., Methods: Seventy-one patients with Parkinson's disease (40 with dyskinesias and 33 with freezing of gait) were continuously monitored at home for a minimum of 5 days using a single wearable sensor. Dedicated machine-learning algorithms were used to categorize patients based on the occurrence of dyskinesias and freezing of gait. Additionally, specific spatiotemporal gait parameters were compared among patients with and without dyskinesias and/or freezing of gait., Results: The wearable sensor algorithms accurately classified patients with and without dyskinesias as well as those with and without freezing of gait based on the recorded dyskinesias and freezing of gait episodes. Standard spatiotemporal gait parameters did not differ significantly between patients with and without dyskinesias or freezing of gait. Both the time spent with dyskinesias and the number of freezing of gait episodes positively correlated with the disease severity and medication dosage., Conclusions: A single inertial wearable sensor shows promise in monitoring complex, episodic movement patterns, such as dyskinesias and freezing of gait, during daily activities. This approach may help implement targeted therapeutic and preventive strategies for Parkinson's disease., Competing Interests: The authors declare no conflicts of interest.
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- 2024
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5. Effects of Continuous Dopaminergic Stimulation on Parkinson's Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion.
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Imbalzano G, Artusi CA, Ledda C, Montanaro E, Romagnolo A, Rizzone MG, Bozzali M, Lopiano L, and Zibetti M
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- Humans, Male, Aged, Female, Middle Aged, Longitudinal Studies, Prospective Studies, Levodopa administration & dosage, Levodopa pharmacology, Parkinson Disease drug therapy, Parkinson Disease complications, Parkinson Disease physiopathology, Gait Disorders, Neurologic etiology, Gait Disorders, Neurologic drug therapy, Gait Disorders, Neurologic physiopathology, Gels, Carbidopa administration & dosage, Carbidopa pharmacology, Drug Combinations, Antiparkinson Agents administration & dosage, Antiparkinson Agents pharmacology
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Background: Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time., Objective: To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity., Methods: This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores., Results: Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation., Conclusion: Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.
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- 2024
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6. Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.
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Artusi CA, Geroin C, Nonnekes J, Aquino C, Garg D, Dale ML, Schlosser D, Lai Y, Al-Wardat M, Salari M, Wolke R, Labou VT, Imbalzano G, Camozzi S, Merello M, Bloem BR, Capato T, Djaldetti R, Doherty K, Fasano A, Tibar H, Lopiano L, Margraf NG, Moreau C, Ugawa Y, Bhidayasiri R, and Tinazzi M
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Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies., Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic., Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps., Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms., Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits., (© 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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7. Longitudinal Assessment of Botulinum Toxin Treatment for Lateral Trunk Flexion and Pisa Syndrome in Parkinson's Disease: Real-life, Long-Term Study.
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Ledda C, Panero E, Dimanico U, Parisi M, Gandolfi M, Tinazzi M, Geroin C, Marchet F, Massazza G, Lopiano L, and Artusi CA
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- Humans, Longitudinal Studies, Electromyography, Muscles, Syndrome, Parkinson Disease drug therapy, Botulinum Toxins adverse effects
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Lateral trunk flexion (LTF) and its severe form, called Pisa syndrome (PS), are highly invalidating axial postural abnormalities associated with Parkinson's disease (PD). Management strategies for LTF lack strong scientific evidence. We present a real-life, longitudinal study evaluating long-term efficacy of botulinum toxin (BoNT) injections in axial muscles to reduce LTF and PS in PD. A total of 13 PD patients with LTF > 5° received ultrasound- and electromyography-guided BoNT injections every 4 months. Seven untreated matched PD patients with LTF served as controls and their changes in posture after 18 months were compared with those of seven patients continuing BoNT over 12 months. 53.8% of patients continued the BoNT injections for at least 12 months. Various individual LTF responses were observed. Overall, BoNT-treated patients obtained a not statistically significant improvement of LTF of 17 ± 41% ( p = 0.237). In comparison, the seven untreated PD patients suffered a deterioration in LTF over 12 months by 36 ± 45% ( p = 0.116), showing a significantly different trajectory of posture change ( p = 0.026). In conclusion, repeated BoNT injections in axial muscles showed varying effects in managing PD-associated LTF, suggesting that: (a) a relevant number of patients with LTF can benefit from BoNT; (b) long-term treatment could prevent LTF worsening; (c) an instrumented, personalized approach is important; and (d) there is a need for prospective, long-term studies.
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- 2023
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8. Deep Brain Stimulation Outcomes in Parkinson's Disease Patients with Cognitive Impairment: Implications and Considerations.
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Romagnolo A, Fabbri M, Artusi CA, Zibetti M, Lopiano L, and Montanaro E
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- 2023
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9. Should we offer deep brain stimulation to Parkinson's disease patients with GBA mutations?
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Artusi CA and Lopiano L
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Parkinson's disease (PD) patients who are carriers of glucosylceramidase β1 (GBA1) gene mutations typically have an earlier age at onset and a more aggressive disease course, with a higher burden of neuropsychological issues. The use of deep brain stimulation (DBS) in PD patients with disabling motor fluctuations and absence of dementia is a widespread therapeutic option, often with good results in terms of improvement in activities of daily living and quality of life. Although all PD patients, when fulfilling the common selection criteria for DBS, can benefit from this intervention, some studies have raised attention toward the fact that PD patients who are carriers of GBA1 variants may have a worse DBS outcome possibly due to an accelerated progression of cognitive decline. From this viewpoint, we summarize the current literature, highlighting the knowledge gaps and proposing suggestions for further research as well as for clinical practice in this timeframe of uncertainty related to using DBS in PD patients who are carriers of GBA1 variants., 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 © 2023 Artusi and Lopiano.)
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- 2023
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10. Camera- and Viewpoint-Agnostic Evaluation of Axial Postural Abnormalities in People with Parkinson's Disease through Augmented Human Pose Estimation.
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Aldegheri S, Artusi CA, Camozzi S, Di Marco R, Geroin C, Imbalzano G, Lopiano L, Tinazzi M, and Bombieri N
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- Humans, Posture physiology, Software, Videotape Recording, Bone and Bones, Postural Balance physiology, Parkinson Disease diagnosis
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Axial postural abnormalities (aPA) are common features of Parkinson's disease (PD) and manifest in over 20% of patients during the course of the disease. aPA form a spectrum of functional trunk misalignment, ranging from a typical Parkinsonian stooped posture to progressively greater degrees of spine deviation. Current research has not yet led to a sufficient understanding of pathophysiology and management of aPA in PD, partially due to lack of agreement on validated, user-friendly, automatic tools for measuring and analysing the differences in the degree of aPA, according to patients' therapeutic conditions and tasks. In this context, human pose estimation (HPE) software based on deep learning could be a valid support as it automatically extrapolates spatial coordinates of the human skeleton keypoints from images or videos. Nevertheless, standard HPE platforms have two limitations that prevent their adoption in such a clinical practice. First, standard HPE keypoints are inconsistent with the keypoints needed to assess aPA (degrees and fulcrum). Second, aPA assessment either requires advanced RGB-D sensors or, when based on the processing of RGB images, they are most likely sensitive to the adopted camera and to the scene (e.g., sensor-subject distance, lighting, background-subject clothing contrast). This article presents a software that augments the human skeleton extrapolated by state-of-the-art HPE software from RGB pictures with exact bone points for posture evaluation through computer vision post-processing primitives. This article shows the software robustness and accuracy on the processing of 76 RGB images with different resolutions and sensor-subject distances from 55 PD patients with different degrees of anterior and lateral trunk flexion.
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- 2023
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11. Assessment of Axial Postural Abnormalities in Parkinsonism: Automatic Picture Analysis Software.
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Artusi CA, Geroin C, Imbalzano G, Camozzi S, Aldegheri S, Lopiano L, Tinazzi M, and Bombieri N
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Background: Software-based measurements of axial postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. An automatic and reliable software to accurately obtain real-time spine flexion angles according to the recently proposed consensus-based criteria would be a useful tool for both research and clinical practice., Objective: We aimed to develop and validate a new software based on Deep Neural Networks to perform automatic measures of PD axial postural abnormalities., Methods: A total of 76 pictures from 55 PD patients with different degrees of anterior and lateral trunk flexion were used for the development and pilot validation of a new software called AutoPosturePD (APP); postural abnormalities were measured in lateral and posterior view using the freeware NeuroPostureApp (gold standard) and compared with the automatic measurement provided by the APP. Sensitivity and specificity for the diagnosis of camptocormia and Pisa syndrome were assessed., Results: We found an excellent agreement between the new APP and the gold standard for lateral trunk flexion (intraclass correlation coefficient [ICC] 0.960, IC95% 0.913-0.982, P < 0.001), anterior trunk flexion with thoracic fulcrum (ICC 0.929, IC95% 0.846-0.968, P < 0.001) and anterior trunk flexion with lumbar fulcrum (ICC 0.991, IC95% 0.962-0.997, P < 0.001). Sensitivity and specificity were 100% and 100% for detecting Pisa syndrome, 100% and 95.5% for camptocormia with thoracic fulcrum, 100% and 80.9% for camptocormia with lumbar fulcrum., Conclusions: AutoPosturePD is a valid tool for spine flexion measurement in PD, accurately supporting the diagnosis of Pisa syndrome and camptocormia., (© 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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12. Visuospatial Deficits Are Associated with Pisa Syndrome and not Camptocormia in Parkinson's Disease.
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Artusi CA, Montanaro E, Erro R, Margraf N, Geroin C, Pilotto A, Magistrelli L, Spagnolo F, Marchet A, Sarro L, Cuoco S, Sacchetti M, Riello M, Capellero B, Berchialla P, Moeller B, Vullriede B, Zibetti M, Rini AM, Barone P, Comi C, Padovani A, Tinazzi M, and Lopiano L
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Background: Pisa syndrome (PS) and camptocormia (CC) are postural abnormalities frequently associated with Parkinson's disease (PD). Their pathophysiology remains unclear, but the role of cognitive deficits has been postulated., Objectives: To identify differences in the neuropsychological functioning of patients with PD with PS or CC compared with matched patients with PD without postural abnormalities., Methods: We performed a case-control study including 57 patients with PD with PS (PS+) or CC (CC+) and 57 PD controls without postural abnormalities matched for sex, age, PD duration, phenotype, and stage. Patients were divided into four groups: PS+ (n = 32), PS+ controls (PS-, n = 32), CC+ (n = 25), and CC+ controls (CC-, n = 25). We compared PS+ versus PS- and CC+ versus CC- using a neuropsychological battery assessing memory, attention, executive functions, visuospatial abilities, and language. Subjective visual vertical (SVV) perception was assessed by the Bucket test as a sign of vestibular function; the misperception of trunk position, defined as a mismatch between the objective versus subjective evaluation of the trunk bending angle >5°, was evaluated in PS+ and CC+., Results: PS+ showed significantly worse visuospatial performances ( P = 0.025) and SVV perception ( P = 0.038) than their controls, whereas CC+ did not show significant differences compared with their control group. Reduced awareness of postural abnormality was observed in >60% of patients with PS or CC., Conclusions: Low visuospatial performances and vestibular tone imbalance are significantly associated with PS but not with CC. These findings suggest different pathophysiology for the two main postural abnormalities associated with PD and can foster adequate therapeutic and prevention strategies., (© 2022 International Parkinson and Movement Disorder Society.)
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- 2022
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13. Task Force Consensus on Nosology and Cut-Off Values for Axial Postural Abnormalities in Parkinsonism.
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Tinazzi M, Geroin C, Bhidayasiri R, Bloem BR, Capato T, Djaldetti R, Doherty K, Fasano A, Tibar H, Lopiano L, Margraf NG, Merello M, Moreau C, Ugawa Y, and Artusi CA
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Background: There is no consensus with regard to the nosology and cut-off values for postural abnormalities in parkinsonism., Objective: To reach a consensus regarding the nosology and cut-off values., Methods: Using a modified Delphi panel method, multiple rounds of questionnaires were conducted by movement disorder experts to define nosology and cut-offs of postural abnormalities., Results: After separating axial from appendicular postural deformities, a full agreement was found for the following terms and cut-offs: camptocormia, with thoracic fulcrum (>45°) or lumbar fulcrum (>30°), Pisa syndrome (>10°), and antecollis (>45°). "Anterior trunk flexion," with thoracic (≥25° to ≤45°) or lumbar fulcrum (>15° to ≤30°), "lateral trunk flexion" (≥5° to ≤10°), and "anterior neck flexion" (>35° to ≤45°) were chosen for milder postural abnormalities., Conclusions: For axial postural abnormalities, we recommend the use of proposed cut-offs and six unique terms, namely camptocormia, Pisa syndrome, antecollis, anterior trunk flexion, lateral trunk flexion, anterior neck flexion, to harmonize clinical practice and future research., (© 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.)
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- 2022
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14. Editorial: Advances in Functional Neurosurgery.
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Artusi CA, Ramirez-Zamora A, and Bozzali M
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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.
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- 2021
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15. G325R GBA mutation in Parkinson's disease: Disease course and long-term DBS outcome.
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Ledda C, Artusi CA, Montanaro E, Martone T, Zibetti M, and Lopiano L
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- Humans, Mutation, Treatment Outcome, Deep Brain Stimulation, Parkinson Disease genetics, Parkinson Disease therapy
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Competing Interests: Declaration of competing interest None.
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- 2021
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16. Digital work engagement among Italian neurologists.
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Brigo F, Ponzano M, Sormani MP, Clerico M, Abbadessa G, Cossu G, Trojsi F, Colucci F, Tortorella C, Miele G, Spina E, Artusi CA, Carmisciano L, Servillo G, Bozzali M, Sparaco M, Leocani L, Lanzillo R, Tedeschi G, Bonavita S, and Lavorgna L
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Background: Digital health, including telemedicine, is increasingly recommended for the management of chronic neurological disorders, and it has changed the roles of patients and clinicians., Methods: In this cross-sectional study we aimed to investigate the digital work engagement of Italian neurologists through a survey collected between September 2020 and January 2021. Questionnaires were anonymous and collected demographic characteristics, attitudes towards digital devices and social media, and details about the clinician-patient relationship. We used logistic-regression models to identify characteristics associated with the propensity to communicate with patients using social media., Results: Among the 553 neurologists who participated to the study, smartphones and computers were widely preferred compared with tablets; wearable devices were not common, although some neurologists desired them. A total of 48% of participants reported communicating with patients using social media but only a few were in favor of social friendship with patients; WhatsApp was the social media most popular for professional (86%) and personal (98%) purposes. Propensity to communicate with social media was significantly higher among those who were older ( p < 0.001) and lived in regions outside northern Italy (center: p = 0.006; south and the islands: p < 0.001). For 58% of responders, social media improved their relationship with patients, but 72% usually warned patients about unreliable websites., Conclusions: The preferred social media were those which were rapid and which safeguard privacy more effectively; neurologists made many efforts to disprove fake news circulating online, providing help to patients in various ways. This analysis can help direct future interventions for the management of chronic neurological disorders., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)
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- 2021
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17. Motor and non-motor outcomes of subthalamic deep brain stimulation in a case of juvenile PARK-PINK1.
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Balestrino R, Ledda C, Romagnolo A, Bozzali M, Giulietti G, Montanaro E, Rizzone M, Zibetti M, Artusi CA, and Lopiano L
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- Humans, Protein Kinases, Deep Brain Stimulation, Parkinson Disease therapy, Subthalamic Nucleus
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Competing Interests: Declaration of competing interest Roberta Balestrino declares no conflict of interest. Claudia Ledda declares no conflict of interest. Alberto Romagnolo has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco, Chiesi Farmaceutici, Medtronic, and UCB Pharma. Marco Bozzali received honoraria for lecturing and travel grants from Biogen and Roche. He sits in the Advisory Board for Roche Pharmaceuticals. Giovanni Giulietti declares no conflict of interest. Elisa Montanaro declares no conflict of interest. Mario Rizzone declares no conflicto of interest. Maurizio Zibetti has received grant support and speaker honoraria from AbbVie, speaker honoraria from Bial Pharmaceuticals and travel grants from Merz, Medtronic, Boston Scientific and UCB Pharma. Carlo Alberto Artusi has received travel grants from Zambon and Abbvie, and educational grants from Ralpharma and Neuraxpharm. Leonardo Lopiano has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie.
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- 2021
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18. Gene Therapy in Movement Disorders: A Systematic Review of Ongoing and Completed Clinical Trials.
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Merola A, Kobayashi N, Romagnolo A, Wright BA, Artusi CA, Imbalzano G, Litvan I, Van Laar AD, and Bankiewicz K
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Introduction: We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit. Methods: We systematically reviewed movement disorders gene therapy clinical trials from PubMed and ClinicalTrials.gov using a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers). Results: We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers). Conclusion: Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders., Competing Interests: AM is supported by NIH (KL2 TR001426) and has received speaker honoraria from CSL Behring, Abbvie, and Cynapsus Therapeutics. He has received grant support from Lundbeck. AR has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco, Chiesi Farmaceutici, Medtronic, and UCB Pharma. BW has received grant support from Acadia and Tilray. CA has received travel grants from Zambon and Abbvie, and educational grants from Ralpharma and Neuraxpharm. IL research is supported by the National Institutes of Health grants: 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025; U19 AG063911-1; 1R21NS114764-01A1; Parkinson Study Group, Michael J. Fox Foundation, Parkinson Foundation, Lewy Body Association, Roche, Abbvie, Biogen, EIP-Pharma, and Biohaven Pharmaceuticals. She was member of the Scientific Advisory Board of a Lundbeck and Corticobasal Degeneration Solutions. She receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology. AV has received grant support from Voyager Therapeutics and is employed by Asklepios BioPharmaceutical, Inc. KB is the founder of Brain Neurotherapy Bio and Voyager Therapeutics, gene companies. He has equity in Brain Neurotherapy Bio, Asklepios BioPharmaceutical, and Voyager Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Merola, Kobayashi, Romagnolo, Wright, Artusi, Imbalzano, Litvan, Van Laar and Bankiewicz.)
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- 2021
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19. Deep Brain Stimulation Selection Criteria for Parkinson's Disease: Time to Go beyond CAPSIT-PD.
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Artusi CA, Lopiano L, and Morgante F
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Despite being introduced in clinical practice more than 20 years ago, selection criteria for deep brain stimulation (DBS) in Parkinson's disease (PD) rely on a document published in 1999 called 'Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease'. These criteria are useful in supporting the selection of candidates. However, they are both restrictive and out-of-date, because the knowledge on PD progression and phenotyping has massively evolved. Advances in understanding the heterogeneity of PD presentation, courses, phenotypes, and genotypes, render a better identification of good DBS outcome predictors a research priority. Additionally, DBS invasiveness, cost, and the possibility of serious adverse events make it mandatory to predict as accurately as possible the clinical outcome when informing the patients about their suitability for surgery. In this viewpoint, we analyzed the pre-surgical assessment according to the following topics: early versus delayed DBS; the evolution of the levodopa challenge test; and the relevance of axial symptoms; patient-centered outcome measures; non-motor symptoms; and genetics. Based on the literature, we encourage rethinking of the selection process for DBS in PD, which should move toward a broad clinical and instrumental assessment of non-motor symptoms, quantitative measurement of gait, posture, and balance, and in-depth genotypic and phenotypic characterization.
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- 2020
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20. Implementation of Mobile Health Technologies in Clinical Trials of Movement Disorders: Underutilized Potential.
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Artusi CA, Imbalzano G, Sturchio A, Pilotto A, Montanaro E, Padovani A, Lopiano L, Maetzler W, and Espay AJ
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- Biomedical Technology instrumentation, Clinical Trials as Topic instrumentation, Humans, Movement Disorders therapy, Telemedicine instrumentation, Biomedical Technology methods, Clinical Trials as Topic methods, Movement Disorders diagnosis, Telemedicine methods, Wearable Electronic Devices
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Mobile health technologies (mHealth) are patient-worn or portable devices aimed at increasing the granularity and relevance of clinical measurements. The implementation of mHealth has the potential to decrease sample size, duration, and cost of clinical trials. We performed a review of the ClinicalTrials.gov database using a standardized approach to identify adoption in and usefulness of mHealth in movement disorders interventional clinical trials. Trial phase, geographical area, availability of data captured, constructs of interest, and outcome priority were collected. Eligible trials underwent quality appraisal using an ad hoc 5-point checklist to assess mHealth feasibility, acceptability, correlation with patient-centered outcome measures, and clinical meaningfulness. A total of 29% (n = 54/184) registered trials were using mHealth, mainly in Parkinson's disease and essential tremor (59.3% and 27.8%). In most cases, mHealth were used in phase 2 trials (83.3%) as secondary outcome measures (59.3%). Only five phase 3 trials, representing 9.3% of the total, used mHealth (1 as primary outcome measure, 3 as secondary, and 1 as tertiary). Only 3.7% (n = 2/54) of all trials used mHealth for measuring both motor and non-motor symptoms, and 23.1% (n = 12/52) used mHealth for unsupervised, ecologic outcomes. Our findings suggest that mHealth remain underutilized and largely relegated to phase 2 trials for secondary or tertiary outcome measures. Efforts toward greater alignment of mHealth with patient-centered outcomes and development of a universal, common-language platform to synchronize data from one or more devices will assist future efforts toward the integration of mHealth into clinical trials.
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- 2020
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21. Levodopa/Carbidopa Intestinal Gel Long-Term Outcome in Parkinson's Disease: Focus on Dyskinesia.
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Fabbri M, Zibetti M, Calandra-Buonaura G, Contin M, Sambati L, Mohamed S, Romagnolo A, Berchialla P, Imbalzano G, Giannini G, Rizzone MG, Artusi CA, Cortelli P, and Lopiano L
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Background: Levodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD)., Objective: To identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients., Methods: PD patients were assessed for clinical and therapeutic variables, before LCIG treatment ( T0 ) and at last outpatient visit ( T1 ). Sub-groups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment., Results: We included 53 PD patients. After a mean of 51.7 ± 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at T1 (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at T1 (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at T1 (sum of the items 32 and 33: P = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration., Conclusion: Dyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients., Competing Interests: The study had no specific funding. The authors report no conflict of interest., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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22. Tuning deep brain stimulation related depression by frequency modulation: A case report.
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Imbalzano G, Artusi CA, Montanaro E, Romagnolo A, Rizzone MG, Lopiano L, and Zibetti M
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- 2020
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23. Smartphone-Based Estimation of Item 3.8 of the MDS-UPDRS-III for Assessing Leg Agility in People With Parkinson's Disease.
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Borzi L, Varrecchia M, Sibille S, Olmo G, Artusi CA, Fabbri M, Rizzone MG, Romagnolo A, Zibetti M, and Lopiano L
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Goal: In this paper we investigated the use of smartphone sensors and Artificial Intelligence techniques for the automatic quantification of the MDS-UPDRS-Part III Leg Agility (LA) task, representative of lower limb bradykinesia. Methods: We collected inertial data from 93 PD subjects. Four expert neurologists provided clinical evaluations. We employed a novel Artificial Neural Network approach in order to get a continuous output, going beyond the MDS-UPDRS score discretization. Results: We found a Pearson correlation of 0.92 between algorithm output and average clinical score, compared to an inter-rater agreement index of 0.88. Furthermore, the classification error was less than 0.5 scale point in about 80% cases. Conclusions: We proposed an objective and reliable tool for the automatic quantification of the MDS-UPDRS Leg Agility task. In perspective, this tool is part of a larger monitoring program to be carried out during activities of daily living, and managed by the patients themselves.
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- 2020
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24. Changing the Side of Pisa Syndrome: A Case of Over-Recovery with Botulinum Toxin.
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Artusi CA, Marchet F, Zanella C, Bortolani S, Dimanico U, and Lopiano L
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Competing Interests: This study did not receive any specific funding, and all authors report no conflicts of interest.
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- 2020
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25. Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?
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Geroin C, Artusi CA, Gandolfi M, Zanolin E, Ceravolo R, Capecci M, Andrenelli E, Ceravolo MG, Bonanni L, Onofrj M, Telese R, Bellavita G, Catalan M, Manganotti P, Mazzucchi S, Giannoni S, Vacca L, Stocchi F, Casali M, Falup-Pecurariu C, Zibetti M, Fasano A, Lopiano L, and Tinazzi M
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Background: Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine deviation. Objective: To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain. Methods: The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves. Results: We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment. Conclusions: The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB., (Copyright © 2020 Geroin, Artusi, Gandolfi, Zanolin, Ceravolo, Capecci, Andrenelli, Ceravolo, Bonanni, Onofrj, Telese, Bellavita, Catalan, Manganotti, Mazzucchi, Giannoni, Vacca, Stocchi, Casali, Falup-Pecurariu, Zibetti, Fasano, Lopiano and Tinazzi.)
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- 2020
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26. Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study.
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Tinazzi M, Gandolfi M, Ceravolo R, Capecci M, Andrenelli E, Ceravolo MG, Bonanni L, Onofrj M, Vitale M, Catalan M, Polverino P, Bertolotti C, Mazzucchi S, Giannoni S, Smania N, Tamburin S, Vacca L, Stocchi F, Radicati FG, Artusi CA, Zibetti M, Lopiano L, Fasano A, and Geroin C
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Introduction: The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables., Methods: For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables., Results: Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with l evodopa , and more likely to be treated with a combination of l evodopa and dopamine agonist, took a higher daily l evodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score., Conclusions: PA are frequent and disabling complications in PD, especially in the advanced disease stages., Competing Interests: Financial support for the study was provided by the Brain Research Foundation Verona O.N.L.U.S. All authors report no disclosures and no conflict of interests.
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- 2019
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27. Pisa Syndrome in Parkinson's Disease Is Associated With Specific Cognitive Alterations.
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Artusi CA, Montanaro E, Tuttobene S, Romagnolo A, Zibetti M, and Lopiano L
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Background: Pisa syndrome (PS) is a lateral flexion of the trunk frequently associated with Parkinson's disease (PD). The pathophysiology of PS remains unclear, but the role of cognitive deficits has been postulated. Methods: We included 12 consecutive PD patients with PS (PS+) and 12 PD patients without PS (PS-) matched for gender, age, level of education, PD duration, and PD stage. As primary aim, we compared the neuropsychological scores of 16 tests evaluating 6 cognitive domains between PS+ and PS-. Additionally, we evaluated the presence of misperception of the trunk position in PS+, defined as a mismatch between the objective vs. subjective evaluation of the trunk bending angle >5°, and analyzed whether a correlation exists between the misperception of the trunk position and alterations in the visual-spatial abilities. Results: PS+ group showed significantly worse performances in the visual-spatial abilities ( p : 0.008), attentional domain ( p : 0.001), and language domain ( p : 0.023). No differences were found in the other cognitive domains nor in the general cognitive assessment. All PS+ patients showed a misperception of the trunk position, with an average underestimation of the trunk bending angle of 11.7° ± 4.3. The degree of misperception of the trunk position showed a trend toward a correlation with the visual-spatial scores ( p : 0.089). Conclusions: The study reveals an association between PS and specific cognitive alterations, suggesting a possible link between the abnormal posture of PD patients with PS and their cognitive functions.
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- 2019
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28. Association of Subthalamic Deep Brain Stimulation With Motor, Functional, and Pharmacologic Outcomes in Patients With Monogenic Parkinson Disease: A Systematic Review and Meta-analysis.
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Artusi CA, Dwivedi AK, Romagnolo A, Pal G, Kauffman M, Mata I, Patel D, Vizcarra JA, Duker A, Marsili L, Cheeran B, Woo D, Contarino MF, Verhagen L, Lopiano L, Espay AJ, Fasano A, and Merola A
- Subjects
- Adolescent, Adult, Humans, Middle Aged, Young Adult, Deep Brain Stimulation, Parkinson Disease epidemiology, Parkinson Disease genetics, Parkinson Disease therapy, Subthalamic Nucleus physiopathology
- Abstract
Importance: Comparative outcomes among different monogenic forms of Parkinson disease after subthalamic nucleus deep brain stimulation (STN DBS) remain unclear., Objective: To compare clinical outcomes in patients with the most common monogenic forms of Parkinson disease treated with STN DBS., Design, Setting, and Participants: Systematic review and meta-analysis in which a PubMed search of interventional and noninterventional studies of Parkinson disease with LRRK2, GBA, or PRKN gene mutations published between January 1, 1990, and May 1, 2018, was conducted. Among the inclusion criteria were articles that reported the Motor subscale of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) before and after STN DBS treatment, that involved human participants, and that were published in the English language. Studies that used aggregated data from patients with different genetic mutations were excluded, and so were studies with assumed but not confirmed genetic data or incomplete follow-up data., Main Outcomes and Measures: Changes in UPDRS-III scores and levodopa equivalent daily dose (LEDD) were analyzed for each monogenic form of Parkinson disease. Additional end points included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), and cognitive function., Results: Of the 611 eligible studies, 17 (2.8%) met the full inclusion criteria; these 17 studies consisted of 8 cohort studies (47.1%), 3 case series (17.6%), and 6 case reports (35.3%), and they involved a total of 518 patients. The UPDRS-III score improved by 46% in LRRK2 (mean change, 23.0 points; 95% CI, 15.2-30.8; P < .001), 49% in GBA (20.0 points; 95% CI, 4.5-35.5; P = .01), 43% in PRKN (24.1 points; 95% CI, 12.4-35.9; P < .001), and 53% in idiopathic Parkinson disease (25.2 points; 95% CI, 21.3-29.2; P < .001). The LEDD was reduced by 61% in LRRK2 (mean change, 711.9 mg/d; 95% CI, 491.8-932.0; P < .001), 22% in GBA (269.2 mg/d; 95% CI, 226.8-311.5; P < .001), 61% in PRKN (494.8 mg/d; 95% CI, -18.1 to -1007.8; P = .06), and 55% in idiopathic Parkinson disease (681.8 mg/d; 95% CI, 544.4-819.1; P < .001). Carriers of the PRKN mutations showed sustained improvements in UPDRS-II and UPDRS-IV, whereas LRRK2 mutation carriers sustained improvements only in UPDRS-IV. Carriers of the GBA mutation showed worse postsurgical cognitive and functional performance., Conclusions and Relevance: Treatment with STN DBS for patients with Parkinson disease with LRRK2, GBA, or PRKN mutations appears to be associated with similar motor outcomes but different changes in dopaminergic dose, activities of daily living, motor complications, and cognitive functions.
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- 2019
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29. Levodopa-Induced Neuropathy: A Systematic Review.
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Romagnolo A, Merola A, Artusi CA, Rizzone MG, Zibetti M, and Lopiano L
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Background: Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible causative role of levodopa metabolic products, such as homocysteine and methylmalonic acid., Methods: We conducted a systematic review of studies reporting cases of PNP in l-dopa-treated PD patients indexed in PubMed between January 1990 and March 2018., Results: We identified 38 articles reporting cases of PNP in PD patients treated with oral l-dopa or with l-dopa/carbidopa intestinal gel infusion (LCIG). Prevalence of PNP was 30.2% in the former group and 42.1% in the latter. Oral l-dopa was mostly associated with slowly progressive PNP, whereas LCIG showed an acute or subacute onset in 35.7% of cases. In both groups, there was an association between PNP and higher l-dopa doses, as well as with the following biochemical alterations: increased homocysteine; reduced vitamin B12; increased methylmalonic acid; and reduced vitamin B6. A skin biopsy was performed in 181 patients, showing signs of small fibers neuropathy in 169 (93.4%). Positive, yet preliminary, results were observed in patients receiving periodic vitamin supplementation., Conclusions: Over one third of PD patients in treatment with l-dopa may develop PNP, with a significantly higher prevalence of acute and subacute forms in those receiving LCIG. Pathogenic mechanisms remain unclear, but possibly related to a complex interplay between peripheral neurodegenerative processes and l-dopa neurotoxic metabolites. Prospective, randomized, clinical trials are required to identify factors associated with the onset and progression of PD-associated PNP and clarify the protective role of B-group vitamin supplementation.
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- 2018
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30. Natalizumab in Multiple Sclerosis: Long-Term Management.
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Clerico M, Artusi CA, Liberto AD, Rolla S, Bardina V, Barbero P, Mercanti SF, and Durelli L
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- Adrenal Cortex Hormones therapeutic use, Animals, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Humans, Immunologic Factors administration & dosage, Immunologic Factors adverse effects, JC Virus isolation & purification, Leukoencephalopathy, Progressive Multifocal diagnosis, Leukoencephalopathy, Progressive Multifocal etiology, Natalizumab administration & dosage, Natalizumab adverse effects, Antibodies, Monoclonal therapeutic use, Immunologic Factors therapeutic use, Multiple Sclerosis drug therapy, Natalizumab therapeutic use
- Abstract
Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients' clinical features and preferences.
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- 2017
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