Publications by authors named "Angelo Antonini"

324 Publications

Consensus on the treatment of dysphagia in Parkinson's disease.

J Neurol Sci 2021 Sep 27;430:120008. Epub 2021 Sep 27.

Department of Clinical and Movement Neurosciences, UCL, Queen Square Institute of Neurology, London, UK.

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.
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http://dx.doi.org/10.1016/j.jns.2021.120008DOI Listing
September 2021

Reduced Effective Connectivity in the Motor Cortex in Parkinson's Disease.

Brain Sci 2021 Sep 12;11(9). Epub 2021 Sep 12.

Department of Neuroscience, Section of Rehabilitation, University of Padova, Via Gustiniani 3, 35128 Padova, Italy.

Fast rhythms excess is a hallmark of Parkinson's Disease (PD). To implement innovative, non-pharmacological, neurostimulation interventions to restore cortical-cortical interactions, we need to understand the neurophysiological mechanisms underlying these phenomena. Here, we investigated effective connectivity on source-level resting-state electroencephalography (EEG) signals in 15 PD participants and 10 healthy controls. First, we fitted multivariate auto-regressive models to the EEG source waveforms. Second, we estimated causal connections using Granger Causality, which provide information on connections' strength and directionality. Lastly, we sought significant differences connectivity patterns between the two populations characterizing the network graph features-i.e., global efficiency and node strength. Causal brain networks in PD show overall poorer and weaker connections compared to controls quantified as a reduction of global efficiency. Motor areas appear almost isolated, with a strongly impoverished information flow particularly from parietal and occipital cortices. This striking isolation of motor areas may reflect an impaired sensory-motor integration in PD. The identification of defective nodes/edges in PD network may be a biomarker of disease and a potential target for future interventional trials.
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http://dx.doi.org/10.3390/brainsci11091200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466840PMC
September 2021

Impact of social and mobility restrictions in Parkinson's disease during COVID-19 lockdown.

BMC Neurol 2021 Aug 30;21(1):332. Epub 2021 Aug 30.

Parkinson and Movement Disorders Unit, Department of Neurosciences, University of Padova, Via Giustiniani 5, 35138, Padua, Italy.

Background: The consequences of strict COVID-19 mobility restrictions on motor/non-motor features in Parkinson's disease (PD) have not been systematically studied but worse mobility and quality of life have been reported. To elucidate this question, 12 mild to moderate PD patients were assessed in March 2020 before and after two months of isolation as part of a clinical study that had to be interrupted due to the pandemic and the implementation of COVID19 mobility restrictions.

Methods: Twelve patients were systematically evaluated before and after the lockdown period as part of a larger cohort that previously underwent thermal water rehabilitation. Clinical outcomes were the Body Mass index, the Mini-Balance Evaluation Systems Test, the MDS-Unified Parkinson's Disease Rating Scale part III, the 6 Minute Walking Test and the New Freezing of Gait Questionnaire. Global cognition was evaluated with the Montreal Cognitive Assessment scale. The impact of COVID-19 restrictions on quality of life and functional independence was evaluated with The Parkinson's disease Quality of life (PDQ-39), the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living questionnaires (IADL) and the Parkinson's disease cognitive functional rating scales (PD-CFRS).

Results: After two months of isolation the Mini-BESTest score worsened (p=0.005), and four patients reported one or more falls during the lockdown. BMI increased (p=0.031) while the remaining clinical variables including quality of life did not change.

Conclusion: We observed moderate worsening at Mini-BESTest, greater risk of falls and increased body weight as consequence of prolonged immobility. We believe negative effects were partially softened since patients were in contact with our multidisciplinary team during the lockdown and had previously received training to respond to the needs of this emergency isolation. These findings highligh the importnace of patient-centered interventions in PD management.
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http://dx.doi.org/10.1186/s12883-021-02364-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404403PMC
August 2021

The contribution of beta-amyloid to dementia in Lewy body diseases: a 1-year follow-up study.

Brain Commun 2021 19;3(3):fcab180. Epub 2021 Aug 19.

Parkinson and Movement Disorders Unit, Department of Neuroscience, University of Padua, Padua, Italy.

Dementia in Lewy Body Diseases (Parkinson's disease and dementia with Lewy Bodies) affects progression of disabilities, quality of life and well-being. Understanding its pathogenetic mechanisms is critical to properly implement disease-modifying strategies. It has been hypothesized that synuclein- and amyloid-pathology act synergistically aggravating cognitive decline in elderly patients but their precise contribution to dementia is debated. In this study, we aimed at exploring if presence of amyloid deposits influences clinical, cognitive and neuroanatomical correlates of mental decline in a cohort of 40 Parkinson's disease patients with normal cognition ( = 5), mild cognitive impairment ( = 22), and dementia ( = 13) as well as in Dementia with Lewy Bodies ( = 10). Patients underwent simultaneous 3 T PET/MRI with [F]-flutemetamol and were assessed with an extensive baseline motor and neuropsychological examination, which allowed level II diagnosis of mild cognitive impairment and dementia. The role of amyloid positivity on each cognitive domain, and on the rate of conversion to dementia at 1-year follow-up was explored. A Kaplan Meier and the Log Rank (Mantel-Cox) test were used to assess the pairwise differences in time-to-develop dementia in Parkinson's disease patients with and without significant amyloidosis. Furthermore, the presence of an Alzheimer's dementia-like morphological pattern was evaluated using visual and automated assessment of T-weighted and T-weighted MRI images. We observed similar percentage of amyloid deposits in Parkinson's disease dementia and dementia with Lewy Bodies cohorts (50% in each group) with an overall prevalence of 34% of significant amyloid depositions in Lewy Body Diseases. PET amyloid positivity was associated with worse global cognition (Montreal Cognitive Assessment and Mini Mental State Examination), executive and language difficulties. At 12-month follow-up, amyloid positive Parkinson's disease patients were more likely to have become demented than those without amyloidosis. Moreover, there was no difference in the presence of an Alzheimer's disease-like atrophy pattern and in vascular load (at Fazekas scale) between Lewy Body Diseases with and without significant amyloid deposits. Our findings suggest that in Lewy Body Diseases, amyloid deposition enhances cognitive deficits, particularly attention-executive and language dysfunctions. However, the large number of patients without significant amyloid deposits among our cognitively impaired patients indicates that synuclein pathology itself plays a critical role in the development of dementia in Lewy Body Diseases.
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http://dx.doi.org/10.1093/braincomms/fcab180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390473PMC
August 2021

Personalised Advanced Therapies in Parkinson's Disease: The Role of Non-Motor Symptoms Profile.

J Pers Med 2021 Aug 7;11(8). Epub 2021 Aug 7.

Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 9RT, UK.

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson's disease (PD). Currently, selection of device-aided therapies is mainly focused on patients' motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.
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http://dx.doi.org/10.3390/jpm11080773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400869PMC
August 2021

Advance Care Planning and Care Coordination for People With Parkinson's Disease and Their Family Caregivers-Study Protocol for a Multicentre, Randomized Controlled Trial.

Front Neurol 2021 5;12:673893. Epub 2021 Aug 5.

Department of Anesthesiology, Pain and Palliative Care, Radboud University Medical Center, Nijmegen, Netherlands.

Parkinson's disease (PD) is a progressive neurodegenerative disease with motor- and non-motor symptoms. When the disease progresses, symptom burden increases. Consequently, additional care demands develop, the complexity of treatment increases, and the patient's quality of life is progressively threatened. To address these challenges, there is growing awareness of the potential benefits of palliative care for people with PD. This includes communication about end-of-life issues, such as Advance Care Planning (ACP), which helps to elicit patient's needs and preferences on issues related to future treatment and care. In this study, we will assess the impact and feasibility of a nurse-led palliative care intervention for people with PD across diverse European care settings. The intervention will be evaluated in a multicentre, open-label randomized controlled trial, with a parallel group design in seven European countries (Austria, Estonia, Germany, Greece, Italy, Sweden and United Kingdom). The "PD_Pal intervention" comprises (1) several consultations with a trained nurse who will perform ACP conversations and support care coordination and (2) use of a patient-directed "Parkinson Support Plan-workbook". The primary endpoint is defined as the percentage of participants with documented ACP-decisions assessed at 6 months after baseline (t1). Secondary endpoints include patients' and family caregivers' quality of life, perceived care coordination, patients' symptom burden, and cost-effectiveness. In parallel, we will perform a process evaluation, to understand the feasibility of the intervention. Assessments are scheduled at baseline (t0), 6 months (t1), and 12 months (t2). Statistical analysis will be performed by means of Mantel-Haenszel methods and multilevel logistic regression models, correcting for multiple testing. This study will contribute to the current knowledge gap on the application of palliative care interventions for people with Parkinson's disease aimed at ameliorating quality of life and managing end-of-life perspectives. Studying the impact and feasibility of the intervention in seven European countries, each with their own cultural and organisational characteristics, will allow us to create a broad perspective on palliative care interventions for people with Parkinson's disease across settings. www.trialregister.nl, NL8180.
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http://dx.doi.org/10.3389/fneur.2021.673893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382049PMC
August 2021

Access and Attitudes Toward Palliative Care Among Movement Disorders Clinicians.

Mov Disord 2021 Aug 25. Epub 2021 Aug 25.

Parkinson Victoria, Surrey Hills, Victoria, Australia.

Background: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited.

Objective: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care.

Methods: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated.

Results: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills.

Conclusions: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28773DOI Listing
August 2021

A multinational consensus on dysphagia in Parkinson's disease: screening, diagnosis and prognostic value.

J Neurol 2021 Aug 21. Epub 2021 Aug 21.

Department of Clinical and Movement Neurosciences, UCL, Queen Square Institute of Neurology, London, UK.

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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http://dx.doi.org/10.1007/s00415-021-10739-8DOI Listing
August 2021

Digital health technology for non-motor symptoms in people with Parkinson's disease: Futile or future?

Parkinsonism Relat Disord 2021 Aug 31;89:186-194. Epub 2021 Jul 31.

King's College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, London, United Kingdom; Parkinson's Foundation Centre of Excellence at King's College Hospital, Denmark Hill, London, United Kingdom.

Introduction: There is an ongoing digital revolution in the field of Parkinson's disease (PD) for the objective measurement of motor aspects, to be used in clinical trials and possibly support therapeutic choices. The focus of remote technologies is now also slowly shifting towards the broad but more "hidden" spectrum of non-motor symptoms (NMS).

Methods: A narrative review of digital health technologies for measuring NMS in people with PD was conducted. These digital technologies were defined as assessment tools for NMS offered remotely in the form of a wearable, downloadable as a mobile app, or any other objective measurement of NMS in PD that did not require a hospital visit and could be performed remotely. Searches were performed using peer-reviewed literature indexed databases (MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials), as well as Google and Google Scholar.

Results: Eighteen studies deploying digital health technology in PD were identified, for example for the measurement of sleep disorders, cognitive dysfunction and orthostatic hypotension. In addition, we describe promising developments in other conditions that could be translated for use in PD.

Conclusion: Unlike motor symptoms, non-motor features of PD are difficult to measure directly using remote digital technologies. Nonetheless, it is currently possible to reliably measure several NMS and further digital technology developments are underway to offer further capture of often under-reported and under-recognised NMS.
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http://dx.doi.org/10.1016/j.parkreldis.2021.07.032DOI Listing
August 2021

Oscillatory EEG-TMS Reactivity in Parkinson Disease.

J Clin Neurophysiol 2021 Jul 6. Epub 2021 Jul 6.

Department of Neuroscience, Section of Rehabilitation, University of Padova, Padova, Italy; Parkinson and Movement Disorders Unit, Study Centre on Neurodegeneration (CESNE), Department of Neuroscience, University of Padova, Padova, Italy; Padova Neuroscience Center, University of Padova, Padova, Italy; and Neurology Section, Cattinara University Hospital, University of Trieste, Trieste, Italy.

Purpose: A dysfunction of beta oscillatory activity is the neurophysiological hallmark of Parkinson disease (PD). How cortical activity reacts to external perturbations may provide insight into pathophysiological mechanisms. This study aims at identifying modifications in EEG rhythms after transcranial magnetic stimulation (TMS) in PD. We hypothesize that single-pulse TMS can modulate brain intrinsic oscillatory properties (e.g., beta excess).

Methods: EEG data were coregistered during single-pulse TMS (100 stimuli over the primary motor cortex [M1, hotspot for Abductor Pollicis Brevis], random intertrial interval from 8 to 13 seconds). We used a time-frequency analysis based on wavelet method to characterize modification of oscillatory rhythms (delta [1-4 Hz], theta [4-7 Hz], alpha [8-12 Hz], and beta [13-30 Hz] in 15 participants with PD compared with 10 healthy controls.

Results: An increase in beta power over the sensorimotor areas was recorded at rest in the PD group (P < 0.05). Brain oscillations in PD transiently reset after TMS: beta power over M1 becomes comparable to that recorded in aged-matched healthy subjects in the 2 seconds following TMS.

Conclusions: Transcranial magnetic stimulation over the dominant motor cortex transiently normalizes cortical oscillations. More user-friendly noninvasive brain stimulation needs to be trialed, based on this proof of concept, to provide practical, portable techniques to treat motor symptoms in PD.
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http://dx.doi.org/10.1097/WNP.0000000000000881DOI Listing
July 2021

Moving towards Integrated and Personalized Care in Parkinson's Disease: A Framework Proposal for Training Parkinson Nurses.

J Pers Med 2021 Jun 30;11(7). Epub 2021 Jun 30.

Parkinson Disease and Movement Disorders Centre, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1Y 4E9, Canada.

Delivering healthcare to people living with Parkinson's disease (PD) may be challenging in face of differentiated care needs during a PD journey and a growing complexity. In this regard, integrative care models may foster flexible solutions on patients' care needs whereas Parkinson Nurses (PN) may be pivotal facilitators. However, at present hardly any training opportunities tailored to the care priorities of PD-patients are to be found for nurses. Following a conceptual approach, this article aims at setting a framework for training PN by reviewing existing literature on care priorities for PD. As a result, six prerequisites were formulated concerning a framework for training PN. The proposed training framework consist of three modules covering topics of PD: (i) comprehensive care, (ii) self-management support and (iii) health coaching. A fourth module on telemedicine may be added if applicable. The framework streamlines important theoretical concepts of professional PD management and may enable the development of novel, personalized care approaches.
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http://dx.doi.org/10.3390/jpm11070623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304750PMC
June 2021

Asymmetric Dopamine Transporter Loss Affects Cognitive and Motor Progression in Parkinson's Disease.

Mov Disord 2021 10 14;36(10):2303-2313. Epub 2021 Jun 14.

Department of General Psychology, University of Padua, Padua, Italy.

Background: Asymmetric hemispheric loss of dopaminergic neurons is one of the characteristic features of Parkinson's disease (PD). However, it is still debated if right or left asymmetry differently affects cognitive and motor progression.

Objectives: The objective of this study was to investigate, for the first time, the relevance of dopamine transporter (DAT) asymmetry on cognitive and motor manifestations at onset and at 4-year progression in drug-naïve PD.

Methods: From the Parkinson's Progression Markers Initiative multicenter cohort, we identified 249 right-handed patients with PD with baseline asymmetry greater than 20% in putamen DAT binding at single-photon emission computed tomography. A predominant putamen asymmetry was found on the left in 143 patients (PD-left), and on the right side in 106 patients (PD-right); we compared them with 196 healthy controls. Patients were followed longitudinally (2-year and 4-year visits), examining their clinical, cognitive, and imaging data.

Results: At baseline, the PD-left group showed worse performance on the Symbol Digit Modality Test, an attention and processing-speed test, and lower cerebrospinal fluid β-amyloid levels than the PD-right group. These differences were maintained at follow-up, declining over time in both groups. By contrast, the PD-right group showed greater motor impairment at baseline, which increased over 4 years. Striatal DAT binding decreased over time in both groups, but the PD-right group showed a steeper decline, particularly during the first 2-year follow-up. Putaminal asymmetry assessed at baseline was maintained over time.

Conclusions: These findings suggest that hemispheric asymmetric dopaminergic denervation influences PD cognitive and motor performance as well as progression. Predominant right hemisphere nigrostriatal dopaminergic loss is associated with greater motor severity, whereas more pronounced left hemisphere denervation affects cognitive manifestations at onset and their progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28682DOI Listing
October 2021

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease.

NPJ Parkinsons Dis 2021 Jun 8;7(1):48. Epub 2021 Jun 8.

University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable "QoL responders"/"non-responders". At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as "QoL non-responders". Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as 'difficulties experiencing pleasure' and 'problems sustaining concentration'. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.
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http://dx.doi.org/10.1038/s41531-021-00174-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187358PMC
June 2021

Clinical utility of DaTscan in patients with suspected Parkinsonian syndrome: a systematic review and meta-analysis.

NPJ Parkinsons Dis 2021 May 24;7(1):43. Epub 2021 May 24.

Department of Neuroscience, University of Padua, Padua, Italy.

Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI: 47-61%) of patients. Change in diagnosis occurred in 31% (95% CI: 22-42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.
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http://dx.doi.org/10.1038/s41531-021-00185-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144619PMC
May 2021

The Parkinson's Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson's Disease in Patients and their Carers.

J Parkinsons Dis 2021;11(3):1309-1323

Department of Clinical and Movement Neurosciences, National Hospital for Neurology and Neurosurgery, London, United Kingdom.

Background: A greater understanding of the everyday experiences of people with Parkinson's disease (PD) and their carers may help improve clinical practice.

Objective: The Parkinson's Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers.

Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson's Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI).

Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8%. Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6).

Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.
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http://dx.doi.org/10.3233/JPD-212611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461669PMC
January 2021

The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on 'Off'-time in Patients with Advanced Parkinson's Disease: A Systematic Review.

Adv Ther 2021 06 20;38(6):2854-2890. Epub 2021 May 20.

King's College London, and Parkinson's Foundation International Centre of Excellence, King's College Hospital, London, UK.

Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.

Methods: Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and 'off'-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: 'off'-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.

Results: Twenty-seven studies were included in this review. The improvement in 'off'-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. 'Off'-time was reduced from baseline to end of follow-up by 38-84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of 'off'-time demonstrated mean relative reductions of 47-82% at 3-6 months and up to 83% reduction at 3-5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.

Conclusion: In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing 'off'-time.

Infographic: Video Abstract.
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http://dx.doi.org/10.1007/s12325-021-01747-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189983PMC
June 2021

Dopamine Receptors in Parkinson's Disease: A Meta-Analysis of Imaging Studies.

Mov Disord 2021 08 6;36(8):1781-1791. Epub 2021 May 6.

Parkinson and Movement Disorders Unit, Department of Neuroscience, University of Padua, Padua, Italy.

Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28632DOI Listing
August 2021

The impact of COVID-19 on palliative care for people with Parkinson's and response to future pandemics.

Expert Rev Neurother 2021 06 19;21(6):615-623. Epub 2021 May 19.

Department of Medicine, Division Neurology, University of Alberta, Edmonton, Canada.

: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.
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http://dx.doi.org/10.1080/14737175.2021.1923480DOI Listing
June 2021

Movement perception of the tonic vibration reflex is abnormal in functional limb weakness.

Parkinsonism Relat Disord 2021 06 20;87:1-6. Epub 2021 Apr 20.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. Electronic address:

Introduction: We tested the hypothesis that functional limb weakness is associated with possible dysfunction of the central processing of proprioceptive information, by evaluating the amount of tonic vibration reflex (TVR) and the perception of the TVR movement.

Methods: The study sample was 20 patients with functional weakness of the lower and/or the upper limbs and 25 healthy controls; delivery of 92-Hz transcutaneous vibration of the biceps brachii tendon of the unrestrained arm stimulated predominantly the muscle spindle afferent and elicited elbow flexion (tonic vibration reflex, TVR). Blindfolded participants had to match the final position of the vibrated arm with their contralateral tracking arm. The TVR and perception of the TVR movement were measured as angle movements of the vibrated arm and the tracking arm, respectively.

Results: The magnitude of the TVR of the vibrated arm and movement perception of the TVR of the tracking arm were significantly reduced in the patients compared to the controls. No correlation was found between magnitude of the TVR and perception of the TVR movement, suggesting that the abnormalities were independent of each other. Moreover, the abnormalities did not differ between the patients with/without bilateral upper limb involvement or between the affected and the unaffected side in patients with unilateral impairment, suggesting that the observed deficits are independent of motor impairment.

Conclusions: Proprioceptive dysfunction may underlie alterations in body movement and in sense of agency in such patients and may play a role in the pathophysiology of functional limb weakness.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.011DOI Listing
June 2021

Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment.

Parkinsonism Relat Disord 2021 05 30;86:124-132. Epub 2021 Mar 30.

Department of Neurology, New York University School of Medicine, New York, NY, USA. Electronic address:

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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http://dx.doi.org/10.1016/j.parkreldis.2021.03.027DOI Listing
May 2021

TaSCA, an Agile Survey on Chemosensory Impairments for Self-Monitoring of COVID-19 Patients: A Pilot Study.

Front Neurol 2021 24;12:633574. Epub 2021 Feb 24.

Padova Neuroscience Center, Padua, Italy.

During the COVID-19 pandemic, smell and taste disorders emerged as key non-respiratory symptoms. Due to widespread presence of the disease and to difficult objective testing of positive persons, the use of short surveys became mandatory. Most of the existing resources are focused on smell, very few on taste or trigeminal chemosensation called chemesthesis. However, it is possible that the three submodalities are affected differently by COVID-19. We prepared a short survey (TaSCA) that can be administered at the telephone or through online resources to explore chemosensation. It is composed of 11 items on olfaction, taste, and chemesthesis, in order to discriminate the three modalities. We avoided abstract terms, and the use of semiquantitative scales because older patients may be less engaged. Statistical handling included descriptive statistics, Pearson's chi-squared test and cluster analysis. The survey was completed by 83 persons (60 females and 23 males), which reported diagnosis of COVID-19 by clinical ( = 7) or molecular ( = 18) means, the others being non-COVID subjects. Cluster analysis depicted the existence of two groups, one containing mostly asymptomatic and one mostly symptomatic subjects. All swab-positive persons fell within this second group. Only one item, related to trigeminal temperature perception, did not discriminate between the two groups. These preliminary results indicate that TaSCA may be used to easily track chemosensory symptoms related to COVID-19 in an agile way, giving a picture of three different chemosensory modalities.
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http://dx.doi.org/10.3389/fneur.2021.633574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943440PMC
February 2021

Patients Stratification Strategies to Optimize the Effectiveness of Scavenging Biogenic Aldehydes: Towards a Neuroprotective Approach for Parkinson's Disease

Curr Neuropharmacol 2021 02 3. Epub 2021 Feb 3.

Department of Biology, University of Padova, Padova. Italy.

Parkinson's disease (PD) is a clinically heterogeneous disorder with a multi-factorial pathology. Various molecular mechanisms are involved in the pathogenesis of PD, converging to oxidative stress and proteinopathy. The accumulation of reactive aldehydes (i.e., the dopamine metabolite DOPAL, lipid-peroxidation products, and advanced glycation end-products) has been reported in PD patients' brains. Aldehydes easily react with primary amines such as lysine residues, which are involved in several regulatory processes in cells. Therefore, aldehyde adducts lead to severe consequences, including neuronal proteostasis, mitochondrial dysfunction, and cell death. In this review, we analyzed the scavenging role of amines toward toxic aldehydes in the brain. Interestingly, small molecules like metformin, rasagiline, hydralazine are already clinically available and used in the therapy for PD and other diseases. Hence, we propose to reevaluate this class of drugs as a disease-modifiers for PD, and we suggest that improved analysis of their pharmacology and bioavailability in the brain, together with a more precise patients stratification, should be considered before planning future clinical trials.
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http://dx.doi.org/10.2174/1570159X19666210203162617DOI Listing
February 2021

Foot Pressure Wearable Sensors for Freezing of Gait Detection in Parkinson's Disease.

Sensors (Basel) 2020 Dec 28;21(1). Epub 2020 Dec 28.

Department of Neuroscience, University of Padova, 35128 Padova, Italy.

Freezing of Gait (FoG) is a common symptom in Parkinson's Disease (PD) occurring with significant variability and severity and is associated with increased risk of falls. FoG detection in everyday life is not trivial, particularly in patients manifesting the symptom only in specific conditions. Various wearable devices have been proposed to detect PD symptoms, primarily based on inertial sensors. We here report the results of the validation of a novel system based on a pair of pressure insoles equipped with a 3D accelerometer to detect FoG episodes. Twenty PD patients attended a motor assessment protocol organized into eight multiple video recorded sessions, both in clinical and ecological settings and both in the ON and OFF state. We compared the FoG episodes detected using the processed data gathered from the insoles with those tagged by a clinician on video recordings. The algorithm correctly detected 90% of the episodes. The false positive rate was 6% and the false negative rate 4%. The algorithm reliably detects freezing of gait in clinical settings while performing ecological tasks. This result is promising for freezing of gait detection in everyday life via wearable instrumented insoles that can be integrated into a more complex system for comprehensive motor symptom monitoring in PD.
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http://dx.doi.org/10.3390/s21010128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794778PMC
December 2020

Functional motor disorders associated with other neurological diseases: Beyond the boundaries of "organic" neurology.

Eur J Neurol 2021 05 2;28(5):1752-1758. Epub 2021 Jan 2.

Movement Disorder Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background And Purpose: The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs").

Methods: For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables).

Results: Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities.

Conclusions: Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.
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http://dx.doi.org/10.1111/ene.14674DOI Listing
May 2021

Impact of Supporting People with Advanced Parkinson's Disease on Carer's Quality of Life and Burden.

Neuropsychiatr Dis Treat 2020 2;16:2899-2912. Epub 2020 Dec 2.

Department of Neuroscience "Rita Levi Montalcini" University of Torino, Azienda Ospedaliero-Universitaria Città Della Salute e Della Scienza di Torino, Torino, Italy.

Purpose: The aim of this study was to assess the burden and the quality of life (QoL) perceived by caregivers assisting advanced Parkinson's disease (PD) patients.

Patients And Methods: Consecutive advanced PD patients treated with levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) or care as usual (CU) and their care partners were recruited during routine visits according to a cross-sectional design. Caregiver's distress was assessed by Zarit Burden Interview (ZBI) and a QoL survey to evaluate and understand the burden experienced by care partners during family and working activities.

Results: A total of 126 patients (53 LCIG, 19 CSAI and 54 CU) and their care partners were enrolled. The ZBI score boxplot showed that LCIG and CU populations have a similar distribution (ZBI inter-quartile range [IQR] values respectively 18-42 for LCIG and 19-43 for CU group), while the CSAI group has a wider score range (IQR 16-52). Caregivers assisting patients in treatment with LCIG have more time to perform family or household duties (p=0.0022), or to engage in leisure activities (p=0.0073) compared to CU, while no difference was found when compared to CSAI group. Approximately 50% of the care partners showed mood changes in the last 6 months and LCIG and CSAI had less impact on caregiver's mood compared to CU. Patients treated with LCIG were more independent in taking a bath or shower without assistance and were more able to move and walk without assistance.

Conclusion: Care partners of advanced PD patients treated with device-aided therapies have more time for their own life and a better perception of their QoL with a tendency to an improvement of mood compared with those of patients treated with CU.
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http://dx.doi.org/10.2147/NDT.S256217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719333PMC
December 2020

Technology-Enabled Care: Integrating Multidisciplinary Care in Parkinson's Disease Through Digital Technology.

Front Neurol 2020 30;11:575975. Epub 2020 Oct 30.

Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, Parkinson's Disease and Movement Disorders Center, The University of Ottawa Brain Research Institute, Ottawa, ON, Canada.

Parkinson's disease (PD) management requires the involvement of movement disorders experts, other medical specialists, and allied health professionals. Traditionally, multispecialty care has been implemented in the form of a multidisciplinary center, with an inconsistent clinical benefit and health economic impact. With the current capabilities of digital technologies, multispecialty care can be reshaped to reach a broader community of people with PD in their home and community. Digital technologies have the potential to connect patients with the care team beyond the traditional sparse clinical visit, fostering care continuity and accessibility. For example, video conferencing systems can enable the remote delivery of multispecialty care. With big data analyses, wearable and non-wearable technologies using artificial intelligence can enable the remote assessment of patients' conditions in their natural home environment, promoting a more comprehensive clinical evaluation and empowering patients to monitor their disease. These advances have been defined as technology-enabled care (TEC). We present examples of TEC under development and describe the potential challenges to achieve a full integration of technology to address complex care needs in PD.
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http://dx.doi.org/10.3389/fneur.2020.575975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673441PMC
October 2020

Prevalence of Extrapyramidal Symptoms in In-Patients With Severe Mental Illnesses: Focus on Parkinsonism.

Front Neurol 2020 10;11:593143. Epub 2020 Nov 10.

Department of Neuroscience, University of Padova, Padova, Italy.

Patients with severe mental illnesses may present extrapyramidal symptoms as part of a concomitant neurological disorder or secondary to medications. Extrapyramidal symptoms are frequently unrecognized, have negative consequences for adherence to treatment, negatively affect quality of life and can induce stigma. We estimated and correlated with demographic and clinical variables prevalence of extrapyramidal symptoms in in-patients with severe mental illnesses. Additionally we evaluated I-FP-CIT SPECT binding to striatal dopamine transporter in subjects with clinical manifestations suggestive of Parkinson's Disease and recorded therapeutic management and clinical evolution for 6-months. Extrapyramidal symptoms were present in 144 out of 285 patients (50.5%), mainly tremor (94 patients, 33%). There were 38 patients (13.3%) with parkinsonism and they had older age, more medical comorbidities and medical treatments. In 15/38 patients striatal dopamine transporter binding was abnormal resulting in dose reduction or change of psychotropic drugs as well as combination with antiparkinson therapy. Our study confirmed the clinical and epidemiological relevance of extrapyramidal symptoms among inpatients with severe mental illnesses. A small percentage of patients with extrapyramidal symptoms had features compatible with possible diagnosis of Parkinson's Disease. I-FP-CIT SPECT was useful to identify dopaminergic dysfunction and initiate dopamine replacement therapy.
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http://dx.doi.org/10.3389/fneur.2020.593143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683803PMC
November 2020
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