Faculty Bibliography

OBJECTIVE:To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS:Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS:At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION/CONCLUSIONS:Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

Movement disorders encompass various conditions affecting the nervous system. The pathological processes underlying movement disorders lead to aberrant synaptic plastic changes, which in turn alter the functioning of large-scale brain networks. Therefore, clinical phenomenology does not only entail motor symptoms but also cognitive and motivational disturbances. The result is the disruption of motor learning and motor behaviour. Due to this complexity, the responsiveness to standard therapies could be disappointing. Specific forms of rehabilitation entailing goal-based practice, aerobic training and the use of non-invasive brain stimulation techniques could "restore" neuroplasticity at motor-cognitive circuitries, leading to clinical gains. This is probably associated with modulations occurring at both molecular (synaptic) and circuitry levels (networks). Several gaps remain in our understanding of the relationships among plasticity and neural networks and how neurorehabilitation could promote clinical gains is still unclear. In this review, we outline first the networks involved in motor learning and behaviour and analyse which mechanisms link the pathological synaptic plastic changes with these networks' disruption in movement disorders. Therefore, we provide theoretical and practical bases to be applied for treatment in rehabilitation.

BACKGROUND:Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS:Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS:Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS:Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.

Parkinson's disease (PD) results in a complex deterioration of motor behavior. Effective pharmacological or surgical treatments addressing the whole spectrum of both motor and cognitive symptoms are lacking. The cumulative functional impairment may have devastating socio-economic consequences on both patients and caregivers. Comprehensive models of care based on multidisciplinary approaches may succeed in better addressing the overall complexity of PD. Neurorehabilitation is a highly promising non-pharmacological intervention for managing PD. The scientific rationale beyond rehabilitation and its practical applicability remain to be established. In the present perspective, we aim to discuss the current evidence supporting integrated motor-cognitive and aerobic rehabilitation approaches for patients with PD while suggesting a practical framework to optimize this intervention in the next future.

Parkinson's disease (PD) is a neurological disorder that mainly affects the motor system. Among other symptoms, hypomimia is considered one of the clinical hallmarks of the disease. Despite its great impact on patients' quality of life, it remains still under-investigated. The aim of this work is to provide a quantitative index for hypomimia that can distinguish pathological and healthy subjects and that can be used in the classification of emotions. A face tracking algorithm was implemented based on the Facial Action Coding System. A new easy-to-interpret metric (face mobility index, FMI) was defined considering distances between pairs of geometric features and a classification based on this metric was proposed. Comparison was also provided between healthy controls and PD patients. Results of the study suggest that this index can quantify the degree of impairment in PD and can be used in the classification of emotions. Statistically significant differences were observed for all emotions when distances were taken into account, and for happiness and anger when FMI was considered. The best classification results were obtained with Random Forest and kNN according to the AUC metric.

Axial disorders, including postural deformities, postural instability, and gait disturbances, are among the most disabling symptoms of Parkinson's disease (PD). Equistasi®, a wearable proprioceptive stabilizer device, has been proposed as neurological rehabilitative device for this set of symptoms. To investigate the effects of the device on gait and balance, 24 participants affected by PD were enrolled in this crossover double-dummy, randomized, controlled study. Subjects were assessed four times before and after 8 weeks treatment with either active or placebo device; one-month wash-out was taken between treatments, in a 20-week timeframe. Gait analysis and instrumented Romberg test were performed with the aid of a sterofotogrammetric system and two force plates. Joint kinematics, spatiotemporal parameters of gait and center of pressure parameters were extracted. Paired T-test (p < 0.05) was adopted after evidence of normality to compare the variables across different acquisition sessions; Wilcoxon was adopted for non-normal distributions. Before and after the treatment with the active device, statistically significant improvements were observed in trunk flexion extension and in the ankle dorsi-plantarflexion. Regarding balance assessment, significant improvements were reported at the frequencies corresponding to vestibular system. These findings may open new possibilities on PD's rehabilitative interventions. Research question, tailored design of the study, experimental acquisition overview, main findings, and conclusions.

Background/UNASSIGNED: Objectives/UNASSIGNED:To explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present. Methods/UNASSIGNED:I-MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed. Results/UNASSIGNED:I-MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached. Conclusions/UNASSIGNED:I-MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.