Self-reported needs of patients with Parkinson's disease during COVID-19 emergency in Italy.

Because of COVID-19 outbreak, regular clinical services for Parkinson's disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9-21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients' needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.

Wearable Electronics Assess the Effectiveness of Transcranial Direct Current Stimulation on Balance and Gait in Parkinson's Disease Patients.

Currently, clinical evaluation represents the primary outcome measure in Parkinson's disease (PD). However, clinical evaluation may underscore some subtle motor impairments, hidden from the visual inspection of examiners. Technology-based objective measures are more frequently utilized to assess motor performance and objectively measure motor dysfunction. Gait and balance impairments, frequent complications in later disease stages, are poorly responsive to classic dopamine-replacement therapy. Although recent findings suggest that transcranial direct current stimulation (tDCS) can have a role in improving motor skills, there is scarce evidence for this, especially considering the difficulty to objectively assess motor function. Therefore, we used wearable electronics to measure motor abilities, and further evaluated the gait and balance features of 10 PD patients, before and (three days and one month) after the tDCS. To assess patients' abilities, we adopted six motor tasks, obtaining 72 meaningful motor features. According to the obtained results, wearable electronics demonstrated to be a valuable tool to measure the treatment response. Meanwhile the improvements from tDCS on gait and balance abilities of PD patients demonstrated to be generally partial and selective.

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers. However, neuropathology of iNPH is so rich and heterogeneous that many processes can be tracked in CSF, including Alzheimer's disease core pathology, subcortical degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has not been provided yet. In this brief survey, we thus attempted to summarize the main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic model. Although defined cut-off values for biomarkers are not available, a better knowledge of CSF characteristics may definitely assist in diagnosing the disease.

Clinical value of CSF amyloid-beta-42 and tau proteins in Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is a four-repeat tauopathy with high phenotypic and neuropathological variability, highlighting the urgent need for effective disease biomarkers. Quantitative analysis of cerebrospinal fluid (CSF) proteins reflecting pathological changes of CNS is currently used as biomarkers of multiple neurodegenerative disorders for both early differential diagnosis and prognostic clustering of patients. In this study, we thus assessed the clinical usefulness of a panel of CSF biomarker in PSP patients presenting with Richardson's Syndrome. CSF levels of 42-beta-amyloid, total-tau, phosphorylated-tau, and both 42-beta-amyloid/phosphorylated-tau and phosphorylated-tau/total-tau ratios were comparatively evaluated in 39 PSP patients, 31 patients with Parkinson's Disease (PD) and 58 gender-/age-matched healthy controls. Specific gold-standard clinical scores were obtained. Diagnostic accuracy and clinical correlates of each biomarker were measured with receiver operating curve analysis and Spearman's test/linear regression, respectively. In PSP, 42-beta-amyloid was lower than either controls or PD; total-tau and phosphorylated-tau were instead reduced compared to controls, but similar to PD. At the cut-off value of 623 pg/ml, 42-beta-amyloid significantly distinguished PSP from controls and PD. Likewise, phosphorylated-tau/total-tau ratio also supported differential diagnosis between PSP and PD (cut-off = 0.185). 42-beta-amyloid was inversely associated with PSP severity, as measured with PSP Rating Scale. Our study demonstrates that CSF 42-beta-amyloid is reduced in PSP patients, proportionally to clinical severity, thus suggesting a potential use as disease biomarker. Moreover, phosphorylated-tau/total-tau ratio resulted helpful in the early differential diagnosis between PSP and PD.

Voice in Parkinson's Disease: A Machine Learning Study.

INTRODUCTION: Parkinson's disease (PD) is characterized by specific voice disorders collectively termed hypokinetic dysarthria. We here investigated voice changes by using machine learning algorithms, in a large cohort of patients with PD in different stages of the disease, OFF and ON therapy. METHODS: We investigated 115 patients affected by PD (mean age: 68.2 ± 9.2 years) and 108 age-matched healthy subjects (mean age: 60.2 ± 11.0 years). The PD cohort included 57 early-stage patients (Hoehn &Yahr ≤ 2) who never took L-Dopa for their disease at the time of the study, and 58 mid-advanced-stage patients (Hoehn &Yahr >2) who were chronically-treated with L-Dopa. We clinically evaluated voices using specific subitems of the Unified Parkinson's Disease Rating Scale and the Voice Handicap Index. Voice samples recorded through a high-definition audio recorder underwent machine learning analysis based on the support vector machine classifier. We also calculated the receiver operating characteristic curves to examine the diagnostic accuracy of the analysis and assessed possible clinical-instrumental correlations. RESULTS: Voice is abnormal in early-stage PD and as the disease progresses, voice increasingly degradres as demonstrated by high accuracy in the discrimination between healthy subjects and PD patients in the early-stage and mid-advanced-stage. Also, L-dopa therapy improves but not restore voice in PD as shown by high accuracy in the comparison between patients OFF and ON therapy. Finally, for the first time we achieved significant clinical-instrumental correlations by using a new score (LR value) calculated by machine learning. CONCLUSION: Voice is abnormal in early-stage PD, progressively degrades in mid-advanced-stage and can be improved but not restored by L-Dopa. Lastly, machine learning allows tracking disease severity and quantifying the symptomatic effect of L-Dopa on voice parameters with previously unreported high accuracy, thus representing a potential new biomarker of PD.

Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson's disease cohort.

Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson's disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients' kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.

Technology-Based Objective Measures Detect Subclinical Axial Signs in Untreated, de novo Parkinson's Disease.

BACKGROUND: Technology-based objective measures (TOMs) recently gained relevance to support clinicians in the assessment of motor function in Parkinson's disease (PD), although limited data are available in the early phases. OBJECTIVE: To assess motor performances of a population of newly diagnosed, drug free PD patients using wearable inertial sensors and to compare them to healthy controls (HC) and differentiate different PD subtypes [tremor dominant (TD), postural instability gait disability (PIGD), and mixed phenotype (MP)]. METHODS: We enrolled 65 subjects, 36 newly diagnosed, drug-free PD patients and 29 HCs. PD patients were clinically defined as tremor dominant, postural instability-gait difficulties or mixed phenotype. All 65 subjects performed seven MDS-UPDRS III motor tasks wearing inertial sensors: rest tremor, postural tremor, rapid alternating hand movement, foot tapping, heel-to-toe tapping, Timed-Up-and-Go test (TUG) and pull test. The most relevant motor tasks were found combining ReliefF ranking and Kruskal- Wallis feature-selection methods. We used these features, linked to the relevant motor tasks, to highlight differences between PD from HC, by means of Support Vector Machine (SVM) classifier. Furthermore, we adopted SVM to support the relevance of each motor task on the classification accuracy, excluding one task at time. RESULTS: Motion analysis distinguished PD from HC with an accuracy as high as 97%, based on SVM performed with measured features from tremor and bradykinesia items, pull test and TUG. Heel-to-toe test was the most relevant, followed by TUG and Pull Test. CONCLUSIONS: In this pilot study, we demonstrate that the SVM algorithm successfully distinguishes de novo drug-free PD patients from HC. Surprisingly, pull test and TUG tests provided relevant features for obtaining high SVM classification accuracy, differing from the report of the experienced examiner. The use of TOMs may improve diagnostic accuracy for these patients.

Ischemic injury precipitates neuronal vulnerability in Parkinson's disease: Insights from PINK1 mouse model study and clinical retrospective data.

INTRODUCTION: Increasing evidence demonstrates the relevant association between Parkinson's disease (PD) and vascular diseases/risk factors, as well as a worse clinico-pathological progression in those patients with vascular comorbidity. The mechanisms underlying this relationship have not been clarified yet, although their comprehension is critical in a perspective of disease-modifying treatments development or prevention. METHODS: We performed an experimental protocol of ischemic injury (glucose-oxygen deprivation, OGD) on PTEN-induced kinase 1 knockout (PINK1-/-) mice, a well-established PD model, looking at both electrophysiological and morphological changes in basal ganglia. In addition, 253 PD patients were retrospectively analysed, to estimate the prevalence of vascular risk factors. RESULTS: In PINK1-/- mice, the OGD protocol induced electrophysiological (prolonged depolarization) and morphological alterations (picnotic cells, cellular loss and swelling, thickening of nuclear chromatin) in striatal medium spiny neurons and nigral dopaminergic neurons. Vascular comorbidity occurred in 75% of PD patients. CONCLUSIONS: The ischemic injury precipitates neuronal vulnerability in basal ganglia of PINK1-/- mice, probably through an impairment of mitochondrial metabolism and higher oxidative stress. These experimental data may provide a potential mechanistic explanation for both the association between vascular diseases and PD and their reciprocal interactions in determining the clinico-pathological burden of PD patients.

Physical Activity Changes and Correlate Effects in Patients with Parkinson's Disease during COVID-19 Lockdown.

Background: COVID-19 outbreak profoundly affected health systems and people's daily life worldwide. Parkinson's disease (PD) patients lost their normal routine and interrupted regular physical activity, either as physiotherapy or sport, with inevitable consequence on their daily-life and well-being. Objectives: To evaluate the changes in physical activity due to COVID-19 emergency, including self-management strategies or technology-assisted activities, and the subsequent clinical implications in PD patients. Methods: Seventy-four patients from an Italian center have been remotely examined during the lockdown (April-May 2020) by an e-mail structured survey, including self-administered scales. We collected and analyzed data on changes, modalities and amount of physical active practice, on the use of technology-based tools, and on self-perceived clinical condition. Results: Sixty percent of patients reported a significant worsening of their general conditions during the lockdown, the reduction of physical activity being the main risk factor for such change. However, patients found ways to practice physical activity, using satisfactorily technology assistance in 50% of cases (mostly women). Conclusions: The COVID-19 emergency has been an ordeal for PD patients. Nevertheless, patients adapted their habits to continue practicing physical activity that resulted a main determinant of their well-being; as well, they successfully approached technology-based assistance. Education, communication, and networking emerge as critical for a constructive reaction to the emergency's challenges.

Long-term treatment with rotigotine in drug-naïve PSP patients.

Progressive supranuclear palsy (PSP) is a severe neurodegenerative disease still lacking of alleviating treatments for either cognitive or motor disturbances. Aimed at widening the spectrum of therapeutic options, here, we describe efficacy and safety of a long-term treatment with Rotigotine, a non-ergolinic dopamine agonist, in PSP. Seven PSP drug-naïve patients, presenting with Richardson's syndrome, received up to 6 mg/24 h transdermal patch for 42 weeks as unique therapy. Adverse effects were recorded; efficacy was measured by comparing baseline and final treatment scores of Montreal Cognitive Assessment (MoCA), Unified Parkinson Disease Rating Scale part3, and PSP rating scale (PSP-RS). At the end of our observation, no significant adverse events occurred; the cognitive item of PSP-RS was improved and MoCA score was similar at baseline. Contrariwise, motor disturbances worsened according to disease progression. Our observation thus suggests that long-term treatment with low doses of rotigotine is well tolerated and may support cognitive functions of PSP patients.

Dopaminergic involvement in a drummer with focal dystonia: A case study.

Musician's Dystonia (MD) represents an intriguing disorder with rich phenomenology and unclear pathophysiology. We observed a MD affecting left upper limb in a professional drummer. DaT-Scan revealed slight reduced uptake in the right putamen; no extrapyramidal or other neurological signs emerged in 2.5 years of follow up. The case offers insight on dopaminergic involvement in MD.