The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), is ...challenging because of an overlap of clinical features and the lack of reliable biomarkers. Neural-derived extracellular vesicles (NDEVs) isolated from blood provide a window into the brain's biochemistry and may assist in distinguishing between PD and APS. We verified in a case-control study whether oligomeric α-Synuclein and Tau aggregates isolated from NDEVs could allow the differential diagnosis of these conditions.
Blood sampling and clinical data, including disease duration, motor severity, global cognition, and levodopa equivalent daily dose (LEDD), were collected from patients with a diagnosis of either PD (n = 70), PSP (n = 21), or CBD (n = 19). NDEVs were isolated from serum by immunocapture using an antibody against the neuronal surface marker L1CAM; oligomeric α-Synuclein and aggregated Tau were measured by ELISA.
NDEVs analyses showed that oligomeric α-Synuclein is significantly augmented in PD compared to APS, whereas Tau aggregates are significantly increased in APS compared to PD (p < 0.0001). ROC analyses showed that these two biomarkers have a “good” power of classification (p < 0.0001 for both proteins), with high sensitivity and specificity, with NDEVs concentration of Tau aggregates and oligomeric α-Synuclein being respectively the best biomarker for PD/PSP and PD/CBD diagnostic differentiation.
Logistic and multiple regression analysis confirmed that NDEVs-derived oligomeric α-Synuclein and Tau aggregates differentiate PD from CBD and PSP (p < 0.001). Notably, a positive correlation between NDEVs oligomeric α-Synuclein and disease severity (disease duration, p = 0.023; Modified H&Y, p = 0.015; UPDRS motor scores, p = 0.004) was found in PD patients and, in these same patients, NDEVs Tau aggregates concentration inversely correlated with global cognitive scores (p = 0.043).
A minimally invasive blood test measuring the concentration of α-synuclein and Tau aggregates in NDEVs can represent a promising tool to distinguish with high sensitivity and specificity PD from CBD or PSP patients. Optimization and validation of these data will be needed to confirm the diagnostic value of these biomarkers in distinguishing synucleinopathies from taupathies.
•PD and atypical Parkinsonian syndromes (APS) differential diagnosis is challenging.•Peripheral Neural Derived Extracellular Vesicles (NDEVs) are source of biomarkers.•Oligomeric α-synuclein in NDEVs is higher in PD than in APS.•Aggregated Tau in NDEVs is higher in APS than in PD.•Oligomeric α-synuclein and Aggregated Tau in NDEVs distinguish PD from APS.
Objective:
To evaluate the feasibility of a smartphone remote patient monitoring approach in a real-life Parkinson's disease (PD) cohort during the Italian COVID-19 lockdown.
Methods:
Fifty-four ...non-demented PD patients who were supposed to attend the outpatient March clinic were recruited for a prospective study. All patients had a known UPDRS-III and a modified Hoehn and Yahr (H&Y) score and were provided with a smartphone application capable of providing indicators of gait, tapping, tremor, memory and executive functions. Different questionnaires exploring non-motor symptoms and quality of life were administered through phone-calls. Patients were asked to run the app at least twice per week (i.e., full compliance). Subjects were phone-checked weekly throughout a 3-week period for compliance and final satisfaction questionnaires.
Results:
Forty-five patients (83.3%) ran the app at least once; Twenty-nine (53.7%) subjects were half-compliant, while 16 (29.6%) were fully compliant. Adherence was hindered by technical issues or digital illiteracy (38.7%), demotivation (24%) and health-related issues (7.4%). Ten patients (18.5%) underwent PD therapy changes. The main factors related to lack of compliance included loss of interest, sadness, anxiety, the absence of a caregiver, the presence of falls and higher H&Y. Gait, tapping, tremor and cognitive application outcomes were correlated to disease duration, UPDRS-III and H&Y.
Discussion:
The majority of patients were compliant and satisfied by the provided monitoring program. Some of the application outcomes were statistically correlated to clinical parameters, but further validation is required. Our pilot study suggested that the available technologies could be readily implemented even with the current population's technical and intellectual resources.
Background
SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ...ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood–brain barrier may then contribute to the occurrence of a brain haemorrhage.
Methods
We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19.
Results
We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES.
Conclusions
Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood–brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis.
Background
Falls could be serious events in Parkinson’s disease (PD). Patient remote monitoring strategies are on the raise and may be an additional aid in identifying patients who are at risk of ...falling. The aim of the study was to evaluate if balance and timed-up-and-go data obtained by a smartphone application during COVID-19 lockdown were able to predict falls in PD patients.
Methods
A cohort of PD patients were monitored for 4 weeks during the COVID-19 lockdown with an application measuring static balance and timed-up-and-go test. The main outcome was the occurrence of falls (UPDRS-II item 13) during the observation period.
Results
Thirty-three patients completed the study, and 4 (12%) reported falls in the observation period. The rate of falls was reduced with respect to patient previous falls history (24%). The stand-up time and the mediolateral sway, acquired through the application, differed between “fallers” and “non-fallers” and related to the occurrence of new falls (OR 1.7 and 1.6 respectively,
p
< 0.05), together with previous falling (OR 7.5,
p
< 0.01). In a multivariate model, the stand-up time and the history of falling independently related to the outcome (
p
< 0.01).
Conclusions
Our study provides new data on falls in Parkinson’s disease during the lockdown. The reduction of falling events and the relationship with the stand-up time might suggest that a different quality of falls occurs when patient is forced to stay home — hence, clinicians should point their attention also on monitoring patients’ sit-to-stand body transition other than more acknowledged features based on step quality.
In the last decades, several studies showed that wearable sensors, used for assessing Parkinson's disease (PD) motor symptoms and recording their fluctuations, could provide a quantitative and ...reliable tool for patient's motor performance monitoring.
The aim of this study is to make a step forward the capability of quantitatively describing PD motor symptoms. The specific aims are: identify the most sensible place where to locate sensors to monitor PD bradykinesia and rigidity, and identify objective indexes able to discriminate PD OFF/ON motor status, and PD patients from healthy subjects (HSs).
Fourteen PD patients (H&Y stage 1-2.5), and 13 age-matched HSs, were enrolled. Five magneto-inertial wearable sensors, placed on index finger, thumb, metacarpus, wrist, and arm, were used as motion tracking systems. Sensors were placed on the most affected arm of PD patients, and on dominant hand of HS. Three UPDRS part III tasks were evaluated: rigidity (task 22), finger tapping (task 23), and prono-supination movements of the hands (task 25). A movement disorders expert rated the three tasks according to the UPDRS part III scoring system. In order to describe each task, different kinematic indexes from sensors were extracted and analyzed.
Four kinematic indexes were extracted: fatigability; total time; total power; smoothness. The last three well-described PD OFF/ON motor status, during finger-tapping task, with an index finger sensor. During prono-supination task, wrist sensor was able to differentiate PD OFF/ON motor condition. Smoothness index, used as a rigidity descriptor, provided a good discrimination of the PD OFF/ON motor status. Total power index, showed the best accuracy for PD vs healthy discrimination, with any sensor location among index finger, thumb, metacarpus, and wrist.
The present study shows that, in order to better describe the kinematic features of Parkinsonian movements, wearable sensors should be placed on a distal location on upper limb, on index finger or wrist. The proposed indexes demonstrated a good correlation with clinical scores, thus providing a quantitative tool for research purposes in future studies in this field.
Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would ...be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets.
Non-motor manifestations are the main features of Parkinson's disease (PD). These have been associated with vitamin D abnormalities, but the role of parathormone (PTH) is still obscure. Among the ...non-motor symptoms of PD, the pathogenesis of restless leg syndrome (RLS) is still debated, but it has been associated with the vitamin D/PTH axis in other disease models. Our study deepens the association between vitamin D and PTH with the prevalence of non-motor symptoms of PD and explores such a relationship in patients reporting leg restlessness.
Fifty patients with PD were extensively investigated with motor and non-motor scales. Data on serum levels of vitamin D, PTH, and related metabolites were obtained, and patients were stratified as having vitamin D deficiency or hyperparathyroidism according to standardized criteria.
Overall, 80% of patients with PD exhibited low vitamin D levels, and hyperparathyroidism was diagnosed in 45%. The analysis of the non-motor symptoms profile using the non-motor symptom questionnaire (NMSQ) revealed 36% of leg restlessness, a main feature of RLS. This was significantly associated with worse motor symptoms, quality of sleep, and quality of life. Moreover, it was associated with hyperparathyroidism (OR: 3.48) and with PTH levels, independent of vitamin D, calcium/phosphate levels, and motor status.
Our results suggest a significant association between the vitamin D/PTH axis and leg restlessness in PD. PTH has a putative role in nociceptive modulation, and previous evidence on hyperparathyroidism has suggested a possible interrelation with RLS. Further investigations are necessary to add PTH to the non-dopaminergic non-motor landscape of PD.
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