Differences in CSF Biomarkers Profile of Patients with Parkinson's Disease Treated with MAO-B Inhibitors in Add-On

Monoamine oxidase type B inhibitors (iMAO-Bs) are a class of largely-used antiparkinsonian agents that, based on experimental evidence, are supposed to exert different degrees of neuroprotection in Parkinson's disease (PD). However, clinical proofs on this regard are very scarce. Since cerebrospinal fluid (CSF) reflects pathological changes occurring at brain level, we examined the neurodegeneration-related CSF biomarkers profile of PD patients under chronic treatment with different iMAO-Bs to identify biochemical signatures suggestive for differential neurobiological effects.Thirty-five PD patients under chronic treatment with different iMAO-Bs in add-on to levodopa were enrolled and grouped in rasagiline (n = 13), selegiline (n = 9), safinamide (n = 13). Respective standard clinical scores for motor and non-motor disturbances, together with CSF biomarkers of neurodegeneration levels (amyloid- β -42, amyloid- β -40, total and 181-phosphorylated tau, and lactate) were collected and compared among the three iMAO-B groups.No significant clinical differences emerged among the iMAO-B groups. CSF levels of tau proteins and lactate were instead different, resulting higher in patients under selegiline than in those under rasagiline and safinamide.Although preliminary and limited, this study indicates that patients under different iMAO-Bs may present distinct profiles of CSF neurodegeneration-related biomarkers, probably because of the differential neurobiological effects of the drugs. Larger studies are now needed to confirm and extend these initial observations

A case report of vibration-induced hand comorbidities in a postwoman

<p>Abstract</p> <p>Background</p> <p>Prolonged exposure to hand-transmitted vibration is associated with an increased occurrence of symptoms and signs of disorders in the vascular, neurological and osteoarticular systems of the upper limbs. However, the available epidemiological evidence is derived from studies on high vibration levels caused by vibratory tools, whereas little is known about possible upper limb disorders caused by chronic exposure to low vibration levels emitted by fixed sources.</p> <p>Case presentation</p> <p>We present the case of a postwoman who delivered mail for 15 years using a low-powered motorcycle. The woman was in good health until 2002, when she was diagnosed with bilateral Raynaud's phenomenon. In March 2003 a bilateral carpal tunnel syndrome was electromyographically diagnosed; surgical treatment was ineffective. Further examinations in 2005 highlighted the presence of chronic tendonitis (right middle finger flexor).</p> <p>Risk assessment</p> <p>From 1987, for 15 years, our patient rode her motorcycle for 4 h/day, carrying a load of 20-30 kg. For about a quarter of the time she drove over country roads. Using the information collected about the tasks carried out every day by the postwoman and some measurements performed on both handles of the motorcycle, as well as on both iron parts of the handlebars, we reconstructed the woman's previous exposure to hand-arm vibration. 8-hour energy-equivalent frequency weighted acceleration was about 2.4 m/s². The lifetime dose was 1.5 × 10⁹(m²/s⁴)hd.</p> <p>Conclusions</p> <p>The particular set of comorbidities presented by our patient suggests a common pathophysiological basis for all the diseases. Considering the level of exposure to vibrations and the lack of specific knowledge on the effects of vibration in women, we hypothesize an association between the work exposure and the onset of the diseases.</p

Brain Functional Connectivity in de novo Parkinson's Disease Patients Based on Clinical EEG

: In Parkinson's disease (PD), cortical-subcortical interplay plays a relevant role in affecting clinical performance. Functional MRI sequences described changes in functional connectivity at different stages of disease. Scarce are, instead, the investigations examining brain connectivity in patients with PD at early stages of disease. For this aim, here we analyzed the differences in functional connectivity between de novo, never treated, PD patients and healthy controls. The analyses were based upon custom-written scripts on the Matlab platform, combined with high-level functions of Fieldtrip, Brainstorm, and Brain Connectivity toolboxes. First, we proceeded to the spectral analysis of the EEG data in the five frequency bands (δ-θ-α-β-γ). Second, we calculated functional connectivity matrices based on both coherency (COH) and imaginary part of coherency (iCOH), in the δ-θ-α-β-γ frequency bands. Then, four network measures (density, transitivity, global efficiency, and assortativity) were computed in identified connectivity matrices. Finally, we compared the spectral density, functional connectivity matrices, and network measured between healthy controls and de novo PD patients through two-samples T-test. A total of 21 de novo PD patients and 20 healthy subjects were studied. No differences were observed in spectral analysis between the two groups, with the exception of the γ band where a significant increase in power density was found in PD patients. A reduced connectivity in the main EEG frequency bands (α-β frequency bands) was observed in PD patients compared to controls, while a hyperconnectivity was found in PD patients in γ band. Among the network measures, a reduced assortativity coefficient was found in de novo PD patients in α frequency band. Our results show the occurrence of early EEG functional connectivity alterations from the initial stages of PD. From this point of view, connectivity analysis may ease a better understanding of the complexity of PD physiopathology

STN-DBS Induces Acute Changes in β-Band Cortical Functional Connectivity in Patients with Parkinson’s Disease

Subthalamic nucleus deep-brain stimulation (STN-DBS), in addition to a rapid improvement of Parkinson’s disease (PD) motor symptoms, can exert fast, local, neuromodulator activity, reducing β-synchronous oscillations between STN and the motor cortex with possible antikinetic features. However, STN-DBS modulation of β-band synchronization in extramotor cortical areas has been scarcely explored. For this aim, we investigated DBS-induced short-term effects on EEG-based cortical functional connectivity (FC) in β bands in six PD patients who underwent STN-DBS within the past year. A 10 min, 64-channel EEG recording was performed twice: in DBS-OFF and 60 min after DBS activation. Seven age-matched controls performed EEG recordings as the control group. A source-reconstruction method was used to identify brain-region activity. The FC was calculated using a weighted phase-lag index in β bands. Group comparisons were made using the Wilcoxon test. The PD patients showed a widespread cortical hyperconnectivity in β bands in both DBS-OFF and -ON states compared to the controls. Moreover, switching on STN-DBS determined an acute reduction in β FC, primarily involving corticocortical links of frontal, sensorimotor and limbic lobes. We hypothesize that an increase in β-band connectivity in PD is a widespread cortical phenomenon and that STN-DBS could quickly reduce it in the cortical regions primarily involved in basal ganglia–cortical circuits

Tau and Amyloid-beta Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters

Relevance of blood-based biomarkers is increasing into the neurodegenerative diseases field, but data on Parkinson's disease (PD) remain still scarce. In this study, we used the SiMoA technique to measure serum content of total tau protein and amyloid-beta peptides (A beta-42, A beta-40) in 22 PD patients and ten control subjects. Serum levels of each biomarker were correlated with the respective CSF levels in both the groups; in PD patients, also the correlations between serum biomarkers and main clinical parameters were tested (motor, non-motor, cognitive scores and levodopa equivalent daily dose). Serum biomarkers did not exhibit quantitative differences between patients and controls; however, only PD patients had inter-fluids (serum-CSF) associations in tau and amyloid-beta-42 levels. Moreover, serum content of tau protein was inversely correlated with cognitive performances (MoCA score). These findings, albeit preliminary, indicate that brain-derived peptides may change in parallel in both peripheral blood and CSF of PD patients, eventually even in association with some clinical features. Further studies are now needed to validate the use of blood-based biomarkers in PD

Olfactory neuron substance P is overexpressed in Parkinson's disease reflecting gut dysfunction

bstance P (SP) and its cognate Neurokinin receptor 1 (NK1R) are tachykinergic neuroinflammatory mediators widely expressed in the central nervous system, peripheral nervous system, enteric nervous system, and immune cells. The SP/NK1R pathway is activated by several noxious stimuli and triggers a sustained inflammatory response by inducing cytokines release from different cell subtypes. In Parkinson's disease (PD), SP colocalizes with α-synuclein in the central and peripheral structures more prone to degeneration, mostly within the gastrointestinal–nervous ascending system, suggesting a potential role in the disease pathogenesis through inflammation-related mechanisms

A multidisciplinary consensus document on follow-up strategies for patients treated with percutaneous coronary intervention

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document