Rasagiline and PD Therapy

Summary Parkinson's disease (PD) is a therapy area with considerable unmet needs. The current key targets for PD treatment include the slowing of disease progression, improved control of motor fluctuations in advanced disease and the treatment of nonmotor symptoms. In view of such major requirements, it is important to consider how new drug treatments fit into the context of PD therapy, and the practical advantages that they may offer in the management of PD in clinical practice. Rasagiline is a novel, second-generation, irreversible, selective monoamine oxidase type B inhibitor that is indicated for the treatment of idiopathic PD, either as initial monotherapy or as adjunct therapy (with levodopa) for patients experiencing end-of-dose motor fluctuations. This review assesses the outcome from several large-scale clinical studies that have investigated the use of rasagiline in early and advanced PD patient populations and discusses the role of rasagiline within the current scope of PD therapy

Survey on broiler pre-slaughter mortality in a commercial abattoir of central Italy

The pre-slaughter mortality was investigated on broilers, in the Mediterranean climate condition, considering the most significant risk factors as the journey length, waiting time, season and the space allowance in cages. At first, the pre-slaughter mortality was studied considering the totality of birds and then by examining in detail three broiler categories: large, medium and small size. The average dead on arrival (DOA) recorded on the totality of birds throughout the year was 0.38% and the values obtained in winter, spring, summer and autumn were 0.52, 0.48, 0.31 and 0.22%, respectively. The mortality rate observed during the year was 0.52, 0.47 and 0.31% for large, medium and small broilers, respectively. In all three groups, the maximum values of mortality were obtained in winter, whereas the minimum ones were recorded in autumn, spring and summer for large, medium, and small size birds, respectively. The increase of journey length could cause a higher mortality rate whereas the increase of the waiting time in the facilities at controlled environmental conditions did not seem to be a risk factor, but rather a mean to reduce the number of dead animals (all P < 0.05). It is concluded that the resistance to the hostile weather conditions, long journeys and extended waiting times was strongly related with the body weight of broilers; therefore, the planning of the slaughtering activity should consider this aspect, in order to avoid animal suffering and the economic loss

Long-term effects of automated mechanical peripheral stimulation on gait patterns of patients with Parkinson's disease

New treatments based on peripheral stimulation of the sensory–motor system have been inspiring new rehabilitation approaches in Parkinson’s disease (PD), especially to reduce gait impairment, levodopa washout effects, and the incidence of falls. The aim of this study was to evaluate the change in gait and the clinical status of PD patients after six sessions of a treatment based on automated mechanical peripheral stimulation (AMPS). Eighteen patients with PD and 15 age-matched healthy individuals (control group) participated in this study. A dedicated medical device delivered the AMPS. PD patients were treated with AMPS six times once every 4 days. All PD patients were treated in the off-levodopa phase and were evaluated with gait analysis before and after the first intervention (acute phase), after the sixth intervention, 48 h after the sixth intervention, and 10 days after the end of the treatment. To compare the differences among the AMPS interventions (pre, 6 AMPS, and 10 days) in terms of clinical scales, a t-test was used (α≤0.05). In addition, to compare the differences among the AMPS interventions (pre, post, 6 AMPS, 48 h and 10 days), the gait spatiotemporal parameters were analyzed using the Friedman test and the Bonferroni post-hoc test (α≤0.05). Also, for comparisons between the PD group and the control group, the gait spatiotemporal parameters were analyzed using the Mann–Whitney test and the Bonferroni post-hoc test (α≤0.05). The results of the study indicate that the AMPS treatment has a positive effect on bradykinesia because it improves walking velocity, has a positive effect on the step and stride length, and has a positive effect on walking stability, measured by the increase in stride length. These results are consistent with the improvements measured with clinical scales. These findings indicate that AMPS treatment seems to generate a more stable walking pattern in PD patients, reducing the well-known gait impairment that is typical of PD; regular repetition every 4 days of AMPS treatment appears to be able to improve gait parameters, to restore rhythmicity, and to reduce the risk of falls, with benefits maintained up to 10 days after the last treatment. The trial was registered online at ClinicalTrials.gov (number identifier: NCT0181528)

Motor fluctuations in Parkinson’s disease: Perceptions and treatment

Background: Levodopa is the gold standard of treatment for Parkinson’s disease, but wearing off leads to motor fluctuations in most patients. Therapeutic strategy for motor fluctuation management relies heavily on physician judgement; however, real-world insight into physician attitudes towards detection and treatment of motor fluctuations is lacking. Methods: Multinational qualitative online surveys were conducted among general neurologists and movement disorder specialists treating patients with Parkinson’s disease in the UK, Germany, Italy, Spain, and Portugal in July 2020 (Wave 1) and September 2021 (Wave 2). The Perceptions and Attitudes questionnaire focused on attitudes towards detection and management of motor fluctuations by rating agreement with statements on a 7-point scale. The Treatment Landscape questionnaire involved completion of patient case reports (PCRs) for the four most recently treated patients with motor fluctuations. Results: Respondents agreed that motor fluctuations place a heavy burden on patients (82%/85% in Wave1/2, respectively) and are underdiagnosed (64%/72%), but most do not routinely use screening tools known to increase their detection. Just 3% of neurologists agreed completely with being confident in fully resolving motor fluctuations to their patient’s satisfaction. In contrast with the current evidence, most physicians perceive duration of levodopa treatment as a predictor of motor complications (72%/77%). Fractionating levodopa was the preferred first therapeutic strategy for motor fluctuation management versus adding an adjunct treatment. PCRs revealed that specialist neurologists used adjunct therapy more frequently than general neurologists, either as a first approach (31% versus 15%, respectively) or secondary to levodopa fractionating (62% versus 45%). Conclusions: These surveys uncovered knowledge gaps around the predictors of motor fluctuations which could be addressed by future educational initiatives. Earlier detection of motor fluctuations and greater use of available adjunct treatments may help to reduce their burden in patients with Parkinson’s disease

Acute modulation of brain connectivity in Parkinson disease after automatic mechanical peripheral stimulation: A pilot study

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.Clinical Trials.gov NCT01815281

Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach

© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Introduction: There is currently a resurgence of levodopa as the initial treatment of choice for most patients with Parkinson's disease, albeit at lower doses than previously used. The addition of adjuvant treatments (including MAO-B inhibitors, COMT inhibitors and dopamine agonists) is an established strategy to reduce motor complications that develop with sustained levodopa therapy. Areas covered: In this narrative review, the authors discuss the evidence underpinning current levodopa optimization strategies, during early disease and once motor complications occur. To support the discussion, the authors performed a broad PubMed search with the terms 'levodopa/L-dopa/L-Dopa, and Parkinson's disease,' restricted to clinical trials. There is now a wealth of evidence that improving levodopa delivery to the brain improves outcomes and we discuss how agents can be combined earlier in the course of disease to leverage the full potential of this strategy. Expert opinion: Levodopa remains the cornerstone of antiparkinsonian therapy. Several promising advances in formulation have been made and include novel extended-release oral drugs as well as non-oral delivery systems. However, evidence has long suggested that anti-parkinsonian medications may be better used in combination earlier in the disease, and consequently patients will benefit from low doses of several agents rather than ever larger levodopa doses.This paper was supported by BIAL, who procured medical writing support but had no other influence on the content of the paper. No author received any remuneration for the preparation of this article.info:eu-repo/semantics/publishedVersio

New evidence of MIS 3 relative sea level changes from the Messina Strait, Calabria (Italy)

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Antonioli, F., Calcagnile, L., Ferranti, L., Mastronuzzi, G., Monaco, C., Orru, P., Quarta, G., Pepe, F., Scardino, G., Scicchitano, G., Stocchi, P., & Taviani, M. New evidence of MIS 3 relative sea level changes from the Messina Strait, Calabria (Italy). Water, 13(19), (2021): 2647, https://doi.org/10.3390/w13192647.Investigation of sea-level positions during the highly-dynamic Marine Isotope Stage 3 (MIS 3: 29–61 kyrs BP) proves difficult because: (i) in stable and subsiding areas, coeval coastal sediments are currently submerged at depths of few to several tens of meters below the present sea level; (ii) in uplifting areas, the preservation of geomorphic features and sedimentary records is limited due to the erosion occurred during the Last Glacial Maximum (LGM) with sea level at a depth of −130 m, followed by marine transgression that determined the development of ravinement surfaces. This study discusses previous research in the Mediterranean and elsewhere, and describes new fossiliferous marine deposits overlaying the metamorphic bedrock at Cannitello (Calabria, Italy). Radiocarbon ages of marine shells (about 43 kyrs cal BP) indicate that these deposits, presently between 28 and 30 m above sea level, formed during MIS 3.1. Elevation correction of the Cannitello outcrops (considered in an intermediate-to-far-field position with respect to the ice sheet) with the local vertical tectonic rate and Glacial Isostatic Adjustment (GIA) rate allows the proposal of a revision of the eustatic depth for this highstand. Our results are consistent with recently proposed estimates based on a novel ice sheet modelling technique.This research received no external funding

Exploring depression in Alzheimer's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management

Background: In Alzheimer's disease (AD), the progressive cognitive impairment is often combined with a variety of neuropsychiatric symptoms, firstly depression. Nevertheless, its diagnosis and management is difficult, since specific diagnostic criteria and guidelines for treatment are still lacking. The aim of this Delphi study is to reach a shared point of view among different Italian specialists on depression in AD. Methods: An online Delphi survey with 30 questions regarding epidemiology, diagnosis, clinical features, and treatment of depression in AD was administered anonymously to a panel of 53 expert clinicians. Results: Consensus was achieved in most cases (86%). In the 80% of statements, a positive consensus was reached, while in 6% a negative consensus was achieved. No consensus was obtained in 14%. Among the most relevant findings, the link between depression and AD is believed to be strong and concerns etiopathogenesis and phenomenology. Further, depression in AD seems to have specific features compared to major depressive disorder (MDD). Regarding diagnosis, the DSM 5 diagnostic criteria for MDD seems to be not able to detect the specific aspects of depression in AD. Concerning treatment, antidepressant drugs are generally considered the main option for depression in dementia, according to previous guidelines. In order to limit side effects, multimodal and SSRI antidepressant are preferred by clinicians. In particular, the procognitive effect of vortioxetine seems to be appealing for the treatment of depression in AD. Conclusions: This study highlights some crucial aspects of depression in AD, but more investigations and specific recommendations are needed

Exploring depression in Parkinson's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management

Background: Depression is a prodromic and a frequent non-motor symptom of Parkinson's disease, associated to reduced quality of life and poor outcomes. The diagnosis of depression in parkinsonian patients represents a challenge due to the overlapping of symptoms typical of the two conditions. Methods: A Delphi panel survey was performed to reach a consensus amongst different Italian specialists on four main topics: the neuropathological correlates of depression, main clinical aspects, diagnosis, and management of depression in Parkinson's disease. Results and conclusion: Experts have recognized that depression is an established risk factor of PD and that its anatomic substrate is related to the neuropathological abnormalities typical of the disease. Multimodal and SSRI antidepressant have been confirmed as a valid therapeutic option in the treatment of depression in PD. Tolerability, safety profile, and potential efficacy on broad spectrum of symptoms of depression including cognitive symptoms and anhedonia should be considered when selecting an antidepressant and the choice should be tailored on the patients' characteristics