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Since its first introduction, levodopa has remained the cornerstone treatment for Parkinson's disease. However, as the disease advances, the therapeutic window for levodopa narrows, leading to motor complications like fluctuations and dyskinesias. Clinicians face challenges in optimizing daily therapeutic regimens, particularly in advanced stages, due to the lack of quantitative biomarkers for continuous motor monitoring. Biochemical sensing of levodopa offers a promising approach for real-time therapeutic feedback, potentially sustaining an optimal motor state throughout the day. These sensors vary in invasiveness, encompassing techniques like microdialysis, electrochemical non-enzymatic sensing, and enzymatic approaches. Electrochemical sensing, including wearable solutions that utilize reverse iontophoresis and microneedles, is notable for its potential in non-invasive or minimally invasive monitoring. Point-of-care devices and standard electrochemical cells demonstrate superior performance compared to wearable solutions; however, this comes at the cost of wearability. As a result, they are better suited for clinical use. The integration of nanomaterials such as carbon nanotubes, metal-organic frameworks, and graphene has significantly enhanced sensor sensitivity, selectivity, and detection performance. This framework paves the way for accurate, continuous monitoring of levodopa and its metabolites in biofluids such as sweat and interstitial fluid, aiding real-time motor performance assessment in Parkinson's disease. This review highlights recent advancements in biochemical sensing for levodopa and catecholamine monitoring, exploring emerging technologies and their potential role in developing closed-loop therapy for Parkinson's disease.

Since its first introduction, levodopa has become the cornerstone for the treatment of Parkinson's disease and remains the leading therapeutic choice for motor control therapy so far. Unfortunately, the subsequent appearance of abnormal involuntary movements, known as dyskinesias, is a frequent drawback. Despite the deep knowledge of this complication, in terms of clinical phenomenology and the temporal relationship during a levodopa regimen, less is clear about the pathophysiological mechanisms underpinning it. As the disease progresses, specific oscillatory activities of both motor cortical and basal ganglia neurons and variation in levodopa metabolism, in terms of the dopamine receptor stimulation pattern and turnover rate, underlie dyskinesia onset. This review aims to provide a global overview on levodopa-induced dyskinesias, focusing on pathophysiology, clinical manifestations, therapy management strategies and future directions.

Introduction: The present study explores brain connectivity in Parkinson's disease (PD) and in age matched healthy controls (HC), using quantitative EEG analysis, at rest and during a motor tasks. We also evaluated the diagnostic performance of the phase locking value (PLV), a measure of functional connectivity, in differentiating PD patients from HCs., Methods: High-density, 64-channels, EEG data from 26 PD patients and 13 HC were analyzed. EEG signals were recorded at rest and during a motor task. Phase locking value (PLV), as a measure of functional connectivity, was evaluated for each group in a resting state and during a motor task for the following frequency bands: (i) delta: 2-4 Hz; (ii) theta: 5-7 Hz; (iii) alpha: 8-12 Hz; beta: 13-29 Hz; and gamma: 30-60 Hz. The diagnostic performance in PD vs. HC discrimination was evaluated., Results: Results showed no significant differences in PLV connectivity between the two groups during the resting state, but a higher PLV connectivity in the delta band during the motor task, in HC compared to PD. Comparing the resting state versus the motor task for each group, only HCs showed a higher PLV connectivity in the delta band during motor task. A ROC curve analysis for HC vs. PD discrimination, showed an area under the ROC curve (AUC) of 0.75, a sensitivity of 100%, and a negative predictive value (NPV) of 100%., Conclusions: The present study evaluated the brain connectivity through quantitative EEG analysis in Parkinson's disease versus healthy controls, showing a higher PLV connectivity in the delta band during the motor task, in HC compared to PD. This neurophysiology biomarkers showed the potentiality to be explored in future studies as a potential screening biomarker for PD patients.

Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). The aim of the present review is to summarize the state of the art regarding dystonia diagnosis focusing on the role of neurophysiology and genetic testing.