Current non-invasive assessments for Parkinson's disease (PD) are predominantly single-modality, leaving an unmet need for an integrated platform combining biomolecular and biomechanical detection. Here, an integrated dual-mode sensing platform based on a flexible non-woven fabric (NWFs) device for PD is provided. Silver nano-contacts are electrolessly deposited onto cotton fibers to form a biomimetic spider-leg-like microarchitecture, which concurrently supports localized surface plasmon resonance (LSPR) for surface-enhanced Raman scattering (SERS) and strain-responsive piezoresistive behavior. The NWFs@Au@Ag substrate exhibits good cytocompatibility with 100% cell viability. Using the NWFs@Au@Ag SERS substrate for standard α-synuclein molecule testing, the 1670-1680 cm-1 band verifies the formation of β-sheet-rich amyloid aggregates. In saliva from PD and MSA patients, SERS detects spectral signatures associated with α-synuclein, most notably an altered amide I band at 1677 cm-1 and the difference in β-sheet is one of the important contributors to the spectral differences. Simultaneously, the piezoresistive mode quantitatively monitors orbicularis oculi strain during blink and eye-scanning movements. The strain signals show strong concordance with the Movement Disorders Society Unified Parkinson's Disease Rating Scale (Part III), and capture disease progression and acute levodopa response with temporal resolution superior to conventional electromyography (EMG). In 30 PD patients, artificial intelligence-assisted analysis of horizontal eye-scanning strain waveforms achieves 90.9% classification accuracy. By combining biomolecular fingerprinting and biomechanical function assessment, this dual-mode platform could overcome the single-modality limitation of existing PD non-invasive evaluation methods and offer an explorable path for point-of-care screening and longitudinal monitoring of disease progression.

Stimuli-responsive hydrogels capable of combining tissue regeneration with on-demand drug delivery represent an attractive strategy for cartilage repair. In this work, bioinspired chondroitin sulfate/poly(levodopa) (CS/P(L-DOPA)) hydrogels were prepared through EDC/NHS-mediated self-crosslinking of CS followed by the in situ polymerization of L-DOPA to generate a secondary eumelanin photothermal network. The hydrogels were characterized by FTIR spectroscopy, swelling measurements, SEM, photothermal performance, NIR-triggered ibuprofen release, cytocompatibility, and chondrogenic differentiation assays. The incorporation of P(L-DOPA) preserved the interconnected porous morphology while reducing equilibrium swelling under physiological conditions through additional intermolecular interactions. CS/P(L-DOPA) hydrogels exhibited an efficient photothermal conversion upon NIR irradiation, reaching temperatures of 43-46 °C. NIR irradiation promotes the ibuprofen release from the hydrogels, demonstrating remote-controlled drug delivery. In vitro studies confirmed cell viabilities above 80% in L-929 fibroblasts and dental pulp stem cells, while cytoskeletal staining revealed enhanced cell organization. Safranin O and Alcian Blue staining showed an increase in glycosaminoglycan- and proteoglycan-rich extracellular matrix deposition, consistent with a chondrogenic response of the stem cells. These findings demonstrate the potential of CS/P(L-DOPA) hydrogels as a multifunctional platform for NIR-controlled drug delivery and cartilage tissue engineering.

Despite improved definition of the problem and better understanding of its phenomenology, freezing of gait (FoG) remains a therapeutic enigma for clinicians and neuroscientists alike. Patients with Parkinson disease (PD) or other neurological disorders experiencing FoG are similarly frustrated, despite the benefits that levodopa and other medications provide for control of PD's primary motor features. For those burdened by episodes of FoG, current therapeutic options are quite limited. Some patients achieve improvements from pharmacotherapy-for example, by adjunctive use of an oral dopaminergic agonist or by subcutaneous infusion of apomorphine. If needed, deep brain stimulation sometimes offers symptomatic improvements. Certain interventions devised by physical therapists (or discovered by patients themselves) can improve FoG. However, successful pharmacotherapy for FoG has lagged behind, though the future holds some promising leads for therapies acting on dopaminergic, adenosinergic, noradrenergic, glutamatergic, and cholinergic circuitry.

Implanted intracerebral devices can lead to infection, hemorrhage, or the formation of fluid-filled cysts. Formation of a perielectrode cyst after deep brain stimulation (DBS) has been reported in a limited number of patients. Additionally, diverse causes and clinical presentations have been associated with these cysts. We present a case of perielectrode cyst formation three months after implantation of a subthalamic nucleus DBS (STN-DBS) for Parkinson's disease (PD). A 59-year-old woman was diagnosed with PD in 2011. In November 2023, the patient underwent staged placement of an STN-DBS without perioperative complications. Immediate postoperative cerebral CT ruled out acute complications. Postoperatively, the patient showed clear clinical improvement, and a substantial reduction in the levodopa dose was achieved (1,500 mg/24 h vs. 250 mg/24 h). There was a significant change in neurocognitive testing three months postoperatively, with a decrease in the Montreal Cognitive Assessment score from 29/30 to 24/30. Follow-up cerebral MRI showed a perielectrode cystic lesion around the left electrode. The patient's clinical status and electrode impedances remained unchanged during follow-up. Serial imaging demonstrated gradual regression of the cyst. Perielectrode cysts after DBS can occur at different locations and at varying postoperative time points. They may present with diverse clinical manifestations or remain completely asymptomatic. Different putative mechanisms and treatment options have been described; however, the paucity of reported clinical cases makes it difficult to speculate on a primary cause.

Motor fluctuations are a common and burdensome complication of Parkinson's disease (PD) when the disease progresses, largely driven by the short half-life and variable absorption of immediate-release (IR) levodopa. IPX203 is a next-generation modified-release levodopa/carbidopa formulation that delivers rapid onset and sustained plasma levodopa concentrations through IR granules and extended-release pellets. Clinical studies have shown that IPX203 increases Good ON time (ON time without dyskinesia plus ON time with non-troublesome dyskinesia, equivalent to ON time without troublesome dyskinesia), reduces OFF time and improves motor symptom control compared with IR levodopa/carbidopa. In anticipation of the introduction of IPX203 in Europe, nine PD specialists convened to develop consensus recommendations for its use in clinical practice. Through a structured process incorporating predefined statements, voting and moderated discussion, the group reached high levels of agreement (88.9% to 100%) across seven topics. These included defining motor symptoms control, identifying patients most likely to benefit from IPX203, positioning of IPX203 within the treatment pathway, practical considerations for switching to IPX203 from current regimens and recommendations for monitoring and follow-up. The experts emphasised that IPX203 should be considered for patients with motor fluctuations insufficiently controlled on optimised oral levodopa therapy, before introduction of device-aided therapies. They highlighted the need for flexible dose adjustments, comprehensive patient and neurologist education and practical tools to support conversion to IPX203. This consensus insight provides practical guidance for integrating IPX203 into routine care of PD patients with motor fluctuations, aiming to increase mobility and reduce treatment burden for patients with PD.

Oral drug delivery remains the predominant administration route, but formulation strategies rarely account systematically for the gut microbiome. The microbiome can alter drug metabolism, excipient behavior, nanocarrier interactions, and interpatient variability. This review integrates evidence on microbial drug metabolism, excipient-microbiome interactions, nanocarrier engineering, microbiota-responsive delivery, and experimental models. Clinically relevant examples include digoxin inactivation by Eggerthella lenta, bacterial levodopa metabolism, and microbial beta-glucuronidase-mediated irinotecan toxicity. Microbiota-degradable polysaccharides may serve as colon-targeted release triggers, whereas some surfactants and polymers may create context-dependent microbiome or barrier risks. Nanocarrier size, charge, coating, mucoadhesion, mucus penetration, biodegradability, enzyme responsiveness, and surfactant burden are treated as microbiome-interface variables. We propose an authors' evidence-informed framework comprising an excipient classification, nanocarrier design rules, microbiota-responsive decision logic, and a tiered testing roadmap. These proposals are not established regulatory classifications; they are intended to support more predictable and patient-relevant oral formulation development.

Gastrointestinal dysfunction is increasingly recognized as a core feature of Parkinson's disease (PD), affecting quality of life, nutrition, medication response, and potentially the earliest stages of pathogenesis. This perspective traces the evolution of the gut from a neglected source of non-motor symptoms to a central component of biological models of PD. Gastrointestinal manifestations are physiologically heterogeneous and require objective phenotyping to distinguish dysphagia, gastroparesis, slow transit, defecatory dysfunction, and overlapping mechanisms. The body-first/brain-first framework further suggests that Lewy pathology may follow distinct anatomical trajectories, with early enteric and autonomic involvement defining a subgroup in which gut-directed biomarkers and therapies may be especially relevant. Alterations of the gut microbiome are reproducibly associated with PD, although geography, constipation, medication, diet, disease stage, and reverse causation complicate interpretation. Emerging work is shifting from taxonomy toward microbial functions and host pathways, including barrier integrity, immune and enteroendocrine signaling, short-chain fatty acids, glucagon-like peptide-1 (GLP-1), host genetic susceptibility, α-synuclein aggregation and propagation, and microbial levodopa metabolism. Trials of probiotics, fecal microbiota transplantation, and dietary interventions remain heterogeneous and have not established disease-modifying efficacy. Progress will require longitudinal studies in prodromal and subtype-defined populations, objective gastrointestinal measurements, integrated microbial, host-genetic and other multi-omics, mechanistic human and animal models, and clinical trials combining target-engagement markers with meaningful outcomes. Such an approach may enable precision gut-brain medicine for appropriately selected patients with PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Genetic testing is traditionally emphasized in early-onset or familial Parkinson's disease (PD), leaving its role in advanced disease uncertain. This mini-review explores, from the perspectives of patients, their family members, and clinical researchers, whether genetic investigation remains meaningful once patients reach advanced PD. In large prospective clinical-genetic screening cohorts, roughly one in seven PD patients has genetic PD. Established genotype-phenotype correlations, spanning cognitive trajectory, levodopa responsiveness, and deep brain stimulation outcomes, continue to inform clinical decision-making even at advanced stages. Thus, patients may gain psychological clarity, receive refined prognostic counseling, and become eligible for gene-specific trials or registries. In addition, patients express altruistic motivations, considering the merit of sharing their genetic testing results with their families and the research community. Unaffected relatives may benefit from more precise, penetrance-informed risk assessment, appropriately scaled surveillance, lifestyle counseling, and reproductive planning, particularly as potential environmental modifiers of penetrance and age at onset become better characterized. Researchers rely on genetically characterized advanced-stage cohorts to identify genotype-phenotype relations, modifiers of onset, progression and treatment response, validate biomarkers, and build the large, deep longitudinal datasets required for emerging gene- and pathway-targeted therapies. Collectively, these perspectives argue against a narrow early-disease "window of opportunity" for genetic testing in PD. Rather than becoming obsolete once the disease reaches a more advanced stage, genetic characterization continues to shape individualized care, family counseling, and translational research. Thus, in the future, the challenge should no longer be to justify genetic testing in advanced PD, but to embed it equitably and systematically within standard care and international research infrastructure across the entire disease course.

A novel simple, direct, selective and rapid fluorometric method is described for the determination of guanine. The method is based on a "turn-on" response by the enhancement of the fluorescence of levodopa (L-3,4-dihydroxyphenylalanine (L-DOPA), under optimized conditions. The reaction is subjected to detailed spectroscopic and thermodynamic investigation. Upon addition of guanine, to levodopa, a significant enhancement of the fluorescence intensity is observed, accompanied by a slight bathochromic shift of ~ 10 nm in the emission maximum. This fluorescence response is consistent with an interaction-dependent change in the local environment of L-DOPA. Spectroscopic and association analyses support non-covalent association under the investigated conditions, although the available data do not establish a unique molecular binding geometry or identify the specific functional groups involved. Among the tested nucleobases, guanine produced the most pronounced fluorescence enhancement, demonstrating a preferential analytical response under the optimized conditions. A linear relationship between fluorescence intensity and guanine concentration is obtained over the concentration range of 0-280 µM guanine, with a detection limit of 0.088 µM (0.0133 µg/ml). The proposed method is validated following the standards of ISO/IEC 17025, AOAC, USP, U.S.EPA, and U.S.FDA by measuring data trueness, accuracy, bias, precision, within-day repeatability, between-days reproducibility, standard deviations, robustness, sensitivity, range, durability, stability, and limit of detection. The results reveal good data quality, reliability, and consistency. The method is applied for the determination of guanine in human serum samples using the standard addition (spiking) technique. An average accuracy of (93.3-102.2%) with good precision (mean RSD = 0.67%, n = 3) are obtained. The method provides a simple, label-free, and low-complexity approach for guanine determination in aqueous media, offering a practical alternative to more elaborate sensing platform.