Search Results (67)

Background/Objectives: Advanced Parkinson’s disease is characterized by severe motor fluctuations and disabling dyskinesias that often become refractory to conventional oral dopaminergic therapies. Methods: This study aimed to evaluate the clinical efficacy of levodopa–entacapone–carbidopa intestinal gel (LECIG) in 50 patients initiated during a four-year period at a tertiary movement disorders center. Motor outcomes were analyzed using Wilcoxon signed-rank and McNemar’s tests, while multivariable logistic regression was employed to identify predictors of improvement. Results: LECIG initiation significantly reduced mean daily OFF time from 4.63 ± 0.75 to 1.62 ± 1.97 h (p < 0.0001) and total dyskinesia duration by 65% (p < 0.0001). Furthermore, the prevalence of early morning akinesia decreased from 80% to 26%, and delayed ON phenomena were completely eliminated (p < 0.0001). Subgroup analyses indicated that patients with troublesome dyskinesia (≥1 h/day) achieved significantly greater reductions in involuntary movements compared to those with lower baseline dyskinesia levels (p = 0.013). Conclusions: These findings suggest that LECIG provides a meaningful and sustained stabilization of motor complications, highlighting its role as a valuable device-aided therapy in managing advanced Parkinson’s disease. Full article

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD. Full article

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD. Full article

Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is frequently underrecognized, particularly when resting oxygen saturation is preserved. Dynamic stress testing, however, may reveal exercise-induced oxygen desaturation, reflecting a latent functional respiratory impairment. The relationship between exertional oxygen desaturation and cognitive performance in PD remains insufficiently explored. Objective: To investigate the association between exercise-induced oxygen desaturation and global cognitive performance in patients with PD, and to explore the contribution of pulmonary gas exchange impairment assessed by diffusing capacity of the lung for carbon monoxide (DLCO). Methods: This prospective, cross-sectional, single-center observational study with consecutive enrollment included 50 patients with idiopathic Parkinson’s disease undergoing multidisciplinary respiratory evaluation following neurological assessment. Participants underwent cognitive evaluation using the Romanian version of the Montreal Cognitive Assessment (MoCA), pulmonary function testing including DLCO and total lung capacity (TLC), and a supervised 6-min walk test (6MWT) with continuous pulse oximetry. Exercise-induced oxygen desaturation was defined as a decrease in SpO₂ of ≥4% from baseline. Correlation analyses and multivariable regression models were applied. Results: Exercise-induced oxygen desaturation was frequent, with 60% of patients exhibiting a ≥4% decrease in SpO₂ during the 6MWT. Greater desaturation was significantly associated with lower MoCA scores (Spearman’s r = −0.383, p = 0.006). No significant associations were found between exertional desaturation and resting pulmonary function parameters, including DLCO and TLC. In multivariable analysis, lower MoCA score and levodopa–carbidopa intestinal gel treatment independently predicted greater oxygen desaturation during exercise. Conclusions: Exercise-induced oxygen desaturation is common in patients with PD despite preserved resting oxygenation and is associated with poorer cognitive performance. These findings suggest that exertional desaturation may reflect a dynamic functional impairment and may be associated with increased physiological vulnerability. Functional exercise testing with oxygen saturation monitoring may provide complementary information beyond resting pulmonary assessments. Full article

Parkinson’s disease (PD) is frequently complicated by dysphagia, undermining timely and reliable oral dopaminergic medication. Levodopa’s short half-life and delayed gastric emptying in advanced PD result in inconsistent absorption, delayed “ON” periods, and challenges to adherence. Orally disintegrating tablets (ODTs) dissolve without water and can mitigate swallowing limitations. Research indicates that selegiline ODT achieves a faster time to peak and higher relative bioavailability via partial buccal absorption, whereas carbidopa/levodopa ODTs are bioequivalent to immediate release tablets (with similar AUC/C_max and approximately 1 h T_max) without consistent motor advantages but with higher patient acceptability. This review synthesizes the clinical burden of dysphagia in PD, pharmacokinetic constraints of current formulations, and the reasons for ODTs. We highlight 3D printing as a route to personalized, dysphagia friendly therapy, which enables dose individualization, polypills, engineered disintegration or release, and point-of-care production. Feasibility studies underscore stability considerations such as carbidopa, throughput and regulatory requirements (QbD/GMP), and bioequivalence information. We outline priorities to integrate 3D printed ODTs into PD care, aligning formulation, pharmacokinetics, and human factors to improve adherence and clinical outcomes. Full article

Introduction: Levodopa (LD) is the most efficacious antiparkinsonian drug. However, long-term conventional LD treatment of Parkinson’s disease (PD) is frequently associated with motor complications. This can be attributed to pulsatile dopaminergic stimulation given the short LD half-life of conventional dosage forms. Tablets capable of delivering more stable and sustained dopaminergic stimulation would better mimic the brain’s natural dopamine activity. Methods: In this study, 3D screen printing technology was used to manufacture oral dosage forms characterized by the sequential release of Carbidopa and Levodopa. This was achieved by separating the two compounds into different compartments within the same dosage form, which were arranged (LXM.5-1) or formulated (LXM.5-2) in a specific way. Both novel dosage forms were compared to conventional immediate release forms such as Sinemet^®. The physicochemical properties of the resulting tablets, LXM.5-1 and LXM.5-2, were assessed in accordance with the USP. Their pharmacokinetic profiles were defined in pigs. Results: The physicochemical properties of LXM.5-1 and LXM.5-2 complied with regulatory requirements. Dissolution studies revealed sequential CD and LD release for both novel dosage forms. They differed regarding the interval between CD and LD release which was shorter for LXM.5-1. PK studies demonstrated that both novel dosage forms exhibited higher LD bioavailability in comparison to Sinemet^®, which was 211.36% and 383.64% for LXM.5-1 and LXM.5-2, respectively. Furthermore, blood levels were more stable and sustained, particularly for LXM.5-2. Conclusions: We conclude that 3D screen-printed LXM.5-1 and LXM.5-2 and variations thereof have the potential to transform the pharmacotherapy of Parkinson’s disease. Full article

Background/Goal: Parkinson’s disease (PD) disrupts dopaminergic transmission, leading to motor deficits and altered activity in the primary motor cortex (M1). While M1 modulation is critical for motor control, its response to dopaminergic degeneration and treatment remains unclear. This study aimed to characterize M1 neuronal activity and motor behavior in hemiparkinsonian rats using in vivo calcium imaging across naïve, lesioned, and levodopa-treated states. Methods: Thirteen Sprague Dawley rats were injected with GCaMP6f in the M1 and implanted with a GRIN lens and guide cannula targeting the medial forebrain bundle. Calcium imaging and motor behavior were assessed longitudinally using a single pellet reaching test (SPRT) before and after unilateral 6-hydroxydopamine (6-OHDA) lesioning and subsequent levodopa/carbidopa treatment. Dopaminergic lesion severity was quantified via tyrosine hydroxylase immunohistochemistry. Calcium event frequency and influx were analyzed with CNMF-E and statistical modeling. Results: Levodopa treatment improved fine motor performance as shown by a significant reduction in grasp errors (mean difference: −8.91, 95% CI: −16.66 to −1.16, p = 0.031) and increased reaching duration (mean difference: 4.13, 95% CI: 0.94 to 7.32, p = 0.019) compared to the lesioned state. M1 calcium activity showed modulation dependent on lesion severity: low-lesion rats exhibited reduced event frequency (mean difference: 0.04 Hz, 95% CI: 0.001 to 0.08, p = 0.045) and increased influx post-lesion (mean difference: −0.20 z·s, 95% CI: −0.38 to −0.02, p = 0.038), while high-lesion rats showed increased influx only after levodopa treatment (mean difference: −0.34 z·s, 95% CI: −0.52 to −0.16, p = 0.003). Correlation analyses revealed that calcium influx, but not frequency, was negatively correlated with lesion severity during levodopa treatment (Spearman r = −0.857, p = 0.024). Conclusion: M1 neuronal activity appears to be differentially modulated by dopaminergic degeneration and levodopa treatment in a lesion-dependent manner. These preliminary findings suggest dynamic cortical responses in PD and support the utility of calcium imaging for monitoring circuit-level changes in disease and therapy. Further research with larger cohorts and complementary methodologies will be necessary to validate and extend these observations. Full article

Background: Parkinson’s disease (PD) in advanced stages becomes, over time, a significant challenge, as oral medication becomes ineffective, and it may become necessary to switch to device-assisted therapy (DAT). This should be personalized according to the stage of the disease, the cognitive status of the patients, the association of frailty syndrome or other comorbidities, the support in care from the family, etc. Levodopa–carbidopa–entacapone intestinal gel can significantly improve the status of patients, provided that they are correctly selected for this type of treatment. Materials and Methods: We conducted a single-center prospective study including 20 advanced PD patients, who received a levodopa–carbidopa–entacapone gel through an intestinal pump, within the Parkinson’s Disease Multimodal Treatment Center of the Neurology Clinic of the “St. Ap. Andrew” County Emergency Clinical Hospital in Galați, Romania. The evaluations were performed at baseline (T0), after intestinal pump insertion (T1), and 6 months after the procedure (T2). Results: In the study group, the administration of the levodopa–carbidopa–entacapone intestinal gel, using the device for intestinal administration, had significant benefits, especially for motor symptoms. The periods of off, no-on, freezing, sudden-off, as well as dyskinesia and morning akinesia, were significantly reduced. Among the non-motor symptoms, depression and sleep disorders improved, with no changes in cognitive status and psychotic disorders. Conclusions: Adding new data for the use of device-assisted therapy in advanced PD, our study also highlights the need to further research this challenging patient profile. Full article

Background: The increased incidence of malignant melanoma is observed in patients with Parkinson’s disease. Methods: The anti-proliferative effects of carbidopa and rasagiline on four human malignant melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were determined in MTT assay. The interaction profiles of rasagiline in combinations with cisplatin (CDDP) and mitoxantrone (MTX) in four human melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were assessed by means of the isobolographic analysis in the MTT test; Results: Rasagiline, but not carbidopa, produced clear-cut anti-proliferative effects on various melanoma cell lines. The median inhibitory concentrations (IC₅₀ values) of rasagiline in the MTT were 280.69 µM for A375, 402.89 µM for SK-MEL28, 349.44 µM for FM55P, and 117.45 µM for FM55M2, respectively. The experimentally-derived selectivity index for rasagiline ranged from 8.22 to 28.18. Flow cytometry assay revealed, in two melanoma cell lines (FM55P and A375), a significant increase in the number of cells in the G0/G1 (up to 76.48% and 75.46% for cell lines, respectively), accompanied by a decrease in the percentage of cells in the S phase (decrease to 9.91% and 10.83% for cell lines, respectively), which may indicate potential cytostatic properties of rasagiline. The combinations of rasagiline with CDDP (at the fixed-ratio of 1:1) exerted either antagonistic interactions (p < 0.05) in the A375 and SK-MEL28, or additive interactions, with a tendency toward antagonism in the FM55P and FM55M2 cell lines in the MTT test. In contrast, the combinations of rasagiline with MTX (ratio of 1:1) produced either synergistic interaction (p < 0.05) in the FM55P cell line or additive interactions with a tendency toward synergy in the FM55M2, SK-MEL28, and A375 cell lines in the MTT test. Conclusions: Rasagiline combined with MTX exerted the most desirable synergistic interactions in relation to the anti-proliferative effects in four malignant melanoma cell lines, as assessed isobolographically. In contrast, rasagiline should not be combined with CDDP during the treatment of malignant melanoma due to the antagonistic interactions in the MTT assay. Full article

Background/Objectives: Parkinson’s Disease (PD) is a neurodegenerative disorder resulting in bradykinesia, rigidity and tremor, as well as numerous non-motor symptoms. Malnutrition in PD is correlated with levodopa-induced dyskinesia, decreased food intake, gastrointestinal symptoms and neurodegenerative processes. With disease progression, oral levodopa treatment becomes insufficient. One of the therapies used in advanced PD is levodopa–carbidopa intestinal gel. Its effect on the weight and nutrition of PD patients is poorly understood. The aim of this prospective single-center observational cohort study was to assess the effect of this treatment on weight, body composition and biochemical parameter changes over a two-year-long observation. The mood, cognition and motor status of the patients were also assessed. Methods: This study included 15 patients with advanced PD treated with levodopa–carbidopa intestinal gel. Body composition analysis, anthropometric measurements, blood tests, psychological assessments and disease control measurements were carried out over a span of two years after the initiation of therapy. Results: Significant improvement in disease management was observed. Anthropometric measurements, biochemical parameters and psychological assessments did not show significant differences. Among the body composition parameters, only resting metabolic rate and extracellular and intracellular water percentages were significantly affected. Conclusions: Our findings indicate a lack of negative effects of levodopa–carbidopa intestinal gel treatment on weight loss in patients with Parkinson’s Disease in a 2-year long observation period. Furthermore, better disease management may result in a lower energy expenditure due to less time with dyskinesia. The limitations of our study include a small study group and limited follow-up. Full article

Sepiapterin Reductase Deficiency (SRD) is a rare inherited neurometabolic disorder caused by variants in the SPR gene, which may lead to developmental delays, psychomotor retardation, and cognitive impairments. Two consanguineous North African and Middle Eastern families are reported with multiple affected individuals presenting with developmental delay, ataxia, hypotonia, fatigue, and ptosis, or parkinsonism and cognitive impairment. Exome sequencing revealed a novel homozygous SPR c.560A>G (p.Glu187Gly) mutation that segregates with disease. According to molecular dynamics analysis, the substitution is predicted to compromise structural integrity, likely affecting ligand binding and catalytic activity. Elevated cerebrospinal fluid sepiapterin and biopterin levels, along with low neurotransmitter levels, were concordant with a genetic diagnosis of SRD and the reclassification of this variant as pathogenic. SRD patients manifest a broad constellation of symptoms, albeit well-managed using low-dose L-dopa/carbidopa. This study highlights the value of genetic testing in expediting early diagnosis and intervention to mitigate the onset of this disorder. Full article

Introduction: The management of sedation during percutaneous endoscopic gastrojejunostomy (PEG-J) placement in patients with advanced Parkinson’s disease (PD) is challenging due to the complex interactions between PD treatment, anesthetic agents, and the disease’s motor and non-motor symptoms. This study evaluates the effectiveness and safety of a target-controlled infusion (TCI) propofol protocol in the context of PEG-J placement in advanced PD patients. Materials and Methods: This prospective study included 169 patients diagnosed with advanced Parkinson’s disease (Hoehn and Yahr stages 4 and 5) who underwent PEG-J placement at Târgu Mureș County Emergency Clinical Hospital, Romania. Sedation was induced and maintained using TCI propofol, with additional benzodiazepines and short-acting opioids, while muscle relaxants were not used. Procedural success rates and adverse outcomes were assessed for 30 days post-procedure. Results: The sedation protocol demonstrated a high procedural success rate. No deaths were reported within 30 days post-procedure. Conclusion: This study highlights the feasibility and clinical applicability of a TCI propofol protocol for PEG-J placement in patients with advanced PD (stages 4 and 5). While no deaths were recorded within the 30-day follow-up, the sample size is insufficient to draw definitive conclusions regarding long-term safety. Full article

Background and Objectives: The rapid growth of the number of advanced Parkinson’s disease (PD) patients has caused a significant increase in the use of device-aided therapies (DATs), including levodopa–carbidopa intestinal gel (LCIG) and continuous subcutaneous apomorphine infusion (CSAI). The objective of this study was to evaluate patients’ satisfaction and the factors influencing preferences for CSAI and LCIG. Materials and Methods: The research focused on individuals diagnosed with advanced PD undergoing DAT at the Neurology Department of the University Hospital in Katowice. A telephone survey conducted between June and July 2024 evaluated the experiences of patients with LCIG and CSAI. The Parkinson’s Disease Questionnaire (PDQ-8) and the Stress Scale for Family Caregivers (BSFC-s) were applied. Based on medical record data comprising reasons for the exclusion of individuals, disease-related and treatment data were collected. Results: Among the original cohort of 64 patients, 50 completed the survey, including 31 who might choose between infusion therapies. The average patient ages were 70.6 ± 4.7 (CSAI) and 71.2 ± 7.2 years (LCIG), with disease durations of 15 (IQR: 12–19) and 18 (IQR: 13–19) years, respectively. LCIG patients presented higher PDQ-8 scores (20 (IQR: 13–27) vs. 13 (IQR: 6–19), p = 0.008), and higher BSFC-s scores (19 (IQR: 12–21) vs. 9 (IQR: 2.5–13), p = 0.011). Furthermore, significant factors influencing patient preferences included fear of surgery (75% vs. 36.8%, p = 0.043) and concerns about DAT safety (83.3% vs. 47.4%, p = 0.049). Conclusions: LCIG and CSAI therapies offer benefits and disadvantages, with safety concerns and fear of surgery seeming to be decisive in the decision-making process. Full article

Background and objective: Staging Parkinson’s disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients’ quality of life and caregivers’ strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon’s signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT. Full article

Pharmaceutical residues in aquatic ecosystems pose significant environmental and public health challenges. Identifying the presence and levels of these pharmaceuticals is crucial. This study developed an analytical method to detect pharmaceuticals used for Alzheimer’s (AD) and Parkinson’s (PD) disease, including psychiatric drugs and the stimulant caffeine, targeting 30 compounds. Optimized mass spectrometric and liquid chromatographic parameters enabled robust detection and quantification. The methodology was applied to 25 surface and wastewater samples. Twenty-one compounds were detected including eight psychiatric drugs, five metabolites (citalopram N-oxide, citalopram propionic acid, desmethylcitalopram, O-desmethylvenlafaxine, and 10,11-epoxycarbamazepine), and seven AD/PD pharmaceuticals along with caffeine. Nine compounds (apomorphine, benserazide, donepezil, didemethylcitalopram, carbidopa, norfluoxetine, galantamine, pramipexole, and safinamide) were not detected. Fluoxetine was found in all samples, and caffeine had the highest concentration at 76,991 ng/L, reflecting its high consumption. Concentrations ranged from 29.8 to 656 ng/L for caffeine, <MDL to 381 ng/L for psychiatric drugs, and <MDL to 37.1 ng/L for AD and PD pharmaceuticals in surface water. In wastewater, concentrations ranged from 140 to 76,991 ng/L for caffeine, <MDL to 5227 ng/L for psychiatric drugs, and <MDL to 206 ng/L for AD and PD pharmaceuticals. These findings highlight the critical need for comprehensive environmental monitoring. Full article