Search Results (314)

Background and purpose: Balance and gait problems pose a significant burden in Parkinson’s disease (PD), and they are often poorly treated with levodopa. We intended to summarize evidence of mid- and long-term impact of various physiotherapeutic interventions (≥3 months post-intervention) on dynamic balance, gait, and general motor function in patients with PD. Method: A systematic search was conducted across the PubMed, Cochrane Library, and Scopus databases to identify controlled clinical trials on sustained effects of various exercise interventions in PD on the outcomes of interest (lasting ≥ 3 months after completion of the exercise program). We conducted meta-analyses on commonly used clinical measures of dynamic balance and gait ability, as well as on UPDRS-III scores using the Comprehensive Meta-Analysis Software (CMA). Results: A total of 26 studies were included in meta-analyses, with a total of 1261 participants in the experimental and 989 participants in the control groups. Positive cumulative effects at the post-exercise follow-up (3 to 23 months) were shown in favor of the intervention group regarding balance (SMD = 0.512, 95% CI [0.240, 0.785], p < 0.001, I² = 87%), gait (SMD = 0.614, 95% CI [0.301, 0.926], p < 0.001, I² = 75%), and general motor function (SMD = 0.922, 95% CI [0.559, 1.285], p < 0.001, I² = 87%). Heterogeneity among studies was high for all three outcomes, apparently reflecting diversity with regard to patient characteristics, type, and duration of intervention, as well as the method of outcome assessment. The certainty of evidence was consequently judged as ‘’low’’ to ‘’moderate,’’ according to the GRADE system. Subgroup analyses revealed that balance can sustainably improve mostly through multimodal rather than targeted balance-oriented exercise but also through dual-task exercise, tai chi, and Pilates. Gait showed improvement at follow-up mainly through multimodal exercise, aerobic exercise, dual-task exercise, and Pilates, with benefits confined to early- and mid-stage disease. Sustained UPDRS-III improvement could be achieved through multimodal exercise, which showed a large overall effect but also through aerobic, resistance, and dual-task training, tai chi and qigong. Conclusions: Exercise interventions can improve balance and gait, as well as preserve the overall motor function in patients with PD, also in the mid- and long-term post-intervention periods. 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

Background: The term dyskinesia describes involuntary movements of the face, body and extremities. Frequently, they appear following and in relation with prior oral long-lasting and high-dose levodopa therapy in Parkinson’s disease patients. Onset of these motion sequences causes patient distress and caregiver embarrassment with declined quality of life. Continuity of nigrostriatal postsynaptic dopamine receptor stimulation delays occurrence of dyskinesia. A pulsatile pattern with temporary too high dopamine receptor excitation promotes manifestation of dyskinesia. Methods: This narrative review describes past pharmacologic approaches for therapy of dyskinesia, such as the principle of continuous dopamine receptor stimulation. Discussion and Conclusions: Novel concepts were tested. They influenced neurotransmission of serotonin and altered stimulation of dopamine receptor subtypes. The translation of successful experimental research outcomes into valuable clinical trial results with consecutive approval of drugs with a new mode of action under the indication “antidyskinetic” repeatedly failed. An exception is the open-channel blocker of the N-methyl-D-aspartate receptor and dopamine reuptake inhibitor amantadine with its moderate dyskinesia-reducing effects, particularly in its extended-release formulation. This antiviral compound also improves impaired motor behavior and reduces “OFF” intervals. Therefore, amantadine is currently experiencing a certain resurgence in regions where its extended-release formulations are marketed for therapy of levodopa-induced dyskinesia. Full article

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive motor and non-motor manifestations, including early gastrointestinal dysfunction. Growing evidence implicates the gut microbiota as an active modulator of host immune tone and neurodegenerative vulnerability, extending beyond descriptive taxonomic associations toward functional and metabolic mechanisms. PD-associated dysbiosis is consistently characterized by altered microbial functional capacity, including reduced short-chain fatty acid (SCFA) production, enrichment of pro-inflammatory metabolic traits, and sustained immune stimulation at the intestinal interface. These shifts promote chronic low-grade inflammation and intestinal barrier perturbations, creating conditions that may facilitate abnormal α-synuclein aggregation within the enteric nervous system. Current management predominantly relies on dopaminergic replacement and related symptomatic strategies, such as levodopa combinations, dopamine agonists, monoamine oxidase-B and catechol-O-methyltransferase (COMT) inhibitors, and device-aided therapies, which alleviate symptoms but do not halt underlying neurodegeneration or modify long-term disease course. These therapeutic limitations have intensified interest in upstream mechanisms that might be amenable to disease-modifying interventions, particularly those arising at the level of the gut microbiota and gut–immune–brain axis. This narrative review integrates clinical, metagenomic, metabolomic, and mechanistic evidence to propose a unified model in which microbiota-driven immune and metabolic perturbations may act as upstream drivers converging on α-synuclein pathology, neuroinflammation, and neurovascular dysfunction. Full article

Transcranial sonography is one of the methods of examination used in atypical parkinsonian syndromes. The assessment is not indicated in the diagnostic criteria of entities in this group e.g., Progressive Supranuclear Palsy, Corticobasal Degeneration, Multiple System Atrophy and Dementia with Lewy Bodies. Atypical parkinsonisms are a group of diseases affected by diverse pathologies including alpha-synuclein or tau among others. Recently broader attention was brought to less common atypical parkinsonisms as Perry syndrome. Atypical parkinsonisms are related to poor response to levodopa treatment, rapid deterioration and unfavorable prognosis. Additionally, the entities often overlap in terms of clinical manifestation, especially in the early stages. Though atypical parkinsonisms are affected by the lack of possibility of obtaining definite in vivo diagnosis, growing interest is associated to supplementary evaluations including neuroimaging. Among these methods could be mentioned magnetic resonance imaging, positron emission tomography, single photon emission computed tomography and transcranial sonography. Transcranial sonography is associated with high accessibility and low cost. The goal of this paper is to highlight the strengths and weaknesses of transcranial sonography in the examination of atypical parkinsonisms. Full article

Background: Abrupt cessation of deep brain stimulation (DBS) in Parkinson’s disease (PD), most commonly due to implantable pulse generator (IPG) battery depletion, may lead to DBS withdrawal syndrome (DBS-WDS). However, withdrawal syndrome does not occur in all patients following stimulation cessation. Methods: We retrospectively analyzed 210 PD patients treated with DBS. Patients with documented stimulation cessation were evaluated for the presence of withdrawal syndrome based on established clinical criteria. Demographic, disease-related, and treatment characteristics were assessed, and descriptive analysis was conducted on severe cases requiring intensive care. Results: DBS battery shutdown occurred in 28 patients (13.3%). Most patients did not develop withdrawal syndrome and experienced only transient motor worsening. Severe DBS-WDS requiring intensive care was rare, occurring in only three patients (1.4%). Battery shutdown alone did not predict withdrawal, nor was preoperative levodopa equivalent daily dose associated with withdrawal risk. Conclusions: DBS battery shutdown is usually not accompanied by withdrawal syndrome, and severe DBS-WDS is uncommon. Proactive battery management may help to prevent this rare but serious complication. Full article

Parkinson disease (PD) and mood disorders represent two substantial global health burdens that increasingly co-occur as both conditions rise in prevalence worldwide. Diagnosing Parkinson disease in patients with pre-existing mood disorders is clinically challenging due to overlapping symptoms, medication effects, and shared neurobiological mechanisms. Apathy, psychomotor slowing, and fatigue may mimic depressive symptoms, leading to delayed recognition of early parkinsonism. Development of an underlying neurodegenerative disorder could account for some treatment-resistant symptoms or treatment failures if not recognized. Therefore, the identification of PD will change the treatment and management plan significantly. Accurate diagnosis of PD requires a detailed neurologic examination focusing on bradykinesia, rigidity, and resting tremor, supported when appropriate by dopamine transporter imaging (DaT scan) or other emerging biomarkers. Understanding the temporal relationship between psychiatric and motor features helps differentiate prodromal PD from primary mood disorders. Management of patients with both mood disorders and PD integrates dopaminergic replacement therapy for motor symptoms with individualized treatment of psychiatric comorbidities. Levodopa remains the cornerstone for motor control, while dopamine agonists, MAO-B inhibitors, and COMT inhibitors can be added as needed. For depression and anxiety, SSRIs and SNRIs are first-line choices; quetiapine or clozapine are preferred when treatment for psychosis is necessary. Intentional, thoughtful polypharmacy is frequently required. Non-pharmacologic interventions—including cognitive behavioral therapy, structured exercise, and patient–caregiver education—enhance mood, function, and quality of life. Multidisciplinary collaboration between neurology, psychiatry, and allied health professionals is essential for optimal outcomes. This review offers guidance to healthcare providers as well as other interested parties involved in patients with mood disorders who may also be developing or have PD, especially to those who may have limited access to neurologic resources. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms (bradykinesia, rigidity, resting tremor) and a wide range of non-motor features. The core pathological process is degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to striatal dopamine deficiency, while additional neurotransmitter systems contribute to non-motor symptoms. PD is a common age-related disorder; global estimates for 2019 indicate that more than 8.5 million people were living with PD, and prevalence increases steeply with age. Current pharmacological therapy is mainly symptomatic and is centered on levodopa and other dopaminergic strategies, but treatment response can be limited by motor fluctuations, dyskinesia, and adverse effects. Therefore, formulation and delivery innovations (e.g., dispersible preparations, intestinal gel, and continuous infusion approaches) aim to stabilize drug exposure and improve convenience, especially in patients with swallowing difficulties or advanced disease. This review summarizes conventional drug classes and their dosage forms, highlights formulation-driven strategies to improve efficacy and tolerability, and outlines emerging pathways and targets being explored for future therapies. Full article

We report a Fe₃O₄@Pt@poly-LDOPA nanozyme that displays enhanced peroxidase (POD)-like activity. Polymerisation of levodopa onto the surface of Fe₃O₄@Pt yields a carboxyl-rich poly-LDOPA shell that is available for bioconjugation with antibodies and other types of receptors. Physicochemical characterisation confirmed the integrity of the Fe₃O₄ core, successful Pt modification, and formation of the polymer coating under acidic and basic conditions. Steady-state kinetic analysis using the Michaelis–Menten model revealed robust catalytic performance toward both substrates: for H₂O₂, V_max = 4.0 × 10⁻⁸ M·s⁻¹ and K_m = 25.13 mM; for TMB, V_max = 6.07 × 10⁻⁸ M·s⁻¹ and K_m = 0.229 mM, indicative of high turnover and strong apparent affinity for the chromogenic substrate. A nanozyme-linked immunosorbent assay for the SARS-CoV-2 nucleocapsid was developed. The anti-nucleocapsid antibodies were immobilised onto Fe₃O₄@Pt@poly-LDOPA via EDC/NHS. In buffer, the calibration range (1.0–100 ng·mL⁻¹) afforded an LOD of 6.95 ng·mL⁻¹. In 10% human serum, reduced background and improved nanozyme dispersion yielded a linear low-concentration response (0.1–10 ng·mL⁻¹), with an LOD of 0.0036 ng·mL⁻¹. These results establish Fe₃O₄@Pt@poly-LDOPA as a promising inorganic–organic nanozyme platform that combines catalytic effectiveness, magnetic manipulability, and facile bioconjugation for immunosensing of various disease-related biomarkers. Full article

Mucuna pruriens (M. pruriens) is a legume that attracts researchers for its benefits and has been used for centuries in Ayurvedic medicine. While its effectiveness has long been recognized, in-depth studies have shown that its activity is mainly due to its high levodopa (L-Dopa) content, but not exclusively. It also contains other structures that can improve its effectiveness and reduce the side effects encountered when using synthetic L-Dopa. Similarly, other molecules that selectively inhibit certain enzymes are present. Various methods of varying effectiveness have been used to extract the active ingredients, and recently, progress has been made in extraction methods. Clinical studies already exist demonstrating its therapeutic benefits, similar to those of synthetic L-Dopa, for several conditions, and showing the limitations of certain side effects such as dyskinesias. Further studies and clinical trials are still needed, but this plant could be a very good alternative in countries that do not have or no longer have access to certain drugs. This legume can be grown without difficulty in these countries, as it has the advantage of being resistant to drastic climatic conditions. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterized by motor and non-motor symptoms that significantly impact patients’ quality of life. Beyond pharmacological treatments, nutrition plays a crucial role in the prevention and management of the disease. Nutritional interventions represent a pivotal strategy for improving clinical outcomes and quality of life in PD patients, addressing issues such as delayed gastric emptying, constipation, weight loss, malnutrition, and chewing or swallowing difficulties. A plant-based diet is particularly suitable for such patients, due to its high fiber content which can enhance gastrointestinal motility, thereby improving levodopa bioavailability, and potentially ameliorateing PD symptoms. For this reason, alongside neurological support, PD patients should receive nutritional counseling. Moreover, food choices can influence the risk of developing the disease: a high consumption of dairy products has been associated with an increased risk of PD; conversely, many plant foods could elicit neuroprotective effects thanks to beneficial phytochemicals such as flavonoids, especially anthocyanins. Furthermore, a moderate coffee consumption could reduce PD risk and progression. The aim of this review is to explore the impact of dietary factors on the risk and progression of PD, evaluate the therapeutic potential of specific foods and dietary patterns in disease management, and highlight the clinical significance of nutritional interventions, specifically focusing on plant-based diets. Full article

Powder melt extrusion (PME) represents an alternative approach for personalized oral dosage forms. Furthermore, the utilization of agricultural waste has gained increasing attention because it helps reduce pollution from waste. This study investigated cellulose powders and short fibers from agricultural waste as supporting materials for the PME-based production of shape-changing levodopa printlets. Formulations containing cellulose powder (CP), cassava short fiber (CSF), and pineapple short fiber (PSF) demonstrated successful printing. The selected formulations were characterized for morphology, thermal transitions, crystallinity, shape-changing behavior, and drug release. CSF demonstrated superior printability, enhanced shape recovery, and the greatest reduction in crystallinity, supporting amorphous solid dispersion formation. Levodopa-loaded printlets showed uniform and high drug content. The formulation containing 5% CSF and levodopa exhibited the fastest initial release, attributed to its low crystallinity and Super Case II transport mechanism. Overall, this study highlights the feasibility of using natural cellulose as an additive in PME to develop sustainable, shape-changing drug delivery systems and advances PME knowledge by integrating agricultural waste derived cellulose fibers with levodopa processing that provide new insight into the material–process–performance relationship in PME systems. Full article

Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem disorder in which metabolic dysfunction may contribute to disease susceptibility and progression. Peripheral insulin resistance (IR) has been implicated in PD, but data in levodopa-naïve patients are currently limited. Objective: To investigate the prevalence of IR and metabolic dysfunction in early-stage, levodopa-naïve PD patients and their association with clinical features. Methods: We conducted an exploratory case–control study including 20 levodopa-naïve PD patients and 40 age-, sex-, and BMI-matched healthy controls. Participants underwent comprehensive clinical and metabolic assessments, including fasting glucose, insulin, lipid profiles, and HOMA-IR calculation. Peripheral IR was defined using HOMA-IR cut-offs of ≥2.0 (primary analysis) and ≥2.5 (sensitivity analysis). ANCOVA adjusted for age, sex, and BMI was used for between-group comparisons. Results: PD patients exhibited higher fasting insulin (10.7 ± 5.2 vs. 8.0 ± 4.4 µIU/mL; p = 0.020) and HOMA-IR (2.63 ± 1.40 vs. 1.89 ± 1.21; p = 0.014) compared to controls. Using a HOMA-IR ≥ 2.0, IR prevalence was 70% in PD vs. 32.5% in controls (OR = 4.85, 95% CI 1.52–15.50, p = 0.012). ANCOVA analysis confirmed group differences after adjusting for covariates (respectively, p = 0.032 for insulin and p = 0.023 for HOMA-IR). A sensitivity analysis excluding six patients receiving dopaminergic therapy further supported the robustness of the results. No significant correlations were observed between IR and disease severity scores. Conclusions: Early-stage, levodopa-naïve PD patients exhibit a higher prevalence of peripheral insulin resistance compared with matched controls. These findings support the hypothesis that metabolic dysfunction is an intrinsic component of PD pathophysiology and may represent a target for early intervention. Full article

Background/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson’s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-naïve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson’s Progression Markers Initiative (PPMI). The sample included 376 treatment-naïve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 ≥ 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [¹²³I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-naïve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores—reflecting greater motor severity—and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-naïve group. No significant differences were found in CSF biomarkers (α-synuclein, amyloid-β, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions. Full article

Background: Catechol-O-methyltransferase (COMT) catalyzes catecholamine O-methylation and contributes to dopamine turnover, potentially influencing levodopa requirements in Parkinson’s disease (PD). We evaluated whether the Gothelf COMT haplotype—and its constituent variants rs2075507, rs4680 (Val158Met), and rs165599—differ in frequency between PD cases and controls. We then tested associations between these variants and clinical phenotypes, with a prespecified focus on levodopa equivalent daily dose (LEDD). Finally, we examined whether haplotype structure and allele-specific context (e.g., background-dependent effects) help explain observed genotype–phenotype relationships in the PD cohort. Aim: Analysis of the rs2075507, rs4680 and rs165599 at individual and haplotype level between control and diseased groups. Furthermore, analysis of association of individual SNPs or haplotype level with clinical outcomes. Subjects and methods: Fifty-five individuals with Parkinson’s disease (PD) and fifty-three neurologically healthy controls were enrolled at a single center. Genomic DNA was isolated from peripheral blood, and three COMT variants—rs2075507 (promoter), rs4680/Val158Met (coding), and rs165599 (3′UTR)—were genotyped by Sanger sequencing. Allele, genotype, and tri-marker haplotype frequencies were estimated, and case–control differences were evaluated. Within the PD cohort, associations with clinical outcomes—primarily levodopa equivalent daily dose (LEDD)—were analyzed using multivariable linear models. Statistical tests were two-sided, with multiplicity control as specified in the corresponding tables. Results: The rs2075507 polymorphism showed a robust additive association with LEDD; each A allele predicted higher dose (LEDD ≈ +1331 mg/day, p = 0.001) after adjusting for age and sex. The tri-haplotype test did not show significant association with LEDD. Nevertheless, rs2075507 SNP strongly marked downstream backgrounds: in AA carriers, rs4680–rs165599 haplotypes were enriched for Val (G) and rs165599-G; in GG carriers, for rs165599-A with mixed Val/Met; and GA was A-loaded at both loci. Exact tests confirmed that AA and GG differed in rs4680–rs165599 composition, whereas GA vs. GG was not significant. Conclusions: The promoter variation at rs2075507 may represent the genetic contributor to levodopa dose requirements when modeled with SNP–SNP interactions, with its effect is modified mostly by rs165599 polymorphism. Tri-haplotypes do not independently predict LEDD. The rs4680 (coding) and rs165599 (3′UTR) context appears to fine-tune rather than determine dosing needs, mainly via interaction with rs2075507 SNP. Full article