Parkinsonian Symptoms Research Articles

Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 μmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 μmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Predictors of stress resilience in Parkinson’s disease and associations with symptom progression

People with Parkinson’s disease (PD) are sensitive to effects of long-term stress, but might differ in stress resilience, i.e. the ability to maintain mental health despite adversity. It is unclear whether stress resilience in PD is predominantly determined by dopamine deficiency, psychosocial factors, or both. In PD animal models, chronic stressors accelerate disease progression, but evidence in humans is lacking. Our objectives were to (1) distinguish stressor-reactive from resilient PD patients, (2) identify resilience factors, and (3) compare symptom progression between stressor-reactive and resilient patients. We conducted a longitudinal survey in Personalized Parkinson Project participants (N = 350 PD). We used the COVID-19 pandemic as a model of a stressor, aligned in time for the entire cohort. COVID-19-related stressors, perceived stress, and PD symptoms were assessed at 11 timepoints (April-October 2020). Both pre-COVID and in-COVID clinical assessments were available. We quantified stressor-reactivity as the residual between actual and predicted perceived stress relative to COVID-19-related stressors, and modeled trajectories of stressor-reactivity across timepoints. We explored pre-COVID predictors of 6-month average stressor-reactivity, and tested whether stressor-reactivity was prospectively associated with one-year clinical progression rates. Latent class trajectory models distinguished patients with high (N = 123) or low (N = 227) stressor-reactivity. Pre-existing anxiety, rumination and non-motor symptom severity predicted high stressor-reactivity (risk factors), whereas quality of life, social support, positive appraisal style and cognitive abilities predicted low stressor-reactivity (resilience factors). PD-specific factors, e.g. disease duration, motor severity, and levodopa use, did not predict stressor-reactivity. The COVID-19 pandemic did not accelerate disease progression, but worsened depressive symptoms in stressor-reactive PD patients.

Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson’s disease

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson’s disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD.Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1β, which is subsequently secreted into the extracellular space. This secreted IL-1β then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Enhancing selegiline hydrochloride efficacy: Box Behnken-optimized liposomal delivery via intranasal route for Parkinson’s disease intervention

The clinical use of selegiline hydrochloride in conventional dosage forms is to reduce the progression of Parkinson’s disease (PD). However, its limited access to the brain, short half-life, and first-pass metabolism minimize brain uptake. Nano-based liposomes offer promising tools for brain-targeted delivery of therapeutics, especially intranasally administered cationic liposomes that target the brain region via the olfactory route and reduce biodistribution. In the present work, cationic liposomes encapsulated with selegiline hydrochloride were fabricated for intranasal administration against PD. The liposomes were initially optimized by Box Behnken design, and the selected run was coated with stearylamine to provide a cationic charge to the liposomes. The final coated liposomes, SH-LP3, demonstrated a minimum size of 173 ± 2.13 nm, an ideal zeta potential of +16 ± 1.98, and achieved a maximum entrapment efficiency of 40.14 ± 1.83%. Morphology analysis showed the spherical shape of liposomes in the size range of 100–200 nm. The in vitro cytotoxicity assay in SHSY5Y cell lines showed a significant decrease in toxicity, almost ten times less, compared to pure selegiline hydrochloride. Animal studies on rotenone-lesioned C57BL6 mice model for PD were performed to investigate the effect of intranasally administered liposomes. The SH-LP3 formulation exhibited remarkable effectiveness in relieving symptoms of PD. This extensive analysis emphasizes the possibility of intranasally administered SH-LP3 liposomes as a feasible treatment option for PD. The formulation not only delivers continuous drug release but also displays better safety and efficacy, providing a platform for additional studies and growth in the domain of PD treatment.

Bodily Maps of Symptoms and Emotions in Parkinson's Disease.

Emotions are reflected in bodily sensations, and these reflections are abnormal in psychiatric conditions. However, emotion-related bodily sensations have not been studied in neurological disorders. The aim of this study was to investigate whether Parkinson's disease (PD) is associated with altered bodily representations of emotions. Symptoms and emotion-related sensations were investigated in 380 patients with PD and 79 control subjects, using a topographical self-report method, termed body sensation mapping. The bodily mapping data were analyzed with pixelwise generalized linear models and principal component analyses. Bodily maps of symptoms showed characteristic patterns of PD motor symptom distributions. Compared with control subjects, PD patients showed decreased parasternal sensation of anger, and longer PD symptom duration was associated with increased abdominal sensation of anger (PFWE < 0.05). The PD-related sensation patterns were abnormal across all basic emotions (P < 0.05). The results demonstrate altered bodily maps of emotions in PD, providing novel insight into the nonmotor effects of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Interaction Between Nutraceuticals and Gut Microbiota: a Novel Therapeutic Approach to Prevent and Treatment Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms. Emerging research has shed light on the role of gut microbiota in the pathogenesis and progression of PD. Nutraceuticals such as curcumin, berberine, phytoestrogens, polyphenols (e.g., resveratrol, EGCG, and fisetin), dietary fibers have been shown to influence gut microbiota composition and function, restoring microbial balance and enhancing the gut-brain axis. The mechanisms underlying these benefits involve microbial metabolite production, restoration of gut barrier integrity, and modulation of neuroinflammatory pathways. Additionally, probiotics and prebiotics have shown potential in promoting gut health, influencing the gut microbiome, and alleviating PD symptoms. They can enhance the gut's antioxidant capacity of the gut, reduce inflammation, and maintain immune homeostasis, contributing to a neuroprotective environment. This paper provides an overview of the current state of knowledge regarding the potential of nutraceuticals and gut microbiota modulation in the prevention and management of Parkinson's disease, emphasizing the need for further research and clinical trials to validate their effectiveness and safety. The findings suggest that a multifaceted approach involving nutraceuticals and gut microbiota may open new avenues for addressing the challenges of PD and improving the quality of life for affected individuals.

Amantadine use in the French prospective NS-Park cohort.

To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Assessing the perception of Parkinson's disease in Al-Ahsa, Saudi Arabia among the visitors of a public campaign: before and after survey.

Insufficient knowledge and beliefs hinder the early diagnosis and provision of adequate treatment and care for PD patients, causing socio-economic burdens. Raising public awareness and understanding the knowledge gap is crucial for effective educational programs and early detection. This study aims to assess the perception of Parkinson's disease (PD) among visitors of a public campaign conducted to raise PD awareness and knowledge to facilitate early detection and management. A before-and-after study was conducted from May to June 2023, to assess the perception of PD among a public PD campaign visitors in Al-Ahsa, Saudi Arabia. The campaign included educational booths discussing PD symptoms, causes, diagnosis, management, and support. Participants completed a self-administered online questionnaire before and after the campaign. The data were analyzed using SPSS. The study included 48 eligible individuals. The mean knowledge score was significantly enhanced following the campaign, rising from 12 to 17.77 points (p < 0.05). The symptoms of PD that showed a significant difference were slow movement, tremors, depression, memory problems, and sleep problems. The campaign had a beneficial effect on participants' general understanding of PD. The study showed that public awareness campaigns successfully raised community awareness of PD. Participants' knowledge improved after the campaign, highlighting its positive effect. Further research could explore measuring the continuity of awareness over a longer period and its impact on improving patients' lives and could expand the sample size.

Predicting Depression in Parkinson's Disease Using Commonly Available PD Questionnaires.

Background: Depression is common in patients with Parkinson's disease (PD) and significantly impacts both the patients and their caregivers. The associations between depression and the responses from commonly used questionnaires for PD patients were assessed. New patients presenting to the Movement Disorder Center completed a number of questionnaires, including assessments of the motor and non-motor symptoms of PD, including depression. Methods: The PD patients were grouped according to severity of depression: none, mild, and moderate-severe, based on the Geriatric Depression Scale (GDS) scores. The mean scores of the Unified PD Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Non-motor Symptoms Scale (NMSS), PD Quality of life (PDQ-39), Hoehn and Yahr score (H&Y), levodopa equivalent daily dose (LEDD), and number of antidepressants used were collected. There were 1214 PD patients included. Results: Increasing depression scores were associated with worsening motor symptoms (according to the UPDRS and H&Y), non-motor symptoms (according to the NMSS), cognition (according to the MoCA), sleepiness (according to the ESS), and quality of life (according to the PDQ-39) (all p-values of p < 0.001). Only half of the patients with mild or moderate-severe depression were taking antidepressants, and the LEDD increased with depression severity. The risk of depression increased by 16% and 5% for every 1-point increase in the NMSS and PDQ-39 scores, respectively. Conclusions: Depression is often unrecognized and undertreated and should be assessed regularly in PD patients, especially in those who demonstrate changes in motor or non-motor symptoms.

Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson's Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods.

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.

An Ensemble of the Convolutional Neural Network Model with Fuzzy Fusion Rank Algorithm for the Identification of Parkinson’s Disease Using Magnetic Resonance Imaging Images

Abstract Background: Parkinson’s disease (PD) is a degenerative condition of the central nervous system primarily affecting the substantia nigra in the brain, resulting in the loss of dopamine-producing neurons and subsequent motor function deterioration. Early symptoms typically include hand tremors followed by bradykinesia, rigidity, postural instability, and decreased balance. Early diagnosis and proactive management are crucial for improving patients’ quality of life. Methods: In this study, an ensemble of deep learning (DL) models was developed to predict PD using DaTscan images. Initially, DL models (VGG16, ResNet50, Inception-V3 were utilized to classify PD in its early stage. Subsequently, to enhance the overall performance of the classification model, an ensemble strategy based on the fuzzy fusion rank algorithm was employed. The Parkinson’s Progression Markers Initiative database served as the evaluation dataset for the proposed model. This may offer some insight into why certain involuntary symptoms of PD occur, such as fatigue, irregular blood pressure, diminished peristalsis, and unexpected decreases in blood pressure. The ensemble model demonstrated superior recognition accuracy, precision, sensitivity, specificity, and F1-score, achieving 98.45%, 98.84%, 98.84%, 97.67%, and 98.84%, respectively. Results: Compared to individual models, the ensemble model demonstrated superior recognition accuracy, precision, sensitivity, specificity, and F1-score, achieving 98.92%, 98.84%, 98.84%, 97.67%, and 98.84%, respectively. In addition, a publicly available graphical user interface (GUI)-based software program was developed, leveraging magnetic resonance imaging for efficient and accurate classification of PD and its subclasses. The method outperformed contemporary techniques in PD detection, offering significant potential for real-time disease identification. Conclusion: The establishment of a GUI-based software application can substantially aid in the timely detection of PD, facilitating proactive management and improving patient outcomes. The study underscores the importance of leveraging advanced DL techniques and ensemble methods for accurate and efficient disease prediction. Moreover, the development of user-friendly software tools holds promise for widespread adoption and enhanced patient care in the field of PD diagnosis and management.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

A Mobile App for Comprehensive Symptom Management in People With Parkinson's Disease: A Pilot Usability Study.

There is an increasing need for highly accessible health management platforms for comprehensive symptoms of Parkinson disease. Mobile apps encompassing nonmotor symptoms have been rarely developed since these symptoms are often subjective and difficult to reflect what individuals actually experience. The study developed an app for comprehensive symptom management and evaluated its usability and feasibility. A single-group repeated measurement experimental design was used. Twenty-two participants used the app for 6 weeks. Monitoring of nonmotor symptoms, games to address motor symptoms, and medication management were incorporated in the app. Quantitative outcomes were self-assessed through an online questionnaire, and one-on-one telephone interviews were conducted to understand the user's point of view. The successful experience of self-monitoring had improved participants' self-efficacy ( Z = -3.634, P < .001) and medication adherence ( Z = -3.371, P = .001). Facilitators included a simple-to-use interface, entertaining content, and medication helps. Barriers included simple forgetfulness and digital literacy, including unfamiliarity with mobile phone manipulation itself. The study suggested insight into the app use related to acceptability of mobile technology. The preliminary effects on self-efficacy and medication adherence will guide future nursing interventions using mobile health. Our approach will contribute to improving the continuum of care for Parkinson disease by promoting self-monitoring of symptoms.

Depression in the elderly and dementia with Lewy bodies: A case report of a challenging diagnosis

IntroductionDepression and dementia with Lewy bodies (DLB) are two fairly common pathologies in the elderly which can have similar presentations or be associated and therefore pose a diagnostic challenge.ObjectivesWe propose to illustrate, through our case, the diagnostic and therapeutic challenge of these two pathologies.MethodsWe present the case of Ms. S. BA aged 67, without organic or psychiatric history, admitted to the psychiatry department for massive anxiety and insomnia. The troubles date back to nineteen months when the patient isolated herself, remained bedridden, lost her appetite and no longer slept. The evolution quickly led to the appearance of an excessive agitation. The patient became distracted, talking and laughing to herself, and ran away from the house. She consulted several free-lance psychiatrists and received several antipsychotic medications without improvement. The admission interview revealed a very anxious patient with a difficult contact. Her speech was centred on well-detailed visual hallucinations with themes of death. The neurological examination was difficult at first. She was started on haloperidol and clonazepam. After 2 days, neurological examination showed a parkinsonian syndrome and a temporal disorientation. Other cognitive functions were difficult to assess. The two diagnoses evoked were DLB and a characterized depressive episode with psychotic features. Standard workup showed mild anaemia and thrombocytopenia. Brain MRI and electroencephalogram and immune tests were normal. However, PET imaging was not available in our hospital. Haloperidol was immediately stopped and the patient was treated with an anticholinergic corrector in combination with quetiapine at 200 mg. The evolution was characterized by a significant reduction in anxiety and visual hallucinations with a marked improvement of the parkinsonian syndrome. Depressive symptoms took the forefront of the clinical presentation; hence we associated sertraline with quetiapine. The subsequent evolution showed a clear improvement in the depressive symptoms with total resolution of the parkinsonian symptoms and a normal cognitive evaluation.ResultsIn our case, the clinical evolution constituted a key element in the diagnostic orientation. So far, it is unlikely that our patient has DLB and the diagnosis retained was a characterized depressive episode with psychotic and melancholic features. Depression in the elderly can have atypical presentations, and raise the possibly of other differential diagnoses. Diagnostic uncertainty should not delay the implementation of treatment.ConclusionsThe choice of molecules must take into account the associated somatic symptoms for a better tolerance. In the absence of a biological or iconographic examination with good sensitivity and specificity, the therapeutic test remains the only way to decide.Disclosure of InterestNone Declared

Repercussões do isolamento social decorrente da pandemia da COVID-19 sobre sinais e sintomas de idosos com doença de Parkinson: revisão integrativa

Objective: To review the literature on the consequences of social isolation resulting from the COVID-19 pandemic on motor and non-motor signs and symptoms of elderly people with Parkinson's disease (PD). Method: This is an integrative review with a search in the following databases: PUBMED, LILACS and SCOPUS with filter for publications (November 2019), being proportional to the beginning of the COVID-19 outbreak (year 2020). Studies available in Portuguese, English or Spanish were included, with the elderly population (≥60 years) with PD, which assessed social isolation resulting from the pandemic as exposure and motor and/or non-motor symptoms of PD as an outcome. Studies that did not answer the guiding question and that did not comply with the proposed criteria were excluded. To analyze the methodological quality and the level of evidenced articles, the Critical Appraisal Skill Program and Agency for Health care and Research and Quality instruments were applied. To summarize the motor and non-motor signs and symptoms that worsened during social isolation, a coding criterion inspired by previous studies was used. Results: The final sample resulted in 8 articles. Elderly PD patients faced worsening motor symptoms, especially tremor and rigidity, and non-motor symptoms such as anxiety, depression, and fatigue. Conclusion: Social isolation resulting from the COVID-19 pandemic may have worsened the motor and non-motor symptoms of elderly people with Parkinson's disease. Therefore, it is important to implement multidisciplinary interventions, with a different perspective and care from the rehabilitation team in order to prevent biopsychosocial problems.

Ethanolic Extract of &lt;i&gt;Alternanthera Sessilis&lt;/i&gt;: A Potential Therapeutic Agent for Behavioral Improvements in Reserpine-Induced Parkinsonian Rats

The present study evaluated the potential of an ethanol extract from Alternanthera sessilis to alleviate reserpine-induced Parkinson's disease (PD) like behavioural manifestations in rats. The animals were grouped into five: a control group, a group receiving only reserpine, a group treated with levodopa and carbidopa, and two groups given different doses of the Alternanthera sessilis extract. Reserpine was used to mimic PD symptoms, while the extract was administered orally at two different concentrations. The behavioral tests were conducted to assess locomotor activity, grip strength, catalepsy, and rearing activity. Locomotor activity was measured using an actophotometer, where interruptions in light beams caused by the rates were recorded over a 10-minute period. Grip strength was evaluated using a rotarod apparatus, measuring the time taken for rats to fall off individual rods. Catalepsy was assessed through a bar test, measuring the time for rats to descend from a horizontal bar to the base. Rearing activity was observed in a round open field arena, with parameters including the occurrence rate of rearing, general movements score, and duration spent in the center of the arena. The results revealed administration of reserpine led to a decrease in body weight, locomotor activity, muscle coordination, catalepsy score, rearing activity, and grip strength compared to the control group. Conversely, treatment with levodopa and carbidopa resulted in increased values for these parameters. Importantly, administration of Alternanthera sessilis extract showed a dose-dependent reversal of the effects induced by reserpine, with significant increases observed in body weight, locomotor activity, muscle coordination, rearing activity, general movement, and grip strength, indicating its potential therapeutic effects. In conclusion, the present study results suggest that the extract from the Alternanthera sessilis plant might protect brain cells and improve symptoms of Parkinson's disease. However, more research is needed to understand how it works and if it can be used safely and effectively clinical trails.

Biochemical properties and biological potential of Syzygium heyneanum with antiparkinson's activity in paraquat induced rodent model.

Syzygium heyneanum is a valuable source of flavonoids and phenols, known for their antioxidant and neuroprotective properties. This research aimed to explore the potential of Syzygium heyneanum ethanol extract (SHE) in countering Parkinson's disease. The presence of phenols and flavonoids results in SHE displaying an IC50 value of 42.13 when assessed in the DPPH scavenging assay. Rats' vital organs (lungs, heart, spleen, liver, and kidney) histopathology reveals little or almost no harmful effect. The study hypothesized that SHE possesses antioxidants that could mitigate Parkinson's symptoms by influencing α-synuclein, acetylcholinesterase (AChE), TNF-α, and IL-1β. Both in silico and in vivo investigations were conducted. The Parkinson's rat model was established using paraquat (1 mg/kg, i.p.), with rats divided into control, disease control, standard, and SHE-treated groups (150, 300, and 600 mg/kg) for 21 days. According to the ELISA statistics, the SHE treated group had lowers levels of IL-6 and TNF-α than the disease control group, which is a sign of neuroprotection. Behavioral and biochemical assessments were performed, alongside mRNA expression analyses using RT-PCR to assess SHE's impact on α-synuclein, AChE, TNF-α, and interleukins in brain homogenates. Behavioral observations demonstrated dose-dependent improvements in rats treated with SHE (600 > 300 > 150 mg/kg). Antioxidant enzyme levels (catalase, superoxide dismutase, glutathione) were significantly restored, particularly at a high dose, with notable reduction in malondialdehyde. The high dose of SHE notably lowered acetylcholinesterase levels. qRT-PCR results indicated reduced mRNA expression of IL-1β, α-synuclein, TNF-α, and AChE in SHE-treated groups compared to disease controls, suggesting neuroprotection. In conclusion, this study highlights Syzygium heyneanum potential to alleviate Parkinson's disease symptoms through its antioxidant and modulatory effects on relevant biomarkers.

Data-driven Gait based Severity Classification for Parkinson's Disease using Duo Spatiotemporal Convoluted Kernel Boosted ResNet model

Parkinson’s disease (PD) is one of the reformed brain syndromes that results in unintended stiffness and difficulty with balance and dexterity. To detect PD in medical scenery, physicians commonly use experimental indicators like motorized and non-motor symptoms and the severity rating depends on the unified PD Rating Scale (UPDRS). However, these medical assessments highly rely on expertized clinicians and lead to inter-variability discrepancies. Nowadays, gait sensor data assists doctors in diagnosing PD and estimates the severity level of gait abnormalities in patients. However, the gait sensor data increases the dimensionality issues and is subjected to high non-linear complexity. Hence, this study suggests an innovative deep learning (DL) technique for accurate PD analysis using gait patterns. Initially, the gait sensor data is preprocessed by performing data cleaning, and decimal scaling normalization (DS- Norm) to enhance the data quality. The Hoehn and Yahr (H&amp;amp;Y) scale is a commonly used rating scale for measuring the progression of Parkinson's disease symptoms. It's typically used to assess motor symptoms like tremors, rigidity, and bradykinesia. The scale ranges from 0 to 5, with higher numbers indicating more severe symptoms and disability. The preprocessed data are then fed into the proposed Duo spatiotemporal convoluted kernel boosted ResNet (DSCK-RNet) model for classifying the PD severity rating by learning the gait spatiotemporal features. The developed method is processed and scrutinized via the Python platform and a publicly available Physio- Net dataset is utilized for the simulation process. Various assessment measures like accuracy, precision, sensitivity, specificity, PPV, FPR, and MCC are examined and compared with traditional studies. In the experimental section, the developed DSCK-RNet model achieved an accuracy of 100%, 99.6%, 99%, and 99.64% for different classes like healthy, severity-2, severity-2.5, and severity-3 respectively. Compared to the conventional techniques, our suggested approach performs better. The experimental findings demonstrate the clinical significance of the suggested approach for the impartial evaluation of gait motor impairment in PD patients.

Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease

IntroductionIntestinal inflammation and gut microbiota dysbiosis can stimulate degeneration of dopaminergic neurons and development of Parkinson's disease (PD) via the gut-brain axis in certain patients. MethodsIn a case-control study, fecal markers of intestinal inflammation and permeability were measured using the ELISA method in PD patients and healthy controls. Motor and nonmotor symptoms were assessed using the Movement Disorder Society (MDS) Unified PD Rating Scale, Hoehn & Yahr scale, MDS Non-Motor Symptom Scale, Scales for Outcomes in PD - Autonomic Dysfunction, PD Sleep Scale - 2, Montreal Cognitive Assessment, Beck Anxiety Inventory, and Beck Depression Inventory-II. A correlation was established between the intestinal inflammation and permeability markers and PD symptoms. ResultsHigher levels of beta-defensin 2, zonulin and lactoferrin were recorded in PD patients compared to controls. Calprotectin and secretory immunoglobulin A showed no significant differences. Regression analysis indicated the roles of beta-defensin 2 and lactoferrin in predicting PD likelihood. Calprotectin yielded positive correlations with disease duration, depression, motor fluctuations, and gastrointestinal symptoms; beta defensin 2 with thermoregulation; and secretory immunoglobulin A with depression. Secretory immunoglobulin A showed negative correlation with age and age at disease onset, while zonulin showed negative correlation with the MDS Unified PD Rating Scale total score. ConclusionsFecal markers differed in PD patients compared to controls and correlated with age, disease duration, and some nonmotor symptoms. Future studies should identify the subgroups of PD patients that are likely to develop intestinal inflammation.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale-HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications.