Parkinson\'s disease (PD) is an idiopathic disease caused by the loss or degeneration of the dopaminergic (dopamine-producing) neurons in the brain and characterized by various inflammatory and apoptotic responses in the neuronal cells. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis is responsible for neuronal survival by providing a number of anti-inflammatory and anti-apoptotic milieu that prevent the progression of PD. Alpha-lipoic acid (ALA) is a natural cofactor that has antioxidant capacity and contributes to various metabolic processes. ALA can penetrate the blood-brain barrier and contribute to numerous neuroprotective effects. It can activate PI3K/AKT pathway with consequent reduction of different inflammatory and oxidative biomarkers. Our work aims to unfold the neuroprotective effects of ALA via targeting PI3k/AKT pathway. Forty male mice were divided into four groups: control, ALA (100 mg/kg/day; i.p.), rotenone (ROT) (1.5 mg/kg/2 days, i.p.) and rotenone + ALA for 21 days. ALA showed obvious neuroprotective effects via significant activation of PI3K/AKT pathway with subsequent decreasing level of Caspase-3. ALA resulted in prominent anti-inflammatory actions by decreasing interlukin-1β (IL-1β), tumor necrosis factor (TNF)-α and nuclear factor kabba (NFk)-B. ALA remarkably induced antioxidant activities via increasing reduced glutathione (GSH) and superoxide dismutase (SOD) levels as well as decreasing malondialdehyde (MDA) level. The substantial behavioral improvement reflected in these results was noticed in the ALA-treated mice as a reflection of the neuroprotective activities of ALA. In conclusion, ALA showed promising neuroprotective effects in rotenone-induced PD via activating the PI3K/AKT pathway and consequent inhibition of apoptotic and inflammatory biomarkers.

BACKGROUND: The efficacy of continuous subcutaneous apomorphine infusion (CSAI) for motor complications of Parkinson\'s disease (PD) is established. However, its effect on cognition and behavior remains controversial. The main objective of this systematic review was to describe the existing literature on the effects of CSAI on cognition and behavior and to determine the quality for each study.
METHODS: PubMed/Medline, Embase, APA PsycInfo®, and Cochrane Library databases were searched, following PRISMA recommendations. Only longitudinal studies evaluating the effect of CSAI on cognition (global cognition, executive functions, visuospatial abilities, language, memory, attention, social cognition) and/or behavior (depression, anxiety, apathy, psychotic symptoms, impulse control disorders, neuropsychiatric fluctuations) in PD were included. The quality of the included studies was also assessed with a questionnaire.
RESULTS: Twenty-three longitudinal studies evaluated the effect of CSAI on cognition and/or behavior. Overall, results were suggestive of positive effects, notably on executive functions and emotion recognition. However, there were some reports of cognitive slowing and long-term global cognitive deterioration. At the behavioral level, no study showed significant adverse effect of CSAI. Occasionally, a slight improvement of depression, anxiety, apathy, and neuropsychiatric fluctuations was reported. Nevertheless, only four studies met good quality criteria and controlled study regarding cognition were lacking.
CONCLUSIONS: The results suggest that CSAI has no obvious negative effects on cognition and behavior in PD. This treatment even shows promise in reducing certain symptoms such as neuropsychiatric fluctuations. However, due to methodological limitations in many studies, no robust conclusions can be drawn. Further multicenter controlled trials are needed to confirm these results.

Amidst rising Parkinson\'s disease (PD) incidence in an aging global population, the need for non-invasive and reliable diagnostic methods is increasingly critical. This review evaluates the strategic role of transcranial sonography (TCS) in the early detection and monitoring of PD. TCS\'s ability to detect substantia nigra hyperechogenicity offers profound insights into its correlation with essential neuropathological alterations-namely, iron accumulation, neuromelanin depletion, and glial proliferation-fundamental to PD\'s pathophysiology. Our analysis highlights TCS\'s advantages, including its non-invasiveness, cost-effectiveness, and ease of use, positioning it as an invaluable tool for early diagnosis and continual disease progression monitoring. Moreover, TCS assists in identifying potential risk and protective factors, facilitating tailored therapeutic strategies to enhance clinical outcomes. This review advocates expanding TCS utilization and further research to maximize its diagnostic and prognostic potential in PD management, contributing to a more nuanced understanding of the disease.

BACKGROUND: Individuals with Parkinson disease (PD) can improve their overall mobility and participation in daily activities as they engage in frequent exercise. Despite the need for individually tailored exercises, persons with PD often face barriers to accessing physical rehabilitation professionals who can provide them. Telerehabilitation (TR) may facilitate access to necessary and individually tailored rehabilitation for individuals with PD.
OBJECTIVE: The purpose of this study was to assess the feasibility of TR for individuals with PD and explore clinical outcomes compared to in-person care.
METHODS: This was a pilot randomized controlled trial conducted at 2 outpatient neurorehabilitation clinics with 3 study groups: clinic+TR, TR-only, and usual care (UC). TR was administered using a web-based application with a mobile app option. One-hour interventions were performed weekly for 4 weeks, in-person for the clinic+TR and UC groups and virtually for the TR-only group. Home exercises were provided on paper for the UC group and via the web-based platform for the clinic+TR and TR-only groups. Feasibility was assessed by recruitment and retention success and patient and therapist satisfaction, as rated in surveys. Clinical outcomes were explored using performance and patient-reported measures in between- and within-group analyses.
RESULTS: Of 389 patients screened, 68 (17.5%) met eligibility criteria, and 20 (29.4% of those eligible) were enrolled (clinic+TR, n=6; TR-only, n=6; and UC, n=8). One patient (TR-only) was withdrawn due to a non-study-related injurious fall. Regardless of group allocation, both patients and therapists generally rated the mode of care delivery as \"good\" or \"very good\" across all constructs assessed, including overall satisfaction and safety. In the analysis of all groups, there were no differences in clinical outcomes at the discharge visit. Within-group differences (from baseline to discharge) were also generally not significant except in the UC group (faster 5-time sit-to-stand time and higher mini balance evaluation systems test balance score) and clinic+TR group (higher mini balance evaluation systems test balance score).
CONCLUSIONS: High satisfaction amongst patients and clinicians regardless of group, combined with nonsignificant between-group differences in clinical outcomes, suggest that TR is feasible for individuals with PD in early-moderate stages. Future trials with a larger sample are necessary to test clinical effectiveness. As larger trials enroll patients with diverse characteristics (eg, in terms of age, disease progression, caregiver support, technology access and capacity, etc), they could begin to identify opportunities for matching patients to the optimal utilization of TR as part of the therapy episode.
BACKGROUND: ClinicalTrials.gov NCT06246747; https://clinicaltrials.gov/study/NCT06246747.

OBJECTIVE: The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell-derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation.
METHODS: Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 × 105 to 1.1 × 105 cells/µL) under real-time intraoperative MRI guidance. The infusates were combined with 1-mM gadoteridol (for intraoperative MRI visualization) and delivered via two tracks per hemisphere (ventral and dorsal) using a transaxial approach. The total volumes of infusion were 25 µL and 50 µL for the right and left putamen, respectively (infusion rate 2.5 µL/min). Animals were evaluated with a battery of clinical and behavioral outcome measures and euthanized 7 or 30 days postsurgery; full necropsies were performed by a board-certified veterinary pathologist. Brain tissues were collected and processed for immunohistochemistry, including against the human-specific marker STEM121.
RESULTS: The optimized surgical technique and tools produced successful targeting of the putamen via the transaxial approach. Intraoperative MR images confirmed on-target intraputaminal injections in all animals. All animals survived to scheduled termination without clinical evidence of neurological deficits. The first 4 animals to undergo surgery had mild brain swelling noted at the end of surgery, of which 3 had transient reduced vision; administration of mannitol therapy and reduced intravenous fluid during the surgical procedure addressed these complications. Immunostaining against STEM121 confirmed the presence of grafted cells along the injection track within the targeted putamen area of DANPC-treated animals. All adverse histological findings were limited in scope and consistent with surgical manipulation, injection procedure, and postsurgical inflammatory response to the mechanical disruption caused by the cannula insertion.
CONCLUSIONS: The delivery system, injection procedure, and DANPCs were well tolerated in all animals. Prevention of mild brain swelling by mannitol dosing and reduction of intravenous fluids during surgery allowed visual effects to be avoided. The results of the study established that this novel transaxial approach can be used to correctly and safely target cell injections to the postcommissural putamen and support clinical investigation.

Movement disorders are chronic neurological syndromes with both treatable and non-treatable causes. The top causes of movement disorders are Parkinson\'s disease and related disorders. Functional imaging investigations with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) images play vital roles in diagnosis and differential diagnosis to guide disease management. Since there have been new advanced imaging technologies and radiopharmaceuticals development, there is a need for up-to-date consensus guidelines. Thus, the Nuclear Medicine Society of Thailand, the Neurological Society of Thailand, and the Thai Medical Physicist Society collaborated to establish the guideline for Nuclear Medicine investigations in movement disorder for practical use in patient care. We have extensively reviewed the current practice guidelines from other related societies and good quality papers as well as our own experience in Nuclear Medicine practice in movement disorders. We also adjust for the most suitability for application in Thailand and other developing countries.

BACKGROUND: Parkinson\'s disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5-10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings.
METHODS: Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features.
RESULTS: A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion \"age of onset < 55 years\" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03).
CONCLUSIONS: Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies.

Parkinson\'s disease (PD) is a progressive neurodegenerative disorder primarily associated with motor dysfunctions. By the time of definitive diagnosis, about 60% of dopaminergic neurons have already been lost; moreover, even if dopaminergic drugs are highly effective in symptoms control, they only help maintaining a near-healthy condition when started as soon as possible. Therefore, interest in identifying early biomarkers of PD has grown in recent years, especially using neurophysiological techniques such as electroencephalography (EEG). This study aims to investigate brain complexity differences in PD patients compared to healthy controls, focusing on the beta band using approximate entropy (ApEn) analysis of resting-state EEG recordings. Sixty participants were recruited, including 25 PD patients and 35 healthy elderly subjects, matched for age and gender. EEG were recorded for each participant and ApEn values were computed in the beta 1 (13-20 Hz) and beta 2 (20-30 Hz) frequency bands for each EEG-channel and for ROIs. PD patients showed statistically lower ApEn values compared to controls in both beta 1 and beta 2 bands. Regarding electrodes analysis, beta 1 band alterations were found in frontocentral areas, while beta 2 band alterations were observed in centroparietal and frontocentral areas. Considering ROIs, statistically lower ApEn values for PD patients has been reported in central and parietal ROIs in the beta 2 band. Complexity reduction in these areas may underlie beta oscillatory activity dysfunction, reflecting impaired cortical mechanisms associated with motor dysfunction in PD. The results suggest that ApEn analysis of resting EEG activity may serve as a potential tool for early PD detection. Further studies are necessary to validate this approach in PD diagnosis and rehabilitation planning.

BACKGROUND: Patients with pre-existing neurologic disorders present a unique set of challenges for shoulder arthroplasty (SA) surgeons due to the presence of concomitant contractures, muscle weakness, and spasticity, which may affect outcomes and complication rates after shoulder arthroplasty. The goal of this systematic review was to evaluate the clinical and functional outcomes after SA in patients pre-existing with neurologic disorders, focusing on complication and reoperation rates.
METHODS: This systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines outlined by Cochrane Collaboration. A search of PubMed, the Medline Library, and EMBASE from inception until September 2023 was conducted to obtain studies reporting on outcomes after SA in patients with neurological disorders. Study demographics and information on outcomes including patient-reported outcomes and complication rates were collected. The methodological quality of included primary studies was appraised using the MINORS scoring system.
RESULTS: Twenty articles published between 1997 and 2023 met inclusion criteria. In total, 13,126 patients with neurological conditions with 7 different neurological disorders (Parkinson\'s disease (PD), epilepsy and seizures, cerebral palsy (CP), poliomyelitis, Charcot neuropathy (CN), cerebrovascular disease (CVD) and multiple sclerosis (MS)) were included. The mean patient age was 64.3 years (range, 33.0 - 75.8 years), 51.4% of patients were male, and the mean postoperative follow-up time was 5.1 years (range, 1.4 - 9.9 years). PD was the most reported neurological disorder (9 studies, 8,033 patients), followed by epilepsy (4 studies, 3,783 patients), and MS (1 study, 1,077 patients). While these patients did experience improvements in outcomes following SA, high complication and revision rates were noted.
CONCLUSIONS: Patients with neurologic disorders demonstrate improvements in pain and function after SA but have higher reported complication and revision rates when compared with patients without neurologic conditions. This systematic review offers valuable data for both the surgeon and patient regarding anticipated clinical results and possible complications from SA in patients with neurologic disorders that may aid in shared decision-making when considering SA.

Objectives. Parkinson patients often suffer from motor impairments such as tremor and freezing of movement that can be difficult to treat. To unfreeze movement, it has been suggested to provide sensory stimuli. To avoid constant stimulation, episodes with freezing of movement needs to be detected which is a challenge. This can potentially be obtained using a brain-computer interface (BCI) based on movement-related cortical potentials (MRCPs) that are observed in association with the intention to move. The objective in this study was to detect MRCPs from single-trial EEG.Approach. Nine Parkinson patients executed 100 wrist movements and 100 ankle movements while continuous EEG and EMG were recorded. The experiment was repeated in two sessions on separate days. Using temporal, spectral and template matching features, a random forest (RF), linear discriminant analysis, and k-nearest neighbours (kNN) classifier were constructed in offline analysis to discriminate between epochs containing movement-related or idle brain activity to provide an estimation of the performance of a BCI. Three classification scenarios were tested: 1) within-session (using training and testing data from the same session and participant), between-session (using data from the same participant from session one for training and session two for testing), and across-participant (using data from all participants except one for training and testing on the remaining participant).Main results. The within-session classification scenario was associated with the highest classification accuracies which were in the range of 88%-89% with a similar performance across sessions. The performance dropped to 69%-75% and 70%-75% for the between-session and across-participant classification scenario, respectively. The highest classification accuracies were obtained for the RF and kNN classifiers.Significance. The results indicate that it is possible to detect movement intentions in individuals with Parkinson\'s disease such that they can operate a BCI which may control the delivery of sensory stimuli to unfreeze movement.