BACKGROUND: Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson\'s disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored.
OBJECTIVE: This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD.
METHODS: Twelve participants with mild PD completed this randomized, double-blind, and sham-controlled experiment. Each of them received either 20-minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society-Unified Parkinson\'s Disease Rating Scale (MDS-UPDRS-III) in the \"medication-on\" state to assess the motor symptoms. The blinding efficacy and side effects were also assessed.
RESULTS: tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS-UPDRS-III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS.
CONCLUSIONS: This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger-scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

OBJECTIVE: The goal of this review was to investigate factors associated with physical activity and sedentary behavior in people with Parkinson disease (PD). The magnitude of these associations were investigated in line with the International Classification of Functioning, Disability and Health components.
METHODS: A systematic literature review was conducted until February 2023, searching 4 databases (PubMed, EMBASE, Web of Science, and Scopus) for original articles investigating associations with physical activity or sedentary behavior in people with PD. Two independent researchers performed data extraction, and the risk of bias in the included studies was assessed using the Quality in Prognosis Studies tool. Meta-analyses were conducted to determine the magnitude of the associations, and significant regression models from the included studies were described.
RESULTS: Forty-two studies were included. Twenty-one factors associated with overall physical activity were identified. Higher levels of physical activity had small association with cognition and body mass index, and fair association with 17 factors related to self-efficacy, physical function, mobility, quality of life, age, PD symptoms, and more. Better manual dexterity and functional gait had moderate to good association with higher levels of physical activity. The regression model with the higher magnitude was composed mostly of contextual factors, except for the body max index. The magnitude of factors associated with physical activity intensity or sedentary behavior could not be identified.
CONCLUSIONS: Functional gait and manual dexterity were the strongest factors related to physical activity in people with PD. Further investigation is needed to understand the factors associated with physical activity intensity and sedentary behavior.
CONCLUSIONS: This study emphasizes the significance of considering contextual factors alongside body function and structure, activity and participation, and the health condition to enhance physical activity improvement during the rehabilitation process. By adopting such holistic approach, rehabilitation professionals can optimize the overall health and wellbeing of individuals with Parkinson disease.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson\'s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD.
METHODS: A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models.
RESULTS: Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1-3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found.
CONCLUSIONS: The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels.
BACKGROUND: NCT04017481.

BACKGROUND: Dysgraphia, a recognized PD motor symptom, lacks effective clinical assessment. Current evaluation relies on motor assessment scales. Computational methods introduced over the past decade offer an objective dysgraphia assessment, considering size, duration, speed, and handwriting fluency. Objective evaluation of dysgraphia may be of help for early diagnosis of PD.
OBJECTIVE: Computerized assessment of dysgraphia in de novo PD patients and its correlation with clinical scales.
METHODS: We evaluated 38 recently diagnosed, premedication PD patients and age-matched controls without neurological disorders. Participants wrote \"La casa de Pamplona es bonita\" three times on paper and once on a Wacom tablet under the paper, totaling four phrases. Writing segments of 5-10 s were analyzed. The Wacom tablet captured kinematic data, including mean velocity, mean acceleration, and pen pressure. Data were saved in.svc format and analyzed using specialized software developed by Tecnocampus Mataró. Standard clinical practice data, Hoehn & Yahr staging, and UPDRS scales were used for evaluation.
RESULTS: Significant kinematic differences existed; patients had lower mean speed (27 ± 12 vs. 48 ± 18, p < 0.0001) and mean acceleration (7.2 ± 3.9 vs. 15.01 ± 7, p < 0.0001) than controls. Mean speed and mean acceleration correlated significantly with UPDRS III scores (speed: r = -0.52, p < 0.0007; acceleration: r = 0.60, p < 0.0001), indicating kinematic parameters\' potential in PD evaluation.
CONCLUSIONS: Dysgraphia is identifiable in PD patients, even de novo, indicating an early symptom and correlates with clinical scales, offering potential for objective PD patient evaluation.

UNASSIGNED: In the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson\'s disease on QoL of affected individuals. The Short Parkinson\'s Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson\'s disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale.
UNASSIGNED: Translation and cultural adaptation were performed. Included patients had diagnosis of Parkinson\'s disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach\'s Alpha and construct validity using Pearson\'s correlation between SPES-SCOPA and the gold standard PDQ-39.
UNASSIGNED: 101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach\'s Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements.
UNASSIGNED: This research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

To investigate the association between COVID-19 and Parkinson\'s disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (β = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.

UNASSIGNED: Remote programming (RP) is an emerging technology that enables the adjustment of implantable pulse generators (IPGs) via the Internet for people with Parkinson\'s disease (PwPD) who have undergone deep brain stimulation (DBS). Previous studies have not comprehensively explored the effectiveness of RP in managing motor symptoms, often omitting assessments such as the rigidity and retropulsion tests during the follow-up. This study evaluates the comprehensive improvements in motor performance and the potential cost benefits of RP for PwPD with DBS.
UNASSIGNED: A retrospective analysis was conducted on two groups of patients-those who received RP and those who received standard programming (SP). Clinical outcomes including motor improvement, quality of life, and daily levodopa dosage were compared between the groups during a 12 (± 3)-month in-clinic follow-up.
UNASSIGNED: A total of 44 patients were included in the study, with 18 in the RP group and 26 in the SP group. No significant differences were observed in the frequency of programming sessions or clinical outcomes between the groups (p > 0.05). However, the RP group experienced significantly lower costs per programming session than the SP group (p < 0.05), despite patients in the former group living further from our center (p < 0.05).
UNASSIGNED: Our findings suggest that RP could significantly reduce the costs of programming for PwPD with DBS, especially without compromising the effectiveness of treatment across all motor symptoms in the short term.

Parkinson\'s disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents.

As a neurologist who has followed up countless Parkinson\'s patients over the last 32 years of my fifty-year career; I denied diagnosing myself with Parkinson\'s disease (PD), although the seldom mild involuntary \"twitches\" that occurred in the thumb of my right hand over a two-year period, resembled Parkinson\'s disease tremor. However, when these involuntary contractions became persistent; considering its similarity to characteristic resting tremor in typical PD, the positive effect of dopaminergic medications, the development of levodopa-induced dyskinesias and other non-motor symptoms, it was clear that the PD diagnosis was accurate. This situation naturally caused me anxiety, and for a year and a half, I kept my diagnosis hidden from everyone except a few close relatives. However, with the encouragement of a psychiatrist friend, when I was able to share my condition with my loved ones, I felt a relative reduction in the burden I was carrying and consequently experienced emotional relief. I am still able to carry out my daily activities independently with a rather low dose of medication, and my PD symptoms do not attract noticeable attention.

UNASSIGNED: Parkinson\'s disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.
UNASSIGNED: Determine the correlation between the time of dopaminergic replacement treatment initiation and the severity of clinical symptoms in PD, including motor and non-motor symptoms.
UNASSIGNED: PD patients were divided between 155 people who were diagnosed de novo and 165 PD patients receiving dopamine replacement therapy. Basic patient characteristics included gender, age, age at onset, disease duration, and the time of dopaminergic replacement treatment initiation. We used MDS-UPDRS scores to evaluate the severity of motor symptoms and we also used the scale to assess the severity of non-motor symptoms such as cognition, mood, sleep, and quality of life.
UNASSIGNED: The mean time between symptom onset and the initiation of drug treatment was 31.0 (22.5) months. After adjusting for age, sex, age at onset, and disease duration, we found that the MDS-Unified Parkinson\'s Disease Rating Scale (UPDRS)-III score increased faster in the de novo group with a similar disease duration (F = 8.7, p = 0.0034) than the treatment group. The cumulative incidence of progression to H-Y score 3 in de novo PD group over disease duration was 39.7% in 50months and 92.2% in 100 months, while in treated group such cumulative incidence was 15.5% in 50 months, 51.4% in 100 months and 81.5% in 150 months. The cumulative incidence of patients in the de novo PD group was higher than that in the treated group (p = 0.001), suggesting that untreated patients were more likely to progress to the advanced stages. Symptoms onset, the time between symptom onset and treatment initiation, age, sex, and disease duration explained 28.95% of the total variation in the MDS-UPDRS-III score for motor symptoms. In drug-naïve patients, the time between symptom onset and treatment initiation explained 20.1% of the total variation in the MDS-UPDRS-III score for motor symptoms (t = 6.15, p < 0.001).
UNASSIGNED: These data in our study showed that early dopaminergic replacement treatment have played a positive role in PD patients, while dopaminergic replacement delayed treatment might be detrimental to motor symptoms and non-motor state of PD patient. Recognizing early stage symptoms of PD and early diagnosis are of great significance to treatment.