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BackgroundIf Parkinson’s Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD patients.ObjectiveIn the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine.MethodA case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored.ResultsOut of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (p < 0.001) and diabetes (p = 0.049) compared to non-COVID-19. In non-COVID-19 PD population (n = 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases.ConclusionA higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it.

Background and purpose Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN‐DBS) on motor and non‐motor symptoms in patients with primary Meige syndrome. Methods Thirty patients who underwent bilateral STN‐DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health‐related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. Results The Burke−Fahn−Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke−Fahn−Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow‐up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. Conclusions Bilateral STN‐DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, best known for its motor symptoms such as resting tremor, muscle rigidity, and bradykinesia. However, autonomic dysfunction is an important non-motor aspect that often brings considerable discomfort and distress to both patients and their families. In this review, we summarize recent advances in understanding the pathophysiological mechanisms of autonomic dysfunction and explore its relationship with other clinical features. Our aim is to discover novel potential diagnostic and therapeutic strategies, alleviate patient suffering, and pave the way for future clinical and basic research.

Parkinson's disease (PD) is often associated with orthostatic hypotension (OH). However, research examining the relationship between OH and PD has yielded inconsistent results. This study conducts a meta-analysis to determine the associations between OH and clinical characteristics in individuals with PD. A systematic review and meta-analysis were performed by searching for studies related to PD and OH in the PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate the odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI) for OH in PD patients. Heterogeneity was assessed using the I statistic. Meta-regression was conducted to detect the potential influences of disease duration on the differences in clinical features between PD patients with and without OH. A total of 26 articles involving 3,992 patients with Parkinson's disease were included in our study. Patients with PD and OH were significantly older at the time of examination compared to those without OH (WMD 2.94 years, 95% CI 1.91-3.97 years; I = 64.1%). PD patients with OH had a significantly longer disease duration than those without OH (WMD 0.73, 95% CI 0.32-1.14). Furthermore, PD patients with OH exhibited significantly lower Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores than those without OH (WMD of - 0.99, 95% CI of -1.91 to -0.07; WMD of -1.86, 95% CI of -2.67 to -1.04). There were no significant differences in gender distribution, Hamilton Anxiety Rating Scale (HAMA) or Hamilton Depression Rating Scale (HAMD) scores among Parkinson's disease patients with or without OH. Patients with PD and OH tend to be older at the time of examination, exhibit a longer disease duration, and demonstrate more severe disease manifestations along with greater cognitive impairment compared to PD patients without OH. https://www.crd.york.ac.uk/prospero/, identifier CRD420251025263.

In Parkinson's Disease (PD), deep brain stimulation of the subthalamic nucleus (STN‐DBS) reliably improves motor symptoms, and the circuits mediating these effects have largely been identified. However, non‐motor outcomes are more variable, and it remains unclear which specific brain circuits need to be modulated or avoided to improve them. Since numerous non‐motor symptoms potentially respond to DBS, it is challenging to independently identify the circuits mediating each one of them. Data compression algorithms such as principal component analysis (PCA) may provide a powerful alternative. This study aimed at providing a proof of concept for this approach by mapping changes along extensive score batteries to a few anatomical fiber bundles and, in turn, estimating changes in individual scores based on stimulation of these tracts. Retrospective data from 56 patients with PD and bilateral STN‐DBS was included. The patients had undergone comprehensive clinical assessments covering changes in appetitive behaviors, mood, anxiety, impulsivity, cognition, and empathy. PCA was implemented to identify the main dimensions of neuropsychiatric and neuropsychological outcomes. Using DBS fiber filtering, we identified the structural connections whose stimulation was associated with change along these dimensions. Then, estimates of individual symptom outcomes were derived based on the stimulation of these connections by inverting the PCA. Finally, changes along a specific non‐motor score were estimated in an independent validation dataset (N = 68) using the tract model. Four principal components were retained, which could be interpreted to reflect (i) general non‐motor improvement; (ii) improvement of mood and cognition and worsening of trait impulsivity; (iii) improvement of cognition; and (iv) improvement of empathy and worsening of impulsive‐compulsive behaviors. Each component was associated with the stimulation of spatially segregated fiber bundles connecting regions of the frontal cortex with the subthalamic nucleus. The extent of stimulation of these tracts was able to explain significant amounts of variance in outcomes for individual symptoms in the original cohort (circular analysis), as well as in the rank of depression outcomes in the independent validation cohort. Our approach represents an innovative concept for mapping changes along extensive score batteries to a few anatomical fiber bundles and could pave the way toward personalized deep brain stimulation. Delivering stimulation to the correct target is a challenge for deep brain stimulation. We propose a new approach that allows condensing a large battery of scores onto a few main dimensions, identifying the structural connections associated with each dimension, and estimating changes in individual scores based on their stimulation.

BackgroundFrailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson’s disease (PD).MethodsWe consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations.ResultsFrail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when “traditional” predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered.ConclusionsThe present findings indicate that the FI is associated with both motor and non-motor features of PD.

Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression. 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. PD patients were divided between 155 people who were diagnosed 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. 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 group with a similar disease duration (F = 8.7, = 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 PD group was higher than that in the treated group ( = 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 ( = 6.15, < 0.001). 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.

Parkinson's disease (PD) is a prevalent, disabling neurodegenerative disorder. Early diagnosis and treatment of PD remains challenging due to the absence of definitive diagnostic tests and the non-specificity of its clinical manifestations. Initial consultations for PD symptoms often involve specialists who are not specifically trained in PD. Consequently, it is imperative to assess the general knowledge regarding PD among these specialists to develop optimal educational strategies and enhance early recognition and diagnosis of PD. We developed a questionnaire covering motor symptoms, non-motor symptoms, prodromal symptoms, risk factors and antiparkinsonian medications based on published guidelines, and conducted the web-based survey via (https://www.wjx.cn/) among physicians not specializing in PD in Guangdong Province, China. A total of 312 respondents, working in 28 diverse departments across 64 hospitals of three different categories, were eligible for data analysis. Notably, 95.2% of the respondents were aware of rest tremor as a motor symptom, yet only 76.9% recognized bradykinesia as a motor symptom. Regarding non-motor symptoms, erectile dysfunction, urinary dysfunction, restless legs, olfactory loss, orthostatic hypotension, rapid eye movement behavior disorder (RBD), lower back pain and diaphoresis, were recognized by less than 50% of the respondents. Additionally, with the exception of subthreshold parkinsonism or abnormal quantitative motor testing, prodromal symptoms such as excessive daytime somnolence, depression (± anxiety), olfactory loss, urinary dysfunction, RBD, and constipation were recognized by 36.5-48.7% of the respondents. First-degree relatives with PD received recognition from 86.5% of the respondents, whereas the remaining risk factors were recognized by 50-60% of the participants. Concerning protective factors for PD, recognition was limited to no more than 23%. Levodopa and dopamine releasers were the most widely recognized antiparkinsonian medications, while the recognition of other medications was below 70%. Variables such as medical degrees, professional titles, hospital categories, and education subjects contributed to statistical differences in PD knowledge. Among non-PD specialists in south China, current knowledge regarding PD, including non-motor symptoms, prodromal symptoms, risk and protective factors, and antiparkinsonian medications, is relatively inadequate. This necessitates targeted education and training to improve their understanding and recognition of PD.

Background Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction (NMJ), driven by T cells, mediated by B cells, and dependent on autoantibodies. In addition to the typical motor symptoms of fluctuating weakness, the non‐motor symptoms are also prevalent among MG patients. This review aims to present the non‐motor symptoms of MG and their potential pathogenesis, hoping to contribute to personalized diagnosis and treatment. Methods This review elaborates the non‐motor symptoms of MG and systematically detail, for the first time, their potential pathogenic mechanisms, offering a new perspective for clinical evaluation. Results The non‐motor symptoms of MG include autonomic disorders (urinary, gastrointestinal, cardiovascular and ocular dysfunction), sensory disability (olfactory abnormalities, gustatory reduction and headaches), cognitive impairment, sleep disturbances, psychological problems (depression and anxiety), and TAMG‐associated specific syndromes. Due to their insidious onset and lack of awareness, these symptoms are often overlooked. We review the non‐motor symptoms of MG and first provide a systematic and detailed discussion on their potential mechanisms, including the influence of MG‐specific antibodies (cross‐reactivity of AChR‐Ab, expression of MuSK‐Ab, and striational antibodies at related functional sites), dysregulation of inflammatory factors and immune cells, collateral effects of motor symptoms, impacts of MG comorbidities, and paraneoplastic syndromes caused by thymoma. Conclusion Non‐motor symptoms are common in MG patients. Given a series of potential mechanisms probably involved exploring these non‐motor symptoms will not only enhance our understanding of MG but also aid in diagnosis and the development of precise, personalized treatments, ultimately improving the overall life quality of patients. We review the non‐motor symptoms of MG and their potential pathogenesis, hoping to contribute to personalized diagnosis and treatment.

Oromandibular dystonia (OMD) refers to a focal dystonia in the stomatognathic system. Health-related quality of life (HRQoL) in isolated dystonia is associated with non-motor symptoms such as depression, anxiety, and pain, as well as motor symptoms. To evaluate HRQoL in patients with OMD, the therapeutic effects of botulinum neurotoxin (BoNT) therapy were assessed using a recently developed and validated comprehensive measurement tool called the Oromandibular Dystonia Rating Scale (OMDRS). Altogether, 408 patients (jaw closing dystonia, n = 223; tongue (lingual) dystonia, n = 86; jaw opening dystonia, n = 50; jaw deviation dystonia, n = 23; jaw protrusion dystonia, n = 13; and lip (labial) dystonia, n = 13) were evaluated at baseline and after the end of BoNT therapy or in a stable status. The total OMDRS score reduced significantly from 149.1 to 57.6 (p < 0.001). Mean improvement was 63.1%. All examiner-rated subscales (severity, disability, and pain) and patient-rated questionnaire scores (general, eating, speech, cosmetic, social/family life, sleep, annoyance, mood, and psychosocial function) were significantly lower at the endpoint than at baseline (p < 0.001). The BoNT injection had a highly positive impact on patient HRQoL, and the OMDRS could evaluate both motor phenomena and non-motor symptoms.