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Background Objectives Methods Results Conclusions Patients with Parkinson's Disease (PD) frequently exhibit non‐motor symptoms, particularly sleep disturbances. Sleep disorders in PD patients are intricately linked to the pathogenesis and progression of PD itself, exacerbating neurodegenerative processes and worsening patient quality of life.This review underscores the significance of sleep disorders in PD, highlighting their prevalence, impact on disease progression, and the bidirectional relationship between sleep disruption and neurodegeneration. It aims to enhance clinician awareness for better diagnosis and management of sleep‐related comorbidities in PD.A comprehensive literature search was conducted in PubMed and Scopus using key terms such as “sleep disorders”, “Parkinson's disease”, “REM sleep behavior disorder”, “restless legs syndrome”, “insomnia”, “obstructive sleep apnea”, “excessive daytime sleepiness”, “circadian rhythm disorders”, “sleep and neurodegeneration”.Sleep disorders are prevalent in PD affecting up to 90% of patients. Conditions such as insomnia, REM sleep behavior disorder, restless legs syndrome, obstructive sleep apnea, excessive daytime sleepiness, and circadian rhythm disorders are commonly reported. These disorders are linked to multifactorial biological mechanisms and are associated with more severe disease phenotypes. Of note, several evidence shows that sleep abnormalities may contribute to neuroinflammation and neurodegeneration, further accelerating the disease course.Sleep disturbances are critical non‐motor symptoms in PD. Early diagnosis and tailored management of sleep disorders are essential for improving clinical outcomes and potentially offering neuroprotective benefits. [ABSTRACT FROM AUTHOR]

Background: Physical activities performed under free-living conditions that are unsupervised in the home or community have the potential to modulate non-motor symptoms in people with Parkinson's disease. Objective: This systematic review investigates the relationships between physical activities performed in free-living conditions and non-motor symptoms in people with Parkinson's disease: cognition, anxiety, apathy, depression, sleep disturbances, fatigue, and pain. Data sources: A database search was performed on Scopus, Web of Science, Ovid (PsycINFO), CINAHL, PubMed, and ProQuest (Health and Medicine). Review methods: Observational studies published from 2000 to 2024 that examined the relationships between physical activity and non-motor symptoms were included. The methodological quality of reports was evaluated using critical appraisal checklists appropriate to the study design. Where appropriate, a meta-analysis was conducted to combine data from the included articles. Results: A total of 14 articles met the criteria and used various tools to evaluate non-motor symptoms and physical activity. Meta-analyses showed that people with Parkinson's who are more physically active have better global cognition [ β ranged from 0.12 to 0.28; p = 0.00–0.02] and less affective disorders [ β -0.20, p = 0.00]. Increased physical activity levels were also associated with better sleep quality (n = 1) and less chronic pain (n = 1). The overall methodological quality of the included articles was considered high. Conclusion: Engagement in increased levels of physical activities performed under free-living conditions is associated with better cognition and less anxiety, apathy, and depression in people with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. Methods: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. Results: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. Conclusion: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms (NMS). NMS including sleep disturbances, depression, anxiety, and constipation are diverse, can precede motor symptoms, and significantly impact patients' quality of life. The severity and type of NMS vary based on age, disease severity, and motor symptoms, and while some respond to dopaminergic treatments, others may be induced or exacerbated by such treatments. NMS also play a role in differentiating PD from drug-induced parkinsonism and are related to gait dysfunction in both early and advanced stages. Genetic factors play a significant role in the development of NMS in PD, with mutations in genes such as SNCA, LRRK2, PRKN, and GBA being associated with severe and early NMS. Familial studies and identification of susceptibility factors have provided insights into the genetic underpinnings of NMS in PD. Neurobehavioral changes, including cognitive decline, are common NMS in PD, and their genetic basis involves a spectrum of mutations shared with other neurodegenerative disorders. Further research is needed to elucidate the functional implications of these genetic factors and their contributions to the pathogenesis of NMS in PD. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = −0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation. [ABSTRACT FROM AUTHOR]

Objective: The objective was to determine the prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease patients in movement disorders outpatient clinics. Methods: We enrolled all consecutive PD patients who visited our movement disorders outpatient clinics between January and December 2023; and agreed to participate in the study. In addition to the evaluation of demographic and clinical features, clinical scales, including the MDS-UPDRS, NMSS, and FOOGQ, were performed. Results: Overall, we enrolled 163 PD subjects with a mean age of 63.9 ± 10.4 (F/M = 27/136). The disease duration was 3.5 (20) y [median (range)]. The median score of the NMSS was 41 points. The NMSs burden levels were severe in 25.2%, and very severe in 25.2% of the subjects. The subitems with the highest scores were sleep/fatigue, mood/cognition, urinary, and miscellaneous. The analyses within the patient group with newly diagnosed PD also revealed high NMSS scores. Comparisons of the NMSS between distinct PD stages revealed greater NMSS scores in the severe stage than in the mild stage (p = 0.001). Correlation analyses between the clinical scores and the NMSS scores revealed positive correlations between the NMSS scores and the scores on all the clinical scales including the MDS-UPDRS 1–4, and FOGQ. Conclusion: We reported the first data regarding the NMS burden in PD patients from Turkey. We found a high prevalence and severity of various domains of NMSs, most of which were sleep/fatigue, mood/cognition, urinary, and miscellaneous. More than half of the patients had severe to very severe NMS burden. Although NMSs were more common severe-stage disease, they were also prevalent in the subgroup with newly diagnosed patients. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson's disease (PD). Based on the cognitive model of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PDFOG+. To test this model, we investigated the FOGrelated phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson's study. Methods: A cross-sectional analysis comparing iPDFOG+ (n = 118) and iPDFOG- (n = 378) individuals was performed, followed by the application of logistic regression models. Consequently, regression models were fitted for a subset of iPDFOG+ (n = 35) vs. iPDFOG- (n = 126), utilizing a detailed neuropsychological battery to assess the association between FOG and cognitive subdomains. Both regression models were adjusted for sociodemographic confounders and disease severity. Results: iPDFOG+ individuals presented with more motor complications (MDSUPDRS IV) compared to iPDFOG- individuals. Moreover, iPDFOG+ individuals exhibited a higher non-motor burden, including a higher frequency of hallucinations, higher MDS-UPDRS I scores, and more pronounced autonomic dysfunction as measured by the SCOPA-AUT. In addition, iPDFOG+ individuals showed lower sleep quality along with lower quality of life (measured by PDSS and PDQ-39, respectively). The cognitive subdomain analysis in iPDFOG+ vs. iPDFOG- indicated lower scores in Benton's Judgment of Line Orientation test and CERAD word recognition, reflecting higher impairment in visuospatial, executive function, and memory encoding. Conclusion: We determined a significant association between FOG and a clinical endophenotype of PD with higher non-motor burden. While our results supported the cognitive model of FOG, our findings point to a more widespread cortical impairment across cognitive subdomains beyond the executive domain in PDFOG+ with additional higher impairment in visuospatial function and memory encoding. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusions Alpha‐synuclein (αSyn) is critical to the pathogenesis of Parkinson's disease (PD). Recognition of non‐motor symptoms as clinical manifestations of PD suggests aggregation of αSyn in extranigral areas.This study aimed to evaluate the association between total αSyn levels in reflex tears with non‐motor symptoms.This cross‐sectional study included 25 people living with PD (PwP) and 38 age‐matched healthy controls (HC). Total αSyn reflex tear levels were measured using an enzyme‐linked immunosorbent assay. PwP were evaluated using the Non‐Motor Symptoms Scale (NMSS), the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), Hoehn and Yahr Stage (HY), and Montreal Cognitive Assessment (MoCA).Total αSyn reflex tear levels were significantly higher in PwP when compared with HC (1.77 pg/mL [IQR 1.75–1.79] vs. 1.73 pg/mL [IQR 1.70–1.75], p < 0.001). The urinary domain was negatively correlated with total αSyn levels in tears (r = −0.416, p = 0.048). No correlation was observed between total αSyn levels in reflex tears with MDS‐UPDRS, HY, or MoCA.Total αSyn levels in reflex tears can differentiate PD from HC. In addition, total αSyn reflex tear levels were associated with the urinary domain of NMSS but are not associated with motor and cognitive symptoms, nor HY. Therefore, our findings suggest that it does not reflect ongoing dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

The effect of subthalamic stimulation (STN-DBS) on patients' personal satisfaction with life and their Parkinson's disease (PD) treatment is understudied, as is its correlation with quality of life (QoL). Therefore, we tested the hypothesis that STN-DBS for PD enhances satisfaction with life and treatment. In a prospective, multicenter study with a 6-month follow-up involving 121 patients, we measured the main outcomes using the Satisfaction with Life and Treatment Scale (SLTS-7). Secondary outcomes included the eight-item PD Questionnaire (PDQ-8), European QoL Questionnaire (EQ-5D-3L), EQ-Visual Analogue Scale (VAS), Non-Motor Symptom Scale (NMSS), Hospital Anxiety and Depression Scale (HADS), and Unified PD Rating Scale (UPDRS). Longitudinal outcome changes, effect sizes (Cohen's d), and correlations between outcome changes were analyzed. SLTS-7 scores improved at the 6-month follow-up, particularly in the domains of 'satisfaction with physical health' and 'satisfaction with treatment'. Change scores correlated strongly (EQ-VAS), moderately (PDQ-8 SI and HADS), and weakly (UPDRS-activities of daily living and EQ-5D-3L) with other scales. Satisfaction with physical health, psychosocial well-being, or treatment was not related to UPDRS-motor examination. This study provides evidence that STN-DBS enhances patients' personal satisfaction with life and treatment. This satisfaction is associated with improvements in the QoL, daily activities, and neuropsychiatric aspects of PD rather than its motor aspects. [ABSTRACT FROM AUTHOR]

In addition to their motor symptoms, almost all Parkinson's disease patients report non-motor symptoms (NMS) and, in the later course of the disease, non-motor fluctuations as well. These NMS encompass e.g. neuropsychiatric, gastrointestinal, urogenital, cardiovascular symptoms and pain. For a long time, these symptoms received no or at best very little attention, but there is a growing trend towards their recognition and treatment. Despite this progress, significant gaps remain, particularly due to the sometimes-limited expertise among neurologists regarding these symptoms. The clinical need to consequently treat these NMS raises the question of whether Movement Disorder specialists should and can address them sufficiently or if additional consultant physicians have to be enrolled. Therefore, our objective is to establish benchmarking criteria to outline a potential way forward. Ideally, Movement Disorder specialists should take on greater responsibility when treating non-motor PD symptoms, integrating diagnostic and therapeutic pathways from other medical disciplines where feasible. [ABSTRACT FROM AUTHOR]

Background: Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. Objective: This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. Methods: A community‐based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. Results: We included 190 persons with MSA and 114 caregivers. Eighty‐seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27–32.08], P = 0.025) and low‐income groups (OR: 5.02 [95% CI: 1.32–19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92–12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54–6.82], P = 0.002). Seventy‐six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti‐inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. Conclusions: Pain is more prevalent than previously reported in MSA and particularly affects women and low‐income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non‐motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cervical dystonia (CD) is a condition characterized by involuntary activity of cervical muscles, which is often accompanied by various non-motor symptoms. Recent studies indicate impaired saccadic eye movements in CD. Local administration of botulinum toxin type A (BoNT/A), which causes temporary paralysis of the injected muscle, is the first-line treatment of focal dystonia, including CD. To our knowledge, concurrent observation of the effect of BoNT/A on smooth eye movements, voluntary saccades, memory-guided saccades, and antisaccades in CD has not yet been explored. The aim of this study was to assess the effect of BoNT/A on eye movements and non-motor symptoms in patients with CD, which, when altered, could imply a central effect of BoNT/A. Methods: Thirty patients with CD performed smooth pursuit, prosaccadic expression, memory-guided saccades, and antisaccade tasks; eye movements were recorded by an eye tracker. Motor and non-motor symptoms, including depression, anxiety, pain, disability, and cognitive changes prior to and after BoNT/A administration, were also evaluated. Results: The number of correct onward counts (p < 0.001), overall correct memory-guided saccades count (p = 0.005), motor symptoms (p = 0.001), and non-motor symptoms, i.e., anxiety (p = 0.04), depression (p = 0.02), and cognition (p < 0.001) markedly improved after BoNT/A administration. Conclusions: Memory-guided saccades, depression, and anxiety improve after BoNT/A in CD. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson’s disease (PD) involves the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impact patients’ quality of life. Safinamide modulates dopaminergic and glutamatergic systems, offering a promising treatment approach. Methods: This meta-analysis evaluated the efficacy of safinamide as an add-on therapy to levodopa for PD patients with motor fluctuations. Following PRISMA guidelines, literature searches were conducted in PubMed and Embase (2014–2022). Inclusion criteria were studies on adult PD patients receiving safinamide with levodopa. Outcomes included on-time without troublesome dyskinesia, off-time, UPDRS Part III motor scores, UPDRS Part II activities of daily living scores, PDQ-39 emotional well-being, and GRID-HAMD scores. Results: Among thirteen eligible studies, safinamide significantly improved on-time without troublesome dyskinesia at 100 mg/day (mean difference [MD]: −0.90; 95% CI: −1.12 to −0.67; p < 0.00001) and 50 mg/day (MD: −0.77; 95% CI: −1.21 to −0.34; p = 0.0005) compared to placebo. It also reduced off-time (100 mg/day: MD: −0.94; 95% CI: −1.19 to −0.70; p < 0.00001; 50 mg/day: MD: −0.72; 95% CI: −1.03 to −0.41; p < 0.00001) and improved UPDRS-III motor scores (100 mg/day: MD: −3.01; 95% CI: −4.15 to −1.86; p < 0.00001; 50 mg/day: MD: −2.93; 95% CI: −5.14 to −0.71; p = 0.001). Mood improvements were noted in PDQ-39 emotional well-being scores (MD: −5.22; 95% CI: −6.90 to −3.54) and GRID-HAMD scores (MD: −0.60; 95% CI: −0.95 to −0.25; p = 0.0009). Safinamide also positively affected pain (RR: 1.10; 95% CI: 1.03 to 1.18). Conclusion: Compared to placebo, safinamide significantly benefits motor and non-motor symptoms in PD patients, but further research is necessary to fully explore its therapeutic potential. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson's disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients. Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients. Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson's Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively). Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients. [ABSTRACT FROM AUTHOR]

Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear. Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status. Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan– Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status. Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19–8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster. Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms. Plain Language Summary: Multiple system atrophy (MSA) is a complex disease that can affect both movement and non-movement functions of patients. However, we do not know much about how these different symptoms relate to how the patient's health might change over time. In this study, we looked at 193 MSA patients to learn more about if the patients can be distinguished into different subgroups at diagnosis and if the subgroups might be associated with their survival and ability to move in the future. We found four main subgroups of patients: group 1 characterized by the dysfunction of cerebellum (a part of the brain), group 2 characterized by sleep and mood problems, group 3 characterized by rigidity and slow movements, and group 4 with diffuse symptoms mentioned above. After tracking 95 patients for nearly 32 months, we found that those characterized by rigidity and slow movements, and those with diffuse symptoms had a higher chance of dying compared to those characterized by sleep and mood problems. Group 3 and 4 also had a higher chance of becoming unable to move out of bed. This suggests that patients with severe symptoms of rigidity and slowness at diagnosis tend to have a worse outlook than those without. And if multiple MSA symptoms are found when the patient is diagnosed, especially trouble with thinking, are also signs that the disease is getting worse quickly. By understanding these disease patterns, we can better tailor treatments and provide better support for people with MSA. [ABSTRACT FROM AUTHOR]

Background: Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). Methods: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. Results: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. Conclusion: This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity. [ABSTRACT FROM AUTHOR]

Mohamed Sheikh Hassan,1 Nur Adam Mohamed,2 Yavuz Yücel,3 Yusuf Abdirisak Mohamed,2 Alper Gökgül1 1Department of Neurology, Mogadishu Somalia Turkiye Training and Research Hospital, Mogadishu, Somalia; 2Department of Psychiatry and Behavioral Sciences, Mogadishu Somalia Turkiye Training and Research Hospital, Mogadishu, Somalia; 3Dicle University, Faculty of Medicine, Neurology Department, Diyarbakir, TurkiyeCorrespondence: Mohamed Sheikh Hassan, Department of Neurology, Mogadishu Somalia Turkiye Training and Research Hospital, Mogadishu, Somalia, Email dr.m.qalaf@gmail.comIntroduction: Depression is one of the most common non-motor symptom of Parkinson’s disease (PD), with an increasing prevalence in recent years. It causes significant psychological consequences that affect the disease course, overall quality of life, and functioning. The objective of this study was to determine the prevalence of depression in outpatients with Parkinson’s disease evaluated in the neurology clinic at tertiary hospital in Mogadishu, Somalia.Methods: A cross-sectional study was conducted among 50 PD patients without dementia to determine the prevalence of depression at the neurology clinic of the Mogadishu Somalia Türkiye Training and Research Hospital between February and November 2022. All eligible participants were interviewed by a team of doctors using a structured questionnaire that consisted of sociodemographics and clinical characteristics, the Beck Depression Inventory-II (BDI-II) for depression assessment, and the Modified Hoehn and Yahr Scale for PD staging.Results: Of the 50 PD participants, 60% were male and 58% were older than 60 years. 20% of them had a family history of PD and HTN as comorbid conditions. The prevalence of depression among the participants was 46% (95% CI 31.8– 60.7). Of the patients with depression, 22% and 24% had mild and moderate depressive symptoms, respectively. The Mann–Whitney U-test revealed a statistically significant association between depression symptoms and the presence of comorbidity (χ 2 = 136.50, p< 0.01). The Kruskal–Wallis test revealed a statistically significant association between depression symptoms and a longer duration of PD (χ 2 (2) = 18.21, p< 0.01) and advanced stages of PD (χ 2 (2) = 13.74, p< 0.01).Conclusion: This is the first study conducted on patients with PD in Somalia and found that a significant proportion of these patients experienced depressive symptoms. We also highlighted that factors such the presence of medical comorbidities, high monthly income, advanced PD stage, longer duration of PD, and use of multiple medications for PD were significantly associated with the presence of depressive symptoms.Keywords: Parkinson’s disease, depressive symptoms, non-motor symptoms, Somalia

Motor and non-motor symptoms of Parkinson’s disease (PD) and their management have been evaluated in numerous studies. Four classical symptoms, including bradykinesia, tremor, rigidity, and postural abnormalities, are used to establish a clinical diagnosis of PD. However, this research is aimed at exploring the range of non-motor symptoms with an emphasis upon their ability to affect the patients with PD and their quality of life. With a slow onset of the known symptoms like tremor or rhythmic shaking of limbs called “pill-rolling tremor”, slowed movement (bradykinesia), muscle rigidity, stooped and altered posture, loss of the ability to blink or smile, and various speech and writing changes; the disease takes a leap into the non-motor symptoms like dementia, drooling, swallowing issues, difficulty urinating, and constipation. The dopaminergic pathophysiology of PD explains the anxiety, slowness of thought, fatigue, and dysphoria. Knowing the non-motor symptoms is crucial to help the clinician to make early diagnosis and to better understand the prognosis of the spectrum of this disease.

Parkinson’s disease (PD) is primarily known as a motor disorder; however, its debilitating non-motor symptoms have a significant impact on patients’ quality of life. The current standard treatment, l-DOPA, is used to relieve motor symptoms, but prolonged use is often associated with severe side effects. This creates an urgent need for effective alternatives targeting both motor and non-motor symptoms.

Cervical dystonia (CD) is a common form of movement disorder with a high incidence of comorbid mental disorders. Rhythmic transcranial magnetic stimulation (rTMS) is effective in depression and other mental disorders, but its efficacy in CD with comorbid mental disorders has been poorly studied.Objective: to investigate the efficacy of rTMS in CD and comorbid mental disorders.Material and methods. Seventeen patients with CD underwent a course of 10 rTMS sessions (protocol: 1 Hz, 600 pulses to the left primary motor cortex). The severity of mental disorders, quality of life and severity of cervical dystonia were assessed using the HADS, SF-36 and CDQ-24 scales.Results. After transcranial magnetic stimulation treatment, a significant reduction in anxiety (from 12.2±4.1 to 6.3±2.1 points; p

Abstract Background Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. Methods A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson’s Progression Marker Initiative (PPMI). Results No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aβ42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. Conclusions APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aβ42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Background: Patients with Multiple System Atrophy (MSA) frequently report non-motor symptoms, and several research groups have highlighted this. Objective: We systematically searched for and reviewed papers assessing prevalence of non-motor symptoms (NMS) in MSA patients as reported in the scientific literature. Methods: We performed a systematic review of studies of subjects with MSA (involving > 10 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947–2022. Results: 23 research papers, with data from 2648 clinically diagnosed and 171 pathologically verified cases of MSA were included, along with 238 controls. Mean age for MSA cases was 61.3 (9.2) years, mean disease duration 3.6 (2.7) years. 57.9% were male. Our analysis showed that the prevalence of cognitive issues in MSA varied widely (between 15–100%); dementia per se was uncommon, but assessment in advanced stages of MSA is impacted by unintelligible speech (which may be noted in a quarter of cases). The prevalence of depressive symptoms in MSA was between 44–88%. Sleep disturbances were reported by 17–89%, with REM-sleep behaviour disorder (RBD) rates as high as 75%. Pain was reported by 40–47% of patients: rheumatic or musculoskeletal sources of pain being commonest. Fatigue was reported by 29–60% of patients. Symptoms of autonomic failure in MSA were seen in 34–96.5% patients at baseline. Conclusion: In routine clinical practice, NMS in MSA are under-recognised by clinicians. These impact hugely on patient quality of life and contribute to their overall morbidity. A methodical ascertainment of these complaints will address an unmet need, and lead to a more holistic approach of care for individuals with MSA. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). Methods: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. Results: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). Conclusion: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population over the age of 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (αSyn)-rich Lewy bodies both manifesting with classical motor signs. αSyn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considered prevalent among individuals prior to PD diagnosis and persisting throughout the patient's life. NMS mainly includes loss of taste and smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings on the impact of αSyn deposits on several prodromal NMS and emphasizes the importance of early detection of αSyn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease. Methods: We searched eight databases from their inception until 14 April 2024, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, China Science and Technology Periodical Database, and Wanfang Database. The search aimed to find randomized controlled trials assessing the effectiveness of acupuncture for neuropsychiatric symptoms in patients with Parkinson's disease. Literature screening and data extraction were performed independently by the authors. Meta-analysis was conducted using RevMan V.5.3 software, and Stata 17.0 software was used for detecting publication bias and performing sensitivity analysis. Results: Twenty-eight studies, involving 2148 participants, met the inclusion criteria. The meta-analysis revealed that acupuncture therapy improved depression-related scale scores (standardized mean difference (SMD) = –0.70, 95%CI [–0.98, −0.42], p < 0.00001), anxiety-related scale scores (SMD = –0.78, 95% CI [–1.43, −0.14], p = 0.02), Montreal Cognitive Assessment scores (weighted mean difference (WMD) = 2.74, 95% CI [2.43, 3.05], p < 0.00001), Mini Mental State Examination scores (WMD = 2.36, 95% CI [0.78, 3.94], p = 0.003), Yale-Brown Obsessive Compulsive Scale scores, and Parkinson's Disease Questionnaire-39 scores (WMD = –2.66, 95% CI [–4.83, −0.49], p = 0.02) compared to controls. Conclusion: This review supports the application of acupuncture to reduce the severity of neuropsychiatric symptoms including depression, anxiety, and impulse control disorders, and to improve cognition and quality of life in patients with Parkinson's disease. The adverse effects associated with acupuncture, either alone or as adjunctive therapy, were relatively minor. [ABSTRACT FROM AUTHOR]

(1) Background: Previous studies, mostly performed in European centers, have shown that in-patient multimodal intensive rehabilitation treatments lasting for two to four weeks can improve both motor and non-motor symptoms of Parkinson's disease (PD) with long-lasting effects. Here, we ascertain the effects of a similar in-patient program in a U.S. center with a retrospective study in a cohort of 153 patients in the moderately advanced stage of PD. (2) Methods: We compared indices of motor and non-motor functions before and immediately after such treatment and investigated the possible differences between men and women. We used the available records of the Beck Depression Inventory, PDQ39, PD Sleep Scale, Timed Up and Go, Vocal Volume, Voice Handicap, and total UPDRS scores. (3) Results: We found that at the end of treatment, which lasted an average of 14 days, all outcome measures significantly improved independently of sex. (4) Conclusions: These results confirm the previous findings with a similar in-patient approach in European centers. They further suggest that this in-patient treatment is a care model that is feasible in U.S. centers and can provide a more immediate benefit to the motor function and quality of life of patients with moderately advanced PD. [ABSTRACT FROM AUTHOR]

Background: The World Health Organisation (WHO) reports that morbidity and mortality due to Parkinson's disease (PD) are increasing faster than for other neurodegenerative conditions. People with Parkinson's (PwP) present with a variety of motor symptoms, such as tremor, bradykinesia, and rigidity. Freezing of gait (FoG) is a significant motor symptom that manifests as temporary episodes of inability to move one's feet, despite the intention to walk. Aims: This study examined the impact of FoG on quality of life (QoL) within an Irish cohort of PwP, from the perspectives of both PwP and their carers, using validated questionnaires that had been adapted for online use. Methods: PwP and their carers were recruited by outreach to the Irish Parkinson's Community. Anonymous online questionnaires were distributed, which combined a demographic survey with several clinically validated surveys, including Freezing of Gait Questionnaire (FoG-Q), Parkinson's Disease Questionnaire 8 (PDQ-8), and Parkinson's Disease Carer Questionnaire (PDQ-C). Results: There was a strong correlation (p < 0.001) between severity of FoG and lower QoL among PwP. Significant correlation was also found between FoG severity and several motor symptoms, such as postural instability and difficulty with balance, and non-motor symptoms, such as cognitive changes and pain/discomfort. FoG severity correlated with disease progression. Significant correlation was also found between FoG and symptoms, as assessed from the perspective of the patients' carers. Conclusions: This study shows that FoG is a significant detriment to the QoL of PwP, from the perspectives of patients and carers. This method of assessing FoG and QoL using online questionnaires has potential to enhance the reach and flexibility of this type of research. These findings will inform future studies on larger cohorts and highlight unmet clinical needs in PwP. [ABSTRACT FROM AUTHOR]

Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted. [ABSTRACT FROM AUTHOR]

Background: Research indicates that people with Parkinson's disease (PwPs) may experience challenges in both peripheral and central auditory processing, although findings are inconsistent across studies. Due to the diversity of auditory measures used, there is a need for standardized, replicable hearing assessments to clarify which aspects of audition are impacted in PWPs and whether they are linked to motor and non-motor symptoms. Objective: To characterize auditory processes and their possible alteration in PwPs. To address this, we collected a comprehensive set of standardized measures of audition using PART, a digital testing platform designed to facilitate replication. Additionally, we examined the relationship between auditory, cognitive, and clinical variables in PwPs. Methods: We included 44 PwPs and 54 age and education matched healthy controls. Assessments included detection of diotic and dichotic frequency modulation, temporal gaps, spectro-temporal broad-band modulation, and speech-on-speech masking. Results: We found no statistically significant differences in auditory processing measures between PwPs and the comparison group (ps > 0.07). In PwPs, an auditory processing composite score showed significant medium size correlations with cognitive measures (0.39 < r<0.41, ps < 0.02) and clinical variables of motor symptom severity, quality of life, depression, and caretaker burden (0.33 < r<0.52, ps < 0.03). Conclusions: While larger datasets are needed to clarify whether PwPs experience more auditory difficulties than healthy controls, our results underscore the importance of considering auditory processing on the symptomatic spectrum of Parkinson's disease using standardized replicable methodologies. Plain Language Summary: It is unknown whether there exists a relationship between Parkinson's disease (PD) and hearing ability. While some studies have found hearing difficulties to be associated with PD, other studies failed to replicate these effects. We suggest that a possible reason for these differing findings are differences in how hearing is measured. To clarify the literature, we tested a group of people with Parkinson's (PwPs) on several aspects of hearing using a freely available tablet-based app. We compared PwPs hearing tests to those of an age and education matched group of people without PD. While we found no clear differences among the groups, we did find better hearing abilities were related to less motor symptom severity and depression, better reported quality of life, and less reported burden of the disease experienced by the caretaker. We conclude that while there is no solid evidence showing the hearing is necessarily impaired in PD, that measuring hearing in PwPs can provide valuable clinical information. This can inform new approaches to treatment for people living with PD such as those related with improving hearing. [ABSTRACT FROM AUTHOR]

Background and objectives: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an emerging technique for the treatment of severe, medication-refractory tremor syndromes. We here report motor and non-motor outcomes 6 and 12 months after unilateral MRgFUS thalamotomy in tremor-dominant Parkinson's disease (tdPD). Methods: 25 patients with tdPD underwent neuropsychological evaluation including standardized questionnaires of disability, quality of life (QoL), mood, anxiety, apathy, sleep disturbances, and cognition at baseline, 6 and 12 months after MRgFUS. Motor outcome was evaluated using the Clinical Rating Scale for Tremor (CRST) and Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS). In addition, side effects and QoL of family caregivers were assessed. Results: 12 months after MRgFUS significant improvements were evident in the tremor subscores. Patients with concomitant rest and postural tremor showed better tremor outcomes compared to patients with predominant rest tremor. There were no differences in the non-motor assessments. No cognitive decline was observed. Side effects were mostly transient (54%) and classified as mild (62%). No changes in the caregivers' QoL could be observed. Conclusion: We found no changes in mood, anxiety, apathy, sleep, cognition or persistent worsening of gait disturbances after unilateral MRgFUS thalamotomy in tdPD. Concomitant postural tremors responded better to treatment than predominant rest tremors. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients' quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Despite intensive research, the current treatment of Parkinson’s disease is still symptomatic treatment and its management is primarily aimed at controlling motor symptoms. Dopaminergic agents that replace the action of the missing dopamine remain the mainstay of current therapy. In recent decades, significant progress has been made in the treatment of advanced stage of disease using interventional methods such as treatment with pump systems and deep brain stimulation. An important part of the treatment is the influence of non-motor symptoms, which significantly affect the quality of life of patients. New treatment strategies capable to affect the development and progression of the disease, which are still in the preclinical and clinical research phase, include various treatment procedures with the aim to influence the formation and aggregation of pathological forms of alpha-synuclein and modify the spread of the pathological process in the brain. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion The Columbia Muscle Cramp Scale (CMCS) is a useful tool for evaluating muscle cramps commonly observed in patients with amyotrophic lateral sclerosis (ALS). The CMCS comprises five subdomains: triggering factors, frequency, location, severity, and the degree to which cramps affect overall daily living.This study aimed to evaluate the reliability of the CMCS, which was translated into Japanese.Thirty patients with ALS (17 men and 13 women) from seven facilities were evaluated twice by two different evaluators (doctors, nurses, physical therapists, occupational therapists, and speech‐language‐hearing therapists). The degree of inter‐ and intra‐rater agreement was evaluated using kappa statistics. Weighted kappa statistics and 95% confidence intervals accounted for multiple‐order responses.The average age was 60.4 (standard deviation: 10.4, range: 39–77) years. The kappa statistics for the inter‐rater reliability of the CMCS items showed moderate to very good agreement, ranging from 0.56 (cramp triggering) to 0.91 (daily activity) at visit 1 and 0.51 (severity) to 0.96 (daily activity) at visit 2. The kappa statistics for the intra‐rater reliability of the CMCS items also showed moderate to good agreement, ranging from 0.45 (frequency) to 0.79 (cramp triggering).The Japanese version of the CMCS demonstrated intra‐ and inter‐rater reliability agreement and is expected to be useful for evaluating muscle cramps in patients with ALS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by diverse motor and non-motor symptoms. Visual evoked potentials (VEPs) provide valuable insights into the neurological changes in PD. This study examines VEP latency to explore potential connections between visual processing and PD progression, focusing on whether inter-eye latency differences are influenced by disease severity and symptomatology. A cross-sectional observational study was conducted with 59 PD patients at the Neurology I Clinic, Cluj-Napoca County Emergency Clinical Hospital, from October 2019 to October 2021. Patients underwent neurological and psychological evaluations, including VEP testing with a reversal pattern technique. P100 wave latency was assessed for both eyes, and associations with clinical indicators like Hoehn and Yahr stages, UPDRS scores, and non-motor symptoms were analyzed. VEP latencies for the right and left eyes were 108.7 ± 10.6 ms and 108.4 ± 9.7 ms, respectively, with no significant inter-eye differences (P = 0.8). UPDRS item 4 scores correlated significantly with both latencies (P = 0.003 for the left eye and P <0.001 for the right). Latency differences between eyes were shorter in patients with symmetrical parkinsonism compared to those with unilateral predominance. Age correlated weakly with P100 latency, and a weak correlation was found between anhedonia scores and right-eye latency. VEP latency is sensitive to PD motor severity, with shorter inter-eye latency differences in symmetrical parkinsonism, suggesting balanced dopaminergic dysfunction. VEP latency differences offer insights into neurophysiological changes in PD, reflecting dopaminergic dysfunction and its impact on visual processing. These findings support the potential of VEPs as diagnostic and prognostic tools in PD assessment. [ABSTRACT FROM AUTHOR]

Fatigue is a common and disabling non-motor symptom (NMS) in Parkinson's disease (PD) patients. However, the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on fatigue has not been widely studied. To determine the effect of STN DBS on fatigue in PD patients, measured by the Non-motor symptoms scale (NMSS). Cross-sectional analysis of 50 patients with PD who underwent STN DBS at King's College Hospital and Salford Royal Hospital with fatigue scores (measured by question number 4 from domain 2 (sleep/fatigue) of the NMSS as the primary outcome measure. Secondary outcome measures included the PD Sleep Scale (PDSS), Scales for Outcome in PD (SCOPA)-motor examination, activities of daily living, motor complications, Hoehn and Yahr (HY) stage and changes in Levodopa Equivalent Daily Dose (LEDD). 50 patients with a mean follow-up period of 1.98 ± 1.36 years were studied. Significant improvement in median fatigue scores (4.00 (0.75–9.00) to 1.00 (0.00–4.50); p =.001) was observed. In addition, improvements in question 5 (sleep maintenance and fragmentation; 8.00 (4.00–12.00) to 0.00 (0.00–4.00); p <.001) and in domain 2 total score (sleep/fatigue; 20.00 (8.75–27.25) to 6.00 (0.75–16.00); p <.001) were also significant, together with improvements in NMSS total score, SCOPA scores and HY stage (p ≤.02). Moreover, LEDD but especially dopamine agonists LEDD was significantly reduced after DBS (310.00 (0.00–480.00) to 150.00 (0.00–300.00); p <.020). Even though open label and not using a validated fatigue scale, this observational analysis suggest that fatigue improves significantly after STN DBS with persisting benefits at two years follow-up. [ABSTRACT FROM AUTHOR]

BackgroundFreezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson’s disease (PD). Based on the cognitive model of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PDFOG+. To test this model, we investigated the FOG-related phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson’s study.MethodsA cross-sectional analysis comparing iPDFOG+ (n = 118) and iPDFOG− (n = 378) individuals was performed, followed by the application of logistic regression models. Consequently, regression models were fitted for a subset of iPDFOG+ (n = 35) vs. iPDFOG− (n = 126), utilizing a detailed neuropsychological battery to assess the association between FOG and cognitive subdomains. Both regression models were adjusted for sociodemographic confounders and disease severity.ResultsiPDFOG+ individuals presented with more motor complications (MDS-UPDRS IV) compared to iPDFOG- individuals. Moreover, iPDFOG+ individuals exhibited a higher non-motor burden, including a higher frequency of hallucinations, higher MDS-UPDRS I scores, and more pronounced autonomic dysfunction as measured by the SCOPA-AUT. In addition, iPDFOG+ individuals showed lower sleep quality along with lower quality of life (measured by PDSS and PDQ-39, respectively). The cognitive subdomain analysis in iPDFOG+ vs. iPDFOG− indicated lower scores in Benton’s Judgment of Line Orientation test and CERAD word recognition, reflecting higher impairment in visuospatial, executive function, and memory encoding.ConclusionWe determined a significant association between FOG and a clinical endophenotype of PD with higher non-motor burden. While our results supported the cognitive model of FOG, our findings point to a more widespread cortical impairment across cognitive subdomains beyond the executive domain in PDFOG+ with additional higher impairment in visuospatial function and memory encoding.

Abstract Background Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. Methods We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. Results Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. Conclusion Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Background: Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression. Objective: 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. Methods: PD patients were divided between 155 people who were diagnosed de novo and 165 PDpatients 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. Results: 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 symptomonset 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is a progressive neurodegenerative disease caused by a CAG trinucleotide expansion in the huntingtin gene. The length of the CAG repeat is inversely correlated with disease onset. HD is characterized by hyperkinetic movement disorder, psychiatric symptoms, and cognitive deficits, which greatly impact patient's quality of life. Despite this clear genetic course, high variability of HD patients' symptoms can be observed. Current clinical diagnosis of HD solely relies on the presence of motor signs, disregarding the other important aspects of the disease. By incorporating a broader approach that encompasses motor as well as non-motor aspects of HD, predictive, preventive, and personalized (3P) medicine can enhance diagnostic accuracy and improve patient care. Methods: Multisymptom disease trajectories of HD patients collected from the Enroll-HD study were first aligned on a common disease timescale to account for heterogeneity in disease symptom onset and diagnosis. Following this, the aligned disease trajectories were clustered using the previously published Variational Deep Embedding with Recurrence (VaDER) algorithm and resulting progression subtypes were clinically characterized. Lastly, an AI/ML model was learned to predict the progression subtype from only first visit data or with data from additional follow-up visits. Results: Results demonstrate two distinct subtypes, one large cluster (n = 7122) showing a relative stable disease progression and a second, smaller cluster (n = 411) showing a dramatically more progressive disease trajectory. Clinical characterization of the two subtypes correlates with CAG repeat length, as well as several neurobehavioral, psychiatric, and cognitive scores. In fact, cognitive impairment was found to be the major difference between the two subtypes. Additionally, a prognostic model shows the ability to predict HD subtypes from patients' first visit only. Conclusion: In summary, this study aims towards the paradigm shift from reactive to preventive and personalized medicine by showing that non-motor symptoms are of vital importance for predicting and categorizing each patients' disease progression pattern, as cognitive decline is oftentimes more reflective of HD progression than its motor aspects. Considering these aspects while counseling and therapy definition will personalize each individuals' treatment. The ability to provide patients with an objective assessment of their disease progression and thus a perspective for their life with HD is the key to improving their quality of life. By conducting additional analysis on biological data from both subtypes, it is possible to gain a deeper understanding of these subtypes and uncover the underlying biological factors of the disease. This greatly aligns with the goal of shifting towards 3P medicine. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IADATCreERT2 strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the swing speed and step sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent non-motor symptoms that emerge in the early stages of dopaminergic neuron degeneration. [ABSTRACT FROM AUTHOR]

Objective: The non-motor symptoms of Parkinson's disease (PD) are an important part of PD. In recent years, more and more non-drug interventions have been applied to alleviate the non-motor symptoms of PD, but the relevant evidence is limited. This systematic review and meta-analysis was designed to evaluate the efficacy of non-drug interventions in patients with non-motor symptoms in patients with PD. Methods: Seven databases, including Pubmed, Embease, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database (WANFANG), VIP database (VIP), and China Biomedical Literature Service System (CBM) were searched from the establishment of the database to December 2023. Non-drug interventions such as acupuncture, cognitive behavioral therapy (CBT), exercise, repetitive transcranial magnetic stimulation (rTMS), and non-motor symptoms of Parkinson's disease were selected as search words, and two independent evaluators evaluated the included literature's bias risk and data extraction. The therapeutic efficacy was evaluated by the Parkinson's Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination (MMSE), and Parkinson's Disease Questionnaire-39 (PDQ-39). RevMan 5.4.1 (Reviewer Manager Software 5.4.1). Cochrane Collaboration, Oxford, United Kingdom analyzed the data and estimated the average effect and the 95% confidence interval (CI). A heterogeneity test is used to assess differences in the efficacy of different non-drug treatments. Results: We selected 36 from 4,027 articles to participate in this meta-analysis, involving 2,158 participants. Our combined results show that: PDSS: [mean difference (MD) =-19.35, 95% CI (-30.4 to -8.28), p<0.0006]; HAMD: [MD = -2.98, 95% CI (-4.29 to -1.67), p<0.00001]; BDI: [MD = -2.69, 95% CI (-4.24 to 4.80), p = 0.006]; HAMA: [MD=-2.00, 95% CI (-2.83 to -1.17), p<0.00001]; MMSE: [MD = 1.20, 95% CI (0.71 to 1.68), p< 0.00001]; CoMA: [MD = 2.10, 95% CI (-0.97 to 3.23), p = 0.0003]; PDQ-39: [MD = -4.03, 95% CI (-5.96 to -1.57), p < 0.00001]. Conclusion: The four non-drug measures used in our review showed significant improvements in sleep, depression, anxiety, cognition, constipation, and quality of life compared with the control group, and no serious adverse events were reported in the included research evidence, and we found that there were some differences among the subgroups of different intervention methods, but due to the less literature included in the subgroup, and the comparison was more indirect. So, we should interpret these results carefully. [ABSTRACT FROM AUTHOR]

Objective: Neuropsychological evaluation is critical to detection and management of cognitive and neuropsychiatric changes associated with Huntington disease (HD). Accurate assessment of non-motor complications of HD is critical given the prominent impact on functional disability, frequently commensurate with or exceeding that of motor symptoms. The increasing emphasis on developing disease-modifying therapies targeting cognitive decline in HD requires consensus on clinical neuropsychological assessment methods. The Neuropsychology Working Group (NPWG) of the Huntington Study Group (HSG) sought to provide evidence and consensus-based, practical guidelines for the evaluation of cognitive and neuropsychiatric symptoms associated with HD. Method: The NPWG recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to inform best practices in assessing, diagnosing, and treating the non-motor symptoms in HD. A review was circulated among the NPWG, and in an iterative process informed by reviewed literature, best practices in neuropsychological evaluation of patients with HD were identified. Results: A brief review of the available literature and rational for a clinical consensus battery is offered. Conclusion: Clinical neuropsychologists are uniquely positioned to both detect and characterize the non-motor symptoms in HD, and further, provide neurologists and allied health professions with clinically meaningful information that impacts functional outcomes and quality of life. The NPWG provides guidance on best practices to clinical neuropsychologists in this statement. A companion paper operationalizing clinical application of previous research-based non-motor diagnostic criteria for HD is forthcoming, which also advises on non-motor symptom screening methods for the non-neuropsychologist working with HD. [ABSTRACT FROM AUTHOR]

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = −0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. [ABSTRACT FROM AUTHOR]

We investigated non-motor symptoms in ALS using sequential questionnaires; here we report the findings of the second questionnaire. A social media platform (Twitter, now known as X) was used to publicize the questionnaires. Data were downloaded from SurveyMonkey and analyzed by descriptive statistics, comparison of means, and regression models. There were 182 people with ALS and 57 controls. The most important non-motor symptoms were cold limbs (60.4% cases, 14% controls, p = 9.67 x 10−10) and appetite loss (29.7% cases, 5.3% controls, p = 1.6 x 10−4). The weaker limb was most likely to feel cold (p = 9.67 x 10−10), and symptoms were more apparent in the evening and night. Appetite loss was reported as due to feeling full and the time taken to eat. People with ALS experienced medium-intensity pain, more usually shock-like pain than burning or cold-like pain, although the most prevalent type of pain was non-differentiated. Non-motor symptoms are an important feature of ALS. Further investigation is needed to understand their physiological basis and whether they represent phenotypic differences useful for subtyping ALS. [ABSTRACT FROM AUTHOR]

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Background: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. Methods: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. Results: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. Conclusion: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG. [ABSTRACT FROM AUTHOR]