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(1) Background: to reveal the prevalence of non-motor disorders in Parkinson’s disease (PD), we analyzed both Russian and international studies on the issue of PD-associated non-motor disorders in Caucasian patients; (2) Methods: We have carried out a search for full-text Englishand Russian-language articles published during the last ten years (from 2010 to 2020) in PubMed, Scopus, Web of Science, Springer, Clinical case, and E-library databases using multiple versions of keywords and their combinations. (3) Results: General prevalence of PD-associated non-motor disorders proved to be high. At the same time, we did not find significant differences between the prevalence of cognitive, affective, or behavioral disorders in PD patients. However, depression was found to be more common in PD patients in the Russian Federation; (4) Conclusions: According to the results of our review, cognitive and affective disorders in PD represent the issues of major concern.

Background Parkinson's disease is characterised by a complex array of motor and non-motor symptoms. Motor symptoms are often prioritised for assessment and treatment. Growing evidence highlights the importance of recognising the impact of non-motor symptoms on the person's quality of life. Objective The aim of this article is to increase awareness of the importance of identifying and addressing non-motor symptoms experienced by people living with Parkinson's disease. Discussion A vignette developed in collaboration with a person living with Parkinson's disease and his wife provides an 'insider perspective'. Regular assessment and monitoring of non-motor symptoms enable the clinician to support the implementation of effective interventions. Team-based care and connections with Parkinson's support groups are essential to enable the person to live well with Parkinson's disease and provide informal carers with the support and information needed.

Parkinson's syndrome is a degenerative brain disease that presents characteristic motor symptoms of tremor, rigidity, and gait disturbance. In addition to these motor symptoms, Parkinson's syndrome also presents non-motor symptoms (NMSs) such as sleep disturbance and cognitive decline. NMSs reduce patient's quality of life and psychosocial functioning and cause economic burden on the patient, so appropriate evaluation and treatment are required. Lewy body dementia is one of the several diseases belonging to Parkinson's syndrome. Its symptoms such as cognitive function, memory impairment, and hallucinations occur with Parkinsonism. Although drug therapy is being used with drug treatment to treat non-motor symptoms, it has limitations such as side effects, which stimulated interest in other complementary treatment methods such as oriental medicine treatment, dance, and yoga.The patient in this case complained of tremor in the right upper extremity, muscle hypertension and pain, and persistent vision, memory, and cognitive decline. The patient was diagnosed with probable Lewy body dementia. The patient was hospitalized for 4 months and received acupuncture and herbal medicines. After treatment, the patient's NMS scale scores decreased from 90 to 63, and the Unified Parkinson's Disease Rating Scale scores (summed I, II, and III) decreased from 17 points to 8 points. The Beck Depression Inventory score decreased from 22 points to 13 points. In addition, the patient's subjective evaluation revealed improvement.In this case, a patient diagnosed with probable Lewy body dementia who did not respond to the standard treatment and did not want to take medications showed improvement in not only motor symptoms but also NMSs after integrative Korean medicine treatment.

Parkinson's disease (PD) is the second most neurodegenerative disease in the United States of America after Alzheimer's disease. The Parkinson's disease patients and scans without evidence for dopaminergic deficit (SWEDD) patients will share the same symptoms, and It's hard to differentiate the PD, SWEDD patients, and healthy controls in the progression of PD. In this research, we classified PD patients, SWEDD patients, and healthy controls by considering motor and non-motor biomarkers, namely MDS-UPDRS part 1, SCOPA score, and QUIP-RS from the PPMI database by using supervised and unsupervised machine learning algorithms, namely Knn, logistic regression, XGBooting, naive Bayes, Decision tree, Random Forest, Support vector machine, multilayer perceptron , and K-means clustering, respectively. Random Forest scored 0.98 percent accuracy among all these algorithms and can identify and differentiate PD, SWEDD, and Healthy controls patients by motor and non-motor biomarkers.

Currently, Parkinson's disease is an equally motor and non-motor disease with a wide range of non-motor symptoms. The article describes the non-motor symptoms of Parkinson's disease, assesses the severity and significance of these symptoms, as well as the possible influence on each other in terms of neurotransmitter dysfunction. A comparative characteristic of the results obtained with the data of international studies is carried out

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);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.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor pathways. A growing body of evidence from recent years suggests that ALS results in a wide range of non-motor symptoms as well, which can have a significant impact on patients’ quality of life. These symptoms could also, in turn, provide useful information as biomarkers for disease progression, and can shed insight on ALS mechanisms. Here we aim to review a wide range of non-motor symptoms of ALS, with emphasis on their importance to research and clinical treatment of patients.

BACKGROUND Parkinson’s disease is a chronic neurodegenerative disorder with a prevalence rate of 108 - 257 per 100,000 people, occurring in later half of life and affecting both genders equally. The progressive nature of the disease is associated with growing disability and has a considerable impact on quality of life. Quality of life (QOL) is an important goal in every rehabilitation process and its impact on disease process, stage and prognosis is closely associated, which often gets neglected. Thus, it was necessary to conduct this study to establish actual impact of Parkinson’s disease on quality of life, emphasizing on disease duration. METHODS A questionnaire based observational study was carried out among patients with Parkinson’s disease in Maharashtra. The survey was conducted in Parkinson’s Association Group by handing over the hard copies of questionnaires to 120 patients and their respective care takers. Questionnaire used was ‘The Parkinson’s Disease Questionnaire (PDQ39)’. It had 39 items grouped into 8 domains. Statistical analysis of the collected data was carried out using InStat software and Microsoft excel. RESULTS In motor symptom-based questions, the impact on quality of life was more significant i.e., 54 % (P < 0.0001) compared to non-motor symptoms which was 46 % (P < 0.0001). Maximum number of subjects were from age group 71 to 80 while minimum number of subjects were from 91 to 100 yrs. CONCLUSIONS There was significant impact of motor as well as non-motor symptoms on patient’s quality of life; but motor symptoms like tremors and slowness of movement had greater impact compared to non-motor symptoms which included speech difficulty and social stigma. There was no co-relation between specific age group and incidence of disease. KEY WORDS Parkinson’s Disease, PDQ - 39 Questionnaire, Quality of Life (QOL), Motor and NonMotor Symptoms, Activities of Daily Living

Functional mobility (FM) is the ability of people to move in different environments, including at home, at work, and in the community, in order to perform functional activities or tasks, independently and safely. Objective: The aim of the present study was to investigate which motor and/or non-motor symptoms (severity of the motor symptoms, depressive symptoms, and fatigue) have the greatest impact on FM assessed by Modified Parkinson Activity Scale (mPAS) in individuals with Parkinson’s disease (PD). Method: The outcome of interest was FM assessed by mPAS, which includes 14 activities covering three domains (chair transfers, gait akinesia, and bed mobility). Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, Beck Depression Inventory (BDI), and Parkinson’s Disease Fatigue Scale-16 (PFS-16) were used. Results: Forty-four individuals (age: 65±11 years) with PD (PD duration: 7±4 years) were eligible to take part in this cross-sectional, exploratory study. The motor symptoms alone explained 36% (F= 17.85, p

Objective: Non-motor symptoms (NMS) play a vital role in managing Parkinson’s disease (PD) and have become the leading cause of deterioration of quality of life with the progression of the disease. The aim of the present study was to investigate the prevalence of NMS in PD with disease duration. Materials and Methods: We selected 75 patients with PD prospectively and all patients were diagnosed according to the United Kingdom PD Brain Bank criteria. All patients were trichotomized based on disease duration (≤4 years, 5-8 years and ≥9 years). The NMS screening questionnaire comprising 30 items was completed by all patients. Results: Out of 75 patients, men constituted 82.6%, the mean age was 59.2±1.51 (range, 45-69) years. The overall prevalence of NMS was 100%. Among the patients with a disease duration of ≤4 years, 5-8 years, and ≥9 years, gastrointestinal symptoms were observed in 38%, 48%, and 86.2%; cardiovascular dysfunction in 47.6%, 44%, and 82.7%; urinary problems in 38%, 40%, and 72.4%; poor sexual performance in 42.8%, 40%, and 79.3%; sleep disturbance in 38%, 36%, and 75.8%; anxiety in 33.3%, 40%, and 79.3%; hallucinations in 33.3%, 36%, and 72.4%; and cognition problems in 38%, 32%, and 72.4%, respectively. Significantly higher prevalences of gastrointestinal symptoms (p=0.006), cardiovascular dysfunctions (p=0.007), urinary problems (p=0.03), poor sexual performance (p=0.007), sleep disturbances (p=0.007), anxiety (p=0.007), hallucinations (p=0.03), and cognitive problems (p=0.007) were noted in patients with ≥9 years disease duration. Conclusion: Our study established that 100% of patients with PD had at least one NMS and there was a higher prevalence of NMS among those with disease duration more than 9 years.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons. Spread of pathology to other brain areas leads to development of non-motor symptoms (NMSs). These usually remain undiagnosed because of overwhelming motor problem and are responsible for significant distress to the patient. Our objective was to explore the burden of various NMSs of patients with ALS, compare between limb-onset and bulbar-onset patients, and to correlate with severity and duration of disease. Methods: Fifty patients with ALS diagnosed according to revised El Escorial Criteria and 50 healthy controls were included in this study. They were assessed with NMS Questionnaire, Beck's Depression Inventory, Center for Neurologic Study-Lability Scale, Drooling Frequency and Severity Scale, Epworth Sleepiness scale, Bengali Mental State Examination, and Frontal Assessment Battery and relevant statistical analyses were carried out. Results: The patients with ALS had significantly increased prevalence of almost all NMSs compared to controls. There was also significant increase in depression, suicidal ideation, pseudobulbar affect, and daytime sleepiness in patients with ALS. The bulbar onset subgroup had significantly increased daytime drooling, dysphagia, nausea and vomiting, whereas the limb onset subgroup reported increased frequency of leg swelling. Executive dysfunction was detected in 24% of patients with ALS and 9.8% had mild cognitive impairment. Weight loss, frequency of falling, insomnia, unpleasant nocturnal leg sensations, difficulty having sex, depression, and cognitive impairment increased significantly with an increase in severity of the disease. Conclusion: NMSs were significantly more prevalent in patients with ALS. Some NMSs worsened with advancement of the disease.

Objective: Our aim was to investigate the relation between unilateral hippocampal and/or nigral alpha-synucleinopathy and cognitive dysfunction, anxiety and anhedonia. Materials and Methods: Female Sprague-Dawley rats were stereotactically injected adeno-associated viruses carrying alpha-synuclein (α-syn) into unilateral dentate gyrus (DG), substantia nigra (SN) or both SN + DG. The animals were tested for motor functions and memory, spatial learning, anxiety and hedony. Levels of α-syn and synaptophysin were evaluated by Western blot (WB) analysis. Results: In apomorphine-induced rotation test, a mild motor dysfunction was found in SN-α-syn group compared to control. DG- α-syn group showed memory impairment in novel object recognition test. All the α-syn injected groups spent more time to find the platform compared to controls in Morris water maze but this difference did not reach statistical significance. DG-α-syn group consumed more sucrose solution in sucrose consumption test and spent more time on the open arm in elevated plus maze, while the opposite was observed in SN-α-syn group compared to controls. We showed α-syn protein expression in the injected areas of all α-syn groups by WB and immunohistochemical staining. In WB analysis, both hippocampal and striatal synaptophysin expression levels were lower in the α-syn groups compared to controls. Conclusion: Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms (NMS). However, an animal model recapitulating NMS with the background of dopaminergic denervation is still lacking. This model may help to investigate hippocampal α-syn pathology correlated especially with cognitive dysfunction and other NMS of PD.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after the dementia of Alzheimer. The clinical presentation of PD is dominated by typical motor symptoms as resting tremor, cogwheel rigidity, bradykinesia, and postural instability. Non-motor symptoms (NMS) of Parkinson's disease are common but are often under-recognized in clinical practice either due to the lack of spontaneous complaints by the patients or to the absence of systematic questioning by healthcare professionals. In contrast to motor dysfunctions, non-motor symptoms frequently remain unreported. Recently, a self-completed NMS questionnaire and NMS scale for identification and evaluation of these symptoms have been validated. An international survey has shown that up to 62% of NMS in PD remain undeclared to healthcare professionals because patients are unaware that NMS symptoms are linked to PD. Based on both clinical and neuropathological data, PD, traditionally accepted as a dopaminergic motor disorder, now can be characterized as a multisystem neurodegenerative disease that involves many neurotransmitter systems and affects not only motor but non-motor functions, too.

CNS involvement in Hodgkin lymphoma is extremely rare, and usually presents with focal weakness, nonspecific sensitive symptoms, headache, altered mental status, and seizures.

Background Non‐motor fluctuations are a major concern in Parkinson's disease (PD), and they have been categorized into neuropsychiatric, autonomic and sensory fluctuations. However, this categorization does not include sleep and sleep‐related features, and the association between daytime sleepiness and other motor and/or non‐motor fluctuations in PD remains to be elucidated. Objective To investigate the relationship between daytime sleepiness and other non‐motor and motor fluctuations in people with PD. Methods A three‐day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and 6 days of accelerometer (Parkinson's KinetiGraph™; PKG™) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2 years). Participants were categorized as motor fluctuators or non‐fluctuators according to the UPDRS part IV and/or the presence of motor and non‐motor fluctuations. Results Fifty‐two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non‐fluctuators (n = 24). Stronger positive within‐individual correlations were found among fluctuators in comparison to non‐fluctuators. In general, PKG data did not correlate with diary data. Conclusion Episodes of daytime sleepiness, as reported by home diaries, were associated with other self‐reported non‐motor and motor fluctuations, but were not supported by PKG data.

Dopamine agonists have been widely used to treat patients with Parkinson's disease, but concerns related to their well-known side effects might prevent their use even when indicated. In this review, the authors describe for the first time the concept of 'Dopamine Agonist Phobia', a pharmacophobia that the authors believe might affect clinicians, and they provide evidence of the benefits of dopamine agonists, focusing on non-motor symptoms.The authors performed an extensive literature research, including studies exploring the use of dopamine agonists for the treatment of non-motor symptoms. The authors indicate the highest level of evidence in each section.'Dopamine Agonist Phobia' may preclude valid therapeutic options in selected cases, specifically for the treatment of non-motor symptoms. Thus, the authors propose a personalized approach in Parkinson's disease treatment, and encourage a thoughtful use of dopamine agonists, rather than an overall nihilism.

Essential tremor (ET) is one of the most common movement disorders. Aside from tremor, patients may exhibit other motor features as well as non-motor features, including neuropsychiatric symptoms. The cerebellum and cerebellar connections are thought to play a key role in the pathophysiology of ET. Cognitive and affective disturbances can occur in the context of cerebellar disease. Our aim was to study the prevalence and clinical correlates of alexithymia and its relationship to depression and anxiety in ET patients and control subjects (CS).We enrolled 100 ET patients and 100 age- and gender-matched CS. The Toronto Alexithymia Scale-20 (TAS-20), the Beck depression inventory-II and the Beck anxiety inventory were administered.Alexithymia levels were significantly higher in ET patients than CS (respective mean TAS-20 scores = 50.63 ± 9.79 vs. 44.05 ± 12.51, p 0.001). There were robust associations between alexithymia, depressive symptoms, and anxiety but, after excluding the ET patients and the CS who had moderate or severe depression or who had moderate or severe anxiety, the total alexithymia score remained significantly higher in the ET than the CS group (46.78 ± 9.19 vs. 41.18 ± 11.79, p ≤ 0.01).This study suggests that prevalence of alexithymia is significantly higher in ET patients. Alexithymia might be another non-motor neuropsychiatric symptom of the disease. Further studies are needed to confirm and expand upon our findings.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. Dystonic movements are typically patterned, associated with twisting of body parts, and may have tremulousness. Dystonia is usually initiated or worsened by voluntary action and associated with overflow muscle activation. Cervical dystonia (CD) is the most prevalent form of dystonia. CD is a condition characterized by cranial muscle overactivity leading to abnormal intermittent or continuous posturing of the head. Non-motor symptoms are comorbidity of dystonia, which significantly hampers the quality of life among these patients. The symptoms can be as a result of the dystonia itself. However, studies have highlighted the involvement of cortical-striatal-thalamocortical circuits in primary dystonia that could be the pathophysiological basis for the non-motor symptoms. The non-motor symptoms that are commonly associated with dystonia are anxiety, depression, restless leg syndrome, excessive daytime sleepiness, cognitive disturbances, and poor sleep. This review attempts to summarize the literature on non-motor symptoms in patients with CD.

Introduction Parkinson’s disease (PD) is the second most common neurodegenerative condition after Alzheimer’s. Historically considered as a movement disorder, the multitude of non-motor symptoms (NMS) are now a recognised cause of significant disease burden. This study aimed to explore the relationship between postural instability and NMS in PD. Methodology We recruited individuals (n=100) in South East Queensland with a pre-existing diagnosis of idiopathic PD into this prospective observational study. Motor assessment was performed via the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Assessment of postural instability was based on the Hoehn & Yahr Scale (H&Y) with a score of ≥3 considered indicative of postural instability. NMS were assessed via the Non-Motor Symptoms Scale (NMSS). Further neuropsychiatric and affective assessment was evaluated with the Geriatric Depression Scale (GDS-15), Geriatric Anxiety Inventory (GAI), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Montreal Cognitive Assessment (MoCA). Results Cohort demographics comprised of 62% male and 38% female with a mean age of 69.1 years (SD 7.35) and mean H&Y 2.34 (SD 0.59). Sixty four participants were H&Y 1 & 2 whilst 36 participants were H&Y ≥3. Participants with postural instability were significantly older (p = 0.033) and had lower MoCA scores (p=0.039). Among the MoCA domains, only the Visuospatial / Executive domain was associated with postural instability (p= 0.005). Among the NMSS domains, only the sexual function domain was significantly associated with the latter group (p=0.029). GDS scores tended to be higher in the postural instability group (p=0.054) but there was no significance in major depressive disorder (p=0.436). Conclusion Postural instability in PD is significantly associated with age and cognitive impairment, in-particular frontal lobe function. The association of sexual dysfunction is supportive of the notion that disorders in dopaminergic and non-dopaminergic systems underpin the pathophysiology substrate of postural instability.

In the clinical picture of essential tremor (ET), in addition to tremulous hyperkinesis, the importance of non-motor manifestations has recently been discussed. Despite their high occurrence, in most cases these manifestations remain unverified. The purpose of this study was to assess the incidence of non-motor symptoms (NMS) in patients with ET. The study included 3 groups comparable by sex and age. Group 1 (the main group) consisted of 53 patients with ET; Group 2 consisted of 57 patients with Parkinson's disease (PD); Group 3 consisted of 111 individuals without ET or PD, and without burdened heredity for extrapyramidal diseases. All subjects filled out the NMSQuest scale, which contains 30 questions for various groups of NMS. The analysis of NMS using the NMSQues scale in the three study groups showed a similarity between ET plus and PD in non-motor manifestations.

This study’s aim was to investigate prevalence of four non-motor symptoms in patients with cervical dystonia and healthy controls to explore whether the presence of multiple non-motor features is associated with cervical dystonia diagnosis. Fifteen patients with cervical dystonia and 15 healthy controls underwent non-invasive testing of spatial discrimination threshold, temporal discrimination threshold, vibration-induced illusion of movement, and kinesthesia. All spatial discrimination threshold, temporal discrimination threshold, and vibration-induced illusion of movement measures were converted to standardized Z scores with scores >2.0 considered abnormal. Any incorrect kinesthesia response was considered abnormal. Prevalence of each abnormal non-motor feature was compared between groups using a chi-squared test. A higher proportion of patients with cervical dystonia had abnormal spatial discrimination threshold (p = 0.01) and abnormal kinesthesia (p = 0.03) scores compared to healthy control subjects. There were no significant differences between the proportion of patients with cervical dystonia versus healthy controls for abnormal temporal discrimination threshold (p = 0.07) or abnormal vibration-induced illusion of movement (p = 0.14). Forty-seven percent of patients with cervical dystonia (7/15) demonstrated one abnormal non-motor feature, 20% (3/15) displayed two abnormal features, and 13% (2/15) displayed three abnormal features. Kinesthesia was the only non-motor feature identified as abnormal in the control group (20%, 3/15). All four tests demonstrated high specificity (80–100%) and low-moderate sensitivity (13–60%). These findings suggest that non-motor feature testing, specifically for spatial discrimination threshold and kinesthesia, could be a highly specific diagnostic tool to inform cervical dystonia diagnosis. Further investigation is needed to confirm these findings.

Background: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson’s Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. Results: Men experienced greater longitudinal decline in self-reported motor (p

Risk factors for long-term non-motor symptoms and quality of life following subthalamic nucleus deep brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease. Data were extracted for 52 patients with Parkinson’s disease (half with predominantly left-sided motor symptoms and half with predominantly right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests, apathy and depression symptoms, as well as quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with predominantly left-sided motor symptoms. Performances of patients with predominantly right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.

Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

ObjectiveTo explore the utility of using patient reported emergence of new symptoms (ES) as an outcome measure during the early phase of the disease.MethodsWe analyzed data from MDS-UPDRS Part IB and Part II from the Safety, Tolerability, and Efficacy Assessment of Isradipine for PD (STEADY-PD3) study, with at least one annual follow-up over two years. We divided the sample into categories of follow-up visit (between 0 and 12-months, and 13 and 24-months) and the number of ES for each part of the scale between participants who started symptomatic treatment and those who did not (STx-yes/no). We assessed ES differences between participants STx in each follow-up visit using Mann-Whitney U test, and the Kaplan-Meier analyses.ResultsOf 331 participants observed for months 0 to 12, 288 (87%) developed ES, and 182 (55%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.86, p = 0.39), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.38, p=0.02). Of 148 participants who continued to be observed for months 13 to 24, 114 (77%) developed ES, and 62 (42%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.33, p = 0.74), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.25, p=0.02).ConclusionsAssessing ES among patient-reported experiences of daily living may provide a useful marker for tracking PD progression.

Parkinson's disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.

Background The non-motor symptoms of Parkinson's disease (PD), pain, depression, anxiety and sleep disturbances are highly prevalent in persons with PD and have a profound impact on their quality of life (QOL). Catastrophizing is a negative coping style known to influence individuals' ability to cope with their medical symptoms and contributes to negative health-related outcomes, yet, it has not been studied in persons with PD. Objective The objectives of this study were to measure catastrophizing in PD and explore its role as a mediator of the relationship between non-motor symptoms and QOL. Methods One-hundred and three individuals diagnosed with PD completed questionnaires regarding pain catastrophizing, QOL and non-motor symptoms: pain, depression, anxiety and sleep disturbances. Results More than half of the sample exhibited high levels of pain, anxiety and sleep disturbances. Catastrophizing was significantly correlated with QOL and with all of the non-motor symptoms. Catastrophizing mediated the relationship between all of non-motor symptoms and QOL as well as the relationship between age and QOL. Conclusions Negative psychologic coping, specifically catastrophizing, has an important role in determining how destructive non-motor symptoms can be on the QOL of persons with PD. This is the first study to measure catastrophizing in this population and demonstrate its negative impact on QOL. Our findings emphasize the need to identify persons at risk for poor QOL and referrer them to appropriate psychological care. Evidence based interventions that target catastrophizing should be tested for their efficacy in persons with PD.

Currently, there is a high increase in production of air vehicles equipped with low-power internal combustion engines. The main demasking factor of such engines is the high noise of their exhaust system. To solve this problem, we made a test bench on which we estimated the efficiency of several alternate designs of mufflers. In the course of work, we studied the influence of various internal elements of the muffler on its hydrodynamic resistance and noise attenuation efficiency. According to the results obtained, we found the best design alternate design of the muffler, which effectively coped with its role.

Background: Different non-motor neurological complaints are reported among the Parkinson’s disease patients. Objective: The purpose of the present study was to see the non-motor neurological complaints of Parkinson’s disease patients. Methodology: This cross-sectional study was carried out in the in-patient and out-patient Department of Medicine and Neurology of Sir Salimullah Medical College and Mitford Hospital, Dhaka from July 2012 to December 2013 for a period of one and half year. All patients with Parkinson’s disease who were admitted under department of Medicine and Neurology and also who visited out-patient department of Medicine and Neurology of Sir Salimullah Medical College and Mitford Hospital, Dhaka were included as study population. Patients who were diagnosed according to Brain Bank clinical criteria for diagnosis of Parkinson’s disease were included in this study. The non-motor neurological complaints were recorded. Result: This study was conducted in Sir Salimullah Medical College and Mitford Hospital with a view to see the non-motor neurological complaints of Parkinson’s disease. The mean age was found 69.15±10.08 years. Most of the patients had a combination of non-motor symptoms and among them more than two third (66.7%) of the patients had cognitive impairment; furthermore more than half (53.8%) of the patients had sleep disturbance. One fourth (25.0%) of patients had sensory, sleep and cognitive disorder; however, 9(22.5%) patients had sleep and cognitive disorder. Conclusion: In conclusion majority Parkinson’s disease patients are suffering from cognitive impairment followed by sleep disturbances. Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 123-126

Background:Primary Parkinson syndrome is mostly treated by dopaminergic drugs, while the progression of the disease is not altered. Some non-dopaminergic are available, which are administered only after the Parkinsonian symptoms get worse.Objective:The objective of this review is to give basic results in order to compare a dopaminergic and non-dopaminergic pharmacotherapy in Parkinson’s disease and to control whether the add-on pharmacotherapy with non-dopaminergic drugs can inhibit the progression of the disease.Methods:In primary Parkinson syndrome, the altered activity of classical neurotransmitters and neuropeptides in the extrapyramidal system is summarized and up-dated. Anatomical studies on neural networks in the basal ganglia are mentioned. The direct, motor facilitatory pathway (D1 dopaminergic neurons) from the substantia nigra to the thalamus, via the internal globus pallidus, and the indirect, motor inhibitory pathway via D2 dopaminergic neurons have been considered. These established anatomical pathways have been brought in line with the neural interactions derived from neurotransmitter balances or imbalances. Besides, preclinical and clinical studies of effective non-dopaminergic anti-Parkinsonian drugs are reviewed.Results:It can be hypothesized that glutamatergic neurons enhance dopamine deficiency in the substantia nigra and putamen through an increased presynaptic inhibition mediated by NMDA receptors. In the putamen, 5-HT2A serotonergic neurons counteract D2 dopaminergic neurons and A2A adenosine neurons antagonize D2 dopaminergic neurons by activating glutamatergic neurons, which presynaptically inhibit via subtype 5 of metabotropic glutamatergic receptors, D2 dopaminergic neurons. In the extrapyramidal system, an up-dated neural network, which harmonizes established anatomical pathways with derived neural interactions, is presented. In Parkinson’s disease, a question should be answered, whether a combination of dopaminergic and non-dopaminergic drugs can promote an increased motor and non-motor functioning.Conclusion:A mono-target pharmacotherapy (using only dopaminergic drugs) and a multi-target pharmacotherapy (i.e. by combining dopaminergic and non-dopaminergic drugs) are compared. The alternate administration of dopaminergic and non-dopaminergic anti-Parkinsonian drugs, administered at different times during the day, must be tested in order to inhibit the progression of the disease. Assessment tools can be used to evaluate motor and cognitive functions. Moreover, imaging examination techniques can be also applied to control the course of the disease.

The aim of this study was to evaluate the correlation between motor and non-motor symptoms in patients diagnosed with Parkinson. We included in our study 72 patients diagnosed with Parkinson disease:28 female and 44 males. Each patient was evaluated using Non-motor Symptoms Questionnaire for Parkinson Disease, for motor status we used Unified Parkinson Disease Rating Scale (UPDRS) part 3 (motor part). The results of our study indicated that there is a correlation between the non-motor state and the motor symptoms but not in all non-motor domains. The study indicates that the digestive symptoms, the, cardiovascular, sleep and miscellaneous correlate with the motor symptoms but urinary symptoms, memory, hallucination, depression and sexual dysfunction does not show an interdependence with the motor state.

Purpose Parkinson's disease (PD) is associated with non-motor symptoms (NMS) that can cause progressive disability and impact quality of life of people with PD (PwP) and increase burden on care partners. This survey was designed to evaluate the prevalence, impact, and educational preferences regarding NMS on PwP and their care partners. Patients and methods A 17-question survey was sent to the total membership of PMDAlliance, a nonprofit organization reaching 3,685 households of PwP. Care partners and other interested individuals could also respond. The survey was conducted using Survey Monkey, an online survey platform, and included distinct questions for respondents with and without NMS. Results A total of 700 individuals responded to the survey. Of the respondents, 378 (54%) were care partners and 287 (41%) were PwP. About 90% of the respondents reported having experience with NMS in PwP, including sleep problems (84%), cognitive symptoms (76%), anxiety (65%), depression (56%), hallucinations (40%), and delusions (23%). NMS in PwP were reported by more care partners (97%) than PwP (80%). NMS had at least some impact on quality of life for 84% of the respondents; 48% indicated that NMS represented a greater challenge than motor symptoms. Care partners were more likely than PwP to report that NMS were more challenging than motor symptoms (58% vs 32%). Respondents with and without NMS indicated a desire for NMS education. Conclusion This survey underscores the significant impact of NMS on the quality of life of PwP and highlights the need for improved recognition and education about its effects.

Background Motor and non-motor behavior analyses are increasingly utilizied in drug discovery and screening, detection of neurobehavioral disorders and chemical toxicology. The emergence of computational approaches has helped to develop different tools to analyse complex behaviors. Analysis of locomotor behavior helps in understanding the motor neuron disorders like Parkinson’s Disease. Although many animal models are available to study the locomotion, adult zebrafish has emerged as a simple and efficient model to study this behavior. An inexpensive and easily customizable tool is required to replace the licensed and expensive set-up to analyse the locomotor behavior. New method In this study we have optimized the ImageJ plugin wrMTrck to analyse motor and non-motor behaviors in adult zebrafish. We have generated a macro to simplify the preprocessing and tracking. Subsequently, we have developed a data analysis sheet to analyse various behavioral end points. Results We have successfully developed an inexpensive video acquisition set-up and optimized wrMTrck for adult zebrafish. In order to demonstrate the efficacy of this method, adult zebrafish were injected with MPTP and motor and non-motor behaviors were analysed. Expectedly, MPTP injected fish showed decrease in dopamine level and dat expression level, which subsequently led to locomotor behavioral defects as well as anxiety, a non-motor symptom of PD. Comparison with existing method(s) Further, the obtained results were validated by another ImageJ macro developed by Pelkowski et al. (2011) and we observed identical trajectories. Conclusions The usefulness of popular ImageJ plugin wrMTrck and this extended protocol will be helpful to quantify motor and non-motor behavioral parameters.

Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD.CSF levels of 42-amyloid-β, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features.We observed that α-synuclein levels were reduced in PD (p 0.05, AUC = 0.8; p 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p 0.014; T = -3.6, p 0.05; item 9: T = -2.1, p 0.05, respectively).Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.

BACKGROUND Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is a result of degeneration of the substantia nigra, pars compacta with dysfunction of dopaminergic nigrostriatal pathway. The three cardinal signs of Parkinson disease are resting tremor, rigidity, and bradykinesia. Apart from these, non-motor symptoms (NMS)s substantially contribute to patient’s quality of life and are a frequent cause of hospitalization which are poorly recognized and inadequately treated. The objectives of the study are- 1) To find out the prevalence of non-motor symptoms in participants and 2) To classify and analyse the non-motor symptoms in them on the basis of system involvement. MATERIALS AND METHODS This is a hospital based observational study conducted on 50 patients of Parkinsonism over a period of 1 year. Parkinson’s disease was confirmed by UKPDS Brain Bank Criteria. Neurological examination was conducted for MMSE scores and H and Y staging. Findings were recorded in predesigned and pretested questionnaire. RESULTS Out of 50 participants, 32% (16) belong to the age group of 61-70 years, and 56% were males. 60% were newly diagnosed during the study period. 50% had duration of illness of