Plasma epidermal growth factor decreased in the early stage of Parkinson's disease.

To explore the incidence of depression in movement disorders and associated factors. A total of 121 Parkinson's disease (PD) patients from August 2010 to June 2011 and 62 ET patients from July 2009 to June 2010 were recruited. All of them were outpatients of our hospital. PD patients received the unified Parkinson's disease rating scale (UPDRS) -motor examination and a modified Hoehn and Yahr scale to stage the severity of their disorders while 62 essential tremor (ET) patients were evaluated with tremor rating scale for tremor-motor examination (items 1 - 15 of rating scale). All participants completed Hamilton depression rating scale (24 items) to measure the presence and degree of symptoms of depression. It was found that 56.2% of PD patients and 53.2% of ET patients were depressed (HAMD score of 8 or higher). Among them, the rates of mild depression were 38.9% and 35.5%, moderate depression 15.7% and 17.7% and severe depression 1.7% and 0% in PD and ET patients respectively. No significant differences existed between each group. The factor scores of cognitive impairment were 1.81 ± 1.86 and 1.04 ± 1.07 in PD and ET patients while those of sense of despair were 2.95 ± 1.97 and 4.09 ± 2.08 in each group. The differences had statistical significance in two factor scores of two groups (P < 0.05). No differences in anxiety/somatization, lose weight, day-and-night changes, block and sleep disorders between two groups. For PD patients, the motor score of UPDRS-III was positively correlated with total HAMD score (r = 0.511, P < 0.01). Similarly, for ET patients, tremor rating scale for tremor-motor subscale score and HAMD score were positively correlated (r = 0.828, P < 0.01). As two common movement disorders, PD and ET have a high incidence of depression. The severity of depression is similar in two groups. There is no significant intra-group difference in severity and frequency of depression. The most common symptoms are anxiety somatization, anhedonia, working difficulty, slowness and sleep disturbance. The depression and motor symptoms are positively correlated. Like the non-motor symptoms in PD, we should also pay attention to the non-motor symptoms in ET.

Models which assess the progression of Lewy pathology in Parkinson's disease have proposed ascending spread in a caudal-rostral pattern. In-vivo human evidence for this theory is limited, in part because there are no biomarkers that allow for direct assessment of Lewy pathology. Here, we measured neurodegeneration via MRI, an outcome which may serve as a proxy for a more direct assessment of ascending models using a combination of (1) MRI-based measures of gray matter density and (2) regions of interest (ROIs) corresponding to cortical and subcortical loci implicated in past MRI and stereological studies of Parkinson's disease. Gray matter density was measured using brain MRI voxel-based morphometry from three cohorts: (1) early Parkinson's disease, (2) more advanced Parkinson's disease and (3) healthy controls. Early Parkinson's disease patients (N = 228, mean age = 61.9 years, mean disease duration = 0.6 years) were newly diagnosed by the Parkinson's Progression Markers Initiative (PPMI). Advanced Parkinson's disease patients (N = 136, mean age = 63.5 years, mean disease duration = 8.0 years) were collected retrospectively from a local cohort undergoing evaluation for functional neurosurgery. Control subjects (N = 103, mean age = 60.2 years) were from PPMI. Comparative analyses focused on gray matter regions ranging from deep gray subcortical structures to the neocortex. ROIs were defined with existing probabilistic cytoarchitectonic brain maps. For subcortical regions of the basal forebrain, amygdala, and entorhinal cortex, advanced Parkinson's disease patients had significantly lower gray matter density when compared to both early Parkinson's disease and healthy controls. No differences were seen in neocortical regions that are “higher” in any proposed ascending pattern. Across early and advanced Parkinson's disease, gray matter density from nearly all subcortical regions significantly decreased with disease duration; no neocortical regions showed this effect. These results demonstrate that atrophy in advanced Parkinson's patients compared to early patients and healthy controls is largely confined to subcortical gray matter structures. The degree of atrophy in subcortical brain regions was linked to overall disease duration, suggesting an organized pattern of atrophy across severity.

Objective: The aim of this study was to test plasma insulin-like growth factor 1 (IGF-1) change in Parkinson's disease (PD) and essential tremor (ET), and assess the association of plasma IGF-1 level with motor and nonmotor symptoms in PD and ET. Methods: Plasma IGF-1 was measured in 100 PD patients, 40 ET patients, and 76 healthy controls. Motor and nonmotor symptoms were assessed by different scales. Spearman correlation test and linear logistic model were used to analyze the correlation of plasma IGF-1 with motor and nonmotor symptoms of PD and ET. Results: The plasma IGF-1 level was significantly increased in PD compared to healthy controls and ET patients. In addition, low plasma IGF-1 was correlated with low Mini-Mental State Examination (MMSE) scores in PD patients. However, no correlation was found between plasma IGF-1 and MMSE scores in ET patients. Conclusion: Plasma IGF-1 increased significantly in PD but remained unchanged in ET. A low plasma IGF-1 level was associated with poor cognitive performance in PD but not in ET patients.

Do non-motor symptoms in Parkinson's disease differ from essential tremor before initial diagnosis? A clinical and scintigraphic study

Gender differences in motor and non-motor symptoms in Parkinson disease (PD) are still controversial. This study aimed to investigate gender differences in clinical characteristics in patients with early PD.This study included 415 PD patients (201 men and 214 women) with modified Hoehn-Yahr stage 1 to 3 and a disease duration of ≤5 years. Demographic information was obtained by interviews, and motor and non-motor PD symptoms were evaluated with appropriate scales.Women with PD had a shorter duration of formal education than men with PD. No significant differences were found in other demographic variables. Women with PD had significantly lower scores in Unified Parkinson Disease Rating Scale part III and postural tremor compared to men with PD, which was significant after controlling for formal education. No significant gender-related differences were found in scores related to other motor symptoms. Concerning non-motor symptoms, men with PD had higher scores of sexual function on the Non-Motor Symptoms Scale, which means sexual dysfunction was more severe or occurred more frequently in men with PD. Women with PD had significantly higher scores of sleep disturbance in the Pittsburgh Sleep Quality Index, which was not significant after adjustment for multiple comparison.The present study suggests that women with PD had milder motor symptoms compared to men with PD, and gender differences in sexual function can be observed as non-motor symptoms.

Subjective cognitive complaints (SCCs), defined as cognitive decline reported by subjects or their informants, are common in the early stage of Parkinson's disease (PD). Previous studies have shown a significant association between SCCs and non-motor features as well as objective cognitive decline in PD patients. However, the discrepancy in SCC prevalence and SCC-related factors between patients with early PD and those with advanced PD remains poorly understood. We recruited a total of 114 and 69 early PD patients and advanced PD patients, respectively. Univariate and multivariate logistic regression analyses were performed for early PD and advanced PD patients. The prevalence of SCCs in the early PD and advanced PD groups was 60.5 and 68.1%, respectively. In the early PD group, the presence of SCCs in early PD participants was significantly associated with a higher nonmotor symptoms questionnaire (NMSQ) score (OR = 1.05, 95% CI = 1.00-1.10, p = 0.040). SCCs in the advanced PD group were related to lower attention scores (OR = 0.24, 95% CI = 0.05-0.90, p = 0.043) and lower visuospatial/executive abilities scores (OR = 0.18, 95% CI = 0.04-0.86, p = 0.032). The prevalence and SCC-related factors are distinct in early PD and advanced PD. These findings suggest that SCCs in PD patients with different disease statuses appear to have different related factors that may depend on different disease severities.

BackgroundParkinson's disease (PD) provides a model for investigating the involvement of the basal ganglia and mesolimbic dopaminergic system in the recognition of emotions from voices (i.e., emotional prosody). Although previous studies of emotional prosody recognition in PD have reported evidence of impairment, none of them compared PD patients at different stages of the disease, or ON and OFF dopamine replacement therapy, making it difficult to determine whether their impairment was due to general cognitive deterioration or to a more specific dopaminergic deficit.MethodsWe explored the involvement of the dopaminergic pathways in the recognition of nonverbal affect bursts (onomatopoeias) in 15 newly diagnosed PD patients in the early stages of the disease, 15 PD patients in the advanced stages of the disease and 15 healthy controls. The early PD group was studied in two conditions: ON and OFF dopaminergic therapy.ResultsResults showed that the early PD patients performed more poorly in the ON condition than in the OFF one, for overall emotion recognition, as well as for the recognition of anger, disgust and fear. Additionally, for anger, the early PD ON patients performed more poorly than controls. For overall emotion recognition, both advanced PD patients and early PD ON patients performed more poorly than controls. Analysis of continuous ratings on target and nontarget visual analog scales confirmed these patterns of results, showing a systematic emotional bias in both the advanced PD and early PD ON (but not OFF) patients compared with controls.ConclusionsThese results i) confirm the involvement of the dopaminergic pathways and basal ganglia in emotional prosody recognition, and ii) suggest a possibly deleterious effect of dopatherapy on affective abilities in the early stages of PD.

Objective To detect the plasma macrophage inflammatory protein (MIP) levels in patients with early Parkinson's disease (PD) and to investigate whether plasma MIP was associated with motor and non-motor symptoms in early PD. Methods Fifty-nine patients with early idiopathic PD (Hoehn-Yahr Staging Scale from 1.0 to 2.5) treated in our hospital from January 28, 2013 to September 30, 2013 and 54 healthy controls were recruited. Plasma MIP-1α and MIP-1β levels were measured by enzyme-linked immunosorbent assay. Motor function was assessed by Unified Parkinson's Disease Rating Scale Part Ⅲ and Hoehn-Yahr Staging Scale during on period. Total non-motor symptoms were assessed by Non-motor Symptoms Questionnaire. Cognitive dysfunction was assessed by Mini Mental State Examination. Autonotic dysfunction was assessed by Scales for Outcomes in Parkinson's disease-Autonomic. Depression was assessed by Hamilton Depressive Scale (HAMD). Rapid eye movement (REM) sleep behavior disorder was assessed by REM sleep behavior disorder screening questionnaire (RBDSQ). Correlation between plasma MIP levels and scale scores was analyzed by Spearman rank correlation. Results Plasma MIP-1α and MIP-1β levels were not significantly different between early PD patients and healthy controls. However, plasma MIP-1α level negatively correlated with depression (HAMD score, r=-0.520, P=0.027) and rapid eye movement sleep behavior disorder (RBDSQ score, r=-0.537, P=0.039). Conclusion MIP-1α may be correlated with depression and RBD in early PD. Key words: Parkinson disease; Macrophage inflammatory protein 1α; Macrophage inffammatory procein 1β; REM sleep behavior disorder; Depression

BackgroundPostural instability and balance problems in patients with Parkinson’s disease (PD) can seriously affect the quality of life and lead to falls with a subsequent increase in the morbidity and mortality. Early identification of gait dysfunction in early stages of PD establishes an effective therapy, prevention of the falls and reducing health care costs. This work aimed to detect gait disorders in patients with PD using the functional gait assessment (FGA) scale and to correlate it with the disease severity in Egyptian PD patients. This is a case–control study in which 40 patients with PD were recruited from the Involuntary Movement Clinic at Alexandria University El-Hadara Hspoital; 20 patients had early stages of PD (Hoehn Yahr stages 1 and 2) and 20 patients had advanced PD (Hoehn Yahr stages 3 and 4). Another 20 subjects were recruited as controls. All recruited subjects underwent gait assessment using FGA scale.ResultsGait analysis using FGA showed significant differences (P < 0.001) between the recruited PD patients and the control group. Upon comparing the early and advanced PD patients’ groups, certain items in the FGA (gait with pivot turn, step over obstacle, gait with eyes closed and backward gait) together with time consumed for 6-m walk with eyes open and close showed significant statistical differences between early and advanced PD patients. The patients’ duration of illness with PD was reversely correlated with the total FGA score.ConclusionThe FGA scale was strongly influenced by the duration of PD among the Egyptian patients and can potentially detect early stages of PD.

Forehead sympathetic skin responses in determining autonomic involvement in Parkinson’s disease

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia

Over the past two decades, the development of functional imaging methods has greatly promoted our understanding on the changes of neurons following neurodegenerative disorders, such as Parkinson's disease (PD). The application of a spatial covariance analysis on 18F-FDG PET imaging has led to the identification of a distinctive disease-related metabolic pattern. This pattern has proven to be useful in clinical diagnosis, disease progression monitoring as well as assessment of the neuronal changes before and after clinical treatment. It may potentially serve as an objective biomarker on disease progression monitoring, assessment, histological and functional evaluation of related diseases. PD is one of the most common neurodegenerative disorders in the elderly. It is characterized by progressive loss of dopamine neurons in the substantia nigra pars compacta. Throughout the course of disease, the most obvious symptoms are movement-related, such as resting tremor, muscle rigidity, hypokinesia and postural instability (Worth, 2013). Currently, a definite diagnosis of PD is made by clinical evaluation with at least 2 years of follow-up (Hughes et al., 2002; Bhidayasiri and Reichmann, 2013), due to the overlap of motor symptoms between early PD and atypical parkinsonism including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). However, this classic diagnostic criterion does not benefit the early diagnosis of disease. The prognostic outcome and treatment option are substantially different between PD and atypical parkinsonism. Thus it is critical to develop biomarkers for earlier and more accurate diagnosis of PD. Generally, appropriate diagnostic biomarker for PD ought to cover several key characteristics: (i) minimal invasiveness to detect the biomarker in easily accessible body tissue or fluids, (ii) excellent sensitivity to explore the patients with PD, (iii) high specificity to prevent false-positive results in PD-free individuals, and (iv) robustness against potential affecting factors. A PD-related spatial covariance pattern (PDRP) with quantifiable expression on 18F-FDG PET imaging has been gradually detected using a spatial covariance method during the last two decades and it has been demonstrated to be the right diagnostic biomarker for PD (Eidelberg et al., 1994). PDRP has proven not only to be effective in early discrimination of PD from atypical parkinsonian disorders, but also to be able to assess the disease progression and treatment response. Thus it is considered as a multifunctional biomarker. In this review, we aim to provide an overview of the development in pattern-based biomarker for PD.

To explore the incidence of cognitive dysfunction and associated factors in 62 essential tremor (ET) cases, 60 normal controls and 61 Parkinson's disease (PD) cases. A total of 62 ET and 61 PD patients from September 2009 to September 2013 were recruited from our outpatient clinic. ET patients received the Tremor Rating Scale for Tremor-motor examination (items 1-15 of rating scale) while 61 PD patients were examined with the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination and a modified Hoehn and Yahr scale for staging disorder severity. All participants completed Montreal Cognitive Assessment (MoCA) Beijing version for measuring cognitive functions. And depression was evaluated by the Hamilton Depression Scale (HAMD). The serum levels of uric acid were tested. A MoCA score <26 (at least mildly cognitive) was observed in 14 (23.3%) normal controls, compared to 24 (38.7%) ET cases and 27 (44.3%) PD cases (P = 0.045 when comparing all 3 groups, and P = 0.532 when comparing ET and PD). The factor scores of visual space/execution were 4.1 ± 1.0, 3.8 ± 1.1 and 3.2 ± 1.6 in normal controls, ET and PD patients, the factor scores of naming 2.9 ± 0.4, 2.8 ± 0.6 and 2.3 ± 0.8 in control, ET and PD patients, the factor scores of delay memory 3.9 ± 0.9, 2.7 ± 1.3 and 2.5 ± 1.7 in control, ET and PD patients. Statistical differences existed in visual space/execution, naming and delay memory (P < 0.05) among 3 groups. Yet there were no statistical differences in attention, language, abstract and directional among 3 groups. Statistical differences existed in visual space/execution and naming between ET and PD patients (P < 0.05). PD cases had the lowest visual space/execution score, followed by ET (intermediate) and highest scores in controls (P < 0.05). In ET patients, cognitive scores were correlated with serum levels of uric acid, education, tremor Rating Scale for Tremor-motor subscale score and depression levels (r = 0.589, P = 0.000; r = 0.449, P = 0.010; r = 0.452, P = 0.009; r = 0.466, P = 0.025). In PD patients, cognitive scores correlated with serum levels of uric acid, education, score of UPDRS-III and depression levels (r = 0.694, P = 0.000; r = 0.614, P = 0.000; r = 0.604, P = 0.000; r = 0.376, P = 0.000). The incidence of cognition is higher in ET and PD. There were no significant inter-group differences for cognition frequency. The most frequently endorsed symptoms were poor visual spatial ability, execution disturbance and delayed recall disorders. Some connition scores in ET were intermediate between those of PD cases and normal controls. Thus a mild form of connition dysregulation may be present in ET. The degree of cognition symptoms is correlated with serum levels of uric acid, education and serious motor.

Introduction: Non motor symptoms are highly prevalent in Parkinson’s Disease (PD) but are often overshadowed by the dominance of motor symptoms. Aim: To assess non motor symptoms in patients with Parkinson’s disease. Materials and Methods: In this prospective observational study, patients of PD fulfilling United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria were recruited, between August 2019 to July 2021, in the Neurology Department of Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. The pattern of Non Motor Symptoms (NMS) in PD was studied using detailed questionnaire and association of NMS with age, gender and modified Hoehn and Yahr stage were assessed. Chi-square test and Student's t-test was calculated where required. Results: Total 102 patients were included, with male constituting 73.5% patients. The mean age was 60.14±13.55 years. Constipation (74, 72.55%) was the most common non motor symptom. Most of the patients belonged to mild stage (52.94%) followed by moderate (40.20%) and severe (6.86%) stages, according to modified Hoehn and Yahr classification. Rapid eye movement sleep behaviour disorder (n=15) and sexual dysfunction (n=28) were significantly more prevalent in male patients. Depression, REM sleep behaviour disorder, olfactory disturbance, visual disturbance, urinary urgency, sweating abnormality, constipation, vomiting and visual blurring were significantly common in patients with earlier disease stages while psychosis in patients with advanced stage. Conclusion: This study showed the high prevalence of non motor symptoms in PD patient which is consistent with other studies, but there are differences in the frequency of individual symptoms which may relate to cultural and geographic differences.

Parkinson's disease (PD) is a progressive, neurodegenerative neurological disorder of unknown etiology. Loss of dopaminergic cells in the substantia nigra of the brain is responsible for motor, affective and cognitive changes observed. No cure is available. Common motor symptoms are tremor, rigidity, and bradykinesia, as well as postural instability in later stages of the disease (Weiner, Shulman, & Lang, 2001). As the disease progresses medication induced motor symptoms, such as dyskinesia--involuntary gross motor wiggling or dance-like movement affecting upper and lower extremities--may emerge (Weiner et al, 2001). Awareness of the importance and impact of nonmotor symptoms has grown with clinical and research experience indicating cognitive and behavioral components substantially contributing to impaired quality of life and increased severity of motor symptoms. Yet, anxiety remains unrecognized and under treated among PD patients. (O'Sullivan, Williams, & Gallagher, 2008; Schulman, Taback, Rabinstein & Weiner, 2002). Anxiety disorders are the most common psychological disorder in the general population (Thyer et al., 1985), while anxiety disorders among older adults often co-occur with medical and neurological disorders (Raj et al., 1993). PD and comorbid anxiety have been documented repeatedly with estimates of 40-75% (Schiffer, et al., 1988; Shulman et al., 2002; Stein, Heuser, Juncos, Uhde, 1990). Clinical treatment, when provided, is primarily pharmacological with anxiolytics, benzodiazepines or antidepressants used. Pathological neurodegenerative changes in noradrenergic mechanisms may be responsible for anxiety experienced by patients with PD (Marsh, 2000). No experimental studies have examined the efficacy of medication in this population. The effects of anxiety on functioning of PD are formidable and further diminish quality of life (Marinus, Leentjens, Visser, Striggelbout & Van Hilten, 2002). Comorbid anxiety results in increased motor dysfunction including more severe tremor, freezing (sudden inability to move), dyskinesia and situational anxiety. Indeed, anxiety may produce excess disability than that observed solely due to PD. Treatment of motor and non motor symptoms of PD focuses on maintaining and improving quality of life. Addressing comorbid anxiety is an important target in this process and relaxation training has been suggested (Marsh, 2000). Despite the wide spread occurrence of comorbid anxiety and PD, few reports of relaxation training with PD patients are available. Schumaker (1980) examined the effect of frontal electromyographic (EMG) biofeedback and progressive muscle relaxation training on manual motor performance of PD patients. No effect of intervention on motor performance was observed. Behavioral Relaxation Training (BRT) has been used to successfully manage tremor of two older adults; one with essential tremor (ET) and another with ET and PD (Chung et al., 1995). Chung et al reported decreased tremor severity and improved performance in activities of daily. Improved psychological adjustment was anecdotally reported. Lundervold (1997) reported that BRT and coping self-instructions were effective with an ET patient in reducing tremor severity related to negative arousal (anger in specific social situations). Decreased emotional distress and EMG activity among four muscle groups was observed. More recently, Lundervold, Pahwa and Lyons (2009) reported using behavioral intervention that included BRT for management of PD and comorbid general anxiety. Two contemporary behavioral accounts describe anxiety and distress among movement disorder patients (Lundervold & Poppen, 2004; Macht & Ellgring, 1998). These reports describe a three component behavioral model. From a behavioral perspective, identification of current maintaining contextual variables, (i.e., setting events, antecedents and consequences) is critical in selection appropriate interventions (Speigler & Guevremont, 2003). …