Baseline predictors of progression of Parkinson’s disease in a sample of Egyptian patients: clinical and biochemical

Background Clinical progression of Parkinson’s disease (PD) is highly heterogeneous, and its predictors are generally lacking. Identifying predictors of early disease progression is important for patients’ management and follow-up. The current study aims to identify clinical, neuroimaging and biochemical baseline predictors of motor progression in patients with PD. Forty-five PD patients were assessed at baseline, 6 months and 1 year using MDS-UPDRS total and subscores, Hoehn and Yahr (H&Y), Schwab and England (S&E), International Physical Activity Questionnaire (IPAQ). Baseline New Freezing of Gait Questionnaire (NFOG-Q), Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), and Time Up and Go Test (TUG), Non-Motor Symptoms Scale (NMSS), Beck Depression Inventory (BDI), PD questionnaire 39 (PDQ-39), MRI brain, uric acid, lipid profile and glycated hemoglobin were performed. Results Significant worsening of MDS-UPDRS total, part III scores, H&Y, S&E and IPAQ (p < 0.001) was detected. One-year progression of H&Y and S&E were significantly correlated to disease duration (p = 0.014, p = 0.025, respectively). Progression of H&Y was correlated to baseline TUG (p = 0.035). S&E progression was correlated to baseline MDS-UPDRS total score (rho = 0.478, p = 0.001) and part III (rho = 0.350, p = 0.020), H&Y (rho = 0.401, p = 0.007), PIGD (rho = 0.591, p < 0.001), NFOG-Q (rho = 0.498, p = 0.001), and TUG (rho = 0.565, p = 0.001). Using linear regression, there was no predictors of clinical progression among the used baseline variables. Conclusion Despite the significant motor and physical activity progression over 1 year that was correlated to baseline motor and gait severity, but without predictive value, further similar and longitudinal studies are warranted to detect predictors of early progression and confirm findings.

Excessive Daytime Sleepiness Is Associated With Non-motor Symptoms of Multiple System Atrophy: A Cross-Sectional Study in China

Objectives: Excessive daytime sleepiness (EDS) in multiple system atrophy (MSA) has received scant attention in the literature, thus the present cross-sectional study aimed to investigate the prevalence of EDS and its potential risk factors among Chinese patients with MSA.Methods: A total of 66 patients with MSA (60.6% males) were consecutively recruited. Eighteen patients (27.3%, 13 men) with Epworth Sleepiness Scale score &gt;10 were defined as having EDS. Demographic, motor [Unified Multiple-System Atrophy (UMSARS)] and non-motor symptoms [Non-Motor Symptoms Scale (NMSS)], and sleep parameters [polysomnography (PSG)] were compared between patients with MSA with and without EDS. A logistic regression analysis was used to calculate the risk factors of EDS in patients with MSA.Results: There were no significant differences in age, sex, MSA onset age, disease duration, MSA sub-type, and motor symptom severity between MSA patients with and without EDS. However, compared with the MSA patients without EDS, their counterparts with EDS had higher scores of NMSS (65.3 ± 23.1 vs. 43.4 ± 25.3, P = .0002), Hamilton Anxiety (HAMA) [15.3 (10.3–20.0) vs. 9.5 (3.0–15.0), P = 0.006], Hamilton Depression (HAMD) [13.7 (12.5–17.8) vs. 9.0 (4.0–13.0), P = 0.015], and Fatigue Severity Scale (FSS) [29.8 (17.3–47.8) vs. 18.7 (10.3–21.8), P = 0.040]. Conversely, the patients with EDS had lower score of Mini-Mental State Examination (MMSE) [23.3 (20.3–27.0) vs. 25.7 (22.0–29.0), P = 0.023]. Similarly, there was a significantly lower percentage of N3 sleep (%) [0.3 (0–0) vs. 2.0 (0–0), P = 0.007] and a higher apnea-hypopnea index (AHI/h) [30.5 (14.5–47.8) vs. 19.3 (5.0–28.7), P = 0.034] in patients with EDS. After adjusting for age, sex, disease duration, MSA sub-type, and UMSARS score, the odds ratio (OR) (95% CI) of EDS was higher while increasing scores in FSS [1.06 (1.02–1.11)], HAMA [1.16 (1.04–1.28)], HAMD [1.13 (1.02–1.25)], NMSS [1.04 (1.01–1.07)], and AHI [1.03 (1.00–1.10)]. The OR of EDS was lower while the MMSE score was increasing [0.85 (0.72–1.00)].Conclusions: The presence and severity of EDS may be significantly associated with the non-motor dysfunction, including fatigue, anxiety, depression, cognitive dysfunction, and sleep-related breathing disorder, but not with the motor dysfunction in MSA.

Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson’s disease patients

Background Parkinson’s disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson’s symptoms. Methods 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson’s symptoms and the potential effects of medications on the serum SCFAs was analyzed. Results Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson’s Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. Conclusions Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson’s symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.

The complex syndrome of functional neurological disorder

Background Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. Methods One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. Results Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. Conclusions We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of ‘functional’ symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

Parkinson’s Disease Subtyping Using Clinical Features and Biomarkers: Literature Review and Preliminary Study of Subtype Clustering

The second most common progressive neurodegenerative disorder, Parkinson’s disease (PD), is characterized by a broad spectrum of symptoms that are associated with its progression. Several studies have attempted to classify PD according to its clinical manifestations and establish objective biomarkers for early diagnosis and for predicting the prognosis of the disease. Recent comprehensive research on the classification of PD using clinical phenotypes has included factors such as dominance, severity, and prognosis of motor and non-motor symptoms and biomarkers. Additionally, neuroimaging studies have attempted to reveal the pathological substrate for motor symptoms. Genetic and transcriptomic studies have contributed to our understanding of the underlying molecular pathogenic mechanisms and provided a basis for classifying PD. Moreover, an understanding of the heterogeneity of clinical manifestations in PD is required for a personalized medicine approach. Herein, we discuss the possible subtypes of PD based on clinical features, neuroimaging, and biomarkers for developing personalized medicine for PD. In addition, we conduct a preliminary clustering using gait features for subtyping PD. We believe that subtyping may facilitate the development of therapeutic strategies for PD.

Comparison Analysis of GLCM and PCA on Parkinson's Disease Using Structural MRI

Parkinson disease (PD) is a neurological disorder where the dopaminergic neurons experience deterioration. It is caused from the death of the dopamine neurons present in the substantia nigra i.e., the mid part of the brain. The symptoms of this disease emerge slowly, the onset of the earlier stages shows some non-motor symptoms and with time motor symptoms can also be gauged. Parkinson is incurable but can be treated to improve the condition of the sufferer. No definite method for diagnosing PD has been concluded yet. However, researchers have suggested their own framework out of which MRI gave better results and is also a non-invasive method. In this study, the MRI images are used for extracting the features. For performing the feature extraction techniques Gray Level Co-occurrence Matrix and Principal Component Analysis are performed and are analysed. Feature extraction reduces the dimensionality of data. It aims to reduce the feature of data by generating new features from the original one.

The Role of Monoamine Oxidase B Inhibitors in the Treatment of Parkinson’s Disease – An Update

Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine level in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles; as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of MAO-B are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti-Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson’s disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models are scarce and warrants further investigation.

Non-Motor Symptoms and their associated factors in Parkinson’s Disease

Aim: To find the frequency of Non Motor Symptoms in patients with Parkinson’s Disease (PD) and describe their association with different factors like age, gender and duration of disease. Methodology: A cross sectional observational study was carried out in Rehman Medical Institute, Peshawar for the period of 1year. All patients of idiopathic Parkinson’s disease (PD) were included. 13 Non motor symptoms (NMS) were evaluated and noted in predesigned proforma. Data was entered and analyzed by SPSS 22. Results: Mean Age was 62.10±10.01 years. 58.82%(n=40) were males. 47.05%(n=32) belong to urban residence. Mean duration of illness was 4.52±3.82 years. NMS were found in 100% (n=68) patients. Among NMS, sleep disturbance was the most common symptom found in 77.9% (n=53) followed by constipation that was present in 75%(n=51) of patients. Depression was significantly associated with advance age (P value 0.01) and in those taking treatment of motor symptoms of PD (P value 0.02). Perspiration was significantly more with longer duration of illness (P value 0.006) and advance age (P value 0.04). Orthostatic hypotension was associated with longer duration of disease. (P value 0.04) There was no other significant association found. Conclusion: NMS were seen in all the patients presenting to Neurology OPD in our study. The most common NMS was sleep disturbance followed by constipation and depression. Autonomic disturbance were associated with longer disease duration while depression was associated with old age.

Outcomes Impacting Quality of Life in Advanced Parkinson’s Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and nonmotor symptoms. Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL, and motor and nonmotor symptoms. Results: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. Conclusion: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.