Background and purpose
The aim of this study was to examine non‐motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL).
Methods
A total ...of 132 patients with early PD with comprehensive motor examinations and non‐motor symptom assessments were included. Motor subtypes were classified based on Stebbins’ method. Non‐motor symptoms were assessed by the Non‐Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire‐8.
Results
We identified 66 patients (50%) with tremor‐dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non‐motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non‐motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD.
Conclusions
Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non‐motor symptoms may improve patients’ QoL.
Background and purpose
Non‐motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health‐related quality of life (QoL) ...over a defined follow‐up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2‐year follow‐up period.
Method
A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non‐Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire‐39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm).
Results
The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow‐up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change.
Conclusion
Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2‐year follow‐up period.
Background and purpose
This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson’s disease (PD) and explored their ...associations with cardiovascular risk factors and cognitive performance.
Methods
A total of 175 non‐demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD‐MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10‐year cardiovascular risk score (mFRS).
Results
A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD‐MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD‐MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD‐MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD‐MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors.
Conclusion
Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.
Summary
Background
B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic ...rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways.
Objective
We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation.
Methods
We analysed B cells from NP or tonsil, or after ILC2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody‐secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT‐PCR.
Results
NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein–Barr virus‐induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with tonsil. Antibody production and the frequency of antibody‐secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro.
Conclusions and Clinical Relevance
Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC‐mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell‐targeted therapies may provide new treatment options for CRSwNP.
A genome-wide association study (GWAS) in the Japanese population identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16) (OMIM 613164) and BST1. We analyzed single nucleotide ...polymorphism (SNPs) located at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population and also conducted a meta-analysis in Asians by pooling 2 independent replication studies from Japan.
We conducted an analysis of 13 SNPs associated with PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese subjects.
PARK16, PARK8, and PARK1 loci but not BST1 were found to be associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1 and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects with PD and 16,669 controls revealed robust association with these 3 loci and also BST1. There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects.
Our study reaffirms the role of GWAS-linked loci in PD in Asian subjects and the strength of association is similar between Chinese and Japanese subjects. Efforts to elucidate the associated gene within PARK16 locus are warranted.
Pathogenesis of nasal polyposis Hulse, K. E.; Stevens, W. W.; Tan, B. K. ...
Clinical and experimental allergy,
February 2015, Letnik:
45, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Summary
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world‐wide and is associated with high cost of ...management and significant morbidity. Yet, there is a lack of population‐based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL‐5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease.
The study of de novo point mutations (new germline mutations arising from the gametes of the parents) remained largely static until the arrival of next-generation sequencing technologies, which made ...both whole-exome sequencing (WES) and whole-genome sequencing (WGS) feasible in practical terms. Single nucleotide polymorphism genotyping arrays have been used to identify de novo copy-number variants in a number of common neurodevelopmental conditions such as schizophrenia and autism. By contrast, as point mutations and microlesions occurring de novo are refractory to analysis by these microarray-based methods, little was known about either their frequency or impact upon neurodevelopmental disease, until the advent of WES. De novo point mutations have recently been implicated in schizophrenia, autism and mental retardation through the WES of case-parent trios. Taken together, these findings strengthen the hypothesis that the occurrence of de novo mutations could account for the high prevalence of such diseases that are associated with a marked reduction in fecundity. De novo point mutations are also known to be responsible for many sporadic cases of rare dominant mendelian disorders such as Kabuki syndrome, Schinzel-Giedion syndrome and Bohring-Opitz syndrome. These disorders share a common feature in that they are all characterized by intellectual disability. In summary, recent WES studies of neurodevelopmental and neuropsychiatric disease have provided new insights into the role of de novo mutations in these disorders. Our knowledge of de novo mutations is likely to be further accelerated by WGS. However, the collection of case-parent trios will be a prerequisite for such studies. This review aims to discuss recent developments in the study of de novo mutations made possible by technological advances in DNA sequencing.
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