In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.
Objectives: To determine the long term survival and predictors of death in patients with primary intracerebral haemorrhage (ICH) in Central Finland. Methods: Data were collected retrospectively on all adult patients with first ever ICH in Central Finland county between September 1985 and December 1991. The survival of all patients at the end of December 2002 was investigated. Kaplan-Meier survival curves were constructed and factors associated with both early ((28 days) and late deaths determined. Long term survival was compared with the general Finnish population of the same age and sex distribution. The causes of death were compared with those of the population of Central Finland. Results: 411 patients with first ever ICH were identified, 199 men (mean age 64.9 years) and 212 women (mean age 69.5); 30 died before hospital admission, and 208 (50.6%) within the first 28 days. In KaplanMeier analysis, at 16 years the cumulative survival was 3.2% for men and 9.8% for women. The 28 day survivors had a 4.5-fold increased annual risk of dying during the first year after ICH, and 2.2-fold during years 2 to 6. On admission, significant independent predictors of death within the first four weeks were unconsciousness, lateral shift of cerebral midline structures, mean arterial pressure >134 mm Hg, hyperglycaemia, anticoagulant treatment, and ventricular extrasystoles. Predictors of late death for the 28 day survivors were old age, male sex, and heart failure. Conclusions: Primary intracerebral haemorrhage has a poor short and long term outcome. The results emphasise the importance of primary and secondary prevention for ICH.
The most important predictor of the 28-day survival was the level of consciousness on admission, followed by first-day MAP. Hypertension was the most important predictor of the first-day MAP, followed by age, which had an inverse effect on the MAP level. At all levels of consciousness, high first-day MAP (especially if > 145 mm Hg) worsened the 28-day survival rate.
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