Pharmacotherapy and generic health-related quality of life in Parkinson's disease.

OBJECTIVES: Improvement of health-related quality of life (HRQoL) is one of the primary objectives of symptomatic therapies in Parkinson's disease (PD). The aim of this observational study was to investigate possible changes in generic HRQoL in relation to changed PD pharmacotherapy in the clinical setting. MATERIALS & METHODS: A total of 219 outpatients with mild to moderate PD (median H&Y score = 2.0), treated with oral antiparkinsonian medications, were investigated twice with a 6-month interval. At baseline, PD medication dose was increased for 82 patients for clinical reasons (median increase of 100 mg levodopa equivalent daily dose or 31.9%), whereas medication remained unchanged for 137 patients. Two generic HRQoL questionnaires, EQ-5D and 15D, were used at baseline and at 6 months, and the baseline and delta HRQoL values were compared between the treatment groups. RESULTS: In the entire sample, the EQ-VAS score decreased during the study period, indicating a general decline in HRQoL (P = 0.04). There were no differences in the baseline HRQoL values or delta values between the treatment groups as measured with EQ-5D or 15D (levodopa dose elevated vs dopamine agonist/MAO-B inhibitor dose elevated vs no change in medication). CONCLUSIONS: An approximately 1/3 increase in antiparkinsonian medication dose did not have an impact on generic HRQoL. Disease-specific QoL may be more sensitive to pharmacotherapy-related changes in PD.

Status epilepticus alters neurogenesis and decreases the number of GABAergic neurons in the septal dentate gyrus of 9-day-old rats at the early phase of epileptogenesis.

The effects of a prolonged seizure, i.e. status epilepticus (SE), on neurogenesis of dentate granule cells (DGCs) in the immature dentate gyrus (DG) and possible changes in the phenotypes of the newborn neurons have remained incompletely characterized. We have now studied neurogenesis of DGCs in 9-day-old (postnatal, P9) rats 1 week after kainate (KA)-induced SE using 5-bromo-2-deoxyuridine (BrdU) immunostaining. The phenotype characterization of the newborn cells was carried out by immunofluorescence double labeling using doublecortin (DCX) and nestin as markers for immature cells, and glial fibrillary acid protein (GFAP) as a marker for glial cells. Newborn GABAergic neurons were further identified with antibodies for parvalbumin, glutamate decarboxylase 67 (GAD67), and the GABAA receptor α1 subunit, and mRNA expression of GABAergic and immature neurons was measured with quantitative real-time PCR (qPCR) in the DG. Our results show that the number of newborn as well as GABAergic neurons was significantly decreased after SE in the superior blade of the septal DG. The majority of the newborn BrdU-stained neurons co-expressed DCX, but neither nestin nor GFAP. In both experimental groups, newborn neurons were frequently localized in close contact, but not co-localized, with the cells positively stained for the GABAergic cell markers. Nestin and calretinin mRNA expression were significantly increased after SE. Our results suggest that SE-induced disruption of DGC neurogenesis and decreased number of GABAergic neurons could modify the connectivity between these cells and disturb the maturation of the GABAergic neurotransmission in the immature DG at the early epileptogenic phase.