Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson's disease patients: the effects of an early therapeutic intervention

To evaluate the long-term effects of entacapone on both mean daily 'on' time and health-related quality of life (QoL) in patients with Parkinson's disease (PD) experiencing 'end-of-dose' motor fluctuations and the benefits of an early therapeutic intervention. A prospective, multicenter, observational, 12-month study was performed with an initial 3-month intervention phase, consisting of a phone call to half of the patients from randomly selected investigators to assess if dose adjustment was necessary. Effectiveness was determined by home diaries ('on' time), subscales II and III of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Parkinson's Disease Questionnaire (PDQ-8). After 3 months of treatment, 4.0% of the intervention group patients discontinued the study, versus 18.4% in the control group ( P  < 0.01). The improvement in 'on' time was significantly increased since the 3-month visit (21%, P  < 0.0001) until the end of the study (23% at 12 months, P  < 0.0001). Entacapone also induced significant reductions in the UPDRS scores for subscales II and III and in the PDQ-8 score. 11.2% of patients experienced at least one adverse reaction. This study confirms the effectiveness of entacapone in reducing motor fluctuations by increasing 'on' time, and in improving QoL of PD patients. An early adjustment of entacapone and levodopa doses reduces the number of treatment discontinuations during the first months of treatment.     

Motor response following repeated apomorphine administration is reduced in Parkinson's disease

Ten patients with Parkinson's disease (PD) with motor fluctuations under levodopa treatment were given repeated equal subcutaneous injections of apomorphine [minimal effective dose (MED)] in 1 day. The MED was defined as the dose of apomorphine necessary to induce at least 60% reduction of motor disability for a minimum period of 10 min. MED was found for each patient in previous study days. In eight a subcutaneous infusion of apomorphine was performed on a different day. Four patients with simple fluctuations ("wearing off") showed a progressive reduction of the motor response to apomorphine injections, but three of the four had a stable response (continuous "on") to apomorphine infusion. Six patients with complicated fluctuations also exhibited a decreasing response to successive apomorphine injections and often completely failed to respond to some of the boluses. The response to a subcutaneous infusion of apomorphine was unstable in three of four cases. These findings indicate that a reduction of striatal dopaminergic receptor sensitivity is associated with repeated "pulsatile" apomorphine administration in parkinsonian patients with oscillations of motor performance. It is suggested that altered regulation of dopaminergic receptor sensitivity following pulsatile stimulation with levodopa may be a relevant phenomenon in the pathogenesis of motor fluctuations in PD.     

Uso de la infusión intestinal continua de levodopa-carbidopa en pacientes con enfermedad de Parkinson avanzada en España. Subanálisis por comunidades autónomas

ObjectivesTo compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain.MethodsA retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients’ clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation.ResultsSignificant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of ≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs).ConclusionsThis study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients’ baseline characteristics, the availability of multidisciplinary teams, and clinical experience.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

Effect of retroviral transduction of canine microvascular endothelial cells on beta(1) integrin subunit expression and cell retention to PTFE grafts

This study evaluated the effect of retroviral transduction on canine microvascular endothelial cell (CMVEC) detachment from fibrin glue coated expanded polytetrafluoroethylene (ePTFE) graft material. CMVEC were isolated from adipose tissue by fluorescent activated cell sorting (FACS). Three treatment groups were evaluated: G-I, transduced CMVEC, selected in antibiotic G418 for 10 days (n=5); G-II, CMVEC selected in G418 and recovered from selection for 4 days (n=5); and G-III, control group of naive CMVEC (n=6). (3)H-thymidine labeled endothelial cells were seeded on fibrin glue coated four-mm diameter PTFE. Grafts were exposed to physiologic shear stresses of 16 dyn/cm(2). Cell detachment was determined by (3)H-thymidine counts in the circuit effluent. beta(1) integrin subunit expression was measured by flow cytometry. After 2 hours of flow exposure, G-I and G-II demonstrated significantly greater cell detachment rates compared with the control seeded grafts. Median peak channel beta(1) integrin subunit value for G-III CMVEC was 2311+/-481.7 vs. 31.5+/-4.51 and 26.3+/-2.0 in the transduced cell groups (p=0.00043). Low beta(1) integrin expression correlated with flow induced high detachment rates of retrovirally-transduced CMVEC.     

Risk of valvular heart disease associated with the use of dopamine agonists in Parkinson’s disease: a systematic review

A literature review was conducted to assess risk of cardiac valve regurgitation (CVR) associated with use of ergot-derived and non-ergot dopamine agonists (DAs) in patients with Parkinson’s disease (PD). Inclusion criteria: case-control/observational studies of >10 patients with PD treated with DAs, including a control group and assessment of incidence/risk of CVR. Of the 166 publications identified, 14 met all inclusion criteria and included 1,750 patients. In 11 of the studies, a significant increase in CVR frequency of any severity (at the aortic, mitral or tricuspid valve) in the ergot group vs. the non-ergot or control group was described. No study reported increased risk of CVR for non-ergot DAs, compared with controls. In the studies identified in the literature, the use of ergot-derived DAs (pergolide and cabergoline) in patients with PD was associated with increased risk of CVR. Increased risk of CVR was not associated with the use of non-ergot DAs.