Continuous subcutaneous apomorphine in advanced Parkinson's disease patients treated with deep brain stimulation.

INTRODUCTION: Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson's disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS. METHODS: We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12 years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments. RESULTS: Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03). CONCLUSION: In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.

Continuous subcutaneous apomorphine infusion in advanced Parkinson's disease: 10-year experience with 230 patients.

Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10 years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0 years. Mean duration of the treatment was 26.3 months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2 years. The main indication for APO was lack of deep brain stimulation criteria (DBS). Twelve patients were on waiting list for DBS. Average time since APO onset was 40.0 months. In the active group, APO decreased off-state in 4 h and allowed reducing levodopa and dopamine agonists. Dyskinesia and balance did not worsen. Cognitive decline did not change within the first 15 months. Hallucinations were the same within the first 39 months. The presence of subcutaneous nodules was the most frequent adverse event in this group. The main reason for discontinuation was side effects, being psychosis the most common. Within the first year, 82 patients stopped APO. Eighteen of these patients eventually got DBS. APO is a good option for advanced PD, since it permits a significant reduction in off-time and other antiparkinsonian drugs. This effect is sustained over time. We have treated 132 patients for over a year. Dyskinesia seems not to worsen. Combining APO with DBS simultaneously or alternatively provides good results.

Synaptotagmin XI in Parkinson's disease: New evidence from an association study in Spain and Mexico.

INTRODUCTION: The pathophysiology of PD (Parkinson's disease) has been related to the ubiquitin proteasome system and oxidative stress. Parkin acts as ubiquitin ligase on several substrates. Because genetic variants often have different frequencies across populations, population specific analyses are necessary to complement and validate results from genome-wide association studies. METHODS: We carried out an association study with genes coding for parkin substrates and cellular stress components in the Galician population (Northern Spain). SNCA and MAPT SNPs were also analyzed. We studied 75 SNPs in a discovery sample of 268 PD patients and 265 controls from Galicia. A replication sample of 271 patients and 260 controls was recruited from Mexico City. RESULTS: We observed significant association between PD and SNPs in MAPT. Nominal p-values<0.05 were obtained in the Galician cohort for SNPs in SYT11, coding for synaptotagmin XI. These results were replicated in the Mexican sample. DISCUSSION: The associated markers lie within a ~140kb strong linkage disequilibrium segment that harbors several candidate genes, including SYT11. SNPs from the GBA-SYT11-RAB25 region have been previously associated with PD, however the functionally relevant variants remain unknown. Our data support a likely role of genetic factors within 1q22 in PD susceptibility.