Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson's disease: A prospective study of 22 patients.

INTRODUCTION: Parkinson's disease (PD) patients usually start treatment with apomorphine infusion (APO) in later stages of advanced PD (aPD). This timing limits the evaluation of its motor efficacy and other potential clinical benefits throughout the full course of aPD. METHODS: We prospectively analyzed the effect of APO on motor and non-motor symptoms, cognitive function and quality of life (QoL) in 22 PD patients with early stage aPD, defined as: age < 71 years and diagnosis of aPD for < 3 years. RESULTS: At baseline, mean (±SD) age and disease duration were 59.4 ± 6.1 and 8.7 ± 3.5 years, respectively. After 6 months of APO treatment, daily off-time decreased from 4.98 ± 2.37 to 1.48 ± 1.47 h (p ≤ 0.001) and UPDRS IV scores from 7.00 ± 2.58 to 5.32 ± 2.48 (p = 0.018). Dyskinesia did not worsen with APO despite an overall increase in levodopa equivalent daily dose. Mean NMSS scores improved with APO, from 52.50 ± 27.24 to 38.68 ± 27.17 (p = 0.002), with particular improvements in apathy and sleep quality. Mean PDQ-39 score was reduced with APO from 31.96 ± 11.93 to 19.27 ± 11.86 (p ≤ 0.001). Overall, cognition did not change after APO, while slight improvements were observed in executive functioning (attention and planning). All but one patient eventually underwent subthalamic deep brain stimulation. CONCLUSION: In patients with early stage initial aPD, s substantial benefit of APO was observed on motor symptoms, driven by a 70% reduction in off-time versus baseline, superior to that observed in previous prospective studies. APO also improved frontal dysfunction in PD patients.

Parkinson's Disease Symptoms Associated with Developing On-State Axial Symptoms Early after Subthalamic Deep Brain Stimulation.

Background: The relationship between axial symptoms in Parkinson's disease (PD) and subthalamic deep brain stimulation (STN-DBS) is still unclear. Purpose: We searched for particular clinical characteristics before STN-DBS linked to on-state axial problems after surgery. Methods: We retrospectively analyzed baseline motor, emotional and cognitive features from PD patients with early axial symptoms (within 4 years after STN-DBS) and late axial symptoms (after 4 years). We also considered a group of PD patients without axial symptoms for at least 4 years after surgery. Results: At baseline, early-axial PD patients (n = 28) had a higher on-state Unified Parkinson's Disease Rating Scale III (15.0 ± 5.6 to 11.6 ± 6.2, p = 0.020), higher axial score (2.4 ± 1.8 to 0.7 ± 1.0, p < 0.001) and worse dopaminergic response (0.62 ± 0.12 to 0.70 ± 0.11, p = 0.005), than non-axial PD patients (n = 51). Early-axial PD patients had short-term recall impairment, not seen in non-axial PD (36.3 ± 7.6 to 40.3 ± 9.3, p = 0.041). These variables were similar between late-axial PD (n = 18) and non-axial PD, but late-axial PD showed worse frontal dysfunction. Conclusions: PD patients with early axial symptoms after DBS may have a significantly worse presurgical motor phenotype, poorer dopaminergic response and memory impairment. This may correspond to a more severe form of PD.

Temporal trends in the incidence and prevalence of Multiple Sclerosis in the Northwest of Spain.

BACKGROUND: During the last decades, the frequency of multiple sclerosis (MS) is increasing worldwide. Nevertheless, the higher sensibility of the new diagnostic criteria obscures the comparison between studies performed in different decades. METHODS: The evolution of the frequency of MS in Santiago de Compostela (North-West of Spain) between 2003 and 2015 was analyzed using Poisson regression. The diagnosis was confirmed according to Poser criteria. Several sources were consulted for case ascertainment: databases from the MS Unit, the Infusion Center, and the Departments of Neurology, Pharmacy, Pediatric Neurology and Codification of the public Hospital of Santiago, private hospitals, neurologists with private activity, general practitioners, and associations of patients. RESULTS: In 12 years, the prevalence increased from 68 to 143 cases/100,000 inhabitants, from 83 to 176 in females; and from 49 to 106 in males (p <0.0001, 0.0001, and 0.0002 respectively). The incidence rise was not significant (from 5 to 8 cases/ 100,000 inhabitants/ year (p=0.4243). The mean age of the population growth 5.7 years (p=0.008). The changes in female: male ratio (12.9%), in the age at the first symptom (2.2 years), and the diagnosis delay (0.12 years) did not achieve significance (p=0.7750, 0.1606, 0.8581). CONCLUSION: The prevalence of MS doubled in 12 years whilst the difference in incidence was lower and not significant. The disproportion in the growth of both parameters, as well as the higher mean age in the last study, suggest a longer survival of patients with MS.

Continuous Subcutaneous Apomorphine Infusion before Subthalamic Deep Brain Stimulation: A Prospective, Comparative Study in 20 Patients.

BACKGROUND: Studies comparing the clinical efficacy of apomorphine infusion (APO) with subsequent subthalamic deep brain stimulation (STN-DBS) in advanced Parkinson's disease (aPD) are currently lacking. Retrospective data have shown that patients treated with APO are usually older, have a more prolonged disease, and a more severe phenotype. OBJECTIVE: To compare the benefit of APO with that of STN-DBS on motor, non-motor, cognitive, and quality of life in the same patient when given sequentially. METHODS: We prospectively analyzed 20 aPD patients over 3 different treatment phases: baseline (optimized medical treatment), during APO treatment, and during subsequent STN-DBS treatment. The APO and STN-DBS phases were stable for 6 months, and evaluation of the different treatments was separated by 6 months. RESULTS: Compared to baseline, APO, and STN-DBS reduced mean daily off time by 70.5% and 89.3% (P = 0.012), respectively, and scores for Unified Parkinson's Disease Rating Scale (UPDRS) IV by 27.5% and 80.5% (P ≤ 0.001), Non-motor symptoms scale (NMSS) by 24.6% and 49.3% (P ≤ 0.001), Montgomery Asberg depression scale (MADRS) by 7.4% and 39.0% (P = 0.27), Starkstein apathy scale (SAS) by 51.1% and 39.9% (P = 0.734), Parkinson's disease sleep scale 2 (PDSS-2) by 25.7% and 56.7% (P ≤ 0.001), and Parkinson's disease questionnaire 39 item (PDQ-39) by 39.6% and 64.9% (P ≤ 0.001). Global cognition did not change with either therapy, but phonetic fluency worsened after STN-DBS compared to APO (P = 0.022). CONCLUSIONS: Both APO and STN-DBS improved motor and non-motor symptoms and quality of life compared to optimized medical treatment in aPD. Overall, STN-DBS was the most effective treatment, but APO showed a pronounced benefit on motor symptoms. Effective treatment for aPD should not be delayed, even when waiting for surgery.

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.

Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

BACKGROUND: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. RESULTS: NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. CONCLUSION: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

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.