Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation.
The aim of this study is to determine whether the balance problems experienced by Parkinson’s disease (PD) patients may in part be due to dysfunctional processing of vestibular information, and to search for factors that may help predict the risk of falls. We evaluated the balance of 45 idiopathic PD patients and 20 healthy subjects by means of computerized dynamic posturography using sensory organization tests (SOT), rhythmic weight shift (RWS) tests and limits of stability (LOS) tests; and by the timed up-and-go (TUG) test. PD patients had poorer scores in the SOT than controls for overall balance and vestibular and visual inputs. They also performed worse in RWS and LOS tests, and were slower in performing the TUG test. Hoehn-Yahr stage did not correlate with vestibular input. Balance impairment in PD patients involves deteriorated processing of vestibular input, but this deterioration is independent of disease progression. Falls are related to PD patients’ reduced limits of stability.
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.
Certain mitochondrial DNA (mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases.
The best knowledge about DBS complications allows for better solutions. In case of infection, conservative treatment or partial removal of the DBS system appears to be safe and reasonable. Intracranial complications related to DBS material such as peri-lead edema and cyst formation have a good prognosis. They may appear long after DBS implantation.
Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.
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