Therapeutic strategies to prevent and manage dyskinesias in Parkinson's disease.

INTRODUCTION: Chronic treatment with levodopa is associated with the development of motor fluctuations and dyskinesias particularly in young Parkinson patients. In some cases, dyskinesias become so severe that they interfere with normal movement and negatively impact quality of life. AREAS COVERED: In this review, we discuss benefits and limits of available therapeutic approaches aimed at delaying or managing dyskinesias as well as new strategies that are currently under investigation. EXPERT OPINION: Among available treatments, monotherapy with dopamine agonists in the early phases of the disease reduces the risk for dyskinesias compared with levodopa. Nevertheless, dopamine agonists are unable to prevent dyskinesias once levodopa is added, which is always required once disease severity progresses. Convincing evidence of dyskinesia improvement has been shown only for deep brain stimulation and to some extent also for duodenal levodopa infusion and subcutaneous apomorphine. These approaches are expensive, have restrictive inclusion criteria and can cause potentially serious side effects. Alternative therapies include drugs targeting nondopaminergic neurotransmitter systems. Amantadine improves dyskinesias but its long-term effect is often unsatisfactory. Glutamatergic and gabaergic compounds have been tested in clinical trials, with promising results. By contrast, adrenergic drugs, fipamezole and idazoxan, did not show antidyskinetic effect.

Effects of rotigotine on Parkinson's disease-related sleep disturbances.

INTRODUCTION: Sleep abnormalities are a frequent non-motor symptom and a prominent cause of disability in patients with Parkinson's disease (PD). AREAS COVERED: This review discusses what is currently known about the characteristics of sleep disturbances in PD patients and attempts to clarify the role of dopaminergic pathways in their pathogenesis as well as the beneficial effect of dopaminergic agents in their treatment. In particular, this review will focus on the effects of transdermal rotigotine on improving PD-related sleep disorders. EXPERT OPINION: Sleep disturbances are common in PD, and these disturbances can be reduced or resolved, in large part, by preventing or attenuating nocturnal and early morning motor and non-motor symptoms of PD. The studies discussed within this review suggest that sleep disorders are not just a consequence of motor impairment and dopaminergic therapy but are an integral part of the neurodegenerative process of PD. This is supported by the appearance of specific sleep disturbances, which are related to degeneration of the brainstem areas involved in the regulation of sleep/wake states in advance of typical PD symptoms. Development of more detailed diagnostic tools aimed at detecting sleep disturbances and at defining the main causative factors of sleep disturbances in PD will lead to improved treatment of these disturbances.

Bilateral subthalamic nucleus stimulation and quality of life in advanced Parkinson's disease.

We examined the impact of the subthalamic nuclei (STN) deep brain stimulation (DBS) on the health-related quality of life (QoL) of patients with advanced Parkinson's disease (PD). Seventeen consecutive patients with refractory motor fluctuations and dyskinesia were included in the study (mean age, 60.9 +/- 7.7 years [range, 43-74 years]; disease duration, 16.4 +/- 8.5 years [range, 7-38 years]; mean off-medication Hoehn and Yahr stage, 4.23 +/- 0.66 [range, 2.5-5]). Each patient's assessment was carried out using common rating scales, following the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Dyskinesia and emotional state were evaluated through the Abnormal Involuntary Movement Scale (AIMS) and the Hospital Anxiety and Depression Scale (HAD). QoL was assessed by means of the Parkinson's Disease Questionnaire Spanish version (PDQ-39). Significant benefit was obtained in the motor manifestations and complications of disease, as well as in the functional state and mood (P < 0.001). Some QoL dimensions (mobility and activities of daily living) and the PDQ-39 Summary Index (PDQ-39SI) showed a significant improvement (P < 0.001). Benefit was modest (P < 0.05) for three other domains (emotional well-being, stigma, bodily discomfort) and nil for the rest. There was no correlation between the change obtained in the QoL (PDQ-39SI) and in the other variables. As measured by the PDQ-39, STN-DBS significantly improves important aspects of QoL in patients with advanced PD.

Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.