21 research outputs found
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Perivascular spaces in basal ganglia — An innocent bystander in Parkinson's disease?
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Sublingual apomorphine in treatment of Parkinson's disease: a review
Purpose: A majority of advanced Parkinson's disease (PD) patients on oral levodopa experience motor fluctuations, including sudden OFF and delayed ON periods. Fast-acting rescue medications are a vital part of the clinician's armamentarium in the treatment of motor fluctuations. Sublingual apomorphine is the first sublingual rescue medication on the market for the treatment of OFF times in PD.Materials and Methods: Here, we review the development and pharmacology of apomorphine in the treatment of PD as well as the safety and efficacy of sublingual apomorphine established in clinical trials. Finally, we compare sublingual apomorphine to the other rescue medications available and provide our opinion on the use of sublingual apomorphine in clinical practice.Results: Clinical trials have demonstrated that sublingual apomorphine is a safe and effective option in the treatment of motor fluctuations in PD. In a Phase II trial, 100% of patients who achieved a full ON response did so within 30 min and 40% did so within 15 min. The mean duration of effect was 50 min. In a Phase III trial, 77.3% of patients achieved a full ON response. Side effects such as nausea, dizziness and somnolence were common but were generally mild. No patients experienced worsening dyskinesia.Conclusions: Sublingual apomorphine will provide patients with motor fluctuations due to advanced PD another safe and effective option for the treatment of OFF times
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Management of Motor Features in Advanced Parkinson Disease
Advanced Parkinson disease (PD) is characterized by the presence of motor fluctuations becoming the focus of treatment, prominent postural instability, significant disability despite levodopa therapy, and the presence of symptoms refractory to levodopa therapy. In this article, the authors review the motor manifestations of patients with advanced PD, as well as the most common pharmacologic and nonpharmacologic available therapies
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Safinamide in the management of patients with Parkinson's disease not stabilized on levodopa: a review of the current clinical evidence
Safinamide (Xadago
) is a novel medication with both dopaminergic and non-dopaminergic effects, approved first by the European Commission and more recently by the US Food and Drug Administration (FDA) as an adjunctive treatment to carbidopa/levodopa in patients with mid- to late-stage Parkinson's disease (PD) and motor fluctuations. It works through multiple mechanisms, namely as a reversible selective monoamine oxidase-B inhibitor and through modulation of glutamate release. Safinamide is extensively metabolized via oxidation to several inactive metabolites that are excreted primarily through the urine. Several large Phase III clinical trials of patients with advanced PD with motor fluctuations have shown that safinamide, administered orally at doses of 50-100 mg daily, increased ON time with no or non-troublesome dyskinesia, decreased daily OFF time, improved overall motor function (as measured by Unified Parkinson's Disease Rating Scale [UPDRS] part III total score), and quality of life (as measured by Clinical Global Impression-Change and 39-item Parkinson's Disease Questionnaire). In large clinical trials of patients with early PD on a single dopamine agonist, safinamide administered orally at a dose of 100 mg daily improved overall motor function as measured by UPDRS part III total score; however, some of the results reported were exploratory. Safinamide is generally well-tolerated and safe, with few to no treatment-related adverse events. Safinamide does not cause new or worsening dyskinesia and may be able to reduce this symptom in patients reporting it at baseline. Evidence suggests that safinamide is a good option for add-on therapy to carbidopa/levodopa in patients with advanced PD with motor complications, but there is still insufficient evidence to recommend it as monotherapy or add-on therapy in patients with early PD
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Uniparental Disomy Causing Myoclonus Dystonia Associated with Russell Silver Syndrome
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Transtentorial Fluctuations and Atypical Parkinsonism After Ventriculo-Peritoneal Shunting
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CVT-301 for the treatment of Parkinson's disease
Introduction: For patients with Parkinson's disease (PD), the treatment of motor and nonmotor fluctuations is tantamount to maintaining quality of life. Subcutaneous apomorphine has been the only commercially available rescue therapy for the treatment of OFF episodes. In December 2018, CVT-301 (Inbrija), an inhaled formulation of levodopa (LD), was approved by the FDA for this indication.
Areas covered: In this review, the authors summarize the armamentarium available to address motor fluctuations in PD, including medications in development. The authors discuss the pharmacological properties of CVT-301 as well as its efficacy and safety as reported in phase I, II, and III studies.
Expert opinion: More than 20 medications or surgical procedures are available or in development to address motor fluctuations in PD. Deep brain stimulation (DBS) is an invasive but effective intervention at the end of the treatment spectrum. Less invasive therapies are used in combination to ameliorate motor fluctuations. Rescue therapies can help patients taking oral medications who experience delayed onset symptom relief (delayed ON), and unexpected wearing OFF by providing rapid and durable symptoms relief. CVT-301, an inhaled LD formulation, provides a safe and effective delivery mechanism that may be preferred by patients over subcutaneous injections
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Deep Brain Stimulation for Disabling “Outflow” Tremors
“Outflow” tremors, sometimes referred to in the literature by a variety of terms (outflow, rubral, midbrain, Holmes), are frequently associated with significant disability and are notoriously unresponsive or only partially responsive to medical treatment. Deep brain stimulation (DBS) has been successfully used in patients with outflow tremors; however, longterm outcomes are not welldocumented because large case series are hard to assemble. This chapter describes a patient with disabling outflow tremors secondary to multiple sclerosis, treated with unilateral thalamic DBS, who achieved excellent tremor control with initial programming but shortly afterward developed rebound tremor. Intensive programming involved alternating the site of stimulation by using different combinations of contacts; this was a successful strategy for maintaining a clinically significant reduction in tremor. Disease progression, worsening of tremor, habituation, and loss of efficacy are known problems with some tremors, and their management can be challenging. The pathophysiology of worsening tremor after DBS is discussed in the chapter, as are potential programming strategies to manage this problem