Istradefylline for OFF Episodes in Parkinson's Disease: A US Perspective of Common Clinical Scenarios.

The effective management of OFF episodes remains an important unmet need for patients with Parkinson's disease (PD) who develop motor complications with long-term levodopa therapy. Istradefylline is a selective adenosine A2A receptor antagonist for the treatment of patients with PD experiencing OFF episodes while on levodopa/decarboxylase inhibitor. Originally approved in Japan, istradefylline was recently approved in the USA. In this article, we provide a specific review of the four clinical studies that the FDA included in the approval of istradefylline in the USA, and discuss common clinical scenarios, based on our experience, where treatment with istradefylline may benefit patients experiencing motor fluctuations.

Cervical Dystonia Resolving After the Onset of Parkinson's Disease.

Dystonia can occur in Parkinson's disease (PD). Dystonia usually presents during the course of the disease or as a side effect of medication. The development of cervical dystonia (CD) before the onset of PD is uncommon but has been described. Complete resolution of CD has not been described to date. We demonstrate a 71-year-old man with a four-year history of CD, who presented with prodromal PD symptoms. Three years later, he was diagnosed with PD. Shortly after initiating treatment for PD, his cervical dystonia started to improve, and eventually, he had complete resolution of CD approximately after two years of PD treatment. In conclusion, the pathological basis of this association is not well understood, but it is important to note that the globus pallidus internus (GPi) plays an important role in connecting these two disorders at a pathological level and as a target for surgery. Increased activity in the GPi may cause resolution of the CD by decreasing unintentional thalamocortical activity.

Multiple System Atrophy - Cerebellar Type: Clinical Picture and Treatment of an Often-Overlooked Disorder.

Multiple system atrophy (MSA) is a rare, progressive, fatal, neurodegenerative disorder. There are two main types: the parkinsonian type (MSA-P) and cerebellar type (MSA-C). The disease usually presents with genitourinary dysfunction, orthostatic hypotension, and rapid eye movement (REM) sleep behavior disorder. Patients rapidly develop balance, speech, and coordination abnormalities. We present a review of the clinical picture and the actualized treatment modalities of the MSA cerebellar type. For the study methods, a PubMed search was done using the following medical subject headings (MeSH) terms: "multiple system atrophy/therapy". Inclusion criteria included studies in English, full papers, human studies, and publications in the last 30 years. Case reports and series were excluded. A total of 157 papers were extracted after applying the inclusion and exclusion criteria, and 41 papers were included for the discussion of this review. This review underlines the therapeutic strategies as well as the clinical picture of multiple system atrophy, and how MSA-C and MSA-P differ from each other. We discussed this review in four topics: ataxia, autonomic dysfunction (neurogenic orthostatic hypotension and urinary disorders), parkinsonism, and REM sleep disorder. In conclusion, the treatment of MSA-C is mainly symptomatic; there are not many studies on MSA-C. The ataxic component and fewer parkinsonian symptoms are the main difference of MSA-C as opposed to MSA-P.

Management of Urologic and Sexual Dysfunction in Parkinson Disease.

Parkinson disease (PD) is a complex of motor and nonmotor symptoms. Among the nonmotor symptoms, urinary and sexual dysfunctions are common and negatively affect the quality of life. More than 50% of patients with PD complain of urinary dysfunction and 20% have sexual dysfunction. Understanding the anatomy and physiology of the urogenital system informs the rationale for the mechanism of action of drug therapies. The management of urinary and sexual dysfunction in PD, including behavioral, medical, and procedural interventions, is reviewed in this article.

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.

Tandem gait abnormality in Parkinson disease: Prevalence and implication as a predictor of fall risk.

INTRODUCTION: We report the prevalence of abnormal tandem gait (TG) in patients with idiopathic Parkinson disease (PD) and its association with symptoms of subjective unsteadiness, falls, freezing of gait, and cognitive impairment. METHODS: We assessed subjective balance impairment, fall history, antero-posterior postural instability, and TG in PD patients (Hoehn and Yahr (HY) stage 0-4). We recorded the age, sex, current medications, HY stage, Schwab and England (S&E) scale score, and MOCA score for each patient. Logistic regression was used to evaluate age-adjusted associations between TG and other demographic and clinical factors. RESULTS: A total of 102 patients with PD were assessed. Of those, 63.5% of HY 2 patients and 100% of HY 2.5 and 3 patients had a TG abnormality. The presence of TG abnormality was associated with subjective imbalance, falls, freezing of gait, S&E < 80, and MOCA score <24 after adjustment for age. CONCLUSIONS: TG abnormality is common in PD, precedes the development of antero-posterior postural instability, is associated with cognitive impairment, and may predict fall risk. A longitudinal study will help determine if TG is a predictor of impending progression from HY 2 to HY 3.

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.