Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial.

Background: Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease.

Methods: A 12-week randomised, double-blind, double-dummy, active-controlled study was done at 65 academic and community study centres in the USA and Australia.

An approach to acute clinical deterioration in patients with late-stage Parkinson's disease.

Background: Idiopathic Parkinson's disease is a slowly progressive neurodegenerative disease. In the absence of disease-modifying therapies, patients inevitably progress to late-stage disease, characterised by a shift towards increasing disability from predominantly non-motor symptoms, which may be poorly levodopa responsive.

Objective: The aim of this article is to provide general practitioners (GPs) with a practical approach to the diagnosis and management of acute clinical deterioration in patients with late-stage Parkinson's disease.

The initial diagnosis and management of Parkinson's disease.

Background: Parkinson's disease is a common, progressive neurodegenerative disorder, the prevalence of which is on the rise. The diagnosis and management of Parkinson's disease is therefore likely to become increasingly frequent in general practice.

Objective: The aim of this article is to provide a practical overview for the general practitioner of the initial diagnosis and management of Parkinson's disease.

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease.

Introduction: In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor.

Updates and advances in the treatment of Parkinson disease.

Parkinson disease (PD) is a complex neurodegenerative disorder that can present heterogeneously with a combination of motor and non-motor symptoms. α-synuclein, a neuronal protein, can undergo aberrant conformational change resulting in the intra-neuronal accumulation of toxic oligomers that form Lewy bodies, the pathological hallmark of PD. There is evidence that pathological α-synuclein exhibits prion-like behaviour in its mode of transmission through the nervous system.

Drug-induced movement disorders.

Many therapeutic and illicit drugs can cause movement disorders. Antipsychotics and antiemetics are most commonly implicated The time of onset of the movement disorder may be acute, subacute, or chronic. The severity can range from mild to severe and life-threatening Early recognition of a drug-induced movement disorder is essential to allow for prompt intervention.

Flexed Truncal Posture in Parkinson Disease: Measurement Reliability and Relationship With Physical and Cognitive Impairments, Mobility, and Balance.

Background And Purpose: Flexed truncal posture is common in people with Parkinson disease (PD); however, little is known about the mechanisms responsible or its effect on physical performance. This cross-sectional study aimed to establish the reliability of a truncal posture measurement and explore relationships between PD impairments and truncal posture, as well as truncal posture and balance and mobility.

Methods: A total of 82 people with PD participated.

Postural tremor and chronic inflammatory demyelinating polyneuropathy.

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) typically presents with a combination of sensory and motor impairments. Tremor is recognized as a common and debilitating feature in CIDP, although the underlying mechanisms are unclear.

Methods: Clinical tremor severity and disability scores were collected prospectively in 25 CIDP patients and compared with 22 neuromuscular controls.

Phenotypic insights into ADCY5-associated disease.

Background: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations.

Methods: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing.

Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.

ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials.

Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson's disease patients.

Objective: The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.

Methods: Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa-carbidopa intestinal gel, n = 12 oral levodopa-carbidopa; open label: n = 144 levodopa-carbidopa intestinal gel).

Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease.

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from patients treated in a single Australian movement disorder centre. We conducted an open-label, 12 month prospective study of treatment with LCIG in patients with advanced Parkinson's disease in a single tertiary referral hospital unit specialising in movement disorders. Patients with levodopa-responsive, advanced Parkinson's disease with motor fluctuations despite optimal pharmacological treatment were enrolled and underwent a 16 hour daily infusion of LCIG for 12 months.

Variants in the SNCA gene associate with motor progression while variants in the MAPT gene associate with the severity of Parkinson's disease.

Introduction: It is well known that α-synuclein (SNCA) and microtubule associated protein (MAPT) genes predispose individuals to develop Parkinson's disease (PD). However, whether these genes contribute to differences in the variable progression observed in PD is obscure. This study aims to evaluate the association of common variants in SNCA (rs11931074, rs894278) and MAPT (rs242557_H1c haplotype, rs3744456) genes with the severity and duration of motor and cognitive performance.

Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials.

Background: Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.

Methods: Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412).