Journal of Parkinson's disease
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Randomized Controlled Trial Multicenter Study
Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A).
Neurogenic orthostatic hypotension (nOH) is common in Parkinson's disease (PD), and represents a failure to generate norepinephrine responses appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an oral norepinephrine prodrug. ⋯ This exploratory analysis of a small dataset failed to show benefit of droxidopa, as compared with placebo by the primary endpoint. Nonetheless, there were signals of potential benefit for nOH, including improvement in dizziness/lightheadedness and reduction in falls, meriting evaluation in further trials.
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Impulse control disorders (ICDs), dopamine dysregulation syndrome (DDS), and dopamine agonist withdrawal syndrome (DAWS) have been reported commonly in Parkinson's disease (PD) populations. The treatment approaches may be widely variable and there is not much information on these syndromes in the setting of deep brain stimulation (DBS). ⋯ The results suggest that addiction-like syndromes and withdrawal syndromes are prevalent in expert PSG centers performing DBS. Most centers reported screening for these issues without the use of a formal battery, and there were a large number of centers reporting ICDs, DAWS and DDS post-DBS. A single treatment strategy did not emerge.
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Sialorrhea may present as a troublesome symptom in patients suffering from Parkinson's disease. Current options for treatment include anticholinergic drugs, irradiation, surgery, oral-motor and behavioural therapies, and injection of botulinum neurotoxin (BoNT) in the salivary glands. The aim of this study is to evaluate the safety and administration of BoNT as a treatment for sialorrhea in patients with Parkinson's disease (PD) based on a review of the studies conducted so far in this field. ⋯ Positive effect is well documented, and there have been relatively few reported adverse effects, which have been mild and transient. Based on this review, a treatment algorithm is proposed. Ultrasound guidance may not be necessary when injecting the parotid gland but may improve the effect and safety of administration, especially when injecting the submandibular glands.
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A major risk-factor for developing Parkinson's disease (PD) is genetic variability in leucine-rich repeat kinase 2 (LRRK2), most notably the p.G2019S mutation. Examination of the effects of this mutation is necessary to determine the etiology of PD and to guide therapeutic development. ⋯ Neuroimaging using dopaminergic PET did not recapitulate prior studies in human LRRK2 mutation carriers. Consistently, LRRK2 p.G2019S rats do not develop overt neurodegeneration; however, they do exhibit behavioral abnormalities.
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The pathophysiology of Parkinson's disease (PD) has not yet been completely elucidated. However, during the past few years, significant progress has been made in understanding the intra- and extracellular mechanisms by which proteins such as alpha-synuclein and neuroinflammatory molecules may display impaired function and/or expression in PD. Recent developments in imaging techniques based on positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to PD in vivo. This article summarizes recent PET and SPECT studies of new radiopharmaceuticals and discusses their potential role and perspectives for use in the fields of new drug development and early diagnosis for PD, as well to aid in differential diagnosis and monitoring of the progression of PD.