BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder.

Background: Post-traumatic stress disorder (PTSD) is a serious, debilitating, and prevalent psychiatric condition occurring in people who are traumatized and experience intense, disturbing thoughts and feelings that persist. BNC210 is a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator developed to treat PTSD.

Methods: ATTUNE was a randomized, double-blind, phase 2b, placebo-controlled trial.

Additional Safety and Exploratory Efficacy Data at 48 and 60 Months from Open-HART, an Open-Label Extension Study of Pridopidine in Huntington Disease.

Background: Open-HART was an open-label extension of HART, a randomized, double-blind, placebo-controlled study of pridopidine in Huntington disease (HD). Previously, we reported safety and exploratory efficacy data after 36 months of treatment with pridopidine 45 mg twice daily. In the interim, emerging data suggests pridopidine may have neuroprotective effects mediated by sigma-1 receptor agonism.

Abnormalities on structural MRI associate with faster disease progression in multiple system atrophy.

Background: The rate of clinical progression in patients with multiple system atrophy (MSA) varies between individuals and predictors for disease progression remain undefined. While the MSA-rasagiline study found no difference in the rates of clinical progression for patients treated with rasagiline versus placebo, it included a large, prospective magnetic resonance imaging (MRI) substudy that can provide new information on the underlying disease progression in patients with early MSA.

Methods: This post-hoc analysis compared the rate of clinical progression in patients with MSA-specific structural changes at baseline (MRI-positive group) versus the rate of progression in patients without evidence of such changes at baseline (MRI-negative group) using a repeated measures ANCOVA.

Tablet-Based Application for Objective Measurement of Motor Fluctuations in Parkinson Disease.

Background: The motor subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) has limited applicability for the assessment of motor fluctuations in the home setting.

Methods: To assess whether a self-administered, tablet-based application can reliably quantify differences in motor performance using two-target finger tapping and forearm pronation-supination tasks in the ON (maximal dopaminergic medication efficacy) and OFF (reemergence of parkinsonian deficits) medication states, we recruited 11 Parkinson disease (PD) patients (age, 60.6 ± 9.

Safety and Exploratory Efficacy at 36 Months in Open-HART, an Open-Label Extension Study of Pridopidine in Huntington's Disease.

Background: Open-HART is an open-label extension of HART, a randomized, placebo-controlled, dose-ranging, parallel-group study.

Objective: To evaluate safety and exploratory efficacy of open-label pridopidine over 36 months in subjects with Huntington's disease (HD).

Methods: Open-HART subjects were treated with pridopidine 45 mg twice daily (BID).

Minimally clinically important decline in the parkinsonian variant of multiple system atrophy.

Introduction: We provide the first characterization of the minimally clinically important difference on the Unified Multiple System Atrophy Rating Scale in patients with the parkinsonian variant of early MSA.

Methods: Data from a randomized controlled trial of rasagiline were analyzed using clinical global impression as an anchor. Because too few patients improved with treatment, analyses were limited to defining scale cutoffs that discriminated between minimal worsening and no change.

The phosphodiesterase 10 positron emission tomography tracer, [18F]MNI-659, as a novel biomarker for early Huntington disease.

Importance: In Huntington disease (HD) striatal neuron loss precedes and predicts motor signs or symptoms. Current imaging biomarkers lack adequate sensitivity for assessing the early stages of HD. Developing an imaging biomarker for HD spanning the time of onset of motor signs remains a major unmet research need.

Descriptive epidemiology of cervical dystonia.

Background: Cervical dystonia (CD), the most common form of adult-onset focal dystonia, has a heterogeneous clinical presentation with variable clinical features, leading to difficulties and delays in diagnosis. Owing to the lack of reviews specifically focusing on the frequency of primary CD in the general population, we performed a systematic literature search to examine its prevalence/incidence and analyze methodological differences among studies.

Methods: We performed a systematic literature search to examine the prevalence data of primary focal CD.

OnabotulinumtoxinA muscle injection patterns in adult spasticity: a systematic literature review.

Background: OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e.

Gastric stasis in migraineurs: etiology, characteristics, and clinical and therapeutic implications.

Background: Migraine is a disabling neurological disorder often complicated by gastrointestinal conditions such as gastric stasis. The association between migraine and gastric stasis has received very little attention in the literature, but the existing evidence suggests that they may share a common etiology.

Results: Patients with migraine and those with gastric stasis exhibit abnormal autonomic nervous system function.

Patient diaries as a clinical endpoint in Parkinson's disease clinical trials.

Parkinson's disease (PD) is the second most common neurodegenerative disorder with an estimated 4 million patients worldwide. L-dopa is standard, and often initial, therapy for patients with this condition; however, with continued dopaminergic treatment and as the disease progresses, the majority of patients experience complications such as "wearing-off" symptoms, dyskinesias, and other motor complications. These complications may become disabling and profoundly affect quality of life.

β-N-methylamino-L-alanine induces neurological deficits and shortened life span in Drosophila.

The neurotoxic non-protein amino acid, β-N-methylamino-L-alanine (BMAA), was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam. Recently, BMAA has been implicated as a fierce environmental factor that contributes to the etiology of Alzheimer's and Parkinson's diseases, in addition to ALS. However, the toxicity of BMAA in vivo has not been clearly demonstrated.

Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE).

Background: A registry of patients with cervical dystonia (Cervical Dystonia Patient Registry for Observation of onaBotulinumtoxinA Efficacy [CD PROBE]) was initiated to capture data regarding physician practices and patient outcomes with onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA, USA). Methods and baseline demographics from an interim analysis are provided.

Objective quantification of neuromotor symptoms in Parkinson's disease: implementation of a portable, computerized measurement tool.

Quantification of neuromotor symptoms with device-based measures provides a useful supplement to clinical evaluation. Research using the CATSYS has established its utility as a computerized measurement system to quantify neuromotor function. The primary objective of this study is to provide technical guidance on the use of the CATSYS in Parkinson's disease (PD).

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.

An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers.

Objective: Adenosine A2A receptor antagonists are potential new treatments for Parkinson disease. We used positron emission tomography (PET) of the A2A receptor radiotracer, [C]SCH442416, to assess binding of the novel A2A antagonist, vipadenant (previously known as BIIB014), to human brain A2A receptors and to investigate the relationship among dose, steady-state plasma levels, and receptor occupancy.

Methods: We used PET to compare [C]SCH442416 uptake before and after blockade with daily oral vipadenant (2.

SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects about five million people worldwide. Diagnosis remains clinical, based on phenotypic patterns. The discovery of laboratory markers that will enhance diagnostic accuracy, allow pre-clinical detection and tracking of disease progression is critically needed.

Melatonin MT1 and MT2 receptor expression in Parkinson's disease.

Background: Idiopathic Parkinson disease (PD) is a multi-system disorder with a multifactorial etiology and diverse clinical phenotype. Selective, regional dopaminergic neuronal degeneration in the substantia nigra and other CNS areas including the amygdala are observed in all patients. Apoptotic mechanisms resulting from oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of the disease.

BMAA neurotoxicity in Drosophila.

We report the establishment of an in vivo model using the fruit fly Drosophila melanogaster to investigate the toxic effects of L-BMAA. We found that dietary intake of BMAA reduced the lifespan as well as the neurological functions of flies. Furthermore, we have developed an HPLC method to reliably detect both free and protein-bound BMAA in fly tissue extracts.

Gain-of-function variant in GLUD2 glutamate dehydrogenase modifies Parkinson's disease onset.

Parkinson's disease (PD), a common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and their terminations in the basal ganglia, is thought to be related to genetic and environmental factors. Although the pathophysiology of PD neurodegeneration remains unclear, protein misfolding, mitochondrial abnormalities, glutamate dysfunction and/or oxidative stress have been implicated. In this study, we report that a rare T1492G variant in GLUD2, an X-linked gene encoding a glutamate dehydrogenase (a mitochondrial enzyme central to glutamate metabolism) that is expressed in brain (hGDH2), interacted significantly with age at PD onset in Caucasian populations.

Contemporary Encephalitis Lethargica: phenotype, laboratory findings and treatment outcomes.

Background: Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL.

Subthreshold depression in Parkinson's disease.

Objective: It is estimated that 40% of patients with Parkinson's disease (PD) are clinically depressed, however, little is known about the frequency and associated features of subthreshold depression in PD. The current study sought to determine the prevalence of subthreshold depression (sD) and to further characterize the associated features in a sample of 111 nondemented patients with moderate to severe PD.

Methods: Patients were classified into the following groups: diagnostic depression (DD), subthreshold depression (sD), or nondepressed (ND) by applying the Diagnostic and Statistical Manual, 4th edn criteria for depression and previously reported criteria for sD to items from the Beck Depression Inventory, 2nd edn.