Feasibility of Simon 2-Stage Futility Trials in Early Parkinson Disease: Analysis of the PRECEPT and DATATOP Trial Datasets.

Background And Objectives: Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required.

Short term effects of contralateral tendon vibration on motor unit discharge rate variability and force steadiness in people with Parkinson's disease.

Background: Vibration of one limb affects motor performance of the contralateral limb, and this may have clinical implications for people with lateralized motor impairments through vibration-induced increase in cortical activation, descending neural drive, or spinal excitability.

Objective: The objective of this study was to evaluate the effects of acute biceps brachii tendon vibration on force steadiness and motor unit activity in the contralateral limb of persons with Parkinson's disease.

Methods: Ten participants with mild to moderate Parkinson's disease severity performed a ramp, hold and de-ramp isometric elbow flexion at 5% of maximum voluntary contraction with the more-affected arm while vibration was applied to the distal biceps brachii tendon on the contralateral, less-affected arm.

Intermuscular coherence of plantar and dorsiflexor muscles in older adults with Parkinson's disease and age-matched controls during bipedal and unipedal stance.

Introduction: Postural instability increases with age and is exacerbated in neurological disorders such as Parkinson's disease (PD). Reducing the base of support from bipedal to unipedal stance increases center of pressure (CoP) parameters and intermuscular coherence in lower-leg muscles of healthy older adults. To further develop an understanding of postural control in an altered state of neurological impairment, we explored intermuscular coherence in lower-leg muscles and CoP displacement in older adults with PD.

Tailoring the use of wearable systems and telehealth for Parkinson's disease.

The increasing need for remote and distributed methods to provide medical care for People with Parkinson Disease has increased the importance of additional tools to monitor symptoms of interest. We present data from a randomized trial of followup care delivered via traditional face to face visits with symptom diaries versus telehealth followup with wearable sensors.

Importance of Maximal Strength and Muscle-Tendon Mechanics for Improving Force Steadiness in Persons with Parkinson's Disease.

Although plantar flexion force steadiness (FS) is reduced in persons with Parkinson's disease (PD), the underlying causes are unknown. The aim of this exploratory design study was to ascertain the influence of maximal voluntary contraction (MVC) force and gastrocnemius-Achilles muscle-tendon unit behaviour on FS in persons with PD. Nine persons with PD and nine age- and sex-matched non-PD controls (~70 years, 6 females per group) performed plantar flexion MVCs and sub-maximal tracking tasks at 5, 10, 25, 50 and 75% MVC.

Perception of Healthcare Access and Utility of Telehealth Among Parkinson's Disease Patients.

Regional patient and physician density patterns pose problems to accessing care for people with Parkinson's disease, though telehealth may improve access. We surveyed and conducted a focus group for people with Parkinson's disease in Interior British Columbia regarding barriers to neurological care. Eighteen individuals completed the survey and seven parties joined the focus group.

PET Molecular Imaging in Familial Parkinson's Disease.

Most cases of Parkinson's disease (PD) are idiopathic, but some characteristics, such as early onset or a positive family history, raise suspicions of an inherited form of the disease. In the last decades several genes have been linked to parkinsonism, with different patterns of inheritance and different clinical phenotypes. Positron emission tomography (PET) imaging has helped to characterize genetic-linked parkinsonism, thanks to the availability of dopaminergic and nondopaminergic tracers.

Investigation of serotonergic Parkinson's disease-related covariance pattern using [C]-DASB/PET.

We used positron emission tomography imaging with [C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)- benzonitrile (DASB) and principal component analysis to investigate whether a specific Parkinson's disease (PD)-related spatial covariance pattern could be identified for the serotonergic system. We also explored if non-manifesting leucine-rich repeat kinase 2 (LRRK2) mutation carriers, with normal striatal dopaminergic innervation as measured with [C]-dihydrotetrabenazine (DTBZ), exhibit a distinct spatial covariance pattern compared to healthy controls and subjects with manifest PD. 15 subjects with sporadic PD, eight subjects with LRRK2 mutation-associated PD, nine LRRK2 non-manifesting mutation carriers, and nine healthy controls participated in the study.

PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins.

Background And Objectives: To study selective regional binding for tau pathology in vivo, using PET with [ C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.

Methods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [ C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region.

Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.

Background: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.

Methods: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada.

A scan without evidence is not evidence of absence: Scans without evidence of dopaminergic deficit in a symptomatic leucine-rich repeat kinase 2 mutation carrier.

Introduction: The basis for SWEDD is unclear, with most cases representing PD mimics but some later developing PD with a dopaminergic deficit.

Methods: We studied a patient initially diagnosed with SWEDD (based on (18)F-dopa PET) who developed unequivocal PD associated with a leucine-rich repeat kinase 2 p.G2019S mutation.

Smart watch accelerometry for analysis and diagnosis of tremor.

Background: Distinguishing the postural re-emergent tremor of Parkinson disease from essential tremor can be difficult clinically. Use of accelerometry to aid diagnosis is limited to laboratory settings. We sought to record and differentiate these tremors using a smart watch device in an outpatient clinic.

Behavior Therapy for Tourette Syndrome: A Systematic Review and Meta-analysis.

When tics caused by Tourette Syndrome cause meaningful impairment for patients, a comprehensive treatment approach includes education of patients, peers, and family, treatment of comorbid behavioral disorders if present, and consideration of behavior therapy and pharmacotherapy for tics themselves. This systematic review and meta-analysis demonstrates that behavior therapies based on Habit Reversal Therapy, including the Comprehensive Behavioral Intervention for Tics are effective in reducing tic severity when compared with supportive psychotherapy. When these behavior therapies are unavailable, Exposure with Response Prevention may also be effective.

Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy.

Objective: The severity of peripheral neuropathy in diabetic patients varies for unclear reasons. Long-term use of metformin is associated with malabsorption of vitamin B(12) (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. The intent of this study was to clarify the relationship among metformin exposure, levels of Cbl, Hcy, and MMA, and severity of peripheral neuropathy in diabetic patients.

An auditory neural correlate suggests a mechanism underlying holistic pitch perception.

Current theories of auditory pitch perception propose that cochlear place (spectral) and activity timing pattern (temporal) information are somehow combined within the brain to produce holistic pitch percepts, yet the neural mechanisms for integrating these two kinds of information remain obscure. To examine this process in more detail, stimuli made up of three pure tones whose components are individually resolved by the peripheral auditory system, but that nonetheless elicit a holistic, "missing fundamental" pitch percept, were played to human listeners. A technique was used to separate neural timing activity related to individual components of the tone complexes from timing activity related to an emergent feature of the complex (the envelope), and the region of the tonotopic map where information could originate from was simultaneously restricted by masking noise.