Introduction

Parkinson's disease (PD) research is hampered by slow, inefficient recruitment and burdensome in-person assessments that may be challenging to conduct in a world affected by COVID-19. Fox Insight is an ongoing prospective clinical research study that enables individuals to participate in clinical research from their own homes by completing online questionnaires. To date, over 45,000 participants with and without PD have enrolled. We sought to validate self-reported PD diagnosis in the Fox Insight cohort, assess the validity of other self-reported health information, and evaluate the willingness of participants to participate in video-based research studies.

Methods

Individuals with and without self-reported PD enrolled in Fox Insight were invited to participate in this virtual research study. Participants completed online questionnaires and two virtual visits, during which we conducted standard cognitive and motor assessments. A movement disorder expert determined the most likely diagnosis, which was compared to self-reported diagnosis.

Results

A total of 203 participants from 40 U.S. states, 159 with remote clinician-determined PD and 44 without, completed the study (59% male, mean (SD) age 65.7 (9.8)). Level of agreement between self-reported PD diagnosis in Fox Insight and clinician-determined diagnosis was very good ((kappa = 0.85, 95% CI 0.76-0.94). Overall, 97.9% of participants were satisfied with the study, 98.5% were willing to participate in a future observational study with virtual visits, and 76.1% were willing to participate in an interventional trial with virtual visits.

Conclusion

Among the Fox Insight cohort, self-reported diagnosis is accurate and interest in virtual research studies is high.

Introduction

A common view is that head tremor (HT) in cervical dystonia (CD) decreases when the head assumes an unopposed dystonic posture and increases when the head is held at midline. However, this has not been examined with objective measures in a large, multicenter cohort.

Methods

For 80 participants with CD and HT, we analyzed videos from examination segments in which participants were instructed to 1) let their head drift to its most comfortable position (null point) and then 2) hold their head straight at midline. We used our previously developed Computational Motor Objective Rater (CMOR) to quantify changes in severity, amplitude, and frequency between the two postures.

Results

Although up to 9% of participants had exacerbated HT in midline, across the whole cohort, paired t-tests reveal no significant changes in overall severity (t = -0.23, p = 0.81), amplitude (t = -0.80, p = 0.43), and frequency (t = 1.48, p = 0.14) between the two postures.

Conclusions

When instructed to first let their head drift to its null point and then to hold their head straight at midline, most patient's changes in HT were below the thresholds one would expect from the sensitivity of clinical rating scales. Counter to common clinical impression, CMOR objectively showed that HT does not consistently increase at midline posture in comparison to the null posture.

Although abnormal head and neck postures are defining features of cervical dystonia (CD), head tremor (HT) is also common. However, little is known about the relationship between abnormal postures and HT in CD. We analyzed clinical data and video recordings from 185 patients enrolled by the Dystonia Coalition. We calculated the likelihood of their HT and HT type ("regular" vs. "jerky") given directionality of abnormal head postures, disease duration, sex, and age. Patients with retrocollis were more likely to have HT than patients with anterocollis (X2 (1, N = 121) = 7.98, p = 0.005). There was no difference in HT likelihood given left or right turning in laterocollis and rotation. Patients with HT had longer disease duration (t(183) = 2.27, p = 0.024). There was no difference in age between patients with and without HT. In a logistic regression model, anterocollis/retrocollis direction (X2 (1, N = 121) = 6.04, p = 0.014), disease duration (X2 (1, N = 121) = 7.28, p = 0.007), and the interaction term between age and disease duration (X2 (1, N = 121) = 7.77, p = 0.005) collectively contributed to HT likelihood. None of the postural directionality or demographic variables were associated with differential likelihood of having regular versus jerky HT. We found that HT is more likely for CD patients with a specific directionality in their predominant posture. Our finding that CD patients with longer disease duration have a higher likelihood of HT also raises the question of whether HT becomes more likely over time in individual patients.

Objective

Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system-the Computational Motor Objective Rater (CMOR)-to quantify multi-axis directionality and severity of head posture in CD using only conventional video camera recordings.

Methods

CMOR is based on computer vision and machine learning technology that captures 3D head angle from video. We used CMOR to quantify the axial patterns and severity of predominant head posture in a retrospective, cross-sectional study of 185 patients with isolated CD recruited from 10 sites in the Dystonia Coalition.

Results

The predominant head posture involved more than one axis in 80.5% of patients and all three axes in 44.4%. CMOR's metrics for head posture severity correlated with severity ratings from movement disorders neurologists using both the TWSTRS-2 and an adapted version of the Global Dystonia Rating Scale (rho = 0.59-0.68, all p <0.001).

Conclusions

CMOR's convergent validity with clinical rating scales and reliance upon only conventional video recordings supports its future potential for large scale multisite clinical trials.

Background

Previous small-scale studies have demonstrated the feasibility of providing remote specialty care via virtual visits. We assessed the feasibility and benefits of a one-time consultation between a remote Parkinson Disease (PD) specialist and an individual with PD at home on a larger scale.

Methods

We conducted a multicenter noncontrolled cohort of virtual visits administered over videoconferencing between remote PD specialists and individuals with PD in their home. Specialists performed a patient history and a PD-specific physical examination and provided recommendations to patients and their local physicians. The primary outcome measures were feasibility, as measured by the proportion of visits completed as scheduled, and the 6-month change in quality of life, as measured by the Parkinson's Disease Questionnaire 39. Additional outcomes included satisfaction with visits and interest in future virtual visits.

Results

A total of 277 participants from 5 states enrolled, 258 participants completed virtual visits with 14 different physicians, and 91% of visits were completed as scheduled. No improvement in quality of life was observed at 6 months (0.4-point improvement; 95% confidence interval -1.5 to 0.6; p = 0.39). Overall satisfaction with virtual visits was high among physicians (94% satisfied or very satisfied) and patients (94% satisfied or very satisfied), and 74% of participants were interested in receiving future care via virtual visits.

Conclusions

Providing specialty care remotely into the homes of individuals with PD is feasible, but a one-time visit did not improve quality of life. Satisfaction with the visits was high among physicians and patients, who were interested in receiving such care in the future.

Classification of evidence

This study provides Class IV evidence that for patients with PD, remote specialty care is feasible but does not improve quality of life.

Clinicaltrialsgov identifier

NCT02144220.

Background

Head tremor (HT) is a common feature of cervical dystonia (CD), usually quantified by subjective observation. Technological developments offer alternatives for measuring HT severity that are objective and amenable to automation.

Objectives

Our objectives were to develop CMOR (Computational Motor Objective Rater; a computer vision-based software system) to quantify oscillatory and directional aspects of HT from video recordings during a clinical examination and to test its convergent validity with clinical rating scales.

Methods

For 93 participants with isolated CD and HT enrolled by the Dystonia Coalition, we analyzed video recordings from an examination segment in which participants were instructed to let their head drift to its most comfortable dystonic position. We evaluated peak power, frequency, and directional dominance, and used Spearman's correlation to measure the agreement between CMOR and clinical ratings.

Results

Power averaged 0.90 (SD 1.80) deg²/Hz, and peak frequency 1.95 (SD 0.94) Hz. The dominant HT axis was pitch (antero/retrocollis) for 50%, roll (laterocollis) for 6%, and yaw (torticollis) for 44% of participants. One-sided t-tests showed substantial contributions from the secondary (t = 18.17, p < 0.0001) and tertiary (t = 12.89, p < 0.0001) HT axes. CMOR's HT severity measure positively correlated with the HT item on the Toronto Western Spasmodic Torticollis Rating Scale-2 (Spearman's rho = 0.54, p < 0.001).

Conclusions

We demonstrate a new objective method to measure HT severity that requires only conventional video recordings, quantifies the complexities of HT in CD, and exhibits convergent validity with clinical severity ratings.

Background

Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort.

Methods

The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread.

Results

Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age.

Conclusions

Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

The IceCube Collaboration has observed a high-energy astrophysical neutrino flux and recently found evidence for neutrino emission from the blazar TXS 0506+ 056. These results open a new window into the high-energy universe. However, the source or sources of most of the observed flux of astrophysical neutrinos remains uncertain. Here, a search for steady point-like neutrino sources is performed using an unbinned likelihood analysis. The method searches for a spatial accumulation of muon-neutrino events using the very high-statistics sample of about 497,000 neutrinos recorded by IceCube between 2009 and 2017. The median angular resolution is ∼ 1 ∘ at 1 TeV and improves to ∼ 0. 3 ∘ for neutrinos with an energy of 1 PeV. Compared to previous analyses, this search is optimized for point-like neutrino emission with the same flux-characteristics as the observed astrophysical muon-neutrino flux and introduces an improved event-reconstruction and parametrization of the background. The result is an improvement in sensitivity to the muon-neutrino flux compared to the previous analysis of ∼ 35 % assuming an E- 2 spectrum. The sensitivity on the muon-neutrino flux is at a level of E2dN/dE=3·10-13TeVcm-2s-1. No new evidence for neutrino sources is found in a full sky scan and in an a priori candidate source list that is motivated by gamma-ray observations. Furthermore, no significant excesses above background are found from populations of sub-threshold sources. The implications of the non-observation for potential source classes are discussed.