Unconstrained human movement can be broken down into a series of stereotyped motifs or 'syllables' in an unsupervised fashion. Sequences of these syllables can be represented by symbols and ...characterized by a statistical grammar which varies with external situational context and internal neurological state. By first constructing a Markov chain from the transitions between these syllables then calculating the stationary distribution of this chain, we estimate the overall severity of Parkinson's symptoms by capturing the increasingly disorganized transitions between syllables as motor impairment increases. Comparing stationary distributions of movement syllables has several advantages over traditional neurologist administered in-clinic assessments. This technique can be used on unconstrained at-home behavior as well as scripted in-clinic exercises, it avoids differences across human evaluators, and can be used continuously without requiring scripted tasks be performed. We demonstrate the effectiveness of this technique using movement data captured with commercially available wrist worn sensors in 35 participants with Parkinson's disease in-clinic and 25 participants monitored at home.
Technological advances in multimodal wearable and connected devices have enabled the measurement of human movement and physiology in naturalistic settings. The ability to collect continuous activity ...monitoring data with digital devices in real-world environments has opened unprecedented opportunity to establish clinical digital phenotypes across diseases. Many traditional assessments of physical function utilized in clinical trials are limited because they are episodic, therefore, cannot capture the day-to-day temporal fluctuations and longitudinal changes in activity that individuals experience. In order to understand the sensitivity of gait speed as a potential endpoint for clinical trials, we investigated the use of digital devices during traditional clinical assessments and in real-world environments in a group of healthy younger (
= 33, 18-40 years) and older (
= 32, 65-85 years) adults. We observed good agreement between gait speed estimated using a lumbar-mounted accelerometer and gold standard system during the performance of traditional gait assessment task in-lab, and saw discrepancies between in-lab and at-home gait speed. We found that gait speed estimated in-lab, with or without digital devices, failed to differentiate between the age groups, whereas gait speed derived during at-home monitoring was able to distinguish the age groups. Furthermore, we found that only three days of at-home monitoring was sufficient to reliably estimate gait speed in our population, and still capture age-related group differences. Our results suggest that gait speed derived from activities during daily life using data from wearable devices may have the potential to transform clinical trials by non-invasively and unobtrusively providing a more objective and naturalistic measure of functional ability.
Vupanorsen (PF‐07285557) is a second‐generation tri‐N‐acetyl galactosamine (GalNAc3)‐antisense oligonucleotide targeted to angiopoietin‐like 3 (ANGPTL3) mRNA, shown to reduce lipids and ...apolipoproteins in subjects with dyslipidemia. To aid bringing innovative drugs to global patients efficiently, a multi‐purpose Japanese phase I study was conducted, with integrated development approaches agreed by the Pharmaceuticals and Medical Devices Agency (PMDA). This randomized, double‐blind, placebo‐controlled, single‐ascending dose (SAD) study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of vupanorsen administered subcutaneously to Japanese adults (20–65 years) with elevated triglycerides (TG). Participants were randomized (1:1:1) to vupanorsen (80:160 mg) or placebo (N = 4 each). Vupanorsen 160 mg was a first‐in‐human (FIH) dose level. Vupanorsen was well‐tolerated with no treatment‐related adverse events reported for either dose. Absorption into the systemic circulation was rapid with median time to maximum concentration (Tmax) of 3.5 and 2.0 h, for vupanorsen 80 and 160 mg, respectively. Following maximum concentration (Cmax), vupanorsen underwent multiphasic decline characterized by a relatively fast initial distribution phase followed by slower terminal elimination phase, with elimination half‐life (t1/2) of 397 and 499 h (80, 160 mg), respectively. Area under the concentration–time curve (AUC) and Cmax increased in a greater than dose‐proportional manner. Pharmacodynamic markers (ANGPTL3, TG, and other key lipids) were reduced with vupanorsen versus placebo. Vupanorsen was safe and well‐tolerated in healthy Japanese participants with elevated TG. This study provided FIH data for vupanorsen 160 mg. Moreover, the SAD study in Japanese participants fulfilled PMDA bridging requirements, and with the totality of global vupanorsen data, supported the PMDA waiver for a local phase II dose‐finding study. ClinicalTrials.gov: NCT04459767.
Background
Measuring free-living gait using wearable devices may offer higher granularity and temporal resolution than the current clinical assessments for patients with Parkinson disease (PD). ...However, increasing the number of devices worn on the body adds to the patient burden and impacts the compliance.
Objective
This study aimed to investigate the impact of reducing the number of wearable devices on the ability to assess gait impairments in patients with PD.
Methods
A total of 35 volunteers with PD and 60 healthy volunteers performed a gait task during 2 clinic visits. Participants with PD were assessed in the On and Off medication state using the Movement Disorder Society version of the Unified Parkinson Disease Rating Scale (MDS-UPDRS). Gait features derived from a single lumbar-mounted accelerometer were compared with those derived using 3 and 6 wearable devices for both participants with PD and healthy participants.
Results
A comparable performance was observed for predicting the MDS-UPDRS gait score using longitudinal mixed-effects model fit with gait features derived from a single (root mean square error RMSE=0.64; R2=0.53), 3 (RMSE=0.64; R2=0.54), and 6 devices (RMSE=0.54; R2=0.65). In addition, MDS-UPDRS gait scores predicted using all 3 models differed significantly between On and Off motor states (single device, P=.004; 3 devices, P=.004; 6 devices, P=.045).
Conclusions
We observed a marginal benefit in using multiple devices for assessing gait impairments in patients with PD when compared with gait features derived using a single lumbar-mounted accelerometer. The wearability burden associated with the use of multiple devices may offset gains in accuracy for monitoring gait under free-living conditions.
Psychogenic dystonia is a challenging entity to diagnose and treat because little is known about its pathophysiology. We describe two cases of psychogenic dystonia who underwent deep brain ...stimulation when thought to have organic dystonia. The intraoperative microelectrode recordings in globus pallidus internus were retrospectively compared with those of five patients with known DYT1 dystonia using spontaneous discharge parameters of rate and bursting, as well as movement‐related discharges. Our data suggest that simple intraoperative neurophysiology measures in single subjects do not differentiate psychogenic dystonia from DYT1 dystonia.
Ultrasound as Diagnostic Tool for Diaphragmatic Myoclonus Ramos, Vesper Fe Marie Llaneza; Considine, Elaine; Karp, Barbara I. ...
Movement disorders clinical practice (Hoboken, N.J.),
May/June 2016, Letnik:
3, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background
Diaphragmatic myoclonus is a rare disorder of repetitive diaphragmatic contractions, acknowledged to be a spectrum that includes psychogenic features. Electromyography has been the ...diagnostic tool most commonly used in the literature.
Methods
To test whether we could perform a noninvasive technique to delineate the diaphragm as the source of abnormal movements and demonstrate distractibility and entrainability, we used B‐mode ultrasound in a patient with diaphragmatic myoclonus.
Results
Ultrasound imaging clearly delineated the diaphragm as the source of her abdominal movements. We were able to demonstrate entrainability of the diaphragm to hand tapping to a prescribed rhythm set by the examiner.
Conclusions
We recommend the use of ultrasound as a noninvasive, convenient diagnostic tool for further studies of diaphragmatic myoclonus. We agree with previous findings that diaphragmatic myoclonus may be a functional movement disorder, as evidenced by distractibility and entrainability demonstrated on real‐time video with ultrasonography.
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