Involuntary Movements

The PKG system consists of a data logger, which is worn on the wrist of the most affected side, proprietary algorithms that provide bradykinesia and dyskinesia scores every two minutes, and the PKG which is the graphical and numerical presentation of this data. The logger contains a rechargeable battery, a triaxial accelerometer, memory and a capacitive sensor to detect removal from the wrist.^{20 (link)} It is worn continuously for 6–7 consecutive days, at the end of which the data is downloaded and analysed using a proprietary algorithm to calculate the following values relevant to this study:
BKS: a bradykinesia score (BKS), calculated every two minutes throughout the period of wearing the logger. The median value of these BKS over the period from 09.00–18.00 for the full recording period is known as the median BKS and this correlates with the UPDRS III assessed at the time of doing the PKG.^{20 (link),21} DKS: a dyskinesia score (DKS) is calculated every two minutes throughout the period of that the logger is worn. The median value of these DKS over the period from 09.00–18.00 for the full recording period is known as the median DKS and this correlates with the modified Abnormal Involuntary Movement Score assessed at the time of donning the PKG.^{20 (link),21} PTI: The Percent Time Immobile over the period from 09.00–18.00. Immobility means that the logger, while being worn by the subject was entirely still for a two-minute period. This has been shown to correlate with the polysomnographic recordings of sleep.^{22 (link)}FDS: The Fluctuation Dyskinesia Score^{23 (link)} estimates the amount of variability in bradykinesia and dyskinesia as measured by the PKG over the course of the 6 days of recording. It provides a measure of the extent of fluctuations in bradykinesia and dyskinesia.
Percent Time Over Target (PTO): This is the amount of time that the BKS was over target and is a representation of “OFF” time in the period from 09.00–18.00 and is the proportion of time that a subject’s BKS is greater than the target used in this study (BKS = 26). The PTO does not include periods of immobility.
PTT: The Percent Time Tremor is the proportion of time in the period from 09.00–18.00 that a subject spends with tremor. Tremor is likely to be present if PTT score >1%.^{24 (link)}

Prior to clinician assessment and cohort assignment, all eligible and consenting patients were asked to complete the EQ-5D-5L [23 (link)], which assesses problems in 5-dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) that can be used to calculate a utility score, which ranges from 0 (health state equivalent to death) to 1 (perfect health). The EQ-5D-5L also includes a visual analog scale (VAS) that measures current health state, which ranges from 0 to 100 (best possible health). Patients were also asked to complete the SDS [24 (link)], which assesses disruption in 3 social functioning domains (work/school, social life, family life/home responsibilities) and includes a total score (sum of domain scores) which ranges from 0 (no disruption) to 30 (extreme disruption).
For severity of possible TD, clinicians and patients were asked to “rate the severity of visible, uncontrollable movements” for each of 4 body regions (head/face, neck/trunk, upper extremities, and/or lower extremities) using simple descriptors of “none”, “some”, or “a lot”. For impact of possible TD, patients who were aware of their abnormal involuntary movements (Cohort 2A) were asked to rate how much “over the past 4 weeks” did these movements “impact your ability” to perform each of 7 different activities/functions (usual activities, talking, eating, breathing, being productive, self-care, socializing), also using the descriptors of “none”, “some”, or “a lot”. For regression analyses, these descriptors were assigned values of 0, 1, and 2, respectively, with the summary score for severity ranging from 0 (“none” in all 4 regions) to 8 (“a lot” in all 4 regions) and the summary score for impact ranging from 0 (“none” in all 7 activities) to 14 (“a lot” in all 7 activities).

Patients were assigned to 1 of 2 cohorts based on clinician assessment (Fig. 1). Training for TD screening (via videos) was provided to all clinical site personnel to promote inter-rater reliability. Cohort 1 was defined in the study protocol as patients who had no abnormal involuntary movements or whose movements were not consistent with possible TD based on clinician assessment. To avoid any potential overlap with patients with possible TD (as described below), this analysis focused on a modified Cohort 1 (no abnormal involuntary movements), which excluded patients with non-TD involuntary movements such as tremor.Fig. 1

Overview of possible TD symptom screen and cohort assignment. EQ-5D-5L, EuroQoL 5-dimension 5-level questionnaire; SDS, Sheehan Disability Scale; TD, tardive dyskinesia

Cohort 2 was defined in the study protocol as patients who had abnormal involuntary movements that were confirmed by their clinician as possible TD. All patients in Cohort 2 had a clinician-rated severity of possible TD as “some” or “a lot” in at least 1 of the following body regions: head/face, neck/trunk, upper extremities, and/or lower extremities. For this analysis, Cohort 2A (“aware”) was defined as patients with clinician-confirmed possible TD who also self-reported having abnormal involuntary movements within the past 4 weeks and had a self-rated severity of “some” or “a lot” in at least 1 of the 4 body regions. Data from Cohort 2NA (“not aware”), defined as patients with possible TD who self-reported having no abnormal involuntary movements in the past 4 weeks, were analyzed to provide supplementary information about the potential effects of patient awareness on HRQoL.