OFF-times before, during, and after nighttime sleep periods in Parkinson's disease patients with motor fluctuations and the effects of opicapone: A post hoc analysis of diary data from BIPARK-1 and -2.

INTRODUCTION: In BIPARK-1 and BIPARK-2, addition of once-daily opicapone to levodopa/carbidopa significantly reduced daily "OFF"-time relative to placebo in adults with Parkinson's disease (PD) and motor fluctuations. Diary data from these studies were pooled and analyzed post hoc to characterize "OFF"-times around nighttime sleep and to explore the effects of opicapone 50 mg. METHODS: "OFF" before sleep (OBS), "OFF during the nighttime sleep period" (ODNSP), early morning "OFF" (EMO), and duration of nighttime sleep and awake periods were analyzed descriptively at baseline. Mean changes from baseline to Week 14/15 (end of double-blind treatment) were analyzed using two-sided t-tests in participants with data for both visits. RESULTS: At baseline, 88.3 % (454/514) of participants reported having OBS (34.0 %), ODNSP (17.1 %), or EMO (79.6 %). Those with ODNSP had substantially shorter mean duration of uninterrupted sleep (4.4 h) than the overall pooled population (7.1 h). At Week 14/15, mean decrease from baseline in ODNSP duration was significantly greater with opicapone than with placebo (-0.9 vs. -0.4 h, P < 0.05). In participants with ODNSP at baseline, the decrease in total time spent awake during the night-time sleep period was significantly greater with opicapone than with placebo (-1.0 vs. -0.4 h, P < 0.05), as was the reduction in percent time spent awake during the night-time sleep period (-12.8 % vs. -4.5 %, P < 0.05). CONCLUSION: "OFF"-times around nighttime sleep were common in BIPARK-1 and BIPARK-2. Opicapone may improve sleep by decreasing the amount of time spent awake during the night in patients with PD who have night-time sleep period "OFF" episodes.

The Tardive Dyskinesia Impact Scale (TDIS), a novel patient-reported outcome measure in tardive dyskinesia: development and psychometric validation.

BACKGROUND: Tardive dyskinesia (TD), a movement disorder in which patients experience abnormal involuntary movements, can have profound negative impacts on physical, cognitive, and psychosocial functioning. The Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is considered the gold standard for evaluating treatment efficacy in TD clinical trials. However, it provides little information about the impacts of uncontrolled movements from a patient perspective and can be cumbersome to administer in clinical settings. The Tardive Dyskinesia Impact Scale (TDIS) was developed as a patient-reported outcome measure to fulfill the need for a disease-specific impact assessment in TD. The objective of the present study was to develop and evaluate the psychometric properties of the TDIS to determine whether it is fit-for-purpose to measure TD impact. METHODS: Data from qualitative studies and phase 3 trials of a VMAT2 inhibitor for the treatment of TD (KINECT3 and KINECT4) were used to determine the psychometric properties of the TDIS. Qualitative research included concept elicitation and cognitive debriefing interviews with TD patients and their caregivers in order to assess how well the TDIS captured key domains of TD impact. Quantitative analyses to examine the psychometric properties of the TDIS included assessing construct validity (factor structure, known groups, and predictive validity) and responsiveness to change. RESULTS: Qualitative results showed that the TDIS captures the key TD impacts reported by patients and caregivers and that the TDIS was interpreted as intended and relevant to patients' experiences. Quantitative results found evidence of 2 underlying domains of the TDIS: physical and socioemotional (Comparative Fit Index > 0.9). Known groups and predictive validity indicated that, compared with the AIMS, the TDIS captures unique content (correlation between AIMS and TDIS = 0.2-0.28). The TDIS showed responsiveness to change in treatment, with TDIS scores improving over 48 weeks in the 2 phase 3 trials. CONCLUSIONS: The TDIS captures relevant information about the impact of TD and is easily administered in a clinician's office or patient's home. It may be used longitudinally to show changes in TD burden over time. The TDIS complements the AIMS; using these assessments together provides a more holistic assessment of TD.

Tardive dyskinesia is a condition where people have uncontrollable movements because of taking certain medications for a long time. It is still poorly understood how these uncontrollable movements affect a person's everyday activities. We created a questionnaire called the Tardive Dyskinesia Impact Scale (TDIS). The TDIS is a questionnaire where people with tardive dyskinesia rate how their symptoms affect daily activities such as speaking and walking. People can also rate how the uncontrollable movements make them feel. We used specific tests called psychometric tests to see if the TDIS measures the correct information and if the information is reliable. Findings from this study show that the TDIS is a good way to measure how a person's uncontrollable movements affect everyday activities. The results also show that when people take medicine to help with their symptoms, their TDIS scores are better. When patients stopped taking the medicine, their symptoms were worse, and their TDIS score was worse. The TDIS can help people explain how their uncontrollable movements affect their daily life. This can then help their doctors understand the person's condition better.

Unmet needs in epileptic encephalopathy with spike-and-wave activation in sleep: A systematic review.

INTRODUCTION: Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS), also referred to as electrical status epilepticus during sleep (ESES) or epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS or EE-CSWS), is a spectrum of rare childhood epileptic encephalopathies that can lead to long-term cognitive impairment. Despite the importance of early diagnosis and intervention for D/EE-SWAS, there is a paucity of well-controlled clinical trial data to inform treatment, and no approved treatments are available. To assess correlations between diagnosis, treatment, and outcomes in D/EE-SWAS, we carried out a systematic review of the literature. METHODS: In August 2020, we conducted comprehensive database searches using search terms including "electrical status epilepticus," "ESES," "CSWS," and "Landau-Kleffner syndrome." Two or more independent reviewers screened titles, abstracts, and full-text articles for those that met the following criteria: prospective studies (randomized controlled trials [RCTs] or open-label trials), retrospective studies (drug evaluations or observational studies/chart reviews), and case series with ≥ 10 participants. Both interventional and non-interventional studies were included (i.e., drug intervention was not an inclusion criterion). Articles published before 2012, review articles, animal studies, and studies of surgical or dietary interventions were excluded. Standardized data extraction templates were used to capture data on study design, patient characteristics, interventions, and outcomes from each of the selected publications. Study quality was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for retrospective, observational studies. RESULTS: A total of 34 studies were included for full data extraction, most of which were uncontrolled and observational. Interpretation of study outcomes was limited by small study populations, variability in inclusion criteria, and inconsistency in methods of assessment and reporting of outcomes, which resulted in large heterogeneity in patients and their presenting symptoms. Despite these limitations, some patterns could be discerned. Several studies found that longer duration of ESES and younger age at onset were correlated with more severe language and cognitive deficits. In addition, several studies reported an association between improvement in cognitive outcomes and reduction in electroencephalogram (EEG) abnormalities and/or seizure frequency. In the 16 prospective or retrospective studies that evaluated drug treatments (e.g., antiseizure medications, corticosteroids, and high-dose diazepam), there was some improvement in EEG, seizure, and/or cognitive outcomes, although the specific outcomes and rates of improvement reported varied from study to study. CONCLUSION: Long-term cognitive deficits remain common in D/EE-SWAS, and data gaps exist in the literature that preclude an evidence-based approach to managing this complex epilepsy indication. Early intervention with more effective medications is needed to optimize long-term outcomes. Sufficiently powered, randomized, double-blind, controlled trials with standardized methods and predefined primary and secondary outcomes are needed.