Antiepileptogenesis after Stroke - Trials and Tribulations: Methodological Challenges and Recruitment Results of a Phase II Study with Eslicarbazepine Acetate.

There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicentre, randomised, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral haemorrhage or acute ischaemic stroke were randomised to receive ESL 800 mg/day or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is occurrence of a first unprovoked seizure within 6 months after randomisation ('failure rate'). Secondary efficacy assessments include occurrence of a first unprovoked seizure during 12 months after randomisation and during the entire study; functional outcomes (Barthel Index original 10-item version; National Institutes of Health Stroke Scale); post-stroke depression (Patient Health Questionnaire-9; PHQ-9); and overall survival. Safety assessments include evaluation of treatment-emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behaviour (PHQ-9 question 9). The protocol aimed to randomise approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID-19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomised. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol

Rates, risks and routes to reduce vascular dementia (R4vad), a UK-wide multicentre prospective observational cohort study of cognition after stroke: Protocol

Background: Stroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment and patient-service needs. Aims: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess potential mechanisms and improve prediction models. Methods: We will recruit at least 2000 patients within six weeks of stroke with or without capacity to consent and collect baseline demographic, clinical, socioeconomic, lifestyle, cognitive, neuropsychiatric and informant data using streamlined patient-centred methods appropriate to the stage after stroke. We will obtain more detailed assessments at four to eight weeks after the baseline assessment and follow-up by phone and post yearly to at least two years. We will assess diagnostic neuroimaging in all and high-sensitivity inflammatory markers, genetics, blood pressure and diffusion tensor imaging in mechanistic sub-studies. Planned outputs: R4VaD will provide reliable data on long-term cognitive function after stroke, stratified by prior cognition, stroke- and patient-related variables and improved risk prediction. It will create a platform enabling sharing of data, imaging and samples. Participants will be consented for re-contact, facilitating future clinical trials and providing a resource for the stroke and dementia research communities

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7-11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke

Motion Analysis in Simulated Clinical Environments (MA-SCE)

ContextThe improved accessibility of high-resolution cameras, and publicly available video footage, have helped advance the fields of pose estimation and action characterisation. Although there is a wealth of colour video depicting a wide range of activities performed in everyday life, the availability of high-quality data within clinical settings is far more limited. Importantly, these technologies are sensitive to prior knowledge of the physical environment and the activities that take place within them. Clinical settings are unusual enough to make seemingly simple activities—such as measuring blood pressure—present complex challenges, especially in the context of the occlusions, wide variation in illumination, and multi-agent interactions characteristic of the clinical domain. Crucially, video capture of real-world clinical scenarios could never be widely available, even at modest scale, owing to insurmountable privacy concerns, except after modification—such as expression-preserving face modification—that presupposes possession of a good model in the first place. Moreover, the minimal performance standard in healthcare is very high, not just in terms of individual-level fidelity but also the invariance across the population that attention to equity of delivered care demands. An individual patient is not rendered less important by being rare.These constraints leave data from realistically simulated clinical environments, such as those used to train clinical staff, as the only plausible solution. The approach further requires appropriately skilled staff to ensure the actions performed are representative of routine clinical care. Currently there are limited datasets representative of clinical activities, with even fewer providing multiple perspectives or multispectral data.Our objective here is to create a rich dataset of video samples depicting common ward-based activities within a simulated hospital setting, performed by trained clinical staff. Each task was recorded simultaneous from two different perspectives, with colour, depth and active infra-red data collected.MethodsHardwareTwo Microsoft Azure Kinect cameras were connected to two independent laptops powered by an Intel Xeon E3-1505 v5 processor with 32GB of RAM and a Samsung NVMe PM951 hard drive; and an Intel i5-8265U processor with 8 GB of RAM and a Kingston NVMe RBU-SNS8154P3, running the Microsoft Windows 10 and Windows 11 operating system respectively.The two cameras were used to record video footage at 30 frames per second. The colour, depth and active infra-red (IR) stream resolutions were recorded at 1920x1080, 640x576 and 1024x1024 respectively. Using the Microsoft Azure Kinect Software Development Kit, the cameras were linked using the external synchronisation method, with the high-angle-view camera acting as master, and the hip-level-view (side-view) camera as subordinate. The pulse width of the infra-red laser is 125-microseconds. A 200-microseconds offset was applied to the subordinate to minimise interference between the two depth cameras.LocationsFilming was conducted at King’s College Hospital NHS Foundation Trust, at their simulation room and simulation ward environments. The simulation room is arranged to resemble a single occupancy room, while the simulation ward is consistent with a bay located on the ward with multiple beds. In both cases, the cameras were arranged to have only one bed in the centre of the field of view.Camera setupEach task was filmed using a two-camera setup, providing a high-angle and hip-level perspectives, with the bed in the centre of the field of view. The two cameras were arranged to encompass the entire bed and a 0.5m surrounding margin.ParticipantsA total of 21 participants were involved across all the clips, with 14 participants assuming the patient role. The mean age of the patients was 41.4 years (SD 17.2 years, range 23-72 years), while the mean age for all participants was 38.0 years (SD 14.8 years, range 26-43 years) with 13 females and 8 males. Based on the UK 2021 census groupings, the participants encompassed Asian or Asian British; Black, Black British, Caribbean or African; White; and Other ethnic group.ActivitiesWe performed a programme of activities under varying levels of illumination, to replicate conditions typically found within a hospital environment. Participants were given an overview of the tasks required for each clip, but afforded freedom regarding how they were performed to encourage more diversity and natural movements. The full programme of activities is listed in the associated clip description file.Data filesThe video data were stored using the Matroska format (www.matroska.org), with the corresponding camera calibration file contained within. No audio data was recorded