Multimodal nocturnal seizure detection in children with epilepsy: A prospective, multicenter, long-term, in-home trial.

OBJECTIVE: There is a pressing need for reliable automated seizure detection in epilepsy care. Performance evidence on ambulatory non-electroencephalography-based seizure detection devices is low, and evidence on their effect on caregiver's stress, sleep, and quality of life (QoL) is still lacking. We aimed to determine the performance of NightWatch, a wearable nocturnal seizure detection device, in children with epilepsy in the family home setting and to assess its impact on caregiver burden. METHODS: We conducted a phase 4, multicenter, prospective, video-controlled, in-home NightWatch implementation study (NCT03909984). We included children aged 4-16 years, with ≥1 weekly nocturnal major motor seizure, living at home. We compared a 2-month baseline period with a 2-month NightWatch intervention. The primary outcome was the detection performance of NightWatch for major motor seizures (focal to bilateral or generalized tonic-clonic [TC] seizures, focal to bilateral or generalized tonic seizures lasting >30 s, hyperkinetic seizures, and a remainder category of focal to bilateral or generalized clonic seizures and "TC-like" seizures). Secondary outcomes included caregivers' stress (Caregiver Strain Index [CSI]), sleep (Pittsburgh Quality of Sleep Index), and QoL (EuroQol five-dimension five-level scale). RESULTS: We included 53 children (55% male, mean age = 9.7 ± 3.6 years, 68% learning disability) and analyzed 2310 nights (28 173 h), including 552 major motor seizures. Nineteen participants did not experience any episode of interest during the trial. The median detection sensitivity per participant was 100% (range = 46%-100%), and the median individual false alarm rate was .04 per hour (range = 0-.53). Caregiver's stress decreased significantly (mean total CSI score = 8.0 vs. 7.1, p = .032), whereas caregiver's sleep and QoL did not change significantly during the trial. SIGNIFICANCE: The NightWatch system demonstrated high sensitivity for detecting nocturnal major motor seizures in children in a family home setting and reduced caregiver stress.

Parental preferences for seizure detection devices: A discrete choice experiment.

OBJECTIVE: Previous studies identified essential user preferences for seizure detection devices (SDDs), without addressing their relative strength. We performed a discrete choice experiment (DCE) to quantify attributes' strength, and to identify the determinants of user SDD preferences. METHODS: We designed an online questionnaire targeting parents of children with epilepsy to define the optimal balance between SDD sensitivity and positive predictive value (PPV) while accounting for individual seizure frequency. We selected five DCE attributes from a recent study. Using a Bayesian design, we constructed 11 unique choice tasks and analyzed these using a mixed multinomial logit model. RESULTS: One hundred parents responded to the online questionnaire link; 49 completed all tasks, whereas 28 completed the questions, but not the DCE. Most parents preferred a relatively high sensitivity (80%-90%) over a high PPV (>50%). The preferred sensitivity-to-PPV ratio correlated with seizure frequency (r = -.32), with a preference for relative high sensitivity and low PPV among those with relative low seizure frequency (p = .04). All DCE attributes significantly impacted parental choices. Parents expressed preferences for consulting a neurologist before device use, personally training the device's algorithm, interaction with their child via audio and video, alarms for all seizure types, and an interface detailing measurements during an alarm. Preferences varied between subgroups (learning disability or not, SDD experience, relative low vs. high seizure frequency based on the population median). SIGNIFICANCE: Various attributes impact parental SDD preferences and may explain why preferences vary among users. Tailored approaches may help to meet the contrasting needs among SDD users.

Timing of syncope in ictal asystole as a guide when considering pacemaker implantation.

INTRODUCTION: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. METHODS: In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause. RESULTS: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. CONCLUSIONS: In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA.

Seizure detection devices: Exploring caregivers' needs and wishes.

INTRODUCTION: User preferences for seizure detection devices (SDDs) have been previously assessed using surveys and interviews, but these have not addressed the latent needs and wishes. Context mapping is an approach in which designers explore users' dreams and fears to anticipate potential future experiences and optimize the product design. METHODS: A generative group session was held using the context mapping approach. Two types of nocturnal SDD users were included: three professional caregivers at a residential care facility and two informal caregivers of children with refractory epilepsy and learning disabilities. Participants were invited to share their personal SDD experiences and briefed to make their needs and wishes explicit. The audiotaped session was transcribed and analyzed together with the collected material using inductive content analysis. The qualitative data was classified by coding the content, grouping codes into categories and themes, and combining those into general statements (abstraction). RESULTS: "Trust" emerged as the most important theme, entangling various emotional and practical factors that influence caregiver's trust in a device. Caregivers expressed several factors that could help to gain their trust in an SDD, including integration of different modalities, insight on all parameters overnight, personal adjustment of the algorithm, recommendation by a neurologist, and a set-up period. Needs regarding alerting seemed to differ between the two types of caregivers in our study: professional caregivers preferred to be alerted only for potentially dangerous seizures, whereas informal caregivers emphasized the urge to be alerted for every event, thus indicating the need for personal adjustment of SDD settings. CONCLUSION: In this explorative study, we identified several key elements for nocturnal SDD implementation including the importance of gaining trust and the possibility to adjust SDD settings for different types of caregivers.

Parental experiences and perspectives on the value of seizure detection while caring for a child with epilepsy: A qualitative study.

INTRODUCTION: Caring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP), may cause high parental stress and increased anxiety. Nocturnal supervision with seizure detection devices may lower SUDEP risk and decrease parental burden of seizure monitoring, but little is known about their added value in family homes. METHODS: We conducted semi-structured in-depth interviews with parents of children with refractory epilepsy participating in the PROMISE trial (NCT03909984) to explore the value of seizure detection in the daily care of their child. Children were aged 4-16 years, treated at a tertiary epilepsy center, had at least one nocturnal major motor seizure per week, and used a wearable seizure detection device (NightWatch) for two months at home. Data were analyzed using inductive thematic analysis. RESULTS: Twenty three parents of nineteen children with refractory epilepsy were interviewed. All parents expressed their fear of missing a large seizure and the possible consequences of not intervening in time. Some parents felt the threat of child loss during every seizure, while others thought about it from time to time. The fear could fluctuate over time, mainly associated with fluctuations of seizure frequency. Most parents described how they developed a protective behavior, driven by this fear. The way parents handled the care of their child and experienced the burden of care influenced their perceptions on the added value of NightWatch. The experienced value of NightWatch depended on the amount of assurance it could offer to reduce their fear and the associated protective behavior as well as their resilience to handle the potential extra burden of care, due to false alarms or technical problems. CONCLUSION: Healthcare professionals and device companies should be aware of parental protective behavior and the high parental burden of care and develop tailored strategies to optimize seizure detection device care.

Automated video-based detection of nocturnal motor seizures in children.

Seizure detection devices can improve epilepsy care, but wearables are not always tolerated. We previously demonstrated good performance of a real-time video-based algorithm for detection of nocturnal convulsive seizures in adults with learning disabilities. The algorithm calculates the relative frequency content based on the group velocity reconstruction from video-sequence optical flow. We aim to validate the video algorithm on nocturnal motor seizures in a pediatric population. We retrospectively analyzed the algorithm performance on a database including 1661 full recorded nights of 22 children (age = 3-17 years) with refractory epilepsy at home or in a residential care setting. The algorithm detected 118 of 125 convulsions (median sensitivity per participant = 100%, overall sensitivity = 94%, 95% confidence interval = 61%-100%) and identified all 135 hyperkinetic seizures. Most children had no false alarms; 81 false alarms occurred in six children (median false alarm rate [FAR] per participant per night = 0 [range = 0-0.47], overall FAR = 0.05 per night). Most false alarms (62%) were behavior-related (eg, awake and playing in bed). Our noncontact detection algorithm reliably detects nocturnal epileptic events with only a limited number of false alarms and is suitable for real-time use.

Ictal autonomic changes as a tool for seizure detection: a systematic review.

PURPOSE: Adequate epileptic seizure detection may have the potential to minimize seizure-related complications and improve treatment evaluation. Autonomic changes often precede ictal electroencephalographic discharges and therefore provide a promising tool for timely seizure detection. We reviewed the literature for seizure detection algorithms using autonomic nervous system parameters. METHODS: The PubMed and Embase databases were systematically searched for original human studies that validate an algorithm for automatic seizure detection based on autonomic function alterations. Studies on neonates only and pilot studies without performance data were excluded. Algorithm performance was compared for studies with a similar design (retrospective vs. prospective) reporting both sensitivity and false alarm rate (FAR). Quality assessment was performed using QUADAS-2 and recently reported quality standards on reporting seizure detection algorithms. RESULTS: Twenty-one out of 638 studies were included in the analysis. Fifteen studies presented a single-modality algorithm based on heart rate variability (n = 10), heart rate (n = 4), or QRS morphology (n = 1), while six studies assessed multimodal algorithms using various combinations of HR, corrected QT interval, oxygen saturation, electrodermal activity, and accelerometry. Most studies had small sample sizes and a short follow-up period. Only two studies performed a prospective validation. A tendency for a lower FAR was found for retrospectively validated algorithms using multimodal autonomic parameters compared to those using single modalities (mean sensitivity per participant 71-100% vs. 64-96%, and mean FAR per participant 0.0-2.4/h vs. 0.7-5.4/h). CONCLUSIONS: The overall quality of studies on seizure detection using autonomic parameters is low. Unimodal autonomic algorithms cannot reach acceptable performance as false alarm rates are still too high. Larger prospective studies are needed to validate multimodal automatic seizure detection.

Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review.

Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty-five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs -21, -19b, and -92a, RNU2-1f, CXCL13, interleukins -6, -8, and -10, soluble interleukin-2-receptor, soluble CD19, soluble CD27, tumour necrosis factor-alfa, beta-2-microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA-21 soluble CD27, and beta-2-microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL-13, beta-2-microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.

An economic evaluation of the NightWatch for children with refractory epilepsy: Insight into the cost-effectiveness and cost-utility.

PURPOSE: We performed an economic evaluation, from a societal perspective, to examine the cost-utility and cost-effectiveness of a wearable multimodal seizure detection device: NightWatch. METHODS: We collected data between November 2018 and June 2020 from the PROMISE trial (NCT03909984), including children aged 4-16 years with refractory epilepsy living at home. Caregivers completed questionnaires on stress, quality of life, health care consumption and productivity costs after two-month baseline and two-month intervention with NightWatch. We used costs, stress levels and quality-adjusted life years (QALYs) to calculate incremental cost-effectiveness ratios (ICERs). Missing items were handled by mean imputation. Sensitivity analyses were performed to examine the robustness of the results including bootstrap sampling. RESULTS: We included 41 children (44% female; mean age 9.8 years, standard deviation (SD) 3.7 years). Total societal costs of the baseline period (T1) were on average €3,238 per patient, whereas after intervention (T2) this reduced to 2,463 (saving €775). The QALYs were similar between both periods (mean QALY 0.90 per participant, SD at T1 0.10, SD at T2 0.13). At a ceiling ratio of €50.000, NightWatch showed a 72% cost-effective probability. Univariate sensitivity analyses, on the perspective and imputation method, demonstrated result robustness. CONCLUSION: Our study suggests that NightWatch might be a cost-effective addition to current standard care for children with refractory epilepsy living at home. Further research with an additional target group for a large timeframe may support the findings of this research.

Quality of reporting and assessment of patient-reported health-related quality of life in patients with brain metastases: a systematic review.

Brain metastases (BMs) have become increasingly prevalent and present unique considerations for patients, including neurocognitive sequelae and advanced disease burden. Therefore, assessing health-related quality of life (HRQoL) via patient-reported outcome measures (PROMs) is an important element of managing these patients. A systematic review of the literature was conducted with the aims of (1) assessing how PROMS used in BM patients were validated, (2) assessing PROM content, and (3) evaluating quality of PROM-results reporting. PROM validation and quality of reporting were assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) grading criteria and International Society of Quality of Life (ISOQOL)-recommended PROM-reporting standards, respectively. Forty-seven studies reporting on 5178 patients with a range of primacy cancer types were included. Eight different PROMs were applied, ranging from general to brain-specific questionnaires. Weaknesses in the validation of these PROMs were assessed by the COSMIN criteria. Many of these PROMs were not developed for BM patients and contained little information on cognitive symptoms. The overall quality of PROM reporting was insufficient based on the ISOQOL scale. Given the unique clinical considerations in BM patients, our results indicate the need for a standardized, validated questionnaire to assess HRQoL in this population. Additionally, there is room for quality improvement with regard to reporting of PROM-related results.

Specific EEG markers in POLG1 Alpers' syndrome.

OBJECTIVE: To examine whether rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS) in EEG allow a reliable early diagnosis of Alpers-Huttenlocher syndrome (AHS) and contribute to recognition of this disease. METHODS: EEGs of nine patients with DNA-proven AHS and fifty age-matched patients with status epilepticus were retrospectively examined by experts for the presence of RHADS and for accompanying clinical signs and high-frequency ripples. Reproducibility of RHADS identification was tested in a blinded panel. RESULTS: Expert defined RHADS were found in at least one EEG of all AHS patients and none of the control group. RHADS were present at first status epilepticus in six AHS patients (67%). Sometimes they appeared 5-10 weeks later and disappeared over time. RHADS were symptomatic in three AHS patients and five AHS patients showed distinct ripples on the (poly)spikes of RHADS. Independent RHADS identification by the blinded panel resulted in a sensitivity of 87.5% (95% CI 47-100) and a specificity of 87.5% (95% CI 77-94) as compared to the experts' reporting. CONCLUSION: RHADS are a highly specific EEG phenomenon for diagnosis of AHS and can be reliably recognized. Clinical expression and EEG ripples suggest that they signify an epileptic phenomenon. SIGNIFICANCE: RHADS provide a specific tool for AHS diagnosis.