Multimodal wearable EEG, EMG and accelerometry measurements improve the accuracy of tonic-clonic seizure detection.

OBJECTIVE: This paper aims to investigate the possibility of detecting tonic-clonic seizures (TCSs) with behind-the-ear, two-channel wearable electroencephalography (EEG), and to evaluate its added value to non-EEG modalities in TCS detection. METHODS: We included 27 participants with a total of 44 TCSs from the European multicenter study SeizeIT2. The wearable Sensor Dot (SD; Byteflies) was used to measure behind-the-ear EEG, electromyography (EMG), electrocardiography (ECG), accelerometry (ACC) and gyroscope (GYR). We evaluated automatic unimodal detection of TCSs, using sensitivity, precision, false positive rate (FPR) and F1-score. Subsequently, we fused the different modalities and again assessed performance. Algorithm-labeled segments were then provided to two experts, who annotated true positive TCSs, and discarded false positives (FPs). RESULTS: Wearable EEG outperformed the other single modalities with a sensitivity of 100% and a FPR of 10.3/24h. The combination of wearable EEG and EMG proved most clinically useful, delivering a sensitivity of 97.7%, an FPR of 0.4/24h, a precision of 43%, and an F1-score of 59.7%. The highest overall performance was achieved through the fusion of wearable EEG, EMG, and ACC, yielding a sensitivity of 90.9%, an FPR of 0.1/24h, a precision of 75.5%, and an F1-score of 82.5%. CONCLUSIONS: In TCS detection with a wearable device, combining EEG with EMG, ACC or both resulted in a remarkable reduction of FPR, while retaining a high sensitivity. SIGNIFICANCE: Adding wearable EEG could further improve TCS detection, relative to extracerebral-based systems.

Spontaneous HFO Sequences Reveal Propagation Pathways for Precise Delineation of Epileptogenic Networks.

Epilepsy, a neurological disorder affecting millions worldwide, poses great challenges in precisely delineating the epileptogenic zone - the brain region generating seizures - for effective treatment. High-frequency oscillations (HFOs) are emerging as promising biomarkers; however, the clinical utility is hindered by the difficulties in distinguishing pathological HFOs from non- epileptiform activities at single electrode and single patient resolution and understanding their dynamic role in epileptic networks. Here, we introduce an HFO-sequencing approach to analyze spontaneous HFOs traversing cortical regions in 40 drug-resistant epilepsy patients. This data- driven method automatically detected over 8.9 million HFOs, pinpointing pathological HFO- networks, and unveiled intricate millisecond-scale spatiotemporal dynamics, stability, and functional connectivity of HFOs in prolonged intracranial EEG recordings. These HFO sequences demonstrated a significant improvement in localization of epileptic tissue, with an 818.47% increase in concordance with seizure-onset zone (mean error: 2.92 mm), compared to conventional benchmarks. They also accurately predicted seizure outcomes for 90% AUC based on pre-surgical information using generalized linear models. Importantly, this mapping remained reliable even with short recordings (mean standard deviation: 3.23 mm for 30-minute segments). Furthermore, HFO sequences exhibited distinct yet highly repetitive spatiotemporal patterns, characterized by pronounced synchrony and predominant inward information flow from periphery towards areas involved in propagation, suggesting a crucial role for excitation-inhibition balance in HFO initiation and progression. Together, these findings shed light on the intricate organization of epileptic network and highlight the potential of HFO-sequencing as a translational tool for improved diagnosis, surgical targeting, and ultimately, better outcomes for vulnerable patients with drug-resistant epilepsy. One Sentence Summary: Pathological fast brain oscillations travel like traffic along varied routes, outlining recurrently visited neural sites emerging as critical hotspots in epilepsy network.

Transcranial electrical stimulation during functional magnetic resonance imaging in patients with genetic generalized epilepsy: a pilot and feasibility study.

Objective: A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a viable adjunct treatment option, having been shown to reduce epileptic seizures in patients with focal epilepsy. Evidence for the use of tDCS in genetic generalized epilepsy (GGE) is scarce. We aimed to establish the feasibility of applying tDCS during fMRI in patients with GGE to study the acute neuromodulatory effects of tDCS, particularly on sensorimotor network activity. Methods: Seven healthy controls and three patients with GGE received tDCS with simultaneous fMRI acquisition while watching a movie. Three tDCS conditions were applied: anodal, cathodal and sham. Periods of 60 s without stimulation were applied between each stimulation condition. Changes in sensorimotor cortex connectivity were evaluated by calculating the mean degree centrality across eight nodes of the sensorimotor cortex defined by the Automated Anatomical Labeling atlas (primary motor cortex (precentral left and right), supplementary motor area (left and right), mid-cingulum (left and right), postcentral gyrus (left and right)), across each of the conditions, for each participant. Results: Simultaneous tDCS-fMRI was well tolerated in both healthy controls and patients without adverse effects. Anodal and cathodal stimulation reduced mean degree centrality of the sensorimotor network (Friedman's ANOVA with Dunn's multiple comparisons test; adjusted p = 0.02 and p = 0.03 respectively). Mean degree connectivity of the sensorimotor network during the sham condition was not different to the rest condition (adjusted p = 0.94). Conclusion: Applying tDCS during fMRI was shown to be feasible and safe in a small group of patients with GGE. Anodal and cathodal stimulation caused a significant reduction in network connectivity of the sensorimotor cortex across participants. This initial research supports the feasibility of using fMRI to guide and understand network modulation by tDCS that might facilitate its clinical application in GGE in the future.

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids.

BACKGROUND AND PURPOSE: The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late-stage clinical outcomes. METHODS: This was a retrospective single-centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. RESULTS: In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow-up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. CONCLUSION: Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.

Is developmental plasticity triggered by DNA methylation changes in the invasive cane toad (Rhinella marina)?

Many organisms can adjust their development according to environmental conditions, including the presence of conspecifics. Although this developmental plasticity is common in amphibians, its underlying molecular mechanisms remain largely unknown. Exposure during development to either 'cannibal cues' from older conspecifics, or 'alarm cues' from injured conspecifics, causes reduced growth and survival in cane toad (Rhinella marina) tadpoles. Epigenetic modifications, such as changes in DNA methylation patterns, are a plausible mechanism underlying these developmental plastic responses. Here we tested this hypothesis, and asked whether cannibal cues and alarm cues trigger the same DNA methylation changes in developing cane toads. We found that exposure to both cannibal cues and alarm cues was associated with local changes in DNA methylation patterns. These DNA methylation changes affected genes putatively involved in developmental processes, but in different genomic regions for different conspecific-derived cues. Genetic background explains most of the epigenetic variation among individuals. Overall, the molecular mechanisms triggered by exposure to cannibal cues seem to differ from those triggered by alarm cues. Studies linking epigenetic modifications to transcriptional activity are needed to clarify the proximate mechanisms that regulate developmental plasticity in cane toads.

Mental health and neurodevelopmental patient-reported outcome measures (PROMs) for children and young people with epilepsy: A systematic review.

Children and young people with epilepsy are at higher risk of mental health disorders and atypical neurodevelopmental outcomes compared to the general population. It is essential to detect such comorbidities early in children with epilepsy and provide appropriate interventions, to improve clinical outcomes. We aimed to identify and evaluate the measurement properties of Patient-Reported Outcome Measures (PROMs) that have been validated specifically to measure mental health and neurodevelopmental outcomes in children and/or young people with epilepsy. We searched Embase, Medline, and PsycINFO in May 2023 for relevant studies. Mental health was defined as psychological symptoms (e.g., anxiety, depression, psychosis) and/or behavioural difficulties (e.g., conduct disorders). Neurodevelopmental outcomes included neurodevelopmental disorder traits such as attention-deficit hyperactivity disorder (ADHD) and autistic spectrum disorders. We assessed methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidance. Twelve papers were identified that psychometrically evaluated 13 relevant PROMs (two epilepsy-specific, eleven generic). The appraisal of the PROMs was limited by the availability of only one or two published articles for each, and incomplete psychometric evaluations in some cases. The tool demonstrating the strongest evidence was The Neurological Disorders Depression Inventory-Epilepsy for Youth. The ADHD Rating Scale-IV and The Paediatric Symptom Checklist -17 demonstrated good evidence in favour of at least two measurement properties. This review identified only a small number of mental health and neurodevelopmental PROMs evaluated specifically in paediatric epilepsy. There is a need for further validation of mental health and neurodevelopmental PROMs in children with epilepsy.

Minimum clinical utility standards for wearable seizure detectors: A simulation study.

OBJECTIVE: Epilepsy management employs self-reported seizure diaries, despite evidence of seizure underreporting. Wearable and implantable seizure detection devices are now becoming more widely available. There are no clear guidelines about what levels of accuracy are sufficient. This study aimed to simulate clinical use cases and identify the necessary level of accuracy for each. METHODS: Using a realistic seizure simulator (CHOCOLATES), a ground truth was produced, which was then sampled to generate signals from simulated seizure detectors of various capabilities. Five use cases were evaluated: (1) randomized clinical trials (RCTs), (2) medication adjustment in clinic, (3) injury prevention, (4) sudden unexpected death in epilepsy (SUDEP) prevention, and (5) treatment of seizure clusters. We considered sensitivity (0%-100%), false alarm rate (FAR; 0-2/day), and device type (external wearable vs. implant) in each scenario. RESULTS: The RCT case was efficient for a wide range of wearable parameters, though implantable devices were preferred. Lower accuracy wearables resulted in subtle changes in the distribution of patients enrolled in RCTs, and therefore higher sensitivity and lower FAR values were preferred. In the clinic case, a wide range of sensitivity, FAR, and device type yielded similar results. For injury prevention, SUDEP prevention, and seizure cluster treatment, each scenario required high sensitivity and yet was minimally influenced by FAR. SIGNIFICANCE: The choice of use case is paramount in determining acceptable accuracy levels for a wearable seizure detection device. We offer simulation results for determining and verifying utility for specific use case and specific wearable parameters.

Body composition estimates using a 2D image analysis system across different environmental conditions: An agreement study.

PURPOSE: This study examined the agreement between %Fat measurements using a smartphone-based application (IMAGE) across different environmental conditions. METHODS: A single reference image was obtained using an 8 MP smartphone camera under Ambient Light in front of a white background. Additional photos were obtained using a 0.7 MP, 5 MP, and 12 MP smartphone cameras; low-, moderate-, and bright-lighting conditions; and various color backgrounds including black, green, orange, and gray. RESULTS: %Fat measured using the 0.7 MP camera (27.8 ± 6.2 %Fat) was higher than the reference (26.8 ± 6.1 %Fat) (p < 0.001). The black (32.0 ± 12.0 %Fat), green (27.5 ± 6.3 %Fat), and gray (27.8 ± 6.3 %Fat) backgrounds yielded higher %Fat than the white (p = 0.03, 0.01, and 0.001). All camera, lighting, and background conditions were strongly correlated with the reference (all intraclass correlation coefficient [ICC] >0.98, all standard error of the estimate [SEE] <1.5 %Fat, all p < 0.001), except the black background which yielded poorer agreement with the white background (ICC = 0.69, SEE = 4.5%, p < 0.001). CONCLUSION: %Fat from IMAGE were strongly correlated across various environmental conditions.

Oxygen Saturation or Tissue Oxygen Determinations on Skin Whose Viability is at Risk.

The triad of ischaemia, neuropathy, and infection are among the principal causes of lower extremity wounds that are commonly prevalent in patients with diabetic foot (DF) a condition in which peripheral arterial disease commonly co-exists. The prevalence of this condition is increasing globally and with it, the mounting costs of its management. One aspect of management is saving limbs and or digits, a crucial part of this process is assessing tissue viability of skin which is a focus of this review: there are other aspects which are well described in the literature. Amputations are offered to limit the damage resulting from acute/chronic ischaemia. Holstein measured skin perfusion pressure using a radioisotope clearance technique to describe critically ischaemic skin; he found 30 mm Hg as the threshold above which healing may reliably be expected. Recent advances in vascular surgery and related technology have informed evidence-based advice to revascularize and save limbs; in practice, this may leave a wound in the distal skin unhealed; managing these raises questions of tissue viability. Much effort has been made to manage, prevent and to better understand these lower extremity wounds using measurements of tissue oxygen, oxygen saturation and skin imaging. The measurement techniques and their relevant merits are examined in this article. Advances in wound management systems and protocols can also facilitate the repair processes, and those which can have a particular impact on restoring or maintaining tissue perfusion are also discussed in the article.

Feasibility and acceptability of an ultra-long-term at-home EEG monitoring system (EEG@HOME) for people with epilepsy.

BACKGROUND: Recent technological advancements offer new ways to monitor and manage epilepsy. The adoption of these devices in routine clinical practice will strongly depend on patient acceptability and usability, with their perspectives being crucial. Previous studies provided feedback from patients, but few explored the experience of them using independently multiple devices independently at home. PURPOSE: The study, assessed through a mixed methods design, the direct experiences of people with epilepsy independently using a non-invasive monitoring system (EEG@HOME) for an extended duration of 6 months, at home. We aimed to investigate factors affecting engagement, gather qualitative insights, and provide recommendations for future home epilepsy monitoring systems. MATERIALS AND METHODS: Adults with epilepsy independently were trained to use a wearable dry EEG system, a wrist-worn device, and a smartphone app for seizure tracking and behaviour monitoring for 6 months at home. Monthly acceptability questionnaires (PSSUQ, SUS) and semi-structured interviews were conducted to explore participant experience. Adherence with the procedure, acceptability scores and systematic thematic analysis of the interviews, focusing on the experience with the procedure, motivation and benefits and opinion about the procedure were assessed. RESULTS: Twelve people with epilepsy took part into the study for an average of 193.8 days (range 61 to 312) with a likelihood of using the system at six months of 83 %. The e-diary and the smartwatch were highly acceptable and preferred to a wearable EEG system (PSSUQ score of 1.9, 1.9, 2.4). Participants showed an acceptable level of adherence with all solutions (Average usage of 63 %, 66 %, 92 %) reporting more difficulties using the EEG twice a day and remembering to complete the daily behavioural questionnaires. Clear information and training, continuous remote support, perceived direct and indirect benefits and the possibility to have a flexible, tailored to daily routine monitoring were defined as key factors to ensure compliance with long-term monitoring systems. CONCLUSIONS: EEG@HOME study demonstrated people with epilepsy' interest and ability in active health monitoring using new technologies. Remote training and support enable independent home use of new non-invasive technologies, but to ensure long term acceptability and usability systems will require to be integrated into patients' routines, include healthcare providers, and offer continuous support and personalized feedback.

Minimally invasive surgery for placement of a subcutaneous EEG implant.

Background: A new class of subcutaneous electroencephalography has enabled ultra long-term monitoring of people with epilepsy. The objective of this paper is to describe surgeons' experiences in an early series of implantations as well as discomfort or complications experienced by the participants. Methods: We included 38 implantation procedures from two trials on people with epilepsy and healthy adults. Questionnaires to assess surgeons' and participants' experience were analyzed as well as all recorded adverse events occurring up to 21 days post-surgery. Results: With training, the implantation could be performed in approximately 15 min. Overall, the implantation procedure was considered easy to perform with only 2 episodes where the implant got fixated in the introducing needle and a new implant had to be used. The explantation procedure was considered effortless. In 2 cases the silicone sheath covering the lead was damaged during the explantation, but it was possible to remove the entire implant without leaving any foreign body under the skin. Especially in the trial on healthy participants, a proportion experienced adverse events in the form of headache or implant-pain up to 21 days post-operatively. In 6 cases, adverse events contributed to the decision to explant and discontinue the study: Four of these cases involved implant pain or headache; One case involved a post-operative local infection; and in one case superficial lead placement resulted in skin perforation a few weeks after implantation. Conclusion: The implantation and explantation procedures are considered swift and easy to perform by both neurosurgeons and ENT surgeons. The implant is well tolerated by most participants. However, headache or pain around the implant can occur for up to 21 days post-operatively as anticipated with any such surgery. The expected benefits from the implant should always outweigh the potential disadvantages.

Study protocol for a case series: implementation and evaluation of an integrated mental and physical healthcare programme to screen for mental health symptoms in people with epilepsy.

INTRODUCTION: The prevalence of mental health symptoms in people with epilepsy (PWE) is elevated compared with that of the general population. These symptoms can negatively impact epilepsy management and patient outcomes but can be treated once recognised. It is, therefore, important to screen for these symptoms to identify needs and put in place appropriate support. Unfortunately, mental health symptoms are rarely addressed in epilepsy services due to time constraints, lack of resources and communication between psychological and medical professionals. These barriers can result in diagnostic overshadowing, where symptoms may be attributed to the disease and reduce the level of support PWE receive. Implementing an online screening tool embedded in the electronic health record (EHR) platform with supported referral pathways may remove some of these barriers. METHODS AND ANALYSIS: We will follow the Integrating Mental and Physical Healthcare: Research Training and Services framework, which is a routine clinical data collection tool used by clinical teams to electronically screen psychological symptoms among patients with long-term physical health conditions. Patient outcomes including mental health, physical health and psychosocial outcomes will be collected and uploaded to the EHR platform in real-time. An appropriate referral pathway will be recommended depending on severity of the outcome scores. We will initially pilot the tool for individuals aged 13 years and above through epilepsy clinics at King's College Hospital. Following this, the acceptability and feasibility of the tool will be assessed at baseline, 6 and 12 months. ETHICS AND DISSEMINATION: Ethics approval was obtained from the National Health Service Research Ethics Committee of South Central-Oxford C, reference: 21/EM/0205. This study is expected to inform the use of integrated electronic mental health screening for youth in epilepsy clinics and improve access to psychological support. The findings will be disseminated through academic peer-reviewed journals, poster presentations and scientific meetings.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Cyclical underreporting of seizures in patient-based seizure documentation.

OBJECTIVE: Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This study analyzes if patient reported seizures provide valid data on such cyclical occurrence. METHODS: We retrospectively studied if circadian cycles derived from patient-based reporting reflect the objective seizure documentation in 2003 patients undergoing in-patient video-EEG monitoring. RESULTS: Only 24.1% of more than 29000 seizures documented were accompanied by patient notifications. There was cyclical underreporting of seizures with a maximum during nighttime, leading to significant deviations in the circadian distribution of seizures. Significant cyclical deviations were found for focal epilepsies originating from both, frontal and temporal lobes, and for different seizure types (in particular, focal unaware and focal to bilateral tonic-clonic seizures). INTERPRETATION: Patient seizure diaries may reflect a cyclical reporting bias rather than the true circadian seizure distributions. Cyclical underreporting of seizures derived from patient-based reports alone may lead to suboptimal treatment schemes, to an underestimation of seizure-associated risks, and may pose problems for valid seizure forecasting. This finding strongly supports the use of objective measures to monitor cyclical distributions of seizures and for studies and treatment decisions based thereon.

A prospective 5-year longitudinal study detects neurocognitive and imaging correlates of seizure remission in self-limiting Rolandic epilepsy.

OBJECTIVE: Self-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child's life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. METHODS: At baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. RESULTS: Longitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044). There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words. Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. CONCLUSIONS: There is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories.

Background and Objectives: The prevalence and progression of respiratory muscle dysfunction in patients with limb girdle muscular dystrophies (LGMDs) has been only partially described to date. Most reports include cross-sectional data on a limited number of patients making it difficult to gain a wider perspective on respiratory involvement throughout the course of the disease and to compare the most prevalent LGMD subtypes. Methods: We reviewed the results of spirometry studies collected longitudinally in our cohort of patients in routine clinical visits from 2002 to 2020 along with additional clinical and genetic data. A linear mixed model was used to investigate the factors associated with the progression of respiratory dysfunction. Results: We followed up 156 patients with 5 different forms of LGMDs for a median of 8 years (range 1-25 years). Of them, 53 patients had pathogenic variants in the Capn3 gene, 47 patients in the Dysf gene, 24 patients in the Fkrp gene, 19 in the Ano5 gene, and 13 in one of the sarcoglycan genes (SCG). At baseline, 58 patients (37.1%) had a forced vital capacity percentage predicted (FVCpp) below 80%, while 14 patients (8.9%) had peak cough flow (PCF) values below 270 L/min. As a subgroup, FKRP was the group with a higher number of patients having FVC <80% and/or PCF <270 L/min at initial assessment (66%). We observed a progressive decline in FVCpp and PCF measurements over time, being age, use of wheelchair, and LGMD subtype independent factors associated with this decline. Fkrp and sarcoglycan patients had a quicker decline in their FVC (Kaplan-Meier curve, F test, p < 0.001 and p = 0.02, respectively). Only 7 of the 58 patients with low FVCpp values reported symptoms of respiratory dysfunction, which are commonly reported by patients with FVCpp below 50%-60%. The number of patients ventilated increased from 2 to 8 during follow-up. Discussion: Respiratory dysfunction is a frequent complication of patients with LGMDs that needs to be carefully studied and has direct implications in the care offered in daily clinics. Respiratory dysfunction is associated with disease progression because it is especially seen in patients who are full-time wheelchair users, being more frequent in patients with mutations in the Fkrp and sarcoglycan genes.

Forecasting seizure likelihood from cycles of self-reported events and heart rate: a prospective pilot study.

BACKGROUND: Seizure risk forecasting could reduce injuries and even deaths in people with epilepsy. There is great interest in using non-invasive wearable devices to generate forecasts of seizure risk. Forecasts based on cycles of epileptic activity, seizure times or heart rate have provided promising forecasting results. This study validates a forecasting method using multimodal cycles recorded from wearable devices. METHOD: Seizure and heart rate cycles were extracted from 13 participants. The mean period of heart rate data from a smartwatch was 562 days, with a mean of 125 self-reported seizures from a smartphone app. The relationship between seizure onset time and phases of seizure and heart rate cycles was investigated. An additive regression model was used to project heart rate cycles. The results of forecasts using seizure cycles, heart rate cycles, and a combination of both were compared. Forecasting performance was evaluated in 6 of 13 participants in a prospective setting, using long-term data collected after algorithms were developed. FINDINGS: The results showed that the best forecasts achieved a mean area under the receiver-operating characteristic curve (AUC) of 0.73 for 9/13 participants showing performance above chance during retrospective validation. Subject-specific forecasts evaluated with prospective data showed a mean AUC of 0.77 with 4/6 participants showing performance above chance. INTERPRETATION: The results of this study demonstrate that cycles detected from multimodal data can be combined within a single, scalable seizure risk forecasting algorithm to provide robust performance. The presented forecasting method enabled seizure risk to be estimated for an arbitrary future period and could be generalised across a range of data types. In contrast to earlier work, the current study evaluated forecasts prospectively, in subjects blinded to their seizure risk outputs, representing a critical step towards clinical applications. FUNDING: This study was funded by an Australian Government National Health & Medical Research Council and BioMedTech Horizons grant. The study also received support from the Epilepsy Foundation of America's 'My Seizure Gauge' grant.

Perceived seizure risk in epilepsy: Chronic electronic surveys with and without concurrent electroencephalography.

OBJECTIVE: Previous studies suggested that patients with epilepsy might be able to forecast their own seizures. This study aimed to assess the relationships between premonitory symptoms, perceived seizure risk, and future and recent self-reported and electroencephalographically (EEG)-confirmed seizures in ambulatory patients with epilepsy in their natural home environments. METHODS: Long-term e-surveys were collected from patients with and without concurrent EEG recordings. Information obtained from the e-surveys included medication adherence, sleep quality, mood, stress, perceived seizure risk, and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed-effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with the seizure forecasting classifiers and device forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC). RESULTS: Fifty-four subjects returned 10 269 e-survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed that increased stress (OR = 2.01, 95% confidence interval [CI] = 1.12-3.61, AUC = .61, p = .02) was associated with increased relative odds of future self-reported seizures. Multivariate analysis showed that previous self-reported seizures (OR = 5.37, 95% CI = 3.53-8.16, AUC = .76, p < .001) were most strongly associated with future self-reported seizures, and high perceived seizure risk (OR = 3.34, 95% CI = 1.87-5.95, AUC = .69, p < .001) remained significant when prior self-reported seizures were added to the model. No correlation with medication adherence was found. No significant association was found between e-survey responses and subsequent EEG seizures. SIGNIFICANCE: Our results suggest that patients may tend to self-forecast seizures that occur in sequential groupings and that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self-predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.