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 (Byteflies) was used to measure behind-the-ear EEG, electromyography (EMG), electrocardiography, accelerometry (ACC) and gyroscope. 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.Results. Wearable EEG outperformed the other single modalities with a sensitivity of 100% and a FPR of 10.3/24 h. The combination of wearable EEG and EMG proved most clinically useful, delivering a sensitivity of 97.7%, an FPR of 0.4/24 h, 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 0.1/24 h, 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.

Automated sleep staging on reduced channels in children with epilepsy.

Objectives: This study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy (WCE), and with drug-resistant epilepsy (DRE). Methods: Overnight video-EEG, along with electrooculogram (EOG) and chin electromyogram (EMG), was recorded in children between 4 and 18 years of age. Classical sleep staging was performed manually as a ground truth. An end-to-end hierarchical recurrent neural network for sequence-to-sequence automatic sleep staging (SeqSleepNet) was used to perform automated sleep staging using three channels: C4-A1, EOG, and chin EMG. Results: In 176 children sleep stages were manually scored: 47 children without epilepsy, 74 with WCE, and 55 with DRE. The 5-class sleep staging accuracy of the automatic sleep staging algorithm was 84.7% for the children without epilepsy, 83.5% for those with WCE, and 80.8% for those with DRE (Kappa of 0.79, 0.77, and 0.73 respectively). Performance per sleep stage was assessed with an F1 score of 0.91 for wake, 0.50 for N1, 0.83 for N2, 0.84 for N3, and 0.86 for rapid eye movement (REM) sleep. Conclusion: We concluded that the tested algorithm has a high accuracy in children without epilepsy and with WCE. Performance in children with DRE was acceptable, but significantly lower, which could be explained by a tendency of more time spent in N1, and by abundant interictal epileptiform discharges and intellectual disability leading to less recognizable sleep stages. REM sleep time, however, significantly affected in children with DRE, can be detected reliably by the algorithm.Clinical trial registration: ClinicalTrials.gov, identifier NCT04584385.

Wearable detection of tonic seizures in childhood epilepsy: An exploratory cohort study.

OBJECTIVE: To investigate the performance of a multimodal wearable device for the offline detection of tonic seizures (TS) in a pediatric childhood epilepsy cohort, with a focus on patients with Lennox-Gastaut syndrome. METHODS: Parallel with prolonged video-electroencephalography (EEG), the Plug 'n Patch system, a multimodal wearable device using the Sensor Dot and replaceable electrode adhesives, was used to detect TS. Multiple biosignals were recorded: behind-the-ear EEG, surface electromyography, electrocardiography, and accelerometer/gyroscope. Biosignals were annotated blindly by a neurologist. Seizure characteristics were described, and performance was assessed by sensitivity, positive predictive value (PPV), F1 score, and false alarm rate (FAR) per hour. Performance was compared to seizure diaries kept by the caretaker. RESULTS: Ninety-nine TS were detected in 13 patients. Seven patients (54%) had Lennox-Gastaut syndrome and six patients (46%) had other forms of (developmental) epileptic encephalopathies or drug-resistant epilepsy. All but one patient had intellectual disability. Overall sensitivity was 41%, with a PPV of 9%, an F1 score of 14%, and a median FAR per hour of 0.75. Performance increased to an F1 score of 66% for nightly seizures lasting at least 10 s (sensitivity 66%, PPV 66%) and 71% for nightly seizures lasting at least 20 s (sensitivity 62%, PPV 82%). For these seizures there were no false alarms in 10 of 13 patients. Sensitivity of seizure diaries reached a maximum of 52% for prolonged (≥20 s) nightly seizures, even though caretakers slept in the same room. SIGNIFICANCE: We showed that it is feasible to use a multimodal wearable device with multiple adhesive sites in children with epilepsy and intellectual disability. For prolonged nightly seizures, offline manual detection of TS outperformed seizure diaries. The recognition of seizure-specific signatures using multiple modalities can help in the development of automated TS detection algorithms.

A novel GABRG2 variant in Sunflower syndrome: A case report and video EEG monitoring.

OBJECTIVE: Sunflower syndrome is a unique photosensitive epilepsy, characterized by heliotropism and stereotyped seizures associated with handwaving. These handwaving events (HWE) are thought to be an ictal phenomenon, although current data are contrasting. Photosensitive epilepsy occurs in 2%-5% of the epilepsy forms and several pathogenic gene variants have been associated with photosensitive epilepsy. However, the genetic etiology of Sunflower syndrome remains unknown. Antiseizure medications (ASM) efficacious in treating photosensitive epilepsy are valproic acid (VPA) and levetiracetam (LEV) although some forms, such as Sunflower syndrome, can be drug-resistant. METHODS AND RESULTS: Here, we report an 8-year-old boy with an early onset of episodes of HWE that was initially categorized as behavioral problems for which risperidone was started. However, the medical history was suggestive of Sunflower syndrome, and subsequent video EEG showed focal mostly temporal and frontotemporal (right and left) epileptiform activity and confirmed the epileptic nature of the HWE. Thus, VPA was started and initially led to seizure frequency reduction. Molecular analyses showed a pathogenic variant in GABRG2 (c.1287G>A p.(Trp429Ter)), which has been associated with photosensitive and generalized epilepsy. SIGNIFICANCE: Overall, clinicians worldwide should be cautious by interpreting HWE and/or other tic-like movements, since an epileptic origin cannot be ruled out. A prompt and correct diagnosis can be made by performing a video EEG early on in the diagnostic process when epileptic seizures are part of the differential diagnosis. Even though the genetic etiology of Sunflower syndrome remains poorly understood, this constellation supports further genetic testing since the detection of a pathogenic variant can help in making correct decisions regarding ASM management.

Automated detection of absence seizures using a wearable electroencephalographic device: a phase 3 validation study and feasibility of automated behavioral testing.

OBJECTIVE: Our primary goal was to measure the accuracy of fully automated absence seizure detection, using a wearable electroencephalographic (EEG) device. As a secondary goal, we also tested the feasibility of automated behavioral testing triggered by the automated detection. METHODS: We conducted a phase 3 clinical trial (NCT04615442), with a prospective, multicenter, blinded study design. The input was the one-channel EEG recorded with dry electrodes embedded into a wearable headband device connected to a smartphone. The seizure detection algorithm was developed using artificial intelligence (convolutional neural networks). During the study, the predefined algorithm, with predefined cutoff value, analyzed the EEG in real time. The gold standard was derived from expert evaluation of simultaneously recorded full-array video-EEGs. In addition, we evaluated the patients' responsiveness to the automated alarms on the smartphone, and we compared it with the behavioral changes observed in the clinical video-EEGs. RESULTS: We recorded 102 consecutive patients (57 female, median age = 10 years) on suspicion of absence seizures. We recorded 364 absence seizures in 39 patients. Device deficiency was 4.67%, with a total recording time of 309 h. Average sensitivity per patient was 78.83% (95% confidence interval [CI] = 69.56%-88.11%), and median sensitivity was 92.90% (interquartile range [IQR] = 66.7%-100%). The average false detection rate was .53/h (95% CI = .32-.74). Most patients (n = 66, 64.71%) did not have any false alarms. The median F1 score per patient was .823 (IQR = .57-1). For the total recording duration, F1 score was .74. We assessed the feasibility of automated behavioral testing in 36 seizures; it correctly documented nonresponsiveness in 30 absence seizures, and responsiveness in six electrographic seizures. SIGNIFICANCE: Automated detection of absence seizures with a wearable device will improve seizure quantification and will promote assessment of patients in their home environment. Linking automated seizure detection to automated behavioral testing will provide valuable information from wearable devices.

Fulminant Wilson Disease in Children: Recovery After Plasma Exchange Without Transplantation.

OBJECTIVES: Since 2005, a New Wilson Index (NWI) ≥11 is used as a predictor of death without transplantation in fulminant Wilson disease (WD). Plasma exchange is advocated as a new treatment modality. METHODS: We present a patient with fulminant WD treated with plasma exchange. All published cases applying plasma exchange for fulminant WD were reviewed systematically. RESULTS: A 14-year-old girl presented with hemolysis and fulminant liver failure. She had no encephalopathy; NWI was 14. As a bridge to transplantation plasma exchange was started immediately. Complete remission was achieved with plasma exchange and later chelation therapy with D-penicillamine. She is now at 3-year transplant-free survival. Literature review identified 37 patients presenting with fulminant WD and NWI ≥11 who were treated with plasma exchange. Seventeen of these patients (ie, 46%) recovered without transplantation. CONCLUSIONS: Multiple case reports and case series demonstrate transplant free survival after plasma exchange and subsequent chelation therapy, despite a NWI ≥11. Plasma exchange affects the clinical course and is a therapeutic option in children and young adults presenting with fulminant WD.

The migration percentage measured on EOS® standing full-leg radiographs: equivalent and advantageous in ambulant children with cerebral palsy.

BACKGROUND: During ambulatory follow-up of patients with cerebral palsy (CP) systematic radiographic screening is required firstly to evaluate hip migration and development in the prevention of hip dislocation and secondly to analyse lower limb alignment and leg length. The Migration Percentage (MP) is a radiographic measurement used to describe the extent of femoral head lateralisation on conventional supine pelvic radiographs. Our goal was to assess the comparability of the MP measured on low radiation dose EOS® standing full-leg radiographs with that of conventional supine pelvic radiographs. METHODS: Patients presenting with CP were prospectively selected from our outpatient follow-up consultation at our institutions CP reference centre and underwent conventional supine pelvic and EOS® standing full-leg radiographs the same day for diagnostic and screening reasons. RESULTS: Out of 28 prospectively selected patients we included 21 (42 hips), of which 10 were female, with a mean age of 9.25 years and GMFCS levels of I, II and III. Seven out of 28 patients were excluded due to insufficient quality of radiographic images. The absolute differences in MP measured on both conventional supine pelvic and EOS® standing full-leg radiographs ranged between - 8 and 6% with an absolute mean difference of 0% (SD ±3.5) and were not statistically significant (p = 0.99). A Bland-Altman plot showed acceptable agreement between both measurements without proportional bias. CONCLUSION: There is no statistical significant difference between the Migration Percentage measured on conventional supine pelvic radiographs and EOS® standing full-leg radiographs in ambulant patients. These images use lower radiation doses and contain more radiographic information. TRIAL REGISTRATION: Approved by the Medical Research Ethics committee of the University Hospitals Leuven ( MP001492 ).