Time to prerandomization seizure count design sufficiently assessed the safety and tolerability of perampanel for the treatment of primary generalized tonic-clonic seizures.

OBJECTIVE: Static assignment of participants in randomized clinical trials to placebo or ineffective treatment confers risk from continued seizures. An alternative trial design of time to exceed prerandomization monthly seizure count (T-PSC) has replicated the efficacy conclusions of traditionally designed trials, with shorter exposure to placebo and ineffective treatment. Trials aim to evaluate efficacy as well as safety and tolerability; therefore, we evaluated whether this T-PSC design also could replicate the trial's safety and tolerability conclusions. METHODS: We retrospectively applied the T-PSC design to analyze treatment-emergent adverse events (TEAEs) from a blinded, placebo-controlled trial of perampanel for primary generalized tonic-clonic seizures (NCT01393743). The safety analysis set consisted of 81 and 82 participants randomized to perampanel and placebo arms, respectively. We evaluated the incidences of TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs of special interest that occurred before T-PSC relative to those observed during the full-length trial. RESULTS: Of the 67 and 59 participants who experienced TEAEs in the perampanel and placebo arms during full-length trial, 66 (99%) and 54 (92%) participants experienced TEAEs with onset occurring before T-PSC, respectively. When limited to treatment-related TEAEs, 55 of 56 (98%) and 32 of 37 (86%) participants reported treatment-related TEAEs that occurred before T-PSC in the perampanel and placebo arms, respectively. There were more TEAEs after T-PSC with placebo as compared to perampanel (Fisher exact odds ratio = 8.6, p = .035), which resulted in overestimation of the difference in TEAE rate. There was a numerical reduction in serious TEAEs (3/13 occurred after T-PSC, one in placebo and two in perampanel). SIGNIFICANCE: Almost all TEAEs occurred before T-PSC. More treatment-related TEAEs occurred after T-PSC for participants randomized to placebo than perampanel, which may be due to either a shorter T-PSC or delayed time to TEAE for placebo.

Detection of focal to bilateral tonic-clonic seizures using a connected shirt.

OBJECTIVE: This study was undertaken to develop and evaluate a machine learning-based algorithm for the detection of focal to bilateral tonic-clonic seizures (FBTCS) using a novel multimodal connected shirt. METHODS: We prospectively recruited patients with epilepsy admitted to our epilepsy monitoring unit and asked them to wear the connected shirt while under simultaneous video-electroencephalographic monitoring. Electrocardiographic (ECG) and accelerometric (ACC) signals recorded with the connected shirt were used for the development of the seizure detection algorithm. First, we used a sliding window to extract linear and nonlinear features from both ECG and ACC signals. Then, we trained an extreme gradient boosting algorithm (XGBoost) to detect FBTCS according to seizure onset and offset annotated by three board-certified epileptologists. Finally, we applied a postprocessing step to regularize the classification output. A patientwise nested cross-validation was implemented to evaluate the performances in terms of sensitivity, false alarm rate (FAR), time in false warning (TiW), detection latency, and receiver operating characteristic area under the curve (ROC-AUC). RESULTS: We recorded 66 FBTCS from 42 patients who wore the connected shirt for a total of 8067 continuous hours. The XGBoost algorithm reached a sensitivity of 84.8% (56/66 seizures), with a median FAR of .55/24 h and a median TiW of 10 s/alarm. ROC-AUC was .90 (95% confidence interval = .88-.91). Median detection latency from the time of progression to the bilateral tonic-clonic phase was 25.5 s. SIGNIFICANCE: The novel connected shirt allowed accurate detection of FBTCS with a low false alarm rate in a hospital setting. Prospective studies in a residential setting with a real-time and online seizure detection algorithm are required to validate the performance and usability of this device.

Multiple back fractures as a result of the first seizure.

Non-traumatic fractures due to seizures are an overlooked diagnostic group. It is well known that patients with generalized tonic-clonic seizures have an increased trauma risk. However, the cause of fracture is rarely due to the violent forces of muscle contractions. Usually, the primary patient examination focuses on the aetiology of the seizure, which sometimes delays the diagnosis of fractures. This is a case report of a 19-year-old woman who sustained three compression fractures of the thoracic spine due to a generalized tonic-clonic seizure, and a discussion of the diagnostic challenges in such a rare case.

Prospective study of epilepsy with generalized tonic-clonic seizures alone: Clinical features, response to treatment, and likelihood of medication withdrawal.

OBJECTIVE: This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic-clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. METHODS: The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new-onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3-h sleep-deprived video-EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow-up. Cumulative time-dependent probabilities of seizure recurrence were calculated using Kaplan-Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. RESULTS: Eighty-nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike-wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient-initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post-ASM discontinuation. SIGNIFICANCE: Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure-free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician-initiated tapering. PLAIN LANGUAGE SUMMARY: Seizures in individuals diagnosed with "epilepsy with generalized tonic-clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision.

Continuous cardiac monitoring in epilepsy: an implantable loop manual activation algorithm for improving ECG signal acquisition accuracy.

BACKGROUND: The muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here. METHODS: One hundred ninety-three patients (18-60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness. RESULTS: Six thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p < 0.0001). Person-activated false-positive events were observed in 30.5% of patients with focal impaired awareness seizures and 27.7% in patients with bilateral tonic-clonic seizures. The highest rate of false-positive events (61.5%) was detected in patients undergoing epileptic status, and the lowest rate (3.8%) - was in patients with focal onset aware seizures. The rate of false-positive events was significantly higher in patients with impaired awareness seizures without aura both in focal impaired awareness (45.5% vs. 19.3%, p < 0.0001) and bilateral tonic-clonic seizure groups (38.8% vs. 5.9%, p < 0.0001). CONCLUSIONS: Arrhythmias with varying clinical outcomes are expected in epilepsy patients and have been monitored continuously. The specified loop recorder external activation algorithm can improve the clinically relevant cardiac arrhythmia detection accuracy in epilepsy patients and the value of future studies.

Mapping progressive damage epicenters in epilepsy with generalized tonic-clonic seizures by causal structural covariance network density (CaSCNd).

AIMS: Mapping progressive patterns of structural damage in epilepsies with idiopathic and secondarily generalized tonic-clonic seizures with causal structural covariance networks and multiple analysis strategies. METHODS: Patients with idiopathic generalized tonic-clonic seizures (IGTCS) (n = 114) and secondarily generalized tonic-clonic seizures (SGTCS) (n = 125) were recruited. Morphometric parameter of gray matter volume was analyzed on structural MRI. Structural covariance network based on granger causality analysis (CaSCN) was performed on the cross-sectional morphometric data sorted by disease durations of patients. Seed-based CaSCN analysis was firstly carried out to map the progressive and influential patterns of damage to thalamus-related structures. A novel technique for voxel-based CaSCN density (CaSCNd) analysis was further proposed, enabling for identifying the epicenter of structural brain damage during the disease process. RESULTS: The thalamus-associated CaSCNs demonstrated different patterns of progressive damage in two types of generalized tonic-clonic seizures. In IGTCS, the structural damage was predominantly driven from the thalamus, and expanded to the cortex, while in SGTCS, the damage was predominantly driven from the cortex, and expanded to the thalamus through the basal ganglia. CaSCNd analysis revealed that the IGTCS had an out-effect epicenter in the thalamus, whereas the SGTCS had equipotent in- and out-effects in the thalamus, cortex, and basal ganglia. CONCLUSION: CaSCN revealed distinct damage patterns in the two types of GTCS, featuring with measurement of structural brain damage from the accumulating effect over a relatively long time period. Our work provided evidence for understanding network impairment mechanism underlying different GTCSs.

Focal electroclinical features in generalized tonic-clonic seizures: Decision flowchart for a diagnostic challenge.

OBJECTIVE: Bilateral tonic-clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal EEG or semiology. METHODS: We retrospectively analyzed video-EEG recordings of 101 bilateral tonic-clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1-year follow-up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. RESULTS: Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7-Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal features with an accuracy of 96.6%. SIGNIFICANCE: Focal semiology associated with bilateral tonic-clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies.

The role of angiotensin receptor blockers in treating epilepsy: a review.

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. METHODS: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. RESULTS: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. SIGNIFICANCE: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Long-term treatment with ganaxolone for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder: Two-year open-label extension follow-up.

OBJECTIVE: In the placebo-controlled, double-blind phase of the Marigold study (NCT03572933), ganaxolone significantly reduced major motor seizure frequency (MMSF) in patients with cyclin-dependent kinase-like 5 deficiency disorder (CDD). We report 2-year safety and clinical outcomes data from the open-label extension (OLE) phase of Marigold. METHODS: Patients with CDD who completed the double-blind phase were eligible to continue in the OLE. Efficacy assessments included MMSF reduction from prerandomization baseline, responder rates, and Clinical Global Impression-Improvement scores, including assessment of seizure intensity and duration (CGI-CSID). Safety assessments included treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. RESULTS: Of 101 patients who enrolled in Marigold, 88 (87.1%) entered the OLE (median age = 5 years, 79.5% female). Median 28-day MMSF at baseline was 50.6. At 2 years in the OLE (months 22-24), MMSF was reduced by a median of 48.2% (n = 50); when missing data were imputed, median reduction in MMSF was 43.8% using a mixed effects model and 27.4% using a last observation carried forward model. During months 22-24, 23 of 50 (46.0%) patients experienced reductions in MMSF of ≥50%; 12 of 50 (24.0%) patients experienced MMSF reductions of ≥75%. During months 22-24, 40 of 49 (81.6%) patients were rated by caregivers as having improvement in seizure-related outcomes based on CGI-CSID scores. Thirty-seven patients discontinued ganaxolone due to lack of efficacy (n = 13), withdrawal by caregiver (n = 12), adverse event (n = 10), physician decision (n = 1), or death (n = 1; unrelated to study drug). The most common treatment-related TEAEs were somnolence (17.0%), seizure (11.4%), and decreased appetite (5.7%). Patients reported serious TEAEs (n = 28, 31.8%); those reported in ≥3% of patients were seizure (n = 6), pneumonia (n = 5), acute respiratory failure (n = 3), aspiration pneumonia (n = 3), and dehydration (n = 3). SIGNIFICANCE: Sustained reductions in MMSF at 2 years in the OLE support the efficacy of ganaxolone in seizures associated with CDD. Safety findings in the OLE were consistent with the double-blind phase.

Idiopathic generalized epilepsy with phantom absences, absence status, and generalized tonic-clonic seizures: A case report.

RATIONALE: Phantom absences refer to mild and short-lasting absence seizures, which are usually accompanied by infrequent generalized tonic-clonic seizures and absence status. Generally, phantom absences do not impair the individual neurological functions. Herein, we report the case of a young woman with idiopathic generalized epilepsy, phantom absences, absence status, and generalized tonic-clonic seizures. PATIENT CONCERNS: A 31-year-old woman presented with a 16-year history of paroxysmal convulsions. DIAGNOSES: Electroencephalogram (EEG) showed recurrent universal and synchronized 3~4 Hz spike waves and spike-slow waves in the interictal phase with normal background activity. During the ictal phases, EEG revealed bursts of 3~4 Hz spike waves and spike-slow waves that were universal, synchronized, and symmetrical. Additionally, there was 1 seizure episode induced by a 3-Hz flash in the current case. Based on these findings, a diagnosis of idiopathic generalized epilepsy was made. INTERVENTIONS: The patient was treated with oral sodium valproate, and the epileptic seizures were controlled. OUTCOMES: The frequency of absence seizures was significantly reduced and there were no generalized tonic-clonic seizures. LESSONS: Idiopathic generalized epilepsy with phantom absences, absence status, and generalized tonic-clonic seizures is an extremely rare condition. EEG is the exclusive method for diagnosis. Antiepileptic drugs are effective for controlling epileptic seizures in this disease.

Bilateral Posterior Fracture-Dislocation of the Shoulders Secondary to Uremic Encephalopathy.

Bilateral posterior fracture-dislocation of the shoulder is an uncommon injury pattern usually caused by epileptic seizures. The cause of the seizure activity remains unknown in most cases, although the injury has been associated with several conditions. A 59-year-old man with uncontrolled hypertension presented with new-onset generalized tonic-clonic seizures. He was diagnosed with uremic encephalopathy and bilateral posterior fracture-dislocation of his shoulders. His medical condition required stabilization leading to a delay in definitive surgery and a subsequent poor outcome. This case highlights the previously unknown association between bilateral fracture-dislocation of the shoulders and seizures caused by uremic encephalopathy. In these complex situations with competing clinical priorities, it is important to initiate prompt treatment of the cause in any new-onset seizures, to facilitate expedient surgical management of the orthopaedic injury.

Non-electroencephalogram-based seizure detection devices: State of the art and future perspectives.

INTRODUCTION AND PURPOSE: The continuously expanding research and development of wearable devices for automated seizure detection in epilepsy uses mostly non-invasive technology. Real-time alarms, triggered by seizure detection devices, are needed for safety and prevention to decrease seizure-related morbidity and mortality, as well as objective quantification of seizure frequency and severity. Our review strives to provide a state-of-the-art on automated seizure detection using non-invasive wearable devices in an ambulatory (home) environment and to highlight the prospects for future research. METHODS: A joint working group of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) recently published a clinical practice guideline on automated seizure detection using wearable devices. We updated the systematic literature search for the period since the last search by the joint working group. We selected studies qualifying minimally as phase-2 clinical validation trials, in accordance with standards for testing and validation of seizure detection devices. RESULTS: High-level evidence (phases 3 and 4) is available only for the detection of tonic-clonic seizures and major motor seizures when using wearable devices based on accelerometry, surface electromyography (EMG), or a multimodal device combining accelerometry and heart rate. The reported sensitivity of these devices is 79.4-96%, with a false alarm rate of 0.20-1.92 per 24 hours (0-0.03 per night). A single phase-3 study validated the detection of absence seizures using a single-channel wearable EEG device. Two phase-4 studies showed overall user satisfaction with wearable seizure detection devices, which helped decrease injuries related to tonic-clonic seizures. Overall satisfaction, perceived sensitivity, and improvement in quality-of-life were significantly higher for validated devices. CONCLUSIONS: Among the vast number of studies published on seizure detection devices, most are strongly affected by potential bias, providing a too-optimistic perspective. By applying the standards for clinical validation studies, potential bias can be reduced, and the quality of a continuously growing number of studies in this field can be assessed and compared. The ILAE-IFCN clinical practice guideline on automated seizure detection using wearable devices recommends using clinically validated wearable devices for automated detection of tonic-clonic seizures when significant safety concerns exist. The studies published after the guideline was issued only provide incremental knowledge and would not change the current recommendations.

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA). METHODS: Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG. RESULTS: Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p = 0.004). SIGNIFICANCE: Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Derailment of Sleep Homeostatic Plasticity Affects the Most Plastic Brain Systems and Carries the Risk of Epilepsy.

Although a critical link between non-rapid eye movement (NREM) sleep and epilepsy has long been suspected, the interconnecting mechanisms have remained obscure. However, recent advances in sleep research have provided some clues. Sleep homeostatic plasticity is now recognized as an engine of the synaptic economy and a feature of the brain's ability to adapt to changing demands. This allows epilepsy to be understood as a cost of brain plasticity. On the one hand, plasticity is a force for development, but on the other it opens the possibility of epileptic derailment. Here, we provide a summary of the phenomena that link sleep and epilepsy. The concept of "system epilepsy", or epilepsy as a network disease, is introduced as a general approach to understanding the major epilepsy syndromes, i.e., epilepsies building upon functional brain networks. We discuss how epileptogenesis results in certain major epilepsies following the derailment of NREM sleep homeostatic plasticity. Post-traumatic epilepsy is presented as a general model for this kind of epileptogenesis.

Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.

Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.