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1.
Ugeskr Laeger ; 186(17)2024 Apr 22.
Article in Danish | MEDLINE | ID: mdl-38704711

ABSTRACT

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.


Subject(s)
Fractures, Compression , Spinal Fractures , Thoracic Vertebrae , Humans , Female , Spinal Fractures/diagnostic imaging , Spinal Fractures/complications , Spinal Fractures/diagnosis , Young Adult , Fractures, Compression/diagnostic imaging , Fractures, Compression/etiology , Fractures, Compression/diagnosis , Fractures, Compression/complications , Thoracic Vertebrae/injuries , Thoracic Vertebrae/diagnostic imaging , Seizures/etiology , Seizures/diagnosis , Fractures, Multiple/diagnostic imaging , Tomography, X-Ray Computed , Epilepsy, Tonic-Clonic/etiology , Epilepsy, Tonic-Clonic/diagnosis
2.
Brain Res ; 1828: 148766, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38242522

ABSTRACT

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.


Subject(s)
Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Epilepsy , Humans , Cross-Sectional Studies , Seizures , Cerebral Cortex , Gray Matter , Magnetic Resonance Imaging/methods , Epilepsy, Generalized/diagnostic imaging
3.
Epilepsia ; 65(3): 725-738, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38279904

ABSTRACT

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.


Subject(s)
Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Humans , Retrospective Studies , Software Design , Seizures/diagnosis , Epilepsy, Generalized/diagnosis , Epilepsy, Generalized/drug therapy , Electroencephalography , Immunoglobulin E/therapeutic use
4.
BMC Cardiovasc Disord ; 24(1): 42, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38218796

ABSTRACT

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.


Subject(s)
Epilepsy, Tonic-Clonic , Epilepsy , Humans , Epilepsy, Tonic-Clonic/diagnosis , Seizures/diagnosis , Arrhythmias, Cardiac , Algorithms , Electrocardiography
5.
Epilepsia ; 65(1): 37-45, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37950390

ABSTRACT

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.


Subject(s)
Anticonvulsants , Epilepsy, Tonic-Clonic , Epileptic Syndromes , Pregnanolone/analogs & derivatives , Spasms, Infantile , Humans , Female , Child, Preschool , Male , Anticonvulsants/adverse effects , Follow-Up Studies , Treatment Outcome , Seizures/drug therapy , Seizures/chemically induced , Epilepsy, Tonic-Clonic/drug therapy , Double-Blind Method , Cyclin-Dependent Kinases/therapeutic use
6.
Neurol Sci ; 45(4): 1437-1445, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38079018

ABSTRACT

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.


Subject(s)
Epilepsies, Partial , Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Epilepsy , Humans , Anticonvulsants/therapeutic use , Epilepsy, Tonic-Clonic/chemically induced , Epilepsy, Tonic-Clonic/drug therapy , Carbamazepine/adverse effects , Angiotensin Receptor Antagonists/therapeutic use , Epilepsy, Generalized/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Epilepsy/drug therapy
7.
Epilepsia ; 65(1): 84-94, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37872695

ABSTRACT

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.


Subject(s)
Epilepsies, Partial , Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Glucosides , Thiazoles , Humans , Anticonvulsants/therapeutic use , Carbamazepine/therapeutic use , Prognosis , Retrospective Studies , Epilepsies, Partial/drug therapy , Epilepsy, Generalized/diagnosis , Epilepsy, Generalized/drug therapy , Seizures/diagnosis , Seizures/drug therapy , Recurrence , Immunoglobulin E/therapeutic use , Epilepsy, Tonic-Clonic/drug therapy
8.
Medicine (Baltimore) ; 102(45): e35601, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37960785

ABSTRACT

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.


Subject(s)
Epilepsy, Absence , Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Status Epilepticus , Female , Humans , Adult , Epilepsy, Generalized/diagnosis , Epilepsy, Generalized/drug therapy , Seizures/diagnosis , Seizures/drug therapy , Seizures/etiology , Epilepsy, Absence/diagnosis , Epilepsy, Absence/drug therapy , Epilepsy, Absence/complications , Status Epilepticus/complications , Valproic Acid/therapeutic use , Electroencephalography , Epilepsy, Tonic-Clonic/diagnosis , Epilepsy, Tonic-Clonic/drug therapy
9.
Epilepsy Behav ; 148: 109486, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37857030

ABSTRACT

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.


Subject(s)
Epilepsy, Absence , Epilepsy, Tonic-Clonic , Wearable Electronic Devices , Humans , Seizures/diagnosis , Electroencephalography
10.
Epilepsia ; 64(12): 3307-3318, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37857465

ABSTRACT

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.


Subject(s)
Epilepsies, Partial , Epilepsy, Tonic-Clonic , Epilepsy , Sleep Apnea, Central , Humans , Sleep Apnea, Central/diagnostic imaging , Sleep Apnea, Central/etiology , Seizures , Epilepsies, Partial/diagnostic imaging , Epilepsies, Partial/complications , Electroencephalography/methods , Amygdala/diagnostic imaging , Apnea
12.
Article in English | MEDLINE | ID: mdl-37796759

ABSTRACT

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.


Subject(s)
Epilepsy, Tonic-Clonic , Fracture Dislocation , Joint Dislocations , Shoulder Dislocation , Shoulder Fractures , Male , Humans , Middle Aged , Shoulder , Shoulder Dislocation/diagnosis , Shoulder Dislocation/etiology , Shoulder Dislocation/surgery , Shoulder Fractures/complications , Shoulder Fractures/diagnostic imaging , Joint Dislocations/complications , Seizures/complications , Epilepsy, Tonic-Clonic/complications , Fracture Dislocation/complications
13.
J Integr Neurosci ; 22(5): 111, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37735129

ABSTRACT

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.


Subject(s)
Epilepsy, Tonic-Clonic , Epilepsy , Epileptic Syndromes , Humans , Brain , Sleep
16.
J Child Neurol ; 38(8-9): 505-512, 2023 08.
Article in English | MEDLINE | ID: mdl-37461321

ABSTRACT

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.


Subject(s)
Epilepsies, Myoclonic , Epilepsy, Absence , Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Child , Humans , Child, Preschool , Epilepsy, Absence/diagnosis , Syndrome , Seizures/diagnosis , Seizures/complications , Epilepsies, Myoclonic/complications , Prognosis , Electroencephalography , Epilepsy, Tonic-Clonic/complications
17.
Epilepsy Res ; 194: 107178, 2023 08.
Article in English | MEDLINE | ID: mdl-37295319

ABSTRACT

Video/cortical electroencephalography (EEG) is monitored to assess progressive severity of generalized tonic clonic seizures (GTCSs) in a transgenic mouse model of adult-onset epilepsy with increased death risk. The mice overexpress the brain derived neurotrophic factor (BDNF) in the forebrain under the calcium/calmodulin dependent protein kinase 2a (termed TgBDNF) and develop GTCSs in response to tail suspension/cage agitation stimulation at 3-4 months of age. With successive GTCSs (a total of 16 across 10 weeks of assessment), seizures became more severe as evidenced by increased duration of postictal generalized EEG suppression (PGES) associated with loss of posture/consciousness. Mice also developed spike wave discharges with behavioral arrest during the seizure recovery that increased in duration as a function of number of GTCSs. Overall seizure duration (from preictal spike to offset of PGES) and ictal spectral power (full spectra) were also increased. Half of the TgBDNF mice expired following a long period of PGES at the last recorded GTCS. Seizure-evoked general arousal impairment was associated with a striking decrease in total number of gigantocellular neurons of the brainstem nucleus pontis oralis along with increase in volumes of the anterior cingulate cortex and dorsal dentate gyrus in severely convulsive TgBDNF mice compared to litter-matched WT controls and non-convulsive TgBDNF mice. The latter effect was accompanied with an increase in total number of hippocampal granule neurons. These results provide structure-function associations in an animal model of adult-onset GTCSs that progressively increase in severity with clinical relevance for sudden unexpected death following generalized seizures.


Subject(s)
Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Epilepsy , Animals , Mice , Mice, Transgenic , Seizures , Epilepsy/complications , Electroencephalography/methods , Death, Sudden , Disease Models, Animal , Brain Stem
18.
Brain Dev ; 45(8): 451-455, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37308336

ABSTRACT

OBJECTIVE: To report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment. METHODS: A retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively. RESULTS: Four patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10-12), and the mean age of starting lacosamide was 17.5 years (range 16-21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300-600). CONCLUSION: Adjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.


Subject(s)
Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Myoclonic Epilepsy, Juvenile , Humans , Child , Adolescent , Young Adult , Adult , Lacosamide/therapeutic use , Myoclonic Epilepsy, Juvenile/complications , Myoclonic Epilepsy, Juvenile/drug therapy , Retrospective Studies , Anticonvulsants , Seizures/drug therapy , Seizures/chemically induced , Epilepsy, Tonic-Clonic/drug therapy , Treatment Outcome
19.
Epilepsia ; 64(8): 2137-2152, 2023 08.
Article in English | MEDLINE | ID: mdl-37195144

ABSTRACT

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.


Subject(s)
Epilepsy, Reflex , Epilepsy, Tonic-Clonic , Humans , Male , Child , Adolescent , Female , Quality of Life , Prospective Studies , Seizures/diagnosis , Seizures/complications
20.
Vet J ; 295: 105986, 2023 May.
Article in English | MEDLINE | ID: mdl-37141933

ABSTRACT

Absence seizures are a type of generalized onset seizure associated in humans with brief activity interruptions, unresponsiveness and staring. Absence seizures are infrequently reported in veterinary patients, visually indistinguishable from focal seizures, and so may be grouped as non-generalized tonic clonic seizures (non-GTCS). The objective of this retrospective study was to provide a preliminary understanding of the frequency of non-GTCS in dogs and estimate its prevalence by evaluating the distribution of seizure types presented to a referral hospital over 4 years (May 2017-April 2021), as determined from the medical record history and electroencephalography (EEG) diagnostic testing where available. A total of 528 cases were included via a medical record search for dogs with epilepsy and/or seizures presented to the neurology or emergency services. Cases were categorized into seizure types based on reported clinical signs. Each year, 53-63 % of seizure cases were described as generalized tonic clonic seizures (GTCS), 9-15 % GTCS with additional events and 29-35 % suspected non-GTCS. EEG confirmed absence seizures in 12 of 44 EEGs, 5 cases having a history of GTCS and seven without prior GTCS. This preliminary study suggests that non-GTCS may be relatively common as one third of seizure cases in the referral population presented with non-GTCS clinical signs. Prospective studies using EEG are merited to definitively determine the prevalence of these different seizure types in dogs. Acknowledging the impact of these seizures will improve awareness, aiding veterinarians in their recognition, diagnosis and potential treatment options.


Subject(s)
Dog Diseases , Epilepsy, Tonic-Clonic , Epilepsy , Humans , Dogs , Animals , Epilepsy, Tonic-Clonic/diagnosis , Epilepsy, Tonic-Clonic/drug therapy , Epilepsy, Tonic-Clonic/veterinary , Retrospective Studies , Prospective Studies , Seizures/diagnosis , Seizures/epidemiology , Seizures/veterinary , Epilepsy/diagnosis , Epilepsy/epidemiology , Epilepsy/veterinary , Electroencephalography/veterinary , Dog Diseases/diagnosis , Dog Diseases/epidemiology
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