Association of cardiovascular risk factors and troponin elevation after generalized tonic-clonic seizures

PurposeTroponins are very sensitive biomarkers of myocardial injury. Conflicting data regarding elevation of troponin levels following a generalized tonic–clonic (GTC) seizure have been reported. In this study we hypothesized that troponin elevation after a GTC seizure occurs more frequently in patients with cardiovascular risk factors.MethodsPatients who presented to the ER after a single GTC seizure with troponin levels assessed by cardiac troponin T (cTnT) and drawn within 12 h of the GTC seizure were included. Patients with cardiac symptoms, elevated CPK levels or renal insufficiency were excluded. The frequency and risk factors for elevated cTnT levels were analyzed.ResultsFourteen patients with a mean age of 54 years (range: 19–87 years) were included. Four patients (28.6%) had elevated cTnT levels (mean = 0.06 μg/L; range: 0.035–0.076 μg/L). Patients with elevated cTnT levels were significantly older than those with normal levels (77.5 years vs. 45.5 years; P = 0.03). Of the eight patients 60 years of age and older, four (50%) had elevated cTnT levels. The coronary heart disease (CHD) score was significantly higher in patients with elevated cTnT levels compared to those with normal levels (13.5 vs. 9.75, P = 0.012).ConclusionsElevated troponin levels can occur after a GTC seizure. Patients at risk are the elderly and those with cardiovascular risk factors. Our results suggest that elevation of troponin levels after a GTC seizure reflects a minor ischemic cardiac injury related to the demand ischemia during the sympathetic overactivity that accompanies a GTC seizure.     

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy

ObjectiveTo 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.MethodsA 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.ResultsFour 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).ConclusionAdjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.     

Contribution to the genetics of symptomatic generalized tonic-clonic seizures: waking and sleep EEGs in siblings

The presence of epileptiform activity (EA) in the EEG of patients' relatives points to the significance of genetics in the etiology of epilepsies. Waking and sleep EEGs were recorded in 83 siblings of 54 patients suffering from symptomatic generalized tonic-clonic seizures. EA was recorded in at least one sibling of 27 (50%) of the 54 patients. When the 83 siblings are taken as a basis, EA was found in 34 (41%) of them. Generalized spike-wave discharges were seen in 32 cases; 2 siblings showed benign sharp wave foci in the right parietal area. EA was seen only in sleep in 44.1 %. The highest rates of EA were seen in the age range up to 15 years. EA was found in 15 of 50 male siblings (30%), but in 18 of 33 female siblings (54.5%). Therefore genetics also play an import role in the etiology of symptomatic generalized tonic-clonic seizures.     

EEG features of absence seizures in idiopathic generalized epilepsy: Impact of syndrome, age, and state

Purpose:   Factors influencing the electroencephalography (EEG) features of absence seizures in newly presenting children with idiopathic generalized epilepsy (IGE) have not been rigorously studied. We examined how specific factors such as state, provocation, age, and epilepsy syndrome affect the EEG features of absence seizures.
Methods:   Children with untreated absence seizures were studied using video-EEG recording. The influence of state of arousal, provocation (hyperventilation, photic stimulation), age, and epilepsy syndrome on specific EEG features was analyzed.
Results:   Five hundred nine seizures were evaluated in 70 children with the following syndromes: childhood absence epilepsy (CAE) 37, CAE+ photoparoxysmal response (PPR) 10, juvenile absence epilepsy (JAE) 8, juvenile myoclonic epilepsy (JME) 6, and unclassified 9. Polyspikes occurred in all syndromes but were more common in JME. They were brought out by drowsiness and sleep in fragments of generalized spike and wave (GSW). Polyspikes were more likely to occur during photic stimulation, but were not influenced by age independently. GSW was more likely to be disorganized in JME than JAE, and in JAE than CAE. Increasing age and levels of arousal were more likely to result in organized GSW. Factors specific to each child independently influenced EEG features; the nature of these factors has not been identified.
Discussion:   The EEG features of absence seizures are influenced by a complex interaction of age, epilepsy syndrome, level of arousal, provoking factors, and other intrinsic factors. Epilepsy syndrome alone cannot predict specific features of GSW; however, JME is more frequently associated with polyspikes and disorganization of the paroxysm.     

The generalized tonic-clonic seizure in partial versus generalized epilepsy: semiologic differences

PURPOSE: To study differences in the clinical manifestations of generalized tonic-clonic seizures (GTCS) of partial versus generalized onset. METHODS: We studied 10 GTCSs in nine patients with idiopathic generalized epilepsy (IGE) and 10 GTCSs in 10 patients with temporal lobe epilepsy (TLE). Videotaped seizures were reviewed for all clinical features, focusing on asymmetries during different phases of each seizure. RESULTS: In the IGE group, focal features were seen before generalized motor activity in seven seizures. The most common was adversive head turn (six seizures). One patient had opposite direction of head turning in two recorded seizures. The tonic phase was always symmetric. In the last generalized clonic phase, asymmetry or asynchrony of motor activity was seen transiently in three seizures. The TLE group showed focal features before generalization in all seizures. Adversive head turning occurred in nine patients and was always contralateral to the focus. Focal clonic activity occurred before generalization in three and was always contralateral to the focus. The generalized tonic phase was usually asymmetric, and in the last clonic phase, motor activity was asymmetric or asynchronous in eight seizures (p<0.05, IGE vs. TLE). CONCLUSIONS: Brief focal features or asymmetry at onset are common in the GTCSs of IGE. However, asymmetry or asynchrony during the last clonic phase are uncommon in IGE, in contrast to TLE.     

Linking generalized spike-and-wave discharges and resting state brain activity by using EEG/fMRI in a patient with absence seizures

PURPOSE: To illustrate a functional interpretation of blood oxygen level-dependent (BOLD) signal changes associated with generalized spike-and-wave discharges in patients with absence seizures and to demonstrate the reproducibility of these findings in one case. METHODS: In a 47 year-old patient with frequent absence seizures, BOLD signal changes during generalized spike-and-wave discharges (GSWD) were mapped by using simultaneous and continuous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) at 1.5 T and 6 months later at 3 T. GSWDs were modeled as individual events and as blocks. RESULTS: The patient studied exhibited frequent generalized spike-wave activity with temporal properties ideal for study with EEG/fMRI. Highly reproducible GSWD-associated fMRI signal decreases (deactivations) were seen in bilateral frontal and temporoparietal cortices and the precuneus, in addition to activations in occipital cortex and, at 3 T, the posterior thalamus. CONCLUSIONS: The GSWD-associated changes seen here involve cortical regions that have been shown to be more active at conscious rest compared with sleep and with various types of extroverted perception and action. These regions have been proposed to constitute the core of a functional "default mode" system. We propose that the findings of deactivation of this distributed brain system during GSWDs mirrors the clinical manifestation of GSWDs (i.e., absence seizures). Furthermore, we suggest that these deactivations may reflect the functional consequences of GSWDs on physiologic brain activity at rest rather than direct hemodynamic correlates of epileptic discharges.     

Decomposition and mapping of generalized spike-wave complexes.

OBJECTIVE: To delineate more precisely the electrical fields of spikes versus waves during absence seizures. METHODS: Five children with 25 absence seizures were investigated with an expanded electrode array. Spikes were separated from waves by appropriate filtering and current source density maps were obtained from different portions of the waves as well as spikes. In order to detect commonalities for spread of activity, averaging of the complexes was also carried out. RESULTS: The anterior head regions (prefrontal and fronto-polar) show independent activity from the posterior ones (parieto-occipital) for spikes as well as waves. Voltage maps give a simplified and therefore misleading picture. The complexity of the process and propagation of events is best appreciated when current source densities (CSD) are mapped and several head views are available. Spike 1 becomes clearly visible upon filtering, even when it is not apparent from raw tracings, and can be mapped. CONCLUSIONS: Future topographic investigations of the SW complex should utilize CSD maps rather than rely entirely on voltages. This applies also to seemingly focal spikes--especially in children--in order to differentiate them from a partial expression of a generalized seizure tendency.     

Musicogenic and spontaneous seizures: EEG analyses with hippocampal depth electrodes

Musicogenic seizure is classified as a rare form of complex reflex seizures. We present a patient with musicogenic seizures from whom invasive recordings were obtained using subdural arrays, as well as hippocampal depth electrodes. Interestingly, this patient had both spontaneous seizures and musicogenic seizures, and they originated from different hippocampi. Due to bilateral independent musicogenic seizures and spontaneous seizures, our patient was not eligible for surgery, but vagal nerve stimulation treatment was almost successful. [Published with video sequence]     

Absence seizures: Individual patterns revealed by EEG‐fMRI

Purpose: Absences are characterized by an abrupt onset and end of generalized 3–4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography–functional magnetic resonance imaging (EEG–fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences. Methods: Seventeen absences from nine patients with absence epilepsy and classical pattern of 3–4 Hz GSWs during EEG‐fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen–level dependent (BOLD) response maps. Results: Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient‐specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses. Discussion: Like a fingerprint, patient‐specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific.     

Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures

Purpose: The aim of the present study was to investigate the correlation between epileptiform discharges on EEGs after febrile seizures and the prognosis of patients in terms of the development of epilepsy and recurrence of febrile seizures. This study also evaluated the characteristics of epileptiform discharges and EEG changes on follow-up examination. Methods: This study consisted of 36 children who presented to our hospital with febrile seizures and whose electroencephalograms (EEG) showed epileptiform discharges. The development of epilepsy and the recurrence of febrile seizures were compared between the study group (n = 36) and the control group (n = 87), which included children with febrile seizure but with normal EEG findings. Results: No significant correlation was detected between the recurrence rate of febrile seizures in patients with normal EEG (23 out of 87, 26.4%) findings and that of patients whose EEGs showed epileptiform discharges (12 out of 36, 33.3%) [adjusted OR 0.67 (0.26–1.68)]. However, 9 (25.0%) out of 36 patients with epileptiform discharges on EEG had epilepsy compared to 2 patients (2.3%) in the control group. The correlation was statistically significant [crude OR 10.88 (2.47–47.88) and adjusted OR 8.75 (1.49–51.6)]. Conclusion: Epileptiform discharges on the EEGs of patients with febrile seizures are important predictive risk factors of the development of epilepsy.     

Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies

Purpose: Electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so‐called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level–dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset. Methods: Twenty‐one patients with IGE underwent EEG‐fMRI coregistration. EEG‐related analyses were run both at the single‐subject and at group level (random effect). The time‐course analysis was conducted for 3 s time windows before, during, and after GSWDs, and they were included until no further BOLD signal changes were observed. Key Findings: Fifteen patients (nine female, mean age 28 years) had GSWDs during EEG‐fMRI coregistration (262 total events, mean duration 4 s). Time‐course group analysis showed BOLD increments starting approximately 10 s before GSWD onset located in frontal and parietal cortical areas, and especially in the precuneus‐posterior cingulate region. At GSWD onset, BOLD increments were located in thalamus, cerebellum, and anterior cingulate gyrus, whereas BOLD decrements were observed in the DMN regions persisting until 9 s after onset. Significance: Hemodynamic changes (BOLD increments) occurred in specific cortical areas, namely the precuneus/posterior cingulate, lateral parietal, and frontal cortices, several seconds before EEG onset of GSWD. A dysfunction of these brain regions, some of which belongs to the DMN, may be crucial in generating GSWDs in patients with IGE.