Frequency Of Seizure Activity Research Articles

Cannabidiol and refractory epilepsy: parental and caregiver perspectives of participation in a compassionate access scheme

BackgroundThe Compassionate Access Scheme (CAS) being delivered through the Queensland Children’s Hospital is designed to allow access to an investigational purified Cannabidiol oral solution to paediatric patients with severe refractory epilepsy. The objectives of this study were to conduct semi-structured interviews to:1. Understand families’ expectations and attitudes about the use of an investigational cannabinoid product for their child’s seizures;2. Understand families’ perceptions of Cannabidiol’s efficacy for their child’s seizures; and other aspects of their child’s behaviour, quality of life and/or cognition.MethodsChildren aged 2-18 years had been enrolled in, or were enrolled in a compassionate access scheme for Cannabidiol at the time of the study. Semi-structured interviews (n = 19) with parents or caregivers (n = 23) of children diagnosed with refractory epilepsy were voice-recorded, transcribed and analysed to generate common themes.ResultsKey themes emerged relating to seizure activity, family and school engagement, drug safety and legal access, efficacy, clinical support, social acceptance of the medication and program delivery. The use of Cannabidiol was perceived to have benefits in relation to reducing the severity and frequency of seizure activity for almost a third of patients experiencing refractory epilepsy. Participants described other benefits including improved social engagement, wakefulness and a reduction of side effects related to a reduction of conventional medication dosage.ConclusionThis study provided unique perspectives of families’ experiences managing untreatable epilepsy, their experiences with conventional and experimental pharmacological treatments and health services. Whilst families’ perceptions showed the use of Cannabidiol did not provide a therapeutic reduction in the seizure activity for all patients diagnosed with refractory epilepsy, it’s use as an additional pharmacological agent was perceived to provide other benefits by some patient families.

Multicenter Evaluation of Prehospital Seizure Management in Children

Background Seizures are a common reason why emergency medical services (EMS) transports children by ambulance. Timely seizure cessation prevents neurologic morbidity, respiratory compromise, and mortality. Implementing recommendations from an evidence-based pediatric prehospital guideline may enhance timeliness of seizure cessation and optimize medication dosing. Objective We compared management of pediatric prehospital seizures across several EMS systems after protocol revision consistent with an evidence-based guideline. Methods Using a retrospective, cross-sectional approach, we evaluated actively seizing patients (0–17 years old) EMS transported to a hospital before and after modifying local protocols to include evidence-based recommendations for seizure management in three EMS agencies. We electronically queried and manually abstracted both EMS and hospital data at each site to obtain information about patient demographics, medications given, seizure cessation and recurrence, airway interventions, access obtained, and timeliness of care. The primary outcome of the study was the appropriate administration of midazolam based on route and dose. We analyzed these secondary outcomes: frequency of seizure activity upon emergency department (ED) arrival, frequency of respiratory failure, and timeliness of care. Results We analyzed data for 533 actively seizing patients. Paramedics were more likely to administer at least one dose of midazolam after the protocol updates [127/208 (61%) vs. 232/325 (71%), p = 0.01, OR = 1.60 (95% CI: 1.10–2.30)]. Paramedics were also more likely to administer the first midazolam dose via the preferred intranasal (IN) or intramuscular (IM) routes after the protocol change [(63/208 (49%) vs. 179/325 (77%), p < 0.001, OR = 3.24 (2.01–5.21)]. Overall, paramedics administered midazolam approximately 14 min after their arrival, gave an incorrect weight-based dose to 130/359 (36%) patients, and gave a lower than recommended dose to 94/130 (72%) patients. Upon ED arrival, 152/533 (29%) patients had a recurrent or persistent seizure. Respiratory failure during EMS care or subsequently in the ED occurred in 90/533 (17%) patients. Conclusions Implementation of an evidence-based seizure protocol for EMS increased midazolam administration. Patients frequently received an incorrect weight-based dose. Future research should focus on optimizing administration of the correct dose of midazolam to improve seizure cessation.

The combination of ribose and adenine promotes adenosine release and attenuates the intensity and frequency of epileptiform activity in hippocampal slices: Evidence for the rapid depletion of cellular ATP during electrographic seizures.

In addition to being the universal cellular energy source, ATP is the primary reservoir for the neuromodulator adenosine. Consequently, adenosine is produced during ATP‐depleting conditions, such as epileptic seizures, during which adenosine acts as an anticonvulsant to terminate seizure activity and raise the threshold for subsequent seizures. These actions protect neurones from excessive ionic fluxes and hence preserve the remaining cellular content of ATP. We have investigated the consequences of manipulation of intracellular ATP levels on adenosine release and epileptiform activity in hippocampal slices by pre‐incubating slices (3 h) with creatine (1 mM) and the combination of ribose (1 mM) and adenine (50 μM; RibAde). Creatine buffers and protects the concentration of cellular ATP, whereas RibAde restores the reduced cellular ATP in brain slices to near physiological levels. Using electrophysiological recordings and microelectrode biosensors for adenosine, we find that, while having no effect on basal synaptic transmission or paired‐pulse facilitation, pre‐incubation with creatine reduced adenosine release during Mg2+−free/4‐aminopyridine‐induced electrographic seizure activity, whereas RibAde increased adenosine release. This increased release of adenosine was associated with an attenuation of both the intensity and frequency of seizure activity. Given the depletion of ATP after injury to the brain, the propensity for seizures after trauma and the risk of epileptogenesis, therapeutic strategies elevating the cellular reservoir of adenosine may have value in the traumatized brain. Ribose and adenine are both in use in man and thus their combination merits consideration as a potential therapeutic for the acutely injured central nervous system.

Seizure activity and neurological sequelae in Ugandan children who have survived an episode of cerebral malaria.

Seizures are a common presenting feature in children with cerebral malaria (CM) and neurologic deficits have been described in survivors of CM. However few prospective studies have described the frequency of seizure activity and neurologic deficits in survivors of CM over time. Eighty-two children aged 3 to 12 years who survived an episode of CM were followed up and monitored for seizure activity and neurologic deficits at discharge, 3, 6 and 24 months. Seventy six children with uncomplicated malaria (UM) and 105 healthy community controls (CC) age 3 to 12 years were recruited as comparison groups and the frequency of seizures in the 6 to 24 month follow-up period was compared in the 3 groups. Cumulative incidence of seizures increased over time in children with CM, with a total of 2 of 76 children (2.6%) reporting seizures at 3 months, 3 of 74 children (4.1%) at 6 months and 11 of 68 children (16.2%) at 24 months (Chi square for trend = 9.36, P=0.002). In contrast, neurologic deficits almost completely resolved over time, occurring in 19 of 76 children with CM (25%) at discharge, 2 of 74 children (2.7%) at 6 months, and 1 of 68 (1.5%) children at 24 months. During the 24 months following a CM episode, neurologic deficits resolve but the cumulative incidence of seizures increases in children with CM. Neurologic impairment after an episode of CM may not be limited to the neurologic deficits seen at discharge.

Neocortical Gliosis in Temporal Lobe Epilepsy: Gender‐Based Differences

Sex hormones can influence the timing and frequency of seizure activity. In addition, gender may influence the age of epilepsy onset and hemispheric location of focal epilepsy. Whether gender alters temporal lobe pathologies differentially is not clear. In this study, we assess if neocortical or hippocampal pathologies from patients who underwent en bloc anteriomedial temporal lobectomy (AMTR) for medically refractory epilepsy differ by gender. Consecutive en bloc AMTR resections (n = 128), including hippocampal tissues, were systematically studied. Cortical and intracortical gliosis from a standardized location, 1.5 cm from the temporal lobe tip, was assessed for quantifiable gliotic change. Corresponding hippocampal sections were characterized according to Watson grade. These outcomes were then compared by gender. Other correlates such as age of epilepsy onset, age of risk exposure, and duration of epilepsy were similarly compared. Subpial and intracortical gliosis was more pronounced in women (p = 0.02, p < 0.01). Cortical thickness was reduced in women compared to men (p < 0.05). No similar gender effects were seen in Watson grade of hippocampal sclerosis or CA1-4 neuronal dropout. Gender may differentially influence neocortical pathologies in patients with refractory temporal lobe epilepsy. No gender effect was seen when studying hippocampal pathologies.

Neuropsychological and behavioral status of children with complex partial seizures.

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Neuropsychological and behavioral status of children with complex partial seizures

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Magnetic Resonance Imaging-Based Computer-Assisted Stereotactic Resection of the Hippocampus and Amygdala in Patients With Temporal Lobe Epilepsy

In patients with medically intractable complex partial seizures of temporal lobe origin, stereotactic amygdalohippocampectomy can now provide excellent results. Target structures can be accurately identified and completely resected with use of a carbon dioxide laser. In a series of 18 patients who underwent this computer-interactive procedure, all experienced a cessation or dramatic reduction in frequency of seizure activity. Because the inferior optic radiations are disrupted with use of the posterolateral approach, nondisabling postoperative visual field deficits always ensue. In addition, two of our patients who underwent left-sided procedures had transient minor speech problems, perhaps attributable to postoperative swelling of the lateral temporal lobe. Patients in whom a surface electroencephalogram discloses a posterior temporal focus of seizure activity are candidates for stereotactic amygdalohippocampectomy.

Incidence of seizures that follow rehydration of hypernatremic rabbits with intravenous glucose or fructose solutions

Hypernatremic dehydration was induced in rabbits during a 3- to 5-day period resulting in mean plasma sodium concentrations of 187 meq/liter. The animals were then rehydrated during a 4-h period by intravenous administration of a 2.5% glucose or fructose solution. The water content of four regions of brain sampled showed a significant ( P < 0.05) increase in brain water content above normal in the rehydrated groups. Brain water content was significantly ( P < 0.01) greater in those animals with seizures compared with those without seizures, suggesting the importance of water intoxication in the pathogenesis of seizure activity. Changes in muscle Na, K, Cl, and water content were not similar to those of brain, indicating that muscle content of these substances was not an accurate reflection of the brain content at a specific time. The incidence of seizures was significantly ( P < 0.05) greater when glucose solution was used for rehydration (49%) compared with the use of fructose solution (25%). The mechanism(s) by which fructose resulted in a lower incidence of seizures is not known. The frequency of seizure activity was directly proportional to the rate of administration of intravenous solutions utilized to correct hypernatremia. In addition, the specific carbohydrate of the solution appeared to play an important role in the pathophysiology of the development of seizures.

The diagnostic value of the short sleep EEG and other provocative methods following sleep deprivation.

One hundred and eighty-five EEGs recorded after deprivation of sleep for 24 h were evaluated. Valuable diagnostic information was found in 59% of the EEG recordings; 24% of the EEGs contained seizure activity. The duration of the stages of sleep and the frequency of seizure activity, paroxysmal sharp wave groups and localizing findings were analyzed. The sleep stages A to C (based on the Loomis scale) were reached for about equal duration by an EEG recording of 30--40 min; sleep stage D was reached only shortly and stage E was not observed. Pathological EEG findings appeared for the most part in the sleep stages A and B. Localized findings were pronounced in stage C. No significant differences pertaining to the occurrence and form of EEG patterns were found between patient groups with primary generalized seizures, psychomotor seizures or those with unclarified disturbances of consciousness. The combination of the short sleep EEG following 24 h of sleep deprivation with subsequent use of the additional provocative methods of hyperventilation, photostimulation and hydration, yielded, in all, new information in 50% of the patients. Each of these additional methods contributed nearly equally to this information.