Prolonged Electrocerebral Silent Barbiturate Coma in Intractable Seizure Disorders

Barbiturate coma (BC) is a known modality for terminating resistant convulsive status epilepticus. It is usually applied until seizure activity ends. We recently adopted a modified protocol of prolonged, electrocerebral silent BC to treat patients with chronic seizure activity resistant to multiple regimens of antiepileptic drugs. Four patients, aged 4 months to 10 years, with long-standing intractable generalized seizures were treated. Seizure frequency ranged from one to two to numerous times per day. Following BC, one patient has been seizure free during 8 months of follow-up, and another has had only two seizures in 18 months. A 4-month-old infant was seizure-free for 2 weeks after BC and then died from underlying CNS disease. A 10-year-old girl died during BC from shock and hyperpyrexia. The results obtained in our patients indicate that prolonged electrocerebral silent BC may exert a beneficial long-term effect in treatment of intractable seizure disorders. This procedure might also be beneficial in other forms of epilepsy.     

Suppression of Pentylenetetrazol-Elicited Seizure Activity by Intraosseous Lorazepam in Pigs

Use of the intraosseous (i.o.) route as an alternative venous access for drug administration has increased. This study examined the efficacy of i.o. lorazepam (LZP) in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, EEG, and electrocortical activity. Seizure activity was induced by PTZ (100 mg/kg i.v.). Sixty seconds after onset of seizure activity, animals either received no drug (control) or LZP (1.0 mg/kg) administered i.v. or i.o. via an 18- or 13-gauge spinal needle inserted in the right proximal tibia. Both i.o. and i.v. LZP significantly suppressed the duration of seizure activity (DSA) (s/min interval) within 1 min following drug administration: DSA control, 46.2 +/- 3.6; i.v. LZP, 25.0 +/- 5.1; i.o. (18-gauge) LZP, 27.6 +/- 6.0; i.o. (13-gauge) LZP, 24.0 +/- 2.4. Seizure activity was essentially abolished at 1 min following LZP infusion. In addition, both i.v. and i.o. LZP did not have significant effects on the basal heart rate and mean arterial blood pressure. The data demonstrate that in swine (1) the i.o. route is an effective alternative venous access for LZP administration, and (2) the size of spinal needles does not affect the antiepileptic efficacy of i.o. infusion of LZP.     

Investigational Antiepileptic Drugs for the Treatment of Childhood Seizure Disorders: A Review of Efficacy and Safety

Summary: Pediatric epileptology is very different from adult epileptology. Although some epileptic disorders occur in both children and adults (e.g., localization-related epilepsy with complex partial seizures and primary generalized epilepsy with tonic-clonic seizures), other disorders can be called the catastrophic epilepsies of childhood (e.g., infantile spasms and the Lennox-Gastaut syndrome). They occur, or at least begin, exclusively in childhood and are often associated with mental retardation. Many of these pediatric disorders are notoriously unresponsive to currently available antiepileptic drugs (AEDs). Although there are undoubtedly many reasons for this, one possible explanation is that the methods used to screen potential AEDs use animal models of adult epilepsy. No screening program uses an animal model of seizures that begin during development and lead to functional decline.     

Ictal and Interictal Electrographic Seizure Durations in Preterm and Term Neonates

Summary: The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty-eight neonates with 644 electrographic seizures were identified retrospectively. Thirty-five full-term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [>31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of ≤31 weeks EGA. Ictal/ interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two-tailed t tests, chi-square calculations, and one-way analysis of variance (ANOVA) with Duncan's multiple-range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi-square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncan's multiple-range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncan's), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncan's). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE. Inhibitory networks responsible for longer interictal periods are more dominant in OPT infants than in YPT infants, reflecting maturational changes that suppress seizure activity during the latter part of the third trimester before the infant reaches an FT corrected age.     

Status Epilepticus of Benign Partial Epilepsies in Children: Report of Two Cases

Benign partial epilepsies of childhood (BPEC) are one of the most frequent types of epilepsy in school-age children. Status epilepticus (SE) of these conditions have not yet been reported. Two children with clinical and EEG features consistent with the diagnosis of BPEC-SE are presented. In neither case did SE respond to current antiepileptic medications and stopped only after administration of steroids. At follow-up 1 and 2 years post SE, neurologic and intellectual development have been normal. Differential diagnoses included an atypical benign partial epilepsy, epilepsy with electrical status epilepticus during slow sleep, acquired epileptic aphasia, Lennox-Gastaut syndrome and epilepsia partialis continua.     

Prognosis of Childhood Seizure Disorders: Present and Future

Summary: The prognoses for seizure disorders have been examined since the beginnings of epileptology, and only recently has the realization emerged that, ultimately, prognosis depends on causation, which, in turn, determines whether a condition is self-limited or progressive. This factor is more important than either mode or alacrity of therapeutic intervention. The epilepsies are a series of conditions that have the final common path of either increasing cerebral irritability or synchronizing normally occurring electrical activity in such a manner that seizures result. In turn, some seizure disorders are characterized by secondary changes in neuronal synaptogenesis, leading to the development of circuits of predilection, which then render the process autonomous. Epilepto-genesis has then become epilepsy, which is the norm in acquired rather than genetic epileptogenesis. An understanding of the basic differences between the primary (idiopathic) epilepsies and the secondary (acquired or symptomatic) epilepsies is basic to a discussion concerning prognosis and to the development of a definitive individualized treatment plan. An elucidation of the genetic factors in idiopathic epilepsy and their neurochemical consequences represents a major frontier in epileptology.     

Seizure frequency in pilocarpine-treated rats is independent of circadian rhythm

Pilocarpine-induced status epilepticus (SE) results in chronic spontaneous recurrent seizures resembling human temporal lobe epilepsy. In this and other experimental models, behaviorally monitored seizure frequency was suggested to vary in a circadian fashion, and to increase with time. We re-addressed those hypotheses using continuous video-electroencephalography (EEG) telemetry in rats with SE at 30 days of age. In 11 chronically epileptic animals monitored up to 300 days after SE in a fixed 12 h light/dark cycle, we found that seizure frequency did not correlate with circadian rhythm.     

Purine Seizure Disorders

Developing antiepileptic agents that are specifically tailored to a patient's individual biochemistry has long been a goal of neurology. Three patients who had hyperuricosuria combined with a seizure disorder that failed to respond to traditional anticonvulsants are described. The patients had the best control of their seizure disorder when a specific metabolic drug, allopurinol, was used as an anticonvulsant. All three patients had onset of the seizure disorder at 22 months of age, a finding possibly related to maturation of purine enzymes. Because elevated uric acid levels in the immediate postictal period may occur in seizure patients, the presence of an elevated uric acid clearance in seizure-free periods is needed to consider the diagnosis of an allopurinol-responsive seizure problem in any individual patient. In the two patients past the onset of puberty, lowering (one case) and cessation (other case) of the dose of allopurinol has been possible.     

Primary Generalized Seizure Disorder: Correlation of Epileptiform Discharges with Seizure Frequency

Summary: The role of routine follow-up EEG in assessment of severity of a seizure disorder is not known. This retrospective chart review study of patients with primary generalized seizure disorders explored the relation between parameters of epileptiform discharge bursts on EEG and number of seizures experienced in the preced ing months. Eighty-seven such patients were found, each with one to seven EEGs and corresponding clinical records, comprising a total of 201 clinicoelectrographic epochs. The 56 chronically attending patients (more than two attendances) differed from the 31 nonchronic attenders in receiving more antiepileptic drugs (AEDs) and having fewer EEG poly spikes; otherwise, the two groups were similar and were analyzed together. We noted a strong relation between number and maximum length of epileptiform bursts in the resting EEG record and number of absence seizures reported in the months preceding the EEG. Age did not affect this relation. After stepdown regression analysis, only the maximum length of epileptiform bursts remained significantly related to the reported number of absence seizures. These findings may prove useful in assessing clinical progress, e.g., in patients whose ability to estimate numbers of attacks is suspect. Neither number nor maximum length of epileptiform bursts in the resting EEG record had a significant relation with the number of generalized tonic-clonic seizures. Presence of polyspikes on resting or "activated" EEG had no added predictive value. The presence of epileptiform bursts after activation by sleep, hyperventilation, or photic stimulation was not associated with an increased likelihood of having had seizures.     

不同类型小儿癫痫持续状态的临床及脑电图分析

目的 分析不同类型儿童癫痫持续状态（ＳＥ）的临床和脑电图（ＥＥＧ）特征,以期对ＳＥ作出早期诊断及处理。方法 用录像脑电图监测的方法对１９９６年３月至１９９９年３月北京医科大学第一医院儿科（２４例）和香港大学儿科部（３例）收治的２７例癫饿按发作类型进行分类,分析不同为临床发作特征及年龄、病因、脑发育水平、诱发因素和药物反应等对ＳＥＲ 影响。结果 本组２７例ＳＥ患儿强直＝阵挛性ＳＥ１例,强直性ＳＥ２例     

Status epilepticus severity score as a predictor for the length of stay at hospital for acute-phase treatment in convulsive status epilepticus

To date, hospital length of stay (LOS) determinants for convulsive status epilepticus’s (CSE) acute-phase treatment have not been sufficiently investigated, as opposed to those for status epilepticus’s (SE) outcome predictors, such as status epilepticus severity score (STESS). Here, we aimed at assessing the significance of STESS in the LOS in patients with CSE. We retrospectively reviewed consecutive adult patients with CSE who were transported to the emergency department of our urban tertiary care hospital in Tokyo, Japan. The study period was from August 2010 to September 2015. The primary endpoint was the LOS of patients with CSE who were directly discharged after acute-phase treatment, and survival analysis for LOS until discharge was conducted. As a result, among 132 eligible patients with CSE admitted to our hospital, 96 (72.7%) were directly discharged with a median LOS of 10 days (IQR: 4–19 days). CSE patients with severe seizures, represented by higher STESS (≥3), had a significantly longer LOS after adjustments with multiple covariates (p = 0.016, in restricted mean survival time analysis). Additionally, prediction for the binomial longer/shorter LOS achieved better performance when STESS was incorporated into the prediction model. Our findings indicate that STESS can also be used as a rough predictor of longer LOS at index admission of patients with CSE.     

Anticonvulsant effects of carbamazepine on spontaneous seizures in rats with kainate-induced epilepsy: comparison of intraperitoneal injections with drug-in-food protocols

PURPOSE: The present study evaluated the effectiveness of intraperitoneal (IP) injections and oral administration of carbamazepine (CBZ) in food on the frequency of spontaneous motor seizures in rats with kainate-induced epilepsy. The purpose was to develop a convenient drug-in-food approach for continuous, long-term administration of potential antiepileptic drugs (AEDs). METHODS: Single IP injections of CBZ (10-100 mg/kg) were compared to vehicle injections via six AED-versus-vehicle tests using a repeated-measures, crossover protocol. Similar protocols were used with CBZ-containing or control food pellets. RESULTS: CBZ significantly reduced motor seizure frequency at 30 and 100 mg/kg after single IP injections, and these doses completely blocked motor seizures during a 6-h postdrug epoch in 25% and 70% of the animals, respectively. Single administrations of 30 mg/kg and 100 mg/kg CBZ in food also significantly reduced motor seizures, and blocked seizures in 33% and 89% of the rats, respectively. CBZ administered in food three times per day (100 mg/kg x3 CBZ in food) continuously blocked nearly all motor seizures over a 5-day period, and completely suppressed motor seizures in 50% of the animals tested. CONCLUSIONS: CBZ strongly suppresses spontaneous motor seizures, and single doses of CBZ in food are as effective as IP injections in rats with kainate-induced epilepsy. CBZ administered regularly in food continuously blocks nearly all motor seizures, and may provide a relatively simple method to test AEDs in chronic models of epilepsy.     

The Management of Refractory Status Epilepticus: An Update

Summary:  Refractory status epilepticus (RSE) is an important and serious clinical problem that typically requires prolonged and high-level intensive care, and is often associated with poor outcome. This review addresses some of the current issues concerning the management of RSE, including recent definitions used for clinical studies, epidemiology, clinical course, and outcome. Current approaches to treatment, including the now relatively standard use of intravenous anesthetic agents, as well as emerging therapies utilizing drugs such as valproate and topiramate, are discussed as well.     

Early-Onset Benign Childhood Occipital Seizure Susceptibility Syndrome: A Syndrome to Recognize

Early-onset benign childhood occipital seizures (EBOS) described by Panayiotopoulos constitute the commoner after the rolandic phenotype of a childhood seizure susceptibility syndrome. EBOS are the clinical representative of occipital spikes. Their cardinal features are infrequent (often single) partial seizures manifested with deviation of the eyes and vomiting, frequently evolving to hemi- or generalized convulsions. Ictal behavioral changes, irritability, pallor, and rarely cyanosis, and eyes wide open are frequent. Retching, coughing, aphemia, oropharyngolaryngeal movements, and incontinence may occur. Consciousness is usually impaired or lost, either from the onset or the course of the fits, but in a few children, it may be preserved. Duration varies from a few minutes to hours (partial status epilepticus). Seizures are usually nocturnal, but semiology is similar in nocturnal or diurnal fits. Onset is between 1 and 12 years with a peak at 5 years. One third of children have a single seizure, the median total number of fits is two to three, and the prognosis is invariably excellent, with remission usually occurring within 1 year from onset. A few children may later develop rolandic or other benign partial seizures. The likelihood to have seizures after age 12 years is exceptional and rarer than that of febrile convulsions. EEG shows occipital paroxysms demonstrating fixation-off sensitivity, but random occipital spikes, occipital spikes in sleep EEG alone, or normal EEG may occur. Centrotemporal and other spike foci may appear in the same or more frequently in subsequent EEGs. The EEG does not reflect clinical course and severity.     

Management of Acute Seizure Episodes

Summary: Acute seizures may represent the initial manifestation of epilepsy or isolated events. Urgent treatment of these episodes is indicated to reduce the risk for permanent neurologic damage. Status epilepticus (SE), one form of acute seizure, has an estimated annual incidence of 100,000–150,000 cases per year in the United States. Management of SE focuses on terminating clinical and electrical seizure activity while providing supportive care and identifying the precipitating factors. Physician preference and patient-related factors may dictate the choice of pharmacologic treatment of SE. However, benzodiazepines, which enter the brain rapidly and offer the opportunity for most rapid seizure cessation, are the foundation for SE management. At our institution, first-line treatment consists of i.v. lorazepam followed by a long-acting antiepileptic drug (AED). When i.v. access cannot be attained, high AED blood levels can be rapidly achieved with rectally administered diazepam (DZP). For management of acute repetitive seizures, it is desirable to have an effective drug that can be safely administered by caregivers outside of the hospital setting. Clinical trial data indicate that rectal administration of a prepackaged viscous DZP solution fulfills these criteria. In these studies, rectal DZP gel reduced seizure frequency and recurrence compared to seizure control, improved patient and family quality of life, and was cost-effective because it reduced the need for emergency and inpatient treatment.     

Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PurposeStatus epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the ‘pediatric Status Epilepticus Research Group’ (pSERG).MethodsA literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network.ResultsThe care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome.ConclusionThe care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE.     

A Survey of Mothers'' Impressions of Seizure Precipitants in Children with Epilepsy

In a survey of 446 children with epilepsy attending a regional EEG unit, mothers of nearly 90% of the children reported factors that appeared to act as precipitants of their children's seizures. The relationship between these factors and the seizures ranged from consistent triggers to an occasional association. There were no differences in incidence according to sex, site of focus, or type of epilepsy. Associations between environmental events or internal states are so commonly perceived by mothers that routine inquiry would appear warranted. If the event can be corroborated as a seizure precipitant, application of psychological methods of seizure control may be appropriate; if the event cannot be corroborated, needless anxiety about particular situations for a child may be avoided.