Febrile Convulsive Status Epilepticus Research Articles

A serial analysis of serum aspartate aminotransferase levels in patients with acute encephalopathy with biphasic seizures and late reduced diffusion and prolonged febrile seizure

BackgroundThere are no established biomarkers for diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in the early acute phase, called “the 1st seizure phase”. Based on our clinical experience, we hypothesized that serial examinations of blood levels of aspartate aminotransferase (AST) in children with febrile convulsive status epilepticus (FCSE) revealed higher levels in patients with AESD in the 1st seizure phase than in those with prolonged febrile seizures (PFs). MethodsTo test our presented hypothesis, we retrospectively investigated changes in serum AST in patients with FCSE due to AESD (n = 11) or PFs (n = 27) who were serially examined within 48 h of the onset of convulsions. ResultsThe rate of increase in AST was significantly higher in patients with AESD than in those with PFs. The rate of increase in AST correlated with previously reported scoring systems, i.e., Yokochi and Tottori scores, for the prediction of AESD. A positive correlation between the rate of increase in AST and creatinine levels in the first examination were observed; however, creatinine levels did not significantly differ between the AESD and PFs groups in the first or second examination. Blood levels of pH, ammonia, and sugar in the first examination and C-reactive protein in the second examination were significantly higher in the AESD group than in the PFs group. ConclusionsThe present study revealed that the rate of increase in AST was significantly higher in patients with AESD than in those with PFs. A novel predictive scoring system needs to be established in combination with the rate of increase in AST and reported clinical parameters, which will improve the prognosis of patients with FCSE.

Prognostic effects of treatment protocols for febrile convulsive status epilepticus in children

BackgroundFebrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence.MethodsThis was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002–December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007–February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013–April 2016), BCT was indicated for FCSE resistant to fPHT or PB.ResultsThe rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40).ConclusionsWhile the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.

Prediction of AESD and neurological sequelae in febrile status epilepticus

ObjectiveThe clinical prediction rule (CPR) for acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was developed with an area under the receiver operating characteristic curve (AUC) of 0.95 – 0.96. Our objective was to verify the AESD CPR in a new cohort and compare the utilities of three CPRs of acute encephalopathy: the Tada, Yokochi, and Nagase criteria. MethodsWe reviewed the clinical data and medical charts of 580 consecutive patients (aged < 18 years) with febrile convulsive status epilepticus lasting for ≥ 30 min in 2002 – 2017 and measured the performance of the CPRs in predicting AESD and sequelae. ResultsThe CPRs predicted AESD with an AUC of 0.84 – 0.88. The Tada criteria predicted AESD with a positive predictive value (PPV) of 0.25 and a negative predictive value (NPV) of 0.99. The Yokochi criteria predicted AESD with a PPV and NPV of 0.20 and 0.95, respectively, after 12 h. The Nagase criteria predicted AESD with a PPV and NPV of 0.14 and 1.00, respectively, after 6 h. The PPVs of the Tada, Yokochi, and Nagase criteria for sequelae were 0.28, 0.28, and 0.17, respectively; the corresponding NPVs were 0.97, 0.95, and 0.98, respectively. ConclusionsThe effectiveness of the AESD CPR in a new cohort was lower than that in the derivation study. CPRs are not sufficient as diagnostic tests, but they are useful as screening tests. The Nagase criteria are the most effective for screening among the three CPRs due to their high NPV and swiftness.

Acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy is a common childhood disease, especially in the nervous system of infants and young children.Recently, a new subtype of childhood acute encephalopathy named acute encephalopathy with biphasic seizures and late reduced diffusion (AESD)has been reported.The patients present with persistent febrile seizures, long-term cognitive impairment and local brain atrophy.Acute infantile encephalopathy predominantly affecting the frontal lobes is a special type of AESD, which mainly impair the frontal lobe the improvement of understanding and early diagnosis of acute encephalopathy in children is particularly important. Key words: Acute encephalopathy; Febrile convulsive status epilepticus; Cognitive impairment

Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics

We studied the efficacy of drugs indicated for mitochondrial dysfunction in the treatment of 21 patients with acute encephalopathy with onset of febrile convulsive status epilepticus at our hospital from January 2006 to December 2014. Among them, 11 patients had been treated with a mitochondrial drug cocktail consisting of vitamin B1, vitamin C, biotin, vitamin E, coenzyme Q10, and l-carnitine (prescription group) and 10 patients were not treated with the cocktail (non-prescription group). We retrospectively reviewed age, trigger, clinical form, treatment start time, and sequelae. Clinical form was classified into a biphasic group presenting acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and a monophasic group. Sequelae were classified as (A) no sequelae group or (B) sequelae group, and differences in the interval between diagnosis and treatment were also evaluated. The sequelae were not different between the mitochondrial drug cocktail prescription and non-prescription groups, but significantly better in the group administered the mitochondrial drug cocktail within 24h (P=0.035). We expect that early treatment with a mitochondrial drug cocktail could prevent sequelae in acute encephalopathy with onset of febrile convulsive status epilepticus.

A Case of Recurrent Acute Encephalopathy with Febrile Convulsive Status Epilepticus with Carnitine Palmitoyltransferase II Variation

Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE.

Temperature management in central nervous infection

Temperature management in central nervous infection

Cerebrospinal fluid and serum levels of vitamin B6 in status epilepticus children

Vitamin B6 (B6) is an essential cofactor of glutamate decarboxylase and catalyzes the decarboxylation of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Although immediate administration of B6 to patients with acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is effective, it is not known whether prolonged seizures in status epilepticus (SE) children prevent the transport of B6 to the central nervous system (CNS) and/or induce the consumption of B6 inside the CNS. We evaluated the B6 concentration in cerebrospinal fluid (CSF) and serum in SE children. Further, we performed a sequential serum B6 analysis on days 1 and 2 after admission and on the day before discharge. Among the several vitamers of B6, we used pyridoxal (PL) as a representative of B6 in this study. We enrolled 15 SE children (8 boys and 7 girls; age range,1–11 years; average age, 3.3 years) and 21 control children (3 boys and 18 girls; age range, 7 months–14 years; average age, 3.0 years) and each group was divided into 2 subgroups according to age (4 months–1 year and 2–14 years). We found no significant differences in the CSF PL levels, CSF/serum PL ratios, and serum PL levels in the SE and control subgroups. Our results suggest that prolonged seizures do not result in B6 deficiency in CSF and serum in SE children. Whenever necessary, B6 should be administered to SE children with caution to prevent possible adverse effects.

Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus

In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito–temporo–parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter.

Clinical trial design in status epilepticus: problems and solutions

This paper is written from a pediatric perspective. The starting point in trial design is the identification of important questions, particularly those about therapeutic purposes. The main justification for clinical trials is that status epilepticus is harmful and therefore needs to be treated. In terms of permanent CNS damage and epilepsy following status epilepticus, the rates in published studies vary between 4% and 40% depending on their quality (Raspall-Chaure et al., 2006) and none have looked for subtle cognitive impairments which might be suggested by the finding of acute hippocampal edema following febrile convulsive status epilepticus (CSE) (Scott et al., 2002, 2003). Thus, we are left with a general view that it would be better if we could safely reduce the time that children are convulsing. However, the expense and effort of a randomized controlled trial (RCT) needs to be justified as alternative approaches for example, well-designed epidemiological studies may also provide useful therapeutic information for achieving this goal. The types of questions requiring clinical trial fall into two groups: drug related and clinical approach related.

Acute encephalopathy associated with influenza and other viral infections

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.

Childhood convulsive status epilepticus: epidemiology, management and outcome

Convulsive status epilepticus (CSE) in childhood is a medical emergency and its aetiology and outcome mean that it should be studied separately from adult CSE. The incidence in developed countries is between 17 and 23/100,000 with a higher incidence in younger children. Febrile CSE is the commonest single group with a good prognosis in sharp distinction to CSE related to central nervous system infections which have a high mortality. The aim of treatment is to intervene at 5 min and studies indicate that intravenous (i.v.) lorazepam may be a better first-line treatment than rectal diazepam and i.v. phenytoin a better second-line treatment than rectal paraldehyde. An epidemiological study strongly supports the development of prehospital treatment with buccal midazolam becoming a widely used but unlicensed option in the community. More than two doses of benzodiazepines increase the rate of respiratory depression without obvious benefit. The 1 year recurrence rate is 17% and the hospital mortality is about 3%.

Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study

Convulsive status epilepticus is the most common childhood medical neurological emergency, and is associated with significant morbidity and mortality. Most data for this disorder are from mainly adult populations and might not be relevant to childhood. Thus we undertook the North London Status Epilepticus in Childhood Surveillance Study (NLSTEPSS): a prospective, population-based study of convulsive status epilepticus in childhood, to obtain a uniquely paediatric perspective. Clinical and demographic data for episodes of childhood convulsive status epilepticus that took place in north London were obtained through a clinical network that covered the target population. We obtained these data from anonymised copies of a standardised admission proforma; accident and emergency, nursing, ambulance, and intensive-care unit notes; and interviews with parents, medical, nursing, and paramedic staff. We investigated ascertainment using capture-recapture modelling. Of 226 children enrolled, 176 had a first ever episode of convulsive status epilepticus. We estimated that ascertainment was between 62% and 84%. The ascertainment-adjusted incidence was between 17 and 23 episodes per 100,000 per year. 98 (56%, 95% CI 48-63) children were neurologically healthy before their first ever episode and 56 (57%, 47-66) of those children had a prolonged febrile seizure. 11 (12%, 6-18) of children with first ever febrile convulsive status epilepticus had acute bacterial meningitis. Conservative estimation of 1-year recurrence of convulsive status epilepticus was 16% (10-24%). Case fatality was 3% (2-7%). Convulsive status epilepticus in childhood is more common, has a different range of causes, and a lower risk of death than that in adults. These paediatric data will help inform management of convulsive status epilepticus and appropriate allocation of resources to reduce the effects of this disorder in childhood.