Clinical and laboratory characteristics of complex febrile seizures in the acute phase: a case-series study in Japan.

BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.

Time course of serum cytokine level changes within 72 h after onset in children with acute encephalopathy and febrile seizures.

BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1ß, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1ß, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.

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

BACKGROUND: Febrile 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. METHODS: This 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. RESULTS: The 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). CONCLUSIONS: While 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.

Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study.

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.

Acute rhabdomyolysis following viral infection with coxsackie A4 in a 50-day-old infant with Fukuyama congenital muscular dystrophy.

BACKGROUND: Fukuyama congenital muscular dystrophy (FCMD), which is characterized by generalized muscle weakness, hypotonia, and motor delay during early infancy, gradually progresses with advanced age. Although acute rhabdomyolysis following infection in patients with FCMD has occasionally been reported, no studies have investigated rhabdomyolysis following viral infection in FCMD patients during early infancy. CASE REPORT: We report the case of a 50-day-old girl with no apparent symptoms of muscular dystrophy who developed severe acute rhabdomyolysis caused by viral infection, resulting in quadriplegia and respiratory failure therefore requiring mechanical ventilation. Brain magnetic resonance imaging incidentally showed the typical characteristics of FCMD, and FCMD was confirmed by genetic analysis, which revealed a 3-kb retrotransposon insertion in one allele of the fukutin gene and a deep intronic splicing variant in intron 5 in another allele. The virus etiology was confirmed to be Coxsackie A4. CONCLUSION: We report a severe case of acute rhabdomyolysis with the earliest onset of symptoms due to the Coxsackie A4 virus in a patient with FCMD. The present findings indicate that physicians should consider FCMD with viral infection a differential diagnosis if the patient presents with acute rhabdomyolysis following a fever.

Nonconvulsive Seizure Detection by Reduced-Lead Electroencephalography in Children with Altered Mental Status in the Emergency Department.

OBJECTIVES: To evaluate the proportion of children presenting to the emergency department (ED) with altered mental status who demonstrate nonconvulsive seizures on reduced-lead electroencephalography (EEG), and to further investigate the characteristics, treatment, and outcomes in these patients compared with patients without nonconvulsive seizures. STUDY DESIGN: In this retrospective cohort study, we reviewed the database and medical records of pediatric patients (aged <18 years) in a single ED between May 1, 2016, and April 30, 2018. We first determined the proportion of nonconvulsive seizures among patients with altered mental status (Glasgow Coma Scale <15). We then compared the clinical presentation, demographic data, clinical diagnosis, EEG results, treatment, and outcomes of patients with altered mental status with nonconvulsive seizures and those without nonconvulsive seizures. RESULTS: In total, 16.9% of the patients with altered mental status (41 of 242; 95% CI, 12.2%-21.6%) evaluated by EEG had detectable nonconvulsive seizure, equivalent to 4.4% (41 of 932) of all patients with altered mental status presenting at our hospital. More than 80% of patients monitored for nonconvulsive seizures had a previous history of seizures, often febrile. Patients with nonconvulsive seizures were older (median, 68.5 vs 36.1 months) and had a higher Pediatric Cerebral Performance Category score at presentation (median, 2.0 vs 1.0). In addition, the proportion of patients admitted to the intensive care unit was significantly higher in the patients with nonconvulsive seizures (30.3% vs 15.0%). However, total duration of hospitalization, neurologic sequelae, and 30-day mortality rate did not differ between the 2 groups. CONCLUSIONS: A relatively high percentage of pediatric patients with altered mental status in the ED experience nonconvulsive seizures. The use of reduced-lead EEG monitoring in the ED might facilitate the recognition and treatment of nonconvulsive seizures, especially among patients with a history of seizures.

Lipid and thyroid hormone levels in children with epilepsy treated with levetiracetam or carbamazepine: A prospective observational study.

Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ±â€¯22.0 mg/dl, 1 month: 63.8 ±â€¯21.6 mg/dl, 6 months: 92.3 ±â€¯63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ±â€¯0.06 ng/dl, 1 month: 1.00 ±â€¯0.16 ng/dl, 6 months: 0.98 ±â€¯0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.

Diurnal occurrence of complex febrile seizure and their severity in pediatric patients needing hospitalization.

Several studies describing the diurnal occurrence of febrile seizures have reported greater seizure frequency early or late in the evening relative to midnight or early morning. However, no articles have reported on the diurnal occurrence of complex febrile seizure. Moreover, no studies have addressed the relationship between seizure severity and diurnal occurrence. We retrospectively evaluated complex febrile seizures in 462 children needing hospitalization, and investigated the relationship between severity and diurnal occurrence according to four categorized time periods (morning, afternoon, evening, and night). Our study showed that complex febrile seizures occurred most often in the evening, peaking around 18:00 (18:00-18:59), and least often at night (02:00-02:59). In addition, the frequency with which patients developed status epilepticus or needed anticonvulsant treatments was also lower during the night. However, the seizure duration and the proportion of the patients who needed anticonvulsant treatment were the same among the four time periods. Furthermore, we compared three subclasses (repeated episodes of convulsions, focal seizures, and prolonged seizures (≧15min)), two of the complex features (focal seizures and prolonged seizures), and all complex features among the four time periods. However, they were the same among the four time periods. Taken together, our data indicate that although the severity of seizures was stable over a 24-hour period, the occurrence of seizures in our cohort of pediatric patients with complex febrile seizures requiring hospitalization was highest in the evening and lowest at night.

Acute focal bacterial nephritis characterized by acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass, and some patients show deterioration of clinical condition with neurological symptoms. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome that is characterized by biphasic seizures and impaired consciousness with reduced diffusion in the subcortical white matter on magnetic resonance imaging, typically observed between days 3 and 9 after clinical onset. Although AFBN sometimes causes neurological symptoms, no cases of AFBN with AESD have been reported, and no studies have presented the cytokine profiles of patients with a severe form of acute encephalopathy with AFBN. We report here a very rare case involving a 6-month-old boy who developed AFBN due to Enterococcus faecalis with both the clinical and radiological features of AESD. In our patient, serum interleukin (IL)-6, IL-10, and interferon (IFN)-γ levels markedly increased on admission, and on day 4, only IL-6 levels significantly increased in the cerebrospinal fluid (CSF). These results suggest that high serum cytokines are produced locally in response to AFBN and elevated IL-6 levels in CSF may have neuroprotective roles.

Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases. METHODS: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique. RESULTS: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet-Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability. CONCLUSIONS: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.

A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency.

Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6-year-old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI-anchored protein that suggested autosomal recessive GPI deficiency. The case underwent target exome sequencing to screen for IGDs. Target exome sequencing of the proband identified an apparently homozygous c.808T > C (p.Ser270Pro) mutation in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents were expecting another child, genetic carrier screening was conducted for the parents. Direct sequencing of the parents identified a heterozygous c.808T > C PIGN mutation in the father but none in the mother. To identify the mother's mutation, we performed semi-quantitative real-time PCR of the PIGN exons and long PCR, identifying a microdeletion in PIGN (del exons 2-14). The proband had inherited this microdeletion from his mother. Prenatal diagnosis of the fetus revealed that it was a heterozygous carrier of the mother's pathogenic allele. Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation and the first case of prenatal diagnosis for GPI deficiency.

A pediatric patient with interstitial pneumonia due to enterovirus D68.

Enterovirus D68 (EV-D68) infection is associated with upper and lower respiratory tract symptoms such as fever, cough, and wheezing. Pediatric patients with EV-D68 infection easily develop more severe respiratory complications compared to patients infected with other species of enterovirus, and consequently, have a higher rate of hospitalization and admission to intensive care units. Therefore, the clinical picture of respiratory complications associated with EV-D68 infection needs to be elucidated. Here, we report a 4-year-old girl of EV-D68 infection that required artificial respiration management within 24 h from the onset of cold symptoms. The patient was diagnosed with interstitial pneumonia on the basis of chest imaging findings with patchy, funicular and frosted glassy shadows, increased blood markers of surfactant protein-A, surfactant protein-D and sialylated carbohydrate antigen KL-6, and increased neutrophils and lymphocytes in the bronchoalveolar lavage. Steroids showed a remarkable effect in her treatment. Further investigations are needed to confirm the efficacy of steroids for interstitial pneumonia due to EV-D68 infection. As rapid deterioration of respiratory status is observed in EV-D68 infection, the possibility of interstitial pneumonia may be considered.

[A woman with beta-propeller protein-associated neurodegeneration identified by the WDR45 mutation presenting as Rett-like syndrome in childhood].

Beta-propeller protein-associated neurodegeneration (BPAN) is one of the neurodegenerative disorders characterized by iron deposition in the brain and is the only known disease in humans to be caused by an aberration in autophagocytosis. Here, we present the case of a 42-year-old woman with BPAN identified by the WDR45 mutation. From early childhood, she was recognized as having global developmental delay, and she frequently sucked her hand, which was considered to be a stereotypical movement. She had a febrile convulsion at 6 months of age but there was no history of epilepsy. The delay in language development was more severe than the delay in motor development; she was able to dress herself, walk unaided, and follow simple instructions until adolescence. After the age of 20, her movement ability rapidly declined. By the time she was 42 years old, she was bedridden and unable to communicate. Brain magnetic resonance imaging (MRI) at 21 years revealed no abnormality except non-specific cerebral atrophy. However, MRI at 39 years revealed abnormalities in the globus pallidus and substantia nigra, with neurodegeneration and iron accumulation in the brain. Genetic analysis for WDR45 revealed that she had a splice site mutation (NM_007075.3: c.830 + 2 T > C) which was previously reported, and a diagnosis of BPAN was confirmed. For specific therapies to be developed for BPAN in the future, it is necessary to establish early diagnosis, including genetic analysis.

Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study.

OBJECTIVE: Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset. METHODS: We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years. RESULTS: In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL). CONCLUSIONS: This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.

Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion.

INTRODUCTION: Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes. METHODS: We studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children's Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS. RESULTS: Of the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013). CONCLUSION: The occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.

Early steroid pulse therapy for children with suspected acute encephalopathy: An observational study.

ABSTRACT: Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels.We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy.Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier.Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition.

Prediction of AESD and neurological sequelae in febrile status epilepticus.

OBJECTIVE: The 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: The 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.

Empyema necessitatis due to Pseudomonas aeruginosa in a child with cerebral palsy.

Empyema necessitatis (EN) is a rare complication of empyema in which the pleural infection spreads outside the pleural space. Lower airway infections are common among children with cerebral palsy (CP). Although harmless to healthy individuals, Pseudomonas aeruginosa can cause invasive infections, including CP, in immunocompromised hosts. Mycobacterium tuberculosis and Actinomyces spp. have been reported as common causative organisms of EN. However, EN caused by P. aeruginosa has never been reported. We report the case of an 8-year-old girl with CP without tracheotomy who was admitted to our hospital with complaints of fever and increased epileptic seizures. First, she was diagnosed with pneumonia and treated with antibiotics. However, seven days after admission, a palpable mobile mass overlying the lower part of the shoulder blade was noticed. Enhanced magnetic resonance imaging revealed broad high signal area on T2-weighted and diffusion-weighted images, indicating empyema of the left lower lung that had penetrated the pleural wall and spread to the subcutaneous area of the left back. Thus, she was diagnosed with EN. Twelve days after admission, P. aeruginosa was detected from the pus culture. Patients with CP who have chronic lung diseases, such as pneumonia, atelectasis, or empyema, may need careful follow up.

Detailed characteristics of acute encephalopathy with biphasic seizures and late reduced diffusion: 18-year data of a single-center consecutive cohort.

OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome characterized by biphasic seizures with impaired consciousness. AESD is rare outside Asia, and consecutive cohort studies are therefore scarce. Herein, we aimed to describe the detailed characteristics of AESD, including clinical course, electroencephalogram data, laboratory data, imaging findings, treatment, and outcomes. METHODS: We reviewed the clinical database and medical charts of 43 consecutive pediatric patients (<18 years old) who developed AESD between October 1, 2002, and September 30, 2019. RESULTS: We found that AESD occurred even though patients did not develop prolonged seizures. A comparison between the two groups (first seizure duration <30 min and first seizure duration ≥30 min) revealed three main findings: first, patients with AESD who had shorter seizures had better prognosis than those with prolonged seizures; second, patients with AESD who had shorter seizures tended to have earlier occurrence of a second seizure; and third, high signal intensity on diffusion-weighted magnetic resonance imaging was observed mainly in frontal areas, not diffusely, in patients with shorter seizures, and in a broader area in patients with prolonged seizures. CONCLUSIONS: Our description of the detailed clinical picture of AESD may add new insight into its pathophysiology.

Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children.

PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.