Hiroaki Nagase

Effects of child seats on the cardiorespiratory function of newborns

Background : This study aims to determine the effect of differently positioned infant car seats on cardiorespiratory parameters in healthy full‐term newborns.

Therapeutic indicators of acute encephalopathy in patients with complex febrile seizures

The aim of this study was to identify predictors of neurologic damage in children with febrile seizures or altered consciousness within 6 h of seizure onset.

Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing.

INTRODUCTION CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes. METHODS We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer. RESULTS We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boys karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance. CONCLUSIONS Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.

Targeted temperature management of acute encephalopathy without AST elevation

BACKGROUND Acute encephalopathy is a leading cause of mortality and neurological sequelae in children. Although many strategies have been proposed, effective therapies have not yet been established. The objective of this retrospective study was to assess the effectiveness of targeted temperature management in children with acute encephalopathy. METHODS We retrospectively evaluated the clinical courses and outcomes of 57 children who were consecutively admitted at Kobe Childrens Hospital between October 2002 and August 2011. These children had acute encephalopathy with serum aspartate aminotransferase (AST) levels below 90 IU/l within 6h of onset. We compared the clinical characteristics and neurological outcomes of children treated with targeted temperature management and those who received conventional care. Targeted temperature management was defined as temperature control (34.5-36°C) with intubation, and the continuous use of anticonvulsants and muscle relaxants induced within 24 h of onset. Outcome was measured using the Pediatric Cerebral Performance Category Scale with grade 1 representing a good clinical outcome and grades 2-6 reflecting poor outcomes. RESULTS Outcomes were good in all children treated with targeted temperature management (n=23) as well as in 24 out of the 34 children who received conventional care (p=0.004). The age, gender, refractory status epilepticus rate, prolonged neurological abnormality rate, preceding infection rate, and laboratory results were not significantly different between the two groups. CONCLUSIONS We determined that targeted temperature management could improve outcome in acute encephalopathy without AST elevation.

Demographics and Outcomes of Patients With Pediatric Febrile Convulsive Status Epilepticus

BACKGROUND Convulsive status epilepticus with fever is common and may be related to neurological sequela in children. However, there are limited data on the demographics and risk factors of this phenomenon. Thus, we aimed to describe the demographics and risk factors of neurological sequela among children with convulsive status epilepticus with fever. METHODS We reviewed convulsive status epilepticus with fever cases in the pediatric intensive care unit at Kobe Childrens Hospital between 2002 and 2013. We included patients with intrinsic neurological disease, and excluded those with obvious central nervous system infection. Cases of neurological worsening were categorized as poor outcome using the pediatric cerebral performance category scale. Possible risk factors for poor outcome included age, sex, neurological medical history, seizure duration, body temperature, and level of consciousness. RESULTS A total of 253 patients (128 males), aged 1 month to 15 years (mean 45 ± 40 months), were enrolled. Three patients (1.2%) died during hospitalization, and 32 (12.6%) patients had a poor outcome. A univariate analysis identified male sex, absence of epilepsy history, body temperature above 40°C on admission, seizure duration longer than 120 minutes, impaired consciousness at 12 hours after onset, and presence of nonconvulsive seizure as potential predictors of poor outcome. A multivariate analysis, revealed that an absence of epilepsy history (odds ratio = 11.18), body temperature above 40°C on admission (odds ratio = 3.39), or impaired consciousness at 12 hours after onset (odds ratio = 41.85) was associated with poor outcome. CONCLUSIONS Our study indicated that absence of epilepsy history, high temperature, and/or prolonged impaired consciousness were associated with brain injury.

Validity of Caregivers’ Reports on Head Trauma Due to Falls in Young Children Aged Less than 2 Years

Objective The clinical presentations of head trauma due to falls among young children aged less than 2 years are controversial, particularly in Japan, as the history of trauma recounted by a caretaker is not always reliable. The purpose of this study was to assess the validity of caregivers reports on head trauma due to falls in young children aged less than 2 years in Japan. Methods All patients <2 years of age presenting with head trauma resulting from a fall who were admitted to 3 childrens hospitals in Japan from January 2001 to December 2005 were retrospectively reviewed (N = 58). The clinical presentations were compared among groups categorized by the heights from which the patient fell (short (≤ 120 cm) or long (>120 cm)) and the surface on which the patient landed (carpet, tatami (Japanese mattress), hardwood floor, or concrete). Results Patients who suffered short falls were more likely to present with subdural hemorrhage (SDH) than those who suffered long falls (74% and 40%, respectively, P = 0.027). More specifically, 62% of short falls showed SDH indicative of shaken baby syndrome (e.g. multilayer SDH). Neurological symptoms, cyanosis, and SDH were more commonly observed inpatients who landed on carpeted or tatami surfaces than in those who landed on hardwood or concrete floors. Conclusions Short falls and landing on soft surfaces resulted in the presentation of severer clinical symptoms than did long falls and landing on hard surfaces, suggesting that the validity of caretakers’ reports on infant or young childrens head trauma due to falls is low. Further research is warranted to investigate the cause of infant head trauma due to falls.

Short and long-term outcomes in children with suspected acute encephalopathy

BACKGROUND The time-dependent changes that occur in children after acute encephalopathy are not clearly understood. Therefore, we assessed changes in brain function after suspected acute encephalopathy over time. METHODS We created a database of children admitted to the pediatric intensive care unit at Kobe Childrens Hospital because of convulsions or impaired consciousness with fever between 2002 and 2013. Clinical courses and outcomes were reviewed and patients who met the following criteria were included in the study: (1) 6months to 15years of age, (2) no neurological abnormality before onset, (3) treated for suspected acute encephalopathy, and (4) followed after 1 (0-2) month and 12 (10-17) months of onset. Outcomes were assessed using the Pediatric Cerebral Performance Category (PCPC) scale, with a score of 1 representing normal performance; 2, mild disability; 3, moderate disability; 4, severe disability; 5, vegetative state; and 6, brain death. RESULTS A total of 78 children (32 male) with a median (range) age at onset of 20 (6-172) months were enrolled. Fifty-one cases scored 1 on the PCPC, 13 scored 2, three scored 3, five scored 4, one scored 5, and five cases scored 6 at discharge. Whereas seven of the 13 cases that scored a 2 on the PCPC recovered normal brain function after 12months, none of the nine cases that scored a 3-5 on the PCPC recovered normal function. CONCLUSIONS Our findings suggest moderate to severe disability caused by acute encephalopathy had lasting consequences on brain function, whereas mild disability might result in improved function.

Two cases of traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) presents a distinct clinical course of biphasic seizures and impaired consciousness. These symptoms are followed by reduced diffusion in the subcortical white matter on magnetic resonance imaging that is typically observed between 3 and 9 days after illness onset. Here, we report two cases of traumatic head injury with clinical and radiological features similar to those for AESD. The similarities between our cases and AESD may be useful in understanding the pathogenesis of AESD.

Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus.

Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure.

Non-convulsive seizures in children with infection-related altered mental status

In the intensive care unit, the use of continuous electroencephalography (cEEG) in children with altered mental status often results in the detection of non‐convulsive seizures (NCS). Children with influenza can occasionally display altered mental status, but the prevalence of NCS in children with influenza with altered mental status is yet to be determined. This study determined the prevalence of NCS in pediatric patients with altered mental status associated with influenza A(H1N1)pdm09 infection.