Acute disseminated encephalomyelitis in China, Singapore and Japan: a comparison with the USA.

BACKGROUND AND PURPOSE: Ethnicity-related differences in the incidence of acute disseminated encephalomyelitis (ADEM) and other demyelinating diseases including multiple sclerosis and neuromyelitis optica spectrum disorders have been reported. Little is reported on the influence of ethnicity and geographical location in ADEM. METHODS: Medical records of patients who presented with ADEM (ICD-9 323.61 and 323.81) at large referral hospitals in China, Singapore and Japan (years 1992-2015) were retrospectively reviewed and data were collected in a centralized database. Presenting features and outcomes of ADEM were compared between this multi-country Asian cohort and a uniformly collected US cohort using risk differences and risk ratios. Both cohorts were standardized to a 35% pediatric population to facilitate the comparison. RESULTS: There were 83 Asian patients (48 male, 16 pediatric) followed for a median of 2 (25th-75th percentile 1-10) months. Asian patients exhibited a 26% higher prevalence of spinal cord involvement on magnetic resonance imaging [95% confidence interval (CI) 0-52%; P = 0.05; 63% vs. 37%], a 39% lower prevalence of preceding events (95% CI 12-65%; P < 0.01; 33% vs. 72%) and a 23% lower prevalence of corpus callosum involvement (95% CI 7-39%; P < 0.01; 8% vs. 31%). No difference was observed between the two cohorts in the probability of relapse over the first year after disease onset. CONCLUSIONS: It is hypothesized that the high proportion of Asian patients with spinal cord lesions relates to genetic vulnerability or the higher incidence of neuromyelitis optica spectrum disorders in Asia or could be a spurious association. ADEM presentations most probably vary across geographical settings or ethnicities.

Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Transient and mild reduction of consciousness during febrile illness in children.

We have studied the clinical and neuroimaging characteristics of transient and mild reduction of consciousness during febrile illness in children. We retrospectively evaluated 58 children admitted with mild reduction of consciousness within 12 h during febrile illness. 53 patients (91%) had delirious behavior, and 5 (9%) had no delirious behavior. We also compared the clinical characteristics, brain magnetic resonance imaging (MRI) findings, and electroencephalography (EEG) findings between patients with and without delirious behavior, and no statistically significant differences were observed in any of them between the 2 patient groups (P≥0.05). MRI was performed 0-4 days after onset in 23 patients. Reversible splenial or callosal and white matter lesions were observed in 2 of 3 patients without delirious behavior vs. 4 of 20 patients with delirious behavior on diffusion-weighted images. EEG was performed 0-3 days after onset in 29 patients. Transient abnormal findings were observed in 3 of 4 patients without delirious behavior vs. 11 of 25 patients with delirious behavior. In conclusion, we consider that transient and mild reduction of consciousness during febrile illness is a unique clinical group that is constituted by children both with and without delirious behavior.

Longitudinal Findings of MRI and PET in West Syndrome with Subtle Focal Cortical Dysplasia.

BACKGROUND AND PURPOSE: Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes of MR imaging and FDG-PET in patients with West syndrome and subtle focal cortical dysplasia. MATERIALS AND METHODS: Among 52 consecutive patients with West syndrome, 4 were diagnosed with subtle focal cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated longitudinally at onset and at 12 and 24 months of age. RESULTS: At the onset of West syndrome, MR imaging demonstrated focal signal abnormalities of the subcortical white matter in 2 patients. In the other 2 patients, focal subcortical high-intensity signals became visible on follow-up T2WI as myelination progressed. PET at onset showed focal cortical hypometabolism in 3 patients, with 1 of these patients also having focal hypermetabolism and 1 having normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal MR imaging and PET findings at onset, focal hyperintensity and hypometabolism first appeared at 24 months of age. The findings on MR imaging and PET in these patients evolved differently with brain maturation and the clinical course. CONCLUSIONS: Subtle focal cortical dysplasia can be undetectable on MR imaging at the onset of West syndrome and is not always accompanied by hypometabolism or hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for detecting such lesions. Even in West syndrome with a congenital structural abnormality, PET findings evolve differently with brain maturation and the clinical condition.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures.

OBJECTIVES: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG. METHODS: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities. RESULTS: Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients. CONCLUSIONS: Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures.

OBJECTIVES: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG. METHODS: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities. RESULTS: Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients. CONCLUSIONS: Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Predominant area of brain lesions in neonates with herpes simplex encephalitis.

OBJECTIVE: Nonspecific manifestations and a varied distribution of brain lesions can delay the diagnosis of herpes simplex encephalitis (HSE) in neonates. The aim of this study was to report predominant brain lesions in neonatal HSE, and then to investigate the association between pattern of predominant brain lesions, clinical variables and neurodevelopmental outcome. STUDY DESIGN: A multicenter retrospective study was performed in neonates diagnosed with HSE between 2009 and 2014. Magnetic resonance (MR) images, including diffusion-weighted images, were obtained in the acute and chronic phase. RESULTS: Three predominant areas of brain injury could be defined based on characteristic MRI findings in 10 of the 13 infants (77%). The inferior frontal/temporal pole area was involved in five (38%) patients. The watershed distribution was present in six (46%) patients. Four (31%) infants involved the corticospinal tract area. No significant association was found between any predominant distribution of brain lesion pattern and sex, country, viral type or viral load. However, the corticospinal tract involvement was significantly associated with motor impairment (P=0.045). CONCLUSION: Three predominant areas of brain lesion could be recognized in neonatal HSE. Recognition of those areas can improve prediction of neurodevelopmental outcome.

White Matter Abnormality Correlates with Developmental and Seizure Outcomes in West Syndrome of Unknown Etiology.

BACKGROUND AND PURPOSE: West syndrome is an epileptic encephalopathy characterized by epileptic spasms, a specific pattern on electroencephalography of hypsarrhythmia, and developmental regression. Our aim was to assess white matter abnormalities in West syndrome of unknown etiology. We hypothesized that diffusion tensor imaging reveals white matter abnormalities, especially in patients with poor seizure and developmental outcomes. MATERIALS AND METHODS: We enrolled 23 patients with new-onset West syndrome of unknown etiology. DTI was performed at 12 and 24 months of age. Fractional anisotropy images were compared with those of controls by using tract-based spatial statistics. We compared axial, radial, and mean diffusivity between patients and controls in the fractional anisotropy skeleton. We determined correlations of these parameters with developmental quotient, electroencephalography, and seizure outcomes. We also compared DTI with hypometabolism on fluorodeoxyglucose positron-emission tomography. RESULTS: At 12 months of age, patients showed widespread fractional anisotropy reductions and higher radial diffusivity in the fractional anisotropy skeleton with a significant difference on tract-based spatial statistics. The developmental quotient at 12 months of age correlated positively with fractional anisotropy and negatively with radial and mean diffusivity. Patients with seizure and abnormal findings on electroencephalography after initial treatments had lower fractional anisotropy and higher radial diffusivity. At 24 months, although tract-based spatial statistics did not show significant differences between patients and controls, tract-based spatial statistics in the 10 patients with a developmental quotient of <70 had significant fractional anisotropy reduction. In patients with unilateral temporal lobe hypometabolism on PET, tract-based spatial statistics showed greater fractional anisotropy reduction in the temporal lobe ipsilateral to the side of PET hypometabolism. CONCLUSIONS: Diffuse abnormal findings on DTI at 12 months of age suggest delayed myelination as a key factor underlying abnormal findings on DTI. Conversely, asymmetric abnormal findings on DTI at 24 months may reflect underlying focal pathologies.

A nationwide survey of pediatric acquired demyelinating syndromes in Japan.

OBJECTIVE: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. METHODS: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. RESULTS: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34-0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58-0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04-0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group. CONCLUSIONS: Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population.

Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers).

An infant who demonstrated clinical features compatible with total asphyxia is reported. Immediately after birth, the patient manifested severe hypotonia and total absence of cranial nerve functions. Magnetic resonance imaging revealed abnormal intensity of the thalamus and putamen, and atrophy of the brainstem. Late components of brainstem auditory evoked potential were absent, but electroencephalography was normal. Postmortem autopsy revealed destructive lesions of the brainstem tegmentum, thalamus, basal ganglia, and spinal cord, but preserved cerebral cortex; findings consistent with those of total asphyxia as reported by Myers, and attributable to prenatal insult.

Cryptogenic localization-related epilepsy of neonatal onset.

We report three patients with localization-related epilepsy of neonatal onset. They exhibited favourable psychomotor development and had no cerebral lesions on neuroimaging studies despite the presence of intractable partial seizures of neonatal onset. Although rare, some cases of epilepsy of neonatal onset may be cryptogenic, i.e. they belong to neither the symptomatic nor the idiopathic group.

[Clinical studies on S-1108 in the field pediatrics].

Clinical studies on S-1108, a new oral cephem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. The peak plasma level of S-1006 when administered after meal at a dose of 4 mg/kg was 2.47 micrograms/ml at an hour, and the serum half-life was 0.81 hour. The 4 hours urinary excretion rate of S-1006 was 35.7%. 2. S-1108 was administered to 15 children with various infections (3 patients with pneumonia, 3 with acute bronchitis, 4 with scarlet fever, 2 with acute tonsillitis, 1 with phlegmon and 2 with urinary tract infections). The overall clinical efficacy rate was 100%. 3. Side effects or abnormal laboratory test values were not observed except for diarrhea in 1 and eosinophilia in 1.

[Laboratory and clinical studies on meropenem in pediatrics].

Laboratory and clinical studies on meropenem (MEPM), a new carbapenem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. The antibacterial activities of MEPM against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous drip infusion of MEPM at a dose of 20 mg/kg to 2 children, the mean peak plasma level of MEPM was 32.7 micrograms/ml at the end of infusion with a mean half-life of 1.45 hours. The mean cumulative urinary recovery rate in the first 6 hours after infusion was 43.6%. 3. Fifteen patients with various bacterial infections were treated with MEPM. The clinical efficacy rate was 100% and the bacteriological efficacy rate was 95.2%. 4. No side effects were observed except in 1 case of mild diarrhea. Some abnormal laboratory test results were obtained, but they were mild with slight elevations of GOT and GPT in 2 cases.

[The prognostic value of neonatal cranial ultrasonography in infants with periventricular leukomalacia].

Serial cranial ultrasonography was performed in 17 preterm infants with periventricular leukomalacia (PVL) in the neonatal period. Periventricular high-echogenicities were observed in all infants, and periventricular cysts in 14/17 infants (82%). We investigated the correlation between these findings and abnormalities on MRI in late infancy. Periventricular high-echogenicity was correlated with the extent of periventricular high-intensities on T2-weighted images of late infantile MRI. The extent of periventricular cysts was correlated with that of volume loss on MRI during late infancy. The degree of periventricular echo-lesion was associated with that of neurological abnormalities of infants. The extent of periventricular echo-lesion has the same prognostic value as findings on MRI in infants with PVL.

[The prognostic value of brain CT scan in infants with periventricular leukomalacia].

Brain CT scan was performed at 40 weeks of conceptional age in 17 preterm infants with periventricular leukomalacia (PVL). The finding of periventricular low density was not useful in differentiating patients with PVL from normal infants, because this finding was seen in 40% of normal infants. The following findings were characteristic of PVL: (1) a marked low density area in centrum semiovale, (2) an irregular outline of ventricular wall, and (3) low density spots in periventricular white matter. The findings of ventricular dilation with irregular wall and marked low density area in centrum semiovale were correlated with a finding of volume loss on MRI during late infancy and the severity of neurological impairment, especially in severely affected patients. Marked low density area in centrum semiovale was characteristic of severe PVL demonstrated on brain CT scan.

[Dramatic improvement with immunoabsorption therapy in a 7-year-old girl with severe Guillain-Barré syndrome after unsuccessful gammaglobulin therapy].

We report a 7-year-old girl with severe Guillain-Barré syndrome (GBS) who showed dramatic improvement after immunoabsorption therapy. She had progressive muscle weakness with resultant respiratory failure. On the 7th day of the illness, she was nearly quadriplegic and dependent on mechanical ventilation. In addition, she had autonomic manifestations, areflexia, abolished or delayed peripheral nerve conduction, and increased CSF protein. Administration of a high dose of gammaglobulin failed to improve the symptoms. Immunoabsorption therapy using a tryptophan column was performed 9 times during 17 days. After 5 times of immunoabsorption therapy, the muscle weakness improved dramatically; she was extubated 16 days after the institution of the therapy and walked without assistance on the 41st day. She regained normal muscle power without any sequelae. The immunoabsorption therapy caused hemolysis and decrease of serum fibrinogen, but no serious complications. The clinical course of this patient suggests the efficacy of immunoabsorption therapy in GBS.

Paradoxical downward seizure pattern on amplitude-integrated electroencephalogram.

The use of amplitude-integrated electroencephalography (aEEG) to assess brain function and detect seizures has been increasing worldwide. Results from previous studies have demonstrated that seizure patterns can be recognized as transient rises on aEEG traces. We report here a case of an infant with neonatal seizures that showed paradoxical transient drops on aEEG traces. The ictal EEG showed initial low-amplitude fast rhythmic activity followed by epileptic recruiting rhythms and high-voltage slow waves. Therefore, downward patterns on aEEG traces should be recognized as suspected seizure patterns.

PET in infancy predicts long-term outcome during adolescence in cryptogenic West syndrome.

BACKGROUND AND PURPOSE: Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome. MATERIALS AND METHODS: From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated. RESULTS: At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03). CONCLUSIONS: Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.

Electroencephalogram and flash visual evoked potentials for detecting periventricular leukomalacia.

OBJECTIVE: The aim of this study was to evaluate the usefulness of a combination of electroencephalogram (EEG) and flash visual evoked potentials (FVEPs) for predicting periventricular leukomalacia (PVL) in the early days of life. STUDY DESIGN: Eighty-six of 108 infants admitted to Anjo Kosei Hospital during 1998 through 2000 were enrolled in this study. All subjects underwent EEG and FVEP during the early neonatal period and were followed-up until 18 months of corrected age. EEG was performed once within 72 h after birth, every 1-2 weeks during the first month and every 2-4 weeks during the second month. FVEPs were recorded at least twice, at the first and the second week of life. RESULTS: Of the 86 infants, 13 were diagnosed as having PVL. Among them, EEG abnormalities were observed in 11 infants and FVEP abnormalities in 10. The sensitivity and specificity of EEG were 0.85 and 0.95, respectively. The sensitivity and specificity of FVEPs were 0.77 and 0.96, respectively. All except one (92%) infant with PVL had EEG and/or FVEP abnormalities. CONCLUSIONS: The combination of EEG and FVEPs can increase the sensitivity, but reduces the specificity to identify infants with PVL. The combination can makes up for the shortcomings of each method.