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 follows244 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.
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.
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.
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).
Three predominant areas of brain lesion could be recognized in neonatal HSE. Recognition of those areas can improve prediction of neurodevelopmental outcome.
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.
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.
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.
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.
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.
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.
Experimental work in animal models of generalized epilepsy and clinical data in humans with idiopathic generalized epilepsy (IGE) indicate that the thalamo‐cortical circuitry is involved in the ...generation of epileptic activity. The purpose of this study was to evaluate in vivo the chemical and structural integrity of the thalamus in patients with IGE. Thalamic proton magnetic resonance spectroscopic imaging (1H‐MRSI), measuring N‐acetylaspartate (NAA), choline‐containing compounds and creatine (Cr) was performed in 20 IGE patients and in a group of age‐matched healthy subjects. Additionally, 1H‐MRSI measurements were taken in the insular cortex, the posterior temporal lobe white matter and the splenium of the corpus callosum. MRI volumetric analysis of the thalamus was performed in all patients. At the time of the examination, seizures were well controlled in 10 IGE patients and poorly controlled in nine. One patient was newly diagnosed and had the MRI and MRSI examination prior to starting the antiepileptic medication. In IGE patients, 1H‐MRSI showed a reduction of mean thalamic NAA/Cr compared with normal controls; no difference was found in NAA/Cr in the other examined areas. There was no difference in NAA/Cr between patients whose seizures were well controlled and those in whom seizures were not controlled. There was no correlation between thalamic NAA/Cr and mean number of spike and wave complexes. We found a significant negative correlation between thalamic NAA/Cr and duration of epilepsy. The mean thalamic volume in patients with IGE was not different from normal controls. These results show evidence of progressive thalamic neuronal dysfunction in patients with IGE supporting the notion of abnormal thalamo‐cortical circuitry as a substrate of seizure generation in this form of epilepsy. The thalamic dysfunction may occur regardless of amount of spike and wave activity.
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.
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