Jun Natsume

MRI volumetry of the thalamus in temporal, extratemporal, and idiopathic generalized epilepsy.

Objective: To examine the specificity of thalamic atrophy in epilepsy. Methods: Thalamic volume measurements were carried out using high-resolution MRI in 40 patients with pharmacologically intractable temporal lobe epilepsy (TLE), 16 patients with extratemporal lobe epilepsy (ETE), and 17 with idiopathic generalized epilepsy (IGE). Thalamic volumes of patients were compared with those of 21 neurologically normal control subjects. Volumes were correlated with duration of epilepsy. The effect of prolonged febrile seizures and generalized seizures on thalamic volumes was examined. Results: Compared with normal control subjects, patients with TLE had a reduction in thalamic volume ipsilateral to the seizure focus. Thalamic volumes in patients with ETE and IGE were not significantly different from those of normal control subjects. In TLE patients, thalamic volumes ipsilateral to the seizure focus were negatively correlated with duration of epilepsy. Patients with a history of prolonged febrile seizures had more severe thalamic atrophy ipsilateral to the seizure focus than those without febrile seizures. Conclusions: Thalamic atrophy ipsilateral to the seizure focus is found in TLE but not in other forms of focal epilepsy or IGE. In TLE, thalamic atrophy is correlated with duration of disease. Patients with a history of prolonged febrile seizures had smaller thalamic volumes ipsilateral to the seizure focus than those without.

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.

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

Objectivesu2002–u2002 To assess hippocampal volumes (HV) and signal changes on diffusion‐weighted imaging (DWI) within 5u2003days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG.

Cortical Hypometabolism and Delayed Myelination in West Syndrome

Summary: Purpose: We examined the relation between cortical hypometabolism and delayed myelination in patients with West syndrome (WS).

Transient splenial lesions in children with “benign convulsions with gastroenteritis”

Benign convulsions with mild gastroenteritis (CwG) is recognized as a benign situation-related seizure. Neuroimaging studies usually do not reveal any abnormalities. We report MRI diffusion-weighted image (DWI) findings of two patients who were clinically diagnosed with CwG. DWI demonstrated a transient abnormality in the splenium of the corpus callosum. Although viral encephalitis or encephalopathy should be carefully differentiated in patients clinically diagnosed with CwG, frequent seizures might cause transient splenial abnormality in patients with CwG.

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan.

OBJECTIVESnWe conducted a nationwide survey of glucose transporter type-1 deficiency syndrome (GLUT-1DS) in Japan in order to clarify its incidence as well as clinical and laboratory information.nnnSUBJECTS AND METHODSnA questionnaire to survey the number of genetically and clinically confirmed cases of GLUT-1DS was sent to 1018 board-certified pediatric neurologists, which resulted in 57 patients being reported. We obtained the clinical and laboratory data of 33 patients through a secondary questionnaire.nnnRESULTSnThe age of the 33 patients (male: 15, female: 18) at the time of the study ranged between 3 and 35 years (mean: 13.5 years). The age of these patients at the onset of initial neurological symptoms ranged between the neonatal period and 48 months (mean: 9.4 months). GLUT-1DS was diagnosed at a mean age of 8.4 years (range: 1 year to 33 years). The initial symptom was convulsive seizures, which occurred in 15 cases, and was followed by abnormal eye movements in 7 cases and apneic or cyanotic attacks in 4 cases. The latter two symptoms most frequently occurred early in infancy. Thirty-two patients (97%) exhibited some type of epileptic seizure. Neurological findings revealed that most patients had muscle hypotonia, cerebellar ataxia, dystonia, and spastic paralysis. Mild to severe mental retardation was detected in all 33 cases. Furthermore, paroxysmal episodes of ataxia, dystonia/dyskinesia, and motor paralysis were described in approximately 1/3 of all patients. The factors that frequently aggravated these events were hunger, exercise, fever, and fatigue, in that order. The mean CSF/blood glucose ratio was 0.36 (0.28-0.48). Pathological mutations in the SLC2A1 gene were identified in 28 out of 32 cases (87.5%).nnnCONCLUSIONnThe results described herein provided an insight into the early diagnosis of GLUT1-DS, including unexplained paroxysmal abnormal eye movements, apneic/cyanotic attacks, and convulsive seizures in infancy, as well as uncommon paroxysmal events (ataxia, atonia, and motor paralysis) in childhood.

Electroencephalographic (EEG) findings in posterior reversible encephalopathy associated with immunosuppressants.

Posterior reversible encephalopathy has been reported in patients who receive immunosuppressants. Compared with radiologic studies, electroencephalographic (EEG) findings are not well described. We performed EEG serially in three children who suffered from posterior reversible encephalopathy associated with tacrolimus or cyclosporine. EEG showed continuous focal rhythmic activities in the acute period. EEG findings normalized after the clinical manifestations had disappeared. We conclude that EEG is useful for the diagnosis and follow-up of posterior reversible encephalopathy. (J Child Neurol 2006;21: 620—623; DOI 10.2310/7010.2006.00147).

Clinical and neuroimaging findings in children with posterior reversible encephalopathy syndrome

OBJECTIVEnTo clarify the clinical and radiological spectrum of posterior reversible encephalopathy syndrome (PRES) in children, and to identify the prognostic factors.nnnMETHODSnThe records of 40 children with PRES were reviewed. Acute clinical symptoms, MRI including apparent diffusion coefficient (ADC) maps in the acute and follow-up periods and neurological sequelae, including epilepsy, were noted.nnnRESULTSnAge at onset ranged from 2 to 16 years. Underlying disorders were hematological or neoplastic disorders (nxa0=xa020), renal diseases (nxa0=xa014) and others (nxa0=xa06). In the acute period, 31 patients had seizures, 25 had altered consciousness, 11 had visual disturbances and 10 had headache. Of 29 patients who had ADC maps in the acute period, 13 had reduced diffusivity as shown by ADC within PRES lesions. Of 26 patients with follow-up MRI, 13 had focal gliosis or cortical atrophy. No patients had motor impairment, and four patients had focal epilepsy. No clinical variables were associated with focal gliosis or cortical atrophy on follow-up MRI, but lesional ADC reduction in the acute period was prognostic for focal gliosis or cortical atrophy on follow-up MRI (pxa0=xa00.005).nnnCONCLUSIONSnTo the best of our knowledge, this is the largest cohort study to date involving PRES in children. Acute symptoms in pediatric patients are similar to those reported in adults, but altered consciousness was more frequent in children. Lesional ADC reduction in the acute period was common and was a good predictor of later, irreversible MRI lesions.

A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma.

Osteopathia striata with cranial sclerosis (OSCS) is an X‐linked dominant sclerosing bone dysplasia. Typically affected females show macrocephaly, characteristic facial appearance, cleft palate, mild learning difficulties, hearing loss, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis and scapulae. Typically affected males usually die at the fetal or early neonatal stage. Because of its variable expressivity, which ranges from asymptomatic to fetal death, clinical diagnosis of OSCS can be difficult. Here, we identify a unique female patient presenting with severe macrocephaly, characteristic facial appearance, developmental delay, and hepatoblastoma. Exome sequencing identified a novel de novo nonsense mutation (c.1045C>T, p.Glu349*) in the WTX gene associated with OSCS. The OSCS diagnosis was confirmed in this patient based on the hallmark appearance of longitudinal striations in long bones when viewed by X‐ray. WTX is also known as a tumor suppressor gene, and somatic mutations in that gene have been identified in Wilms tumors. In addition to this patient, although two patients with OSCS have been reported to have colorectal cancer or ovarian cancer, Wilms tumor has never been reported in association with this disorder. Tumor susceptibility in patients with OSCS is discussed.

Delayed myelination in West syndrome

Intractable epileptic seizures beginning at infancy is a major problem because maturation of the central nervous system tends to be attributed to seizure disorder in this period. It is well known that age-dependent epileptic encephalopathies, such as early infantile epileptic encephalopathy, the West and Lennox-Gastaut syndromes, constitute a major part of intractable epilepsy in infancy despite intensive AED treatment. In this study generalized epilepsies were observed in 15 cases which including four cases of myoclonic-astatic epilepsy and two cases of Lennox-Gastaut syndrome. Also, SE-MISF was observed in nine cases. Severe epilepsy with MISF which shows clinically generalized seizures despite multiple independent cortical spike foci in the EEG has been reported. The clinico-electroencephalographic haracteristics are as follows: (i) the monoseizure type of tonic spasms was mainly observed; (ii) seizures and complications of both mental and motor disturbances were frequently observed; (iii) SE-MISF tended to be transitioned from agedependent epileptic encephalopathy; and (iv) disorganized EEG background activities and abnormal sleep pattern such as rapid rhythm and clusters of the fast activity were frequently seen. Eight of nine cases with SE-MISF were followed by West syndrome, and most cases had the monoseizure type of tonic spasms and/or not only tonic spasms but also other seizures (myoclonic, atypical absence, complex partial seizures). Noriega-Sanchez and Markand reported that abnormality of independent multifocal spike discharges on the EEG can occur at any age, but was more frequent between 4 and 7 years.2 Additionally, most patients had extensive bilateral cerebral lesions which occurred in the prenatal, perinatal or postnatal periods. In this study all but one case had definite underlying pathologies and 25 (50%) of 30 cases had pathologies contributing to the pre/perinatal abnormalities. This study suggests that multiple independent spike discharges on the EEG were frequently observed in intractable epilepsy beginning at infancy and those which may have originated from pre/perinatal abnormalities.