Akihiro Yasuhara

Epilepsy with Continuous Spike‐Waves During Slow Sleep and Its Treatment

SUMMARY: Five children with epilepsy with “continuous spike‐waves during slow sleep” (CSWS) are reported. The main clinical features of CSWS include (a) onset between 5 and 7 years of age, (b) the occurrence of several types of seizure (i.e., partial motor, generalized motor, and atypical absence), and (c) the presence of language disturbances and abnormal behavior based on emotional impairment. The EEG findings were characterized by sleep tracings showing almost continuous (>95%), diffuse slow spike and wave activity. After treatment with valproate (VPA) (or ethosuximide, ESM) and clonazepam (CZP), the spike and wave complex status disappeared. Symptoms and signs of the CSWS also decreased. We suggest that combined treatment is an appropriate treatment for CSWS.

Angelman Syndrome in Three Siblings: Characteristic Epileptic Seizures and EEG Abnormalities

Summary: Neurologic findings in 3 siblings with Angelman syndrome (AS) with apparently normal karyotype but DNA deletion of 15q11‐q12 deriving from their mother are described. Increased auditory brainstem response (ABR) thresholds were noted in all 3. Interictal EEG findings included periodic 2‐ to 3‐Hz high‐voltage slow wave bursts bioccipitally and sporadic slow spike wave complexes mainly bifrontally. EEG findings suggestive of minor epileptic status were apparent in the elder brother and may be a characteristic feature in young AS patients. Seizures suggestive of generalized epilepsy have been reported in 90% of AS patients. AS is considered a good model of symptomatic generalized epilepsy associated with chromosomal DNA deletion of the (GABA), receptor β3‐subunit gene.

Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD)

Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Childrens Clinic in Osaka, Japan, were included in this study. Each participants EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms.

Successful control with bromide of two patients with malignant migrating partial seizures in infancy

A 3-month-old male and a 4-month-old female infant with intractable seizures were diagnosed as having malignant migrating partial seizures in infancy (MMPSI) with developmental arrest on the basis of characteristics of symptoms, clinical courses and EEGs. We treated these two patients with potassium bromide (80 mg/kg) after conventional antiepileptic drugs failed to adequately control the seizures. The potassium bromide therapy resulted in complete control of seizures in one patient, and more than 95% reduction in seizure frequency in the other.

Genotype–phenotype correlations in alternating hemiplegia of childhood

Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype–phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. Results: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. Conclusions: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

Life-Threatening Infantile Diarrhea from Fluoroquinolone-Resistant Salmonella enteric Typhimurium with Mutations in Both gyrA and parC

Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella.

When do brain abnormalities in cerebral palsy occur? An MRI study

The authors used MRI to analyse retrospectively the brain images of patients with cerebral palsy (CP) to evaluate its the role in the assessment of brain abnormalities and injury, and the relationship of pre‐, peri‐ and postnatal events to CP. 70 patients with CP aged two to 16 years who underwent MRI were divided into four groups: group 1 (26 patients) comprised subjects whose CP was considered to have been caused by neuronal migration disorders in the embryonal stage; group 2 (30 patients) contained subjects whose cause was vascular disorders; in group 3 patients (five) the cause was intra‐uterine infection; and CP clearly attributable to birth asphyxia (group 4) was noted in only nine patients. The results indicate that CP of term infants is often the result of prenatal factors, and their MRI findings indicated migration and cerebral infarction. Brain MRI is an essential examination in identifying the factors causing brain damage in CP.

Mutation analysis of methyl-CpG binding protein family genes in autistic patients

Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patients father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC)4 to 5, were detected in MBD2, and several polymorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis.

Blink reflex elicited by auditory stimulation in the rabbit

The pathway of the blink reflex, elicited by auditory stimulation, was investigated electrophysiologically. The reflex was recorded as microvibrations of the eyelid and was named the auditory-evoked eyelid microvibration (AMV). Pharmacophysiological studies suggest that AMV is closely related to the midbrain reticular formation and studies of electrical lesions in the midbrain reticular formation support this. Lesions in several parts of the central nervous system provide evidence that the inferior colliculus has an important role in AMV, and the cerebral cortex may have an inhibitory influence. Studies of brainstem transections indicate that the reflex pathway of AMV exists between the lower midbrain and the upper medulla. Because of its ease and simplicity, AMV is believed to be a useful test for evaluation of the function of the brainstem.

Reye-like syndrome associated with valproic acid

A case of a Reye-like syndrome during the course of treatment with VPA was reported. Hyperammonemia and severe liver damage as well as diffuse small droplets in the liver biopsy material were demonstrated. On analysis by gas chromatography/mass spectrometry of the urine immediately after the onset, the metabolites of VPA were detected together with lactate and other substances, and electron microscopic observation of liver biopsy material revealed deformation of mitochondria, disappearance of cristae and electron dense deposits in the matrix.