Characterization of childhood-onset complex partial seizures associated with autism spectrum disorder.

Autism spectrum disorder (ASD) has a close relationship with epilepsy. A previous study showed complex partial seizures (CPS) to be the most frequent type of epileptic seizures in cases of ASD. Patients with childhood-onset CPS were retrospectively studied to investigate the prevalence of ASD and to characterize the association between CPS and ASD. The study cohort comprised 86 patients with CPS manifesting at 1 to 9 years of age. Symptomatic CPS and Panayiotopoulos syndrome were excluded. Patients with ASD (ASD group) were compared with those without ASD (non-ASD group). Of the 86 patients with childhood-onset CPS, 36 (42%) also had ASD. This ASD group was predominantly male (68.6%), with higher rates of intellectual disability (69%), and reported frequent seizures (60% had monthly or more frequent seizures). CPS without secondary generalization were more common in the ASD group (69%) than in the non-ASD group (36%), as were frontal paroxysms on EEG (54.5% vs 30%, respectively). In the non-ASD group, 82% of cases had been seizure free for 2 or more years, in comparison to 50% in the ASD group. ASD is frequently associated with childhood-onset CPS. Male gender, cognitive deficits, frequent seizures, and frontal paroxysms are risk factors for the association of ASD with CPS.

Classic Rett syndrome in a boy with R133C mutation of MECP2.

About 80% of female patients with Rett syndrome (RTT) display a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, but most males with MECP2 mutation experience severe fatal encephalopathy or non-specific X-linked mental retardation (XLMR). The existence of male RTT has been extensively discussed. We report herein a boy with classic RTT in a family with a missense mutation in MECP2. The mother exhibited slight mental retardation and was a carrier for R133C. The patient could stand with support at 12-months-old, and stereotypic hand movements appeared at 3-years-old. He became bed-ridden by 8-years-old. The R133C mutation was present in MECP2 without somatic mosaicism. A sister with R133C displayed classic RTT. The R133C mutation has been detected in female patients with classic and preserved speech variant RTT, but not in males with non-specific XLMR. These results suggest that clinical phenotypes caused by DNA mutation in MECP2 are determined by position of the mutation in the gene, and R133 represents a critical amino acid residue in the induction of RTT symptoms in humans.

Possible contribution of interferon-alpha to febrile seizures in influenza.

The systemic symptoms associated with influenza infection are mainly attributable to cytokines. To elucidate whether the high incidence of creatine kinase elevation and febrile seizures in influenza infection could be related to cytokines, we examined the serum levels of creatine kinase and cytokines (interferon-alpha, interleukin-6, and tumor necrosis factor-alpha) in patients with influenza and other febrile illness. Among those in the influenza group, 12 of 43 patients demonstrated elevated levels of creatine kinase (more than 200 IU/L), whereas in the control group two of 14 patients demonstrated elevated creatine kinase levels. When age was limited to under 7 years, seven of 32 patients (21.9%) in the influenza group had febrile seizures, whereas one of seven patients (14.3%) had a seizure in the control group. The influenza group demonstrated significantly high levels of interferon-alpha and interleukin-6. There was no correlation between cytokine levels and duration of fever or serum creatine kinase levels. The number of patients with high levels of interferon-alpha (>400 pg/mL) was significantly larger in the febrile seizure group than in the control group (six of seven patients in the febrile seizure group, 16 of 36 in the control group; P < 0.05). The present findings suggest the possible contribution of interferon-alpha in the pathogenesis of febrile seizures.

[Two cases of Costello syndrome].

We report two unrelated cases of Costello syndrome, presenting with poor postnatal growth, mild mental retardation, poor feeding, curly hair, coarse characteristic face, loose skin, hypotonia, and cardiac involvement. Nasal papilloma and acanthosis nigricans were the most characteristic features of this syndrome. Both cases had atrial fibrilation from infancy to early childhood. One patient had hypertonia in the lower extremities and pes equinovarus, while the other had hypotonia and pes planovalgus.

Frequent association of autism spectrum disorder in patients with childhood onset epilepsy.

Autism spectrum disorder (ASD) has a close relationship with epilepsy. This study retrospectively examined patients with epilepsy associated with ASD. Among the 519 patients with epilepsy, 79 patients (15.2%) had ASD. Sixty-two patients had idiopathic ASD and 17 had secondary ASD. The epilepsy patients with idiopathic ASD were retrospectively analyzed. There were 47 males and 15 females, ranging from 2 to 43 years of age (median 11 years). The most frequent age at the onset of seizures was 4 years, and 85% occurred before 10. ASD was detected after the onset of epilepsy in 29 cases (46.8%), and eight of them had been overlooked for more than five years. Most of these were high-functioning ASD cases. The most frequent type of seizure was a complex partial seizure (CPS; 68%). Paroxysmal activities on EEG were localized in the frontal area in about half of the cases. Multiple anti-epileptic drugs were used in 33.8% cases (two in 17.7%, three in 16.1%), and 67.3% of the patients were seizure-free for more than two years. An amelioration of the autistic symptoms occurred after epilepsy treatment in five cases (8%). CPS with frontal paroxysms occurring from one to nine years of age seems to be characteristic of epilepsy associated with ASD.

Inhibition of human glioma cell growth by a PHS-2 inhibitor, NS398, and a prostaglandin E receptor subtype EP1-selective antagonist, SC51089.

Prostaglandin H synthase (PHS) is a key enzyme in the synthesis of prostaglandins (PGs). Recently, enhanced expression of PHS-2 in brain tumors and the correlation between the PHS-2 level and the histopathological grade of glioma has been reported. Furthermore, in vitro inhibition of glioma cell growth by a specific PHS-2 inhibitor, NS398, has been demonstrated. It has also been shown that prostaglandin E2 (PGE2) contributes to colon carcinogenesis by binding to the prostaglandin E receptor subtype EP1. We therefore evaluated the effects of NS398 and two EP1 antagonists, SC51089 and AH6809, on glioma cell lines. To evaluate mechanisms of NS398's action, two glioma cell lines, a PHS-2-positive cell line (KMG4) and a PHS-2-deficient cell line (A 172), were used. NS398 inhibited both the anchorage-dependent and -independent growth of glioma cell lines regardless of PHS-2 expression, suggesting that some PHS-2-independent mechanisms underlie the antineoplastic effect of NS398. However, the antineoplastic effect was attenuated by the addition of PGE2, which is one of the main products of PHS, suggesting the predominant mechanism is PHS-dependent. The EP1 antagonists, SC51089 and AH6809, inhibited the growth of glioma cell lines in vitro. Furthermore, NS398 or SC51089 slowed tumor growth in vivo, which was assessed using KMG4 tumor xenografts on SCID mice. PHS-2 inhibitors and EP1 antagonists might be useful in the prevention and/or treatment of glioma.