[A case of anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratoma showing excellent recovery with decreasing of anti-N-methyl-D-aspartate receptor antibody].

We report a case of a 17-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms. Pelvic MRI revealed a right ovarian tumor that was suspected of being an ovarian teratoma. On the 27th day after onset, the patient underwent right salpingo-oophorectomy. The histopathological diagnosis was immature ovarian teratoma. Subsequently, 4 double filtration plasmapheresises (DFPP) were performed from day 34 to day 43. Methylprednisolone (1,000 mg/day for 3 days) was started on day 38. With these treatments, consciousness disturbance completely improved, and the patient was discharged on day 50. The serum and cerebrospinal fluid were positive for antibodies against the GluRzeta1 (NR1)-EGFP/GluRepsilon2 (NR2B) heteromer and the GluRzeta1 (NR1) subunit of NMDAR. The patient was hence diagnosed as having anti-NMDAR encephalitis with ovarian teratoma Serial analysis show that the antibodies against NMDAR decreased with improvement of symptoms after the immunotherapy including DFPP treatment.

[Effective cyclophosphamide pulse therapy for an young infant with severe dermatomyositis].

We herein report a 3 year-old boy, who showed proximal muscle weakness and pain at the age of one and a-half years. When he visited our hospital at the age of 1 year and 11 months, he could hardly move by himself. He also had difficulty in swallowing and suffered from multiple dermal ulcers. His blood test showed slightly elevated muscle enzyme activity, and magnetic resonance imaging suggested severe inflammation of the muscles. Radiological examination proved hypoperistalsis of the esophagus. With additional skin and muscle biopsies, we diagnosed him with juvenile dermatomyositis (JDM). Methyl-prednisolone pulse therapy was not effective enough, thus oral methotrexate, cyclosporine A and monthly cyclophosphamide pulse therapy were added. After the fourth cyclophosphamide pulse therapy, his muscular strength was restored, and the ulcers healed dramatically. Due to scarcity of severe cases, neither standardized classification nor grading system for severity in JDM has ever been established, which perplexes physicians in finding the best therapeutic strategy. Further investigation, experience and efforts are necessary to standardize an evaluating system and therapeutic strategy against JDM.

[Brain hypothermia therapy for newborns with severe birth asphyxia: an experience from a single neonatal intensive care unit].

The object of this study was to determine the efficacy and safety of brain hypothermia therapy (BHT) for neonates with severe birth asphyxia in our neonatal intensive care unit (NICU). We retrospectively reviewed medical records to analyze the prognosis and the factors affecting the prognosis of 21 patients who underwent BHT at the NICU between 2001 and 2007. The prognosis of those 21 patients at the time of discharge from the NICU was as follows: good-11 patients (52.4%); disability-5 patients (23.8%); and death-5 patients (23.8%). The ten poor prognosis patients (disability: 5, death: 5) had a shorter gestational period, a lower Apgar score, and a significantly higher blood lactate level in comparison with good-prognosis newborns. In particular, a gestational period of less than 34 weeks (3 patients) and a blood lactate level of at least 200 mg/dl (6 out of 7 patients) are considered to be factors for a poor prognosis. In addition, intraventricular hemorrhage was recorded in 7 patients of the 10 poor-prognosis patients and 4 of those patients developed acute renal failure during BHT. Consequently, these disorders are considered to worsen the prognosis. This study supports the efficacy and safety of BHT for neonates with severe birth asphyxia. On the other hand, BHT for the above mentioned types of high-risk patients still requires further consideration for the adoption and methods of BHT.

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B.

To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminals of human GluN1 and GluN2B, and examined internalization of NMDA-type GluRs in HEK293T cells using confocal microscopy. Internalization of NMDA-type GluRs occurred from at least 10 min after incubation with antibodies to GluN1 and or GluN2B and was temperature-dependent. These findings confirm that antibodies to N-terminals of GluN1 and GluN2B present in the cerebrospinal fluid of patients with NMDAR encephalitis can mediate prompt internalization of NMDA-type GluR complexes.

Detection of autoantibody against extracellular epitopes of N-methyl-D-aspartate receptor by cell-based assay.

The concept of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a severe, potentially lethal, treatment-responsive disorder, mediated by autoantibodies against NMDAR was proposed. Because paraneoplastic anti-NMDAR encephalitis has a better prognosis after tumor resection and immunotherapy, rapid quantitative systems for detecting functional autoantibodies against extracellular epitopes of NMDAR are necessary. To detect autoantibodies recognizing extracellular epitopes of NMDAR, we stably expressed mutant NMDAR that decreases Ca(2+) permeability on a heterologous cell surface without any antagonist. Serum and CSF samples from patients were analysed using the cells expressing mutant NMDAR subunits by immunocytochemistry and on-cell Western analysis using live cells stably expressing mutant NMDAR. Furthermore, we were able to express mutant GluRζ1(NR1, GluN1) subunit of NMDAR alone on the cell surface and obtained direct evidence of the presence of autoantibodies recognizing extracellular epitopes of GluRζ1 and the induction of internalization by autoantibodies in serum and CSF from patients. The specificity of on-cell Western analysis was improved at 37°C. The combination of this rapid quantitative assay using our on-cell western analysis, detailed analysis of extracellular epitopes of NMDAR, and internalization assay of NMDAR will be valuable for the diagnosis, evaluation of clinical treatments, and follow-up of anti-NMDAR encephalitis.